ScienceBlogs - Where the world discusses science en A conversation with a Rigvir flack <span>A conversation with a Rigvir flack</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><p>Over the last two Mondays, I've been <a href="">writing about an unproven cancer therapy</a> that I hadn't really heard much about before. The cancer treatment is called Rigvir; it is manufactured in Latvia and marketed primarily through a Latvian entity called the International Virotherapy Center (IVC). To recap, Rigvir is an unmodified Echovirus, specifically ECHO-7, that, according to the IVC, seeks out cancer cells, replicates in them, and thus lyses the cancer cells (causes their membranes to break, spilling out the cancer cells contents, thus killing the cell), hence the term "oncolytic virus." Somehow, mysteriously Rigvir was approved by the Latvian equivalent of the FDA in 2004 for the treatment of malignant melanoma despite what appears to have been grossly inadequate supporting evidence and then even more mysteriously placed on the Latvian Health Ministry's list of reimbursable medications in 2011. I suspect that the reason that I didn't look into Rigvir earlier was probably because its use had been primarily restricted to Latvia, Georgia, and Armenia. Also, there was the language barrier. Nearly everything available on the web about Rigvir is in Latvian, a situation that has only recently begun to change. </p> <!--more--><p> It was Antonio Jimenez and Ty Bollinger who plucked Rigvir from obscurity. Dr. Jimenez runs the <a href="">Hope4Cancer Institute</a> clinics in <a href="" rel="nofollow">Baja and Cancun, Mexico</a>, and, for whatever reason (probably profit), these clinics started offering Rigvir relatively recently. Then, Jimenez, who's clearly worked with Bollinger in the past, must have turned Bollinger on to Rigvir, and Bollinger included it in a long segment of Episode 3 of his <a href="">The Truth About Cancer</a> (TTAC) propaganda series of videos. It was this connection and the deceptive use of patient testimonials by both Bollinger and the International Virotherapy Center to sell Rigvir that formed the basis of my <a href="">second post on Rigvir last week</a>. As you might imagine, apparently the management of the IVC was not happy about my posts. In fact, so unhappy was the management of the IVC that within 15 hours of <a href="">my first post about Rigvir</a> going live I got an e-mail from someone named Lelde Lapa, whose title was listed as Assistant of Business Development Department at the IVC, protesting and attempting to refute my post. As <a href="">I noted before</a>, I was amazed at how fast I received such a long e-mail after publishing my post. Clearly the IVC has many Google Alerts set for Rigvir and its name and was fast to act. What followed was an exchange that currently stands at five e-mails, three from Ms. Lapa, with two responses from me, with Ms. Lapa's tone (if it indeed was only one person writing these) becoming more strident as the exchange went on. Because these e-mails are a great insight into the thinking (such as it is) at the IVC, I decided that a most excellent way to conclude my series on Rigvir as a trilogy would be to annotate and publish these e-mails, and then to compose a final response to Ms. Lapa's third email, at the end of which Ms. Lapa told me that I didn't need to respond. Clearly <a href="">she don't know me vewy well, do she</a>? So let's begin. Remember that English is not Ms. Lapa's native language; so be kind. I wasn't kind, but not because of any difficulties Ms. Lapa might have had with English.</p> <h2>Rigvir strikes back, round 1</h2> <p>So on the afternoon after <a href="">my first post about Rigvir</a> went live, I was greeted by this in my e-mail in box:</p> <blockquote><p>From: Lelde Lapa &lt; [REDACTED]; To: [redacted] Subject: Blog about RIGVIR Date: Tue, 19 Sep 2017 00:54:53 +0300 Organization: RIGVIR Development department Orac: Yesterday we encountered one of your blogs (<a href=";utm_medium=twitter">…</a>) Due to the fact that this blog is now widely spread by non-professionals with the title – independent conclusion from international expert, we believe we have the rights to inform you that you are used now as a tool in competition wars. Which we believe was never your intention. The medicine RIGVIR has a clinical experience for more than 50 years and it is registered for melanoma for more than 13 years and before the era of modern trials and most of the evidences is not published. Doctors and clinics in Latvia use this medicine for majority of melanoma patients in Latvia for many years. In Latvia medicine is prescribed only in national clinics and by certified doctors and they have also other alternatives, so probably they know what they do. 2 years ago we started EMA (centralised EU) commercialisation process and even obtained EU commission support from Horizon2020 grant, we also obtained EMA regulatory advice. There is no doubts about the efficacy and safety of the medicine, however we acknowledge that we miss modern trials for centralised registration and we are working on them. This was never a secret to discover. But year ago a group of very active, mostly anonymous people appeared that started to attack us, our cooperation partners, even EU commission, spreading bias data or even lies. They are very aggressive. Part of the sources they use does not exists, part of materials are generated by them self and republished in different sources mostly social networks, then in blogs and then cross-referenced. Part of material is made as compilation of different phrases and translated in English with certain pseudo professionals on them (By the way two such persons appears also in your blog, these persons however has no proper educations, has never been involved in medicine or science). Moreover at the spring anonymous letter (your blog also indicated it ) appeared. It was signed by few professional organisations of which only 2 are related to oncology and in fact were represented by the same people, this letter contains ~80 lies and tendentious distortion of information. Unfortunately there is no author on the horizon to be responsible for aspersion, but there have been cases when TV and portals have withdrawn similar articles and information about us already. Mostly your blog analyses openly available data, but partially it contains false information. It contains also comments of pseudo professionals or anti-PR specialists but the producer of RIGVIR was never approached for clarification or comments. Which is sad especially, referring to the statement from the blog: “Somehow I doubt Rigvir will make it that far. At least, I sincerely hope that it doesn’t….” We believe that also blogs should be objective and respectable professors should use only proven data and also verified sources. So please consider to here also our position and obtain more information about virotherapy with RIGVIR, like clinical trial data and post-registration experience. We do provide special trainings for doctors and medical scientists. I hope you are interested, Looking forward for your replay. Best Regards, Lelde Lapa Assistant of Business Development Department <a href=""></a></p></blockquote> <p>Of course, I had no idea who this Lelde Lapa was. I couldn't really find anything about her. A <a href=";as_epq=Lelde+Lapa&amp;as_oq=&amp;as_eq=&amp;as_nlo=&amp;as_nhi=&amp;lr=&amp;cr=&amp;as_qdr=all&amp;;as_occt=any&amp;safe=images&amp;as_filetype=&amp;as_rights=">Google search of the IVC website for her name</a> didn't reveal anything. For my purposes, it doesn't really matter, but I did find it odd. I can't help but note here that, although I do not claim to be completely objective, my bias is rather well known: I favor science as the basis of determining which medical treatments do and do not work. I make no bones about that. Moreover, I couldn't help but immediately note that it's pretty hard to use "only proven data" when there is so little in the way of proven data upon which to evaluate Rigvir. That was, in fact, my key problem with the drug, that it is unproven and being marketed without sufficient scientific and clinical evidence that it does what is claimed for it. Here was my response, sent later that evening:</p> <blockquote><p>Dear Ms. Lapa: The Virotherapy Institute must be very on top of its social media to have noticed my post and composed such a lengthy e-mail to me within 15 hours or so after my post went live. If you have any specific examples of errors in my post, feel free to point them out. What I see in your letter is not that; rather, it is spin, as nothing you wrote actually casts into doubt any facts included in my post or in any of my interpretations of those facts. Yes, I used publicly available information because that’s what many bloggers do when they compose posts. Besides, I was interested in what I view as the irresponsible marketing of Rigvir for more than just melanoma, and there is plenty of that to be found on the Internet and social media. The two videos on your website that I discussed fall into that category, without a doubt. In your e-mail, you state that there are "no doubts about the efficacy and safety of the medicine,” but there are doubts—a lot of doubts—so much so that my jaw dropped when I read that. The reason is simple. You yourself said it: “...we miss modern trials for centralised registration.” Basically, you don’t have anything resembling the level of scientific evidence required before we accept any drug as effective and safe. You have no randomized double-blind clinical trials. All you have are a handful of case reports, a couple of very poorly done retrospective studies, and ancient evidence from decades ago that cannot be inspected and assessed for scientific rigor. In my country, our Food and Drug Administration would laugh at such data. If you’re making health claims for your product, particularly the glowing claims made about Rigvir’s anticancer activity, then all that matters to me is whether there is solid evidence to back up those claims published in the peer-reviewed medical literature as indexed on PubMed. Of course, this evidence must be in the form of papers reporting improved recurrence-free and overall survival in well-designed, randomized double blind clinical trials of your product for every cancer for which a claim of efficacy has been made. I do not care about unpublished data that I cannot examine myself. I do not care about claims. I do not care about “registration,” as clearly the registration process in Latvia at the time Rigvir was registered left a lot to be desired. I do not care about pilot grants to start to work on approval by the EU. None of that matters when evaluating a therapy if there is no good clinical trial evidence supporting its efficacy and safety. Unless you can provide me with those data, I have no choice but to find your complaints about my article to be without merit. If Rigvir has been proven safe and effective and isn’t quackery, then why are you selling it to quack clinics in Mexico and Germany? I’m serious. Hope4Cancer, for instance, is a notorious quack cancer clinic that attracts Americans with cancer. This is not in dispute and can be verified by simply reading the Hope4Cancer website and examining the treatments it offers cancer patients. Also, if Rigvir has been proven safe and effective and isn’t quackery, then why was it featured on Ty Bollinger’s “The Truth About Cancer” video series and, more importantly, why is the administration of the International Virology Center proud of being featured in his videos? Bollinger is a notorious promoter of cancer quackery. (I can provide many examples of him promoting dubious, unproven, and quack treatments for cancer.) No reputable company selling a cancer treatment scientifically proven to be effective and safe would ever want to be associated in any way with the likes of Hope4Cancer or Ty Bollinger, because it would tarnish its brand and bring it into disrepute. In actuality, your response makes me more confident than I was originally that I was correct in my assessment. Your paranoia, for instance, is makes me very suspicious. You rail against “anonymous people” attacking Rigvir and the Virotherapy Center, but isn’t it true that the complaints to the Latvian Health Ministry came from the two main oncology professional associations in Latvia? That’s hardly “anonymous.” They are respected professional medical societies! I also have seen quite a few criticisms of Rigvir on blogs and have been able to identify everyone making the criticisms so far. Perhaps you meant The Mad Virologist, but he isn’t really anonymous either. His name is in his Facebook profile, which I found in two minutes. Complaints about “anonymous” people out to disparage a product always make me think a company has something to hide. Finally, I understand that you and Latvia are proud of Prof. Muceniece’s accomplishments, but ask yourself this: If she were alive today, would she want her name associated with selling her discovery before it’s actually scientifically demonstrated to prolong the lives of cancer patients or cure specific cancers? Orac</p></blockquote> <p>In actuality, I had no idea whether Prof. Muceniece would care what the IVC is doing. I just wanted to see if there was any sense of shame over what the IVC was doing with her invention.</p> <h2>Rigvir strikes back, round 2</h2> <p>A couple of days later, I received this. For reference, the blog by Eduards Ritums was discussed in my first post and used in part as a basis for some of my criticisms. In any case, note the somewhat paranoid tone. I also showed my e-mails to a skeptic from Latvia who has been active investigating Rigvir, who thought that the style changed enough that it might have been written by someone else. I don't know for sure if that is the case (you can judge for yourself), but I do know that the fallacies and dubious arguments flow freely and with paranoia:</p> <blockquote><p>From: Lelde Lapa &lt; [REDACTED]; To: '[REDACTED] Subject: RE: Blog about RIGVIR Date: Thu, 21 Sep 2017 10:03:42 +0300 Organization: RIGVIR Development department Dear Orac As we indicated in our last email your blog now is spread widely in Latvia as a proof that our medicine is not effective. Was it a goal of your blog? We got impression that the blog is a part of wider campaign that is currently in place in Latvia and therefore we just wanted to warn you ASAP and protect your reputation by providing more information if you are ready to hear it. Part of your blog is based on the article that is published by author E.Ritums initially in very specific marketing magazine for Pharmacies. This magazine is published by Medicine Information Centre (<a href=""></a> ) that is not registered in the register of mass media and even provide marketing services (<a href=""></a>). In addition the content of this magazine (according to law in Latvia) is considered to be specialised publication and may not have public access. The author however (based on google search) is young graduate from faculty of Chemistry that in addition to this particular article has published few (~3) more small articles and hardly is respectable journalist. Particular publication consists of number of fact errors and doubtful allegations and there is no respectable or proven sources, books or reviewed publications indicated as reference. Moreover former manager (for 12 years) of the same publisher and magazine Inara Rubene ( <a href=""></a>) is presented as independent expert here. The biggest issue is, however, the fact that this article later, bypassing limited access info (according to law) to specialists, was translated (with inconsistencies) and spread widely with help of very small, non registered NGO – Skeptiskā Biedrība (<a href=";ref=LurTop&amp;regcode=&amp;task=search&amp;company_name=&amp;tipas=&amp;CompanySearchForm%5BcompanyName%5D=Skeptisk%C4%81+Biedr%C4%ABba&amp;CompanySearchForm%5Bcountry%5D=&amp;utf=0&amp;general=Skeptisk%C4%81+Biedr%C4%ABba&amp;cid=LVA_NG_PROD">;ref=LurTop&amp;regcode=&amp;task=searc…</a>), that operates web site – <a href=""></a>. Do you consider this as trustworthy source to build part of your story on? Please note that official page of the product RIGVIR is and there is no marketing at all. Page is mostly dedicated to therapy not medicine – there are news, testimonials and trainings. It is not a clinic or pharmacy to speak about marketing. Should we hide testimonials, if there are such? In Latvia there are very strict regulations for marketing of pharmaceuticals and there is no official judgment from Latvian Health Inspection about as you say “irresponsible marketing”. Moreover the only one claim from Latvian Health Inspection, that initially was stated so, is already changed clearly stating that we cannot be responsible for third party activities. As you know the clinical studies are done mostly for official approval of medicine and according to Bloomberg at least one third of studies are never published. So if you are clearly stating that you don’t care about unpublished data, then please adjust title of your blog to something like “Analysis of published data of RIGVIR”. Because ignoring unpublished clinical trials for more than 30 years, you simply don’t have all the facts to loudly state that our medicine is not effective or it should be avoided. Let us clarify that medicine RIGVIR is registered in Latvia in 2004 for Melanoma, before the era of modern requirements for trials, but based on clinical trials during 30 years period in which ~700 patients was treated with the medicine RIGVIR (there is also registration in Georgia and Armenia). The medicine is used as conventional therapy in Latvian, Georgian and Armenian clinics. In addition to that, patients from all over the world are coming to Latvia or sometimes are sending relatives or trust-persons to Latvia to buy this medicine in case traditional therapies have not succeeded or are not well tolerated. Yes we do train medical doctors from all over the world and probably their patients also have acquired medicine from Latvia. We know that the medicine is effective, we have seen it working on many thousand cases and we clearly know that it has no side effects. So knowing that, should we refuse to help patients of any Doctor? We are not company that is developing innovative solution and according to the heritage of the founder prof. A.Muceniece the medicine should be available to as many patients as possible. We are not refusing the knowledge and information to any official doctor, official clinic or patient groups. So we don’t see any problem also from appearing in The Truth About Cancer series. Most of our critics and also yours complains are catch-22 logic – “give us evidences before you use it -&gt; new evidences requires investments -&gt; to provide investments we need to use medicine –&gt; to use medicine we need to be commercialised -&gt; but with the existing evidences you doubt us to be commercialised …” As if only rich pharmaceutical or biotechnological companies may work in the field… You are stating that you don’t care about existing registration, but unfortunately your analysis is used to doubt the registration. Which is off course strange, because nowhere in the world rules and regulations (in our case standards for clinical trials) are used with backward date. Yes for new registrations - we know the rules – we will provide proper RCT data, but as for now, please respect that the medicine is prescription medicine that is prescribed only in national clinics and by certified doctors for last 13 years. They have alternatives and even reimbursed ones. So obviously these doctors have deeper knowledge about the therapy with RIGVIR, than just analysis of published data, since it is used for more than 70% of Melanoma patients in Latvia. We suggest you to learn about this therapy and try it yourself for your patients (that follows entrance criteria) as well. In such case and with your commitment to make case report and publish it, we would provide all the necessary assistance and medicine free of charge. Best Regards, Lelde</p></blockquote> <p>Gee, Ms. Lapa makes the observation that my blog post has been circulated far and wide in Latvia as evidence that Rigvir doesn't work as though that were a <em>bad</em> thing! In actuality I can't help but feel a bit of a warm and fuzzy feeling in the pit of my cold, black heart that my post has actually been circulated far and wide in Latvia. Those behind IVC will probably take this as evidence that I'm out to get them, but I'm not. I'm out to protect cancer patients. If the IVC had the goods, as far as evidence, the easiest thing for its management to do would have been to publish it or somehow show it to me and other skeptics who are concerned that Rigvir is cancer quackery. We can be persuaded, but it takes evidence. Finally, notice that last part, in which "Ms. Lapa" tries to co-opt me, thinking that if I were to try Rigvir I would conclude that it works. I've noticed this pattern before, and <a href="">where I've noticed before</a> it isn't flattering to Rigvir or the IVC. You see, I've discovered that when it comes to cancer quackery or unproven cancer treatments I seem to have special cachet because I am a cancer surgeon and researcher. Thus, from time to time, cancer quacks try to convince me to try the treatment they are selling on my own patients. In my response, I decided to stomp down hard on this offer after giving a bit of a lecture. See what you think:</p> <blockquote><p>Ms, Lapa, Although I appreciate your concern about my reputation, I think I’m probably the best judge of what will or will not damage it. In other words, I’ll take my chances. Regarding Eduards Ritums’ article, which I did cite extensively, I tend to judge an article and its main arguments far more by quality in terms of evidence, science, and reason than by who wrote it. Even though the article I read was an English language translation, Mr. Ritums’ central thesis and arguments nonetheless came across as very sound. It doesn’t matter if he’s young and early in his career and thus hasn’t published very many articles yet. In other words, who cares if Mr. Ritums published his article in a pharmacy magazine and is a new journalist? I certainly don’t. As for whether the magazine is “registered” or not, as far as I’m concerned that is a matter of your country’s specific laws and ways of doing things. It means very little to me as an American reading a translation of the article. In fact, it wouldn’t matter to me if Mr. Ritums wrote for an unregistered blog under a pseudonym if his arguments, science, and evidence were sound. Certainly, you have not demonstrated that they are not sound; you state that there are a “number of fact errors and doubtful allegations,” but, oddly enough, you have not actually specified the errors of fact or “doubtful allegations,” much less used evidence and science to show that they are factual errors or doubtful allegations. You have instead engaged in nothing but ad hominem, which is a logical fallacy. To convince me, you’re going to have to get a lot more specific and provide the evidence to back up your criticisms, something you have not yet done after two long e-mails. I find this very telling. As for your claim that official Rigvir website is not about marketing, I beg to differ. The whole website is clearly all about marketing, as all pharmaceutical company websites are. Indeed, it looks just like any other pharmaceutical company webpage promoting its products, complete with slick videos, like the one on this page. Basically, your website looks like any of a number of websites pharmaceutical companies maintain for individual products, like Herceptin, OncoTypeDX, or various new drugs. It’s not quite as slick, but it is very similar in appearance and content. True, it doesn’t contain patient testimonials, but that doesn’t make it any less a marketing website. Regarding the testimonials on the Virotherapy Center website, as a surgical oncologist, I find them quite misleading. Insufficient information is provided to allow me to judge whether Rigvir might have had an effect, and one in particular is definitely not evidence that Rigvir had a positive effect. Again, when I accused you of irresponsible marketing, I did it from my perspective as a cancer surgeon and researcher. Again, I really don’t care what Latvian law says with respect to marketing pharmaceuticals. Clearly, from my perspective, Latvian law is far too lax if it allows you to market Rigvir. You say that Rigvir was registered in 2004, “before the era of modern requirements for trials.” I hate to tell you this, but the basic standards for modern clinical trials were codified decades before that. In the US, it was 55 years ago in 1962 when the Kefauver-Harris Amendment to the law creating the FDA mandated that the FDA to require rigorous clinical trial evidence of efficacy and safety before it approves a drug for marketing. Are you honestly telling me that 42 years after that Latvia still didn’t require such evidence before approving a drug? If true, I find that shocking. Be that as it may, Latvia’s lax drug regulation 13 years ago is not an argument in support of the efficacy and safety of Rigvir even for melanoma, much less other cancers. Certainly, it doesn’t excuse you from selling the drug to a quack clinic in Mexico. And, make no mistake, Hope4Cancer is a quack cancer clinic, as I have documented elsewhere. (It even offers coffee enemas.) I’d suggest that, if you really want Rigvir to be accepted outside of Latvia, Georgia, and Armenia, selling it to a quack clinic to market to patients it is not a winning strategy. It will taint Rigvir with the stench of quackery. I’d highly suggest that you sever all ties with these clinics immediately, but I suspect that suggestion will fall on deaf ears. You say over and over that you “know” that Rigvir is effective. The fact is that you do not, at least not based on science and clinical trials, which is how doctors are supposed to know which drugs work and which do not. You claim that I ignored 30 years worth of clinical trials. Whose fault is that? You haven’t published them in a form that can be critically examined. If you had, I would have critically examined them. You wouldn’t even have to translate them into English. I’m sure I could find someone to translate the data for me if you were to publish all this data. Why don’t you? No, I will not change the title of my post. It is accurate, as far as I am concerned. I stand by my opinions and conclusions, and, yes, I still strongly believe that you should stop marketing Rigvir until such a time as clinical trials show it to be safe and effective. Certainly it should not be used for any cancer other than melanoma, and even for melanoma I don’t think you’ve shown sufficient evidence that it works to justify marketing it. Again, I say this because you can’t show me any decent scientific or clinical trial evidence to change my mind. Again, why is that? Does this evidence actually exist, or does it actually show Rigvir has such miraculous effects against melanoma? I suspect that it either does not exist or is not nearly as impressive as you claim. Indeed, there is a contradiction here. You say that 70% of melanoma patients in Latvia since 2004 have been treated with Rigvir. Why is it, then, that you could only find 52 melanoma patients treated with Rigvir for your 2015 Melanoma Research paper? Finally, although I am intrigued by your offer to provide Rigvir for free for me to try on my patients, unfortunately I don’t see how I can do it. Let me explain to you how we do things in the US. Doctors here can’t just go around administering unapproved drugs willy-nilly to patients if we feel like it. Were I to administer Rigvir to patients without proper approvals, I would quickly find myself in deep legal trouble—and rightly so! Were I to want to administer Rigvir to patients, it would have to be in the form of a clinical trial. I would first have to submit an Investigational New Drug (IND) application to the FDA, because Rigvir is not approved in the US. The FDA would then have to approve it. Next, I would have to write a protocol for a clinical trial. Let’s say I chose to do a phase I clinical trial, which would not require randomization. That application would have to be approved by the FDA and approved by my institution, specifically my cancer center's Protocol Review and Monitoring Committee and my university's Institutional Review Board (IRB). Both would almost certainly say no, based on lack of evidence to justify the trial. They would want preclinical evidence in cell culture and animal models, at the very least, or more compelling human evidence. You can provide me with neither. Of course, certainly I would be happy to review the educational materials you provide doctors who wish to administer Rigvir to patients. Maybe they would start to change my mind, although I’ll be honest with you and inform you that I doubt it. However, contrary to what you think, my mind is not closed. What it takes to open it more is high quality scientific and clinical evidence. Provide it, and perhaps it will convince me. If you continue to fail to provide it, and you’ll never change my mind. The ball is in your court. Sincerely Orac</p></blockquote> <h2>Rigvir strikes back, round 3</h2> <p>The IVC didn't respond right away. It took a few days. Indeed, I was beginning to wonder if Ms. Lapa was going to respond again at all, particularly after nothing arrived immediately after <a href="">my second post about Rigvir</a>. Then, just as I was about to send a quick e-mail to tweak Ms. Lapa and see if I could get a response, this hit my e-mail in box:</p> <blockquote><p>From: Lelde Lapa &lt; [REDACTED]; To: [REDACTED] Subject: RE: Blog about RIGVIR Date: Tue, 26 Sep 2017 18:55:40 +0300 Organization: RIGVIR Development department Dear, Dr. Orac ...We are very grateful for every objectively critical remark that is addressed to RIGVIR and we always are trying to provide additional information to the source in order to improve objectivity. This time we however are relay surprised that someone who calls for scepticism and ask for proves, can easily believe to articles without any proven references or sources, that contains statement from people openly in conflict of interest and that is published in non-official portals in order to avoid responsibility for aspersion. And particularly we are sad that you was never interested in our position or in our facts that we openly offered and that are not published. During last month we have seen lots of false news and lies that was spread in Latvia in order to neglect RIGVIR, part of these news is spread under the name of respectable organisations. But unfortunately most of the stories does not have real authors. Most of this campaign is done via social networks so we need time to respond to attacks and we will inform you about the results. In the meantime we are open to organise professional seminars and conventions to share our information. For example, last Friday during the 8th Latvian Doctors Congress, satellite symposium about virotherapy and RIGVIR took place. Reports on clinical trials and post-marketing experience in clinical practice were presented to doctors. Around 5000 doctors were invited and everybody had chance to ask any question to our leading managers. We however received no question from the audience. Regarding rigorous clinical trials, most probably the definition has changed over time. For example the RCT ever was run just after the WWII. What we today call rigorous was defined only in the late 1990ies. While for example the FDA started requiring 5 year survival data for oncologic drugs, in the early 2000 those kind of data were still available only for a portion of NDAs. However A very direct outcome of WWII was that Latvia lost its independence. As a consequence, Latvia was literally thrown decades back, as well as held back, in all aspects of an advanced society. You may find that shocking to learn in 2017, but we can assure you that was a shocking "experience" already at that time on site. And it lasted for 50+ years. A slight and minor side effect, was that regulatory requirements did not adhere to the US framework. They were the so called Soviet style, which include lack of publication as well. Today, however, Latvia is part of EMA territory with the most up-to-date regulatory requirements. Therefore, the mode of showing efficacy has changed both over time and in space. Nevertheless, the requirements regarding efficacy were and are fulfilled. And this again is approved by the Ministry of Health of the Republic of Latvia that on 4th of September 2017 issued official statement supporting that RIGVIR is registered and included in the list of reimbursed medicines appropriately (see English translation enclosed) and here is in latvian source: <a href="">…</a> Regarding the use of Rigvir in Latvia. It may also come as a surprise to you that the medical records system in Latvia has not really changed since WWII. This, of course is not the companies responsibility. It may perhaps assist you in appreciating inclusion criteria used and the effort in managing the analysis published in Melanoma Research. When you discuss about our clinical trials or reproach us about lack of publications we are kindly ask you take into consideration also the economic differences between USA and Latvia fully into account, for example GDP per Capita in Latvia is around 15 thousand Dollars, while in USA it is 52 thousand Dollars or for example the whole budget for melanoma treatment of Latvia is around 0.7 MUSD. In other words you know how much those things costs and you should not judge from the stand point of the most advanced economy with the highest healthcare and science budgets. We are founders (Prof. A.Muceniece) family owned company that’s heritage is to provide this innovative treatment to any patient in the world who needs it and we will not discriminate any patient regardless from which clinic the patient comes. In your latest blog you have analysed part of testimonials about virotherapy with RIGVIR (Please note however that Ty Bolinger’s activates are not related to us). We have seen complains that stories of our patients was just coincidence or that there were other factors behind the survival. But what if we would provide you with many dozens of such testimonials and cases? Is there something at all to convince you? This brings us back to the offer to you - to try the medicine for your patient. For early stage patient they should use medical tourism to Latvia, but with late stages or in cases where there are no other treatment solutions, you might consider in application of extended use of non-registered medicine on-name basis to use the medicine in USA. Off course all the time with your supervision to monitor closely the efficacy. This means that it would be case analysis not a clinical trial. Due to work with EMA we would not initiate any activity with FDA yet, although we have preclinical and clinical evidences to start. We find this discussion, your blog and your activity in twitter really wired. If you suggest that there are better medicine for cancer patients, please use it. We have never limited anyone doing that. RIGVIR is a prescription medicine, patients cannot get the medicine by them self without doctor involvement. So to wrap up - if you would like to explore virotherapy and use it as a treatment, we are ready to cooperate with you and teach you about our evidences. But further correspondence and the exchange of opinions is not necessary any more. Sincerely, Lelde</p></blockquote> <p>Ms. Lapa (or whoever I've been corresponding with) might not think that an exchange of opinons "is not necessary any more" and that she can flounce off, digitally speaking, but I beg to differ. So, instead of responding right away, I decided that a public response would be more appropriate, to be unveiled this morning. So here's my response to Ms. Lapa. I'll be sure to send her a link to this after this post goes live. After all, why bother if the person to whom I respond doesn't see my response? So here we go. Here's my response written over the weekend:</p> <blockquote><p>Dear Ms. Lapa: You clearly don't know me very well if you thought I would not respond to this. Indeed, given what Rigvir Holding and the IVC are doing, I think it's a public service to show what you have been telling me to my readers. It's also not true that I am not interested in your position. If that were the case, I would never have bothered to engage in this lengthy e-mail exchange. That's the point. I've been trying to find out what evidence you have to support all the claims being made for Rigvir's efficacy in melanoma and other cancers. All that's indexed in PubMed is very thin gruel indeed when it comes to clinical evidence. It's not at all convincing. Yet you keep claiming you have this highly convincing evidence while making excuses for not publishing it and whining about people criticizing Rigvir on social media. Well, I have news for you: That's the world. Social media matters. You keep claiming that what's being said about Rigvir is false, but somehow you never actually bother to prove it to be false. And do you know how you could prove that it's false? Show us the data, just like drug companies in the US and EU have to do! So you had a satellite symposium on virotherapy at the 8th Latvian Doctors Congress. That's great, but not enough. A Google search shows that you <a href=";theater" rel="nofollow">had this conference</a> but <a href="" rel="nofollow">nothing about its results</a>. Most satellite conferences publish abstracts of the work presented at the meeting, at least. Such abstracts are not viewed as being as convincing as a publication in a peer-reviewed journal indexed on PubMed, but they are at least something. After your conference, I am currently still left with nothing. It wouldn't even matter to me if the abstracts or conference proceedings were in Latvian. Show me the data! You claim to have clinical trial results and postmarketing results presented at this conference? Publish them! After my previous two posts on Rigvir, I'm sure that I can find someone to translate them if necessary. In the end, I can't help but wonder if your symposium was more of a marketing presentation than an actual scientific conference. Next, I do not need a discourse on the history of clinical trials and FDA requirements for approval of drugs, as I am well aware of that history and when the first randomized clinical trials (RCTs) similar to what we do now were carried out. I mentioned the 1962 Kefauver-Harris Amendment to the law creating the FDA mandated that the FDA to require rigorous clinical trial evidence of efficacy and safety simply to point out that evidence from high quality RCTs has long been a requirement for drug approval in the US and Europe. In oncology at first that meant measuring an endpoint known as overall (or objective) response rates (ORR), which measures what percentage of the patients treated demonstrate tumor shrinkage. Unfortunately, ORR is not a great surrogate for overall survival. So by the early 1980s, the FDA started to require <a href="">evidence of improvement in OS</a>. While it is true that these days, in order to speed up the process of drug approval, the FDA has been accepting surrogates for OS, such as pathologic complete response (pCR) and granting provisional approval for drugs that produce such surrogate endpoints, I note that Rigvir has no convincing published data supporting the conclusion that it can even meet those lower standards for provisional approval. I also do not buy your excuse that Latvia's medical record system hasn't changed since World War II. Believe it or not, until very recently, many US hospitals still used paper charts and relatively primitive record keeping. Many private practices still do. It took laws and incentives from the US government to prod our medical system into adopting electronic health records, and, even then, I note that we will probably never have the excellent centralized medical record systems that some countries in Europe do. As for your excuse that Latvia is a poor country. I counter that the very fact that Latvia is a poor country relative to the US and much of Europe is a very good reason that its government shouldn't be wasting money on cancer treatments whose manufacturer cannot produce strong evidence of efficacy! Yet, since I took an interest in Rigvir recently, I've seen claims that up to 70% of melanoma patients in Latvia are treated with Rigvir. In a country like Latvia, that is insanity if true! Think of what could be done with all that money if it were redirected to treatments that work! I also see Rigvir <a href="" rel="nofollow">being advertised as effective</a> against a wide variety of cancers when not even you have claimed to me that it is effective against any cancer other than melanoma. You claim that Ty Bollinger's activities are not related, but I don't see it that way. In making the long segment on Rigvir in Episode 3 of <cite>The Truth About Cancer</cite> (<cite>TTAC</cite>), Bollinger obviously had the full cooperation of the IVC's leadership. He brought Dr. Antonio Jimenez with him, who runs the quack cancer clinic Hope4Cancer and is now selling Rigvir in Mexico. He had access to your clinic and interviewed luminaries such as Dr. Ivars Kalvins, your medical director Dr. Kaspars Losans, and your director of research and development Dr. Peteris Alberts, as well as three of your patients. The resulting segment was highly laudatory and presented Rigvir as a miracle cure based on dubious testimonials. Like many cancer patients who found out about Rigvir from <cite>TTAC</cite>, I had heard very little about your virotherapy before <cite>TTAC</cite> was released and view the video series as the best marketing for Rigvir I've seen anywhere. Somehow, I doubt that you would have cooperated so much with Mr. Bollinger if you thought his segment would do anything other than praise Rigvir and the IVC the way it did. I conclude by again addressing your offer. I will be blunt. My opinion is that it is unethical, and I will not accept it. Basically, you appear to be paying for case reports that you can publish. My impression of this is backed up by this article on your website about <a href="" rel="nofollow">grants for publications</a>, in which the IVC announces that it is offering €5,000 "grants" for "publications on clinical studies of oncolytic virotherapy, observations or clinical cases in a publication that can be quoted in PubMed" and that the study "is intended on using oncolytic virotherapy rather than using oncolytic virotherapy in combination with other cancer therapies, medication etc." In other words, you want case reports or studies looking only at virotherapy, which, given the doubt about Rigvir's efficacy, would be highly unethical. I note that you also request that grant applicants "inform IVC on the publication topic and present to IVC the document draft before commencing the project and submitting it to the chosen journal." To me this sounds as though you expect the paper to be written, regardless of whether the study has already been done or not, but in fairness I will allow that the ambiguity could be due to a poor grasp of English on the part of whoever wrote this web page. Finally, before you express such disappointment with my blog posts and my activity on Twitter, I note that the Business Development Manager of Rigvir Holding, Kārlis Urbāns, has been attacking me on Twitter using fake news sources. He's been quite nasty. Here are examples:</p> <blockquote class="twitter-tweet" data-lang="en"><p dir="ltr" lang="lv" xml:lang="lv">Jā ļoti neatkarīgs Onkologs no ASV, kas nez kāpēc perfekti citē Latviešu valodu un jau iepriekš barojies no farmas - <a href=""></a></p> <p>— Karlis Urbans (@kurbans) <a href="">September 29, 2017</a></p></blockquote> <script async="" src="//" charset="utf-8"></script><p> I note that he cites a post made by a notorious antivaccine blog, Age of Autism. I note that the bloggers at Age of Autism don't like me because I routinely skewer antivaccine pseudoscience. Here's another example:</p> <blockquote class="twitter-tweet" data-lang="en"><p dir="ltr" lang="lv" xml:lang="lv">Un cik nav fake itkā-onkologu vēstule?<br /> Ir jau vēl daudz, piemēram, <a href=""></a></p> <p>— Karlis Urbans (@kurbans) <a href="">September 29, 2017</a></p></blockquote> <script async="" src="//" charset="utf-8"></script><p> TruthWiki is a fake wiki maintained by Mike Adams, who runs the quack and alt right (yes, both) website and <a href="">got his start selling Y2K scams</a>. The conversation after that is quite amusing, even though I can only read it through the stilted English from computer translation from Latvian on Twitter. I note that Mike Adams has been defaming me on his website for a year and a half now and is up to around 40 lie-filled posts about me. You'll excuse me if I don't take your lamentations about how mean and nasty I've been to the IVC seriously when the BDM and CFO of Rigvir Holding is quoting fake news sources that routinely lie about me and trying to portray me as a tool of big pharma out to destroy Rigvir. So to wrap up – if you would like to provide acceptable scientific and clinical evidence for the efficacy of Rigvir against any cancer, I am ready to cooperate with you and learn about it. Otherwise, further correspondence and the exchange of opinions are not necessary any more. Sincerely, Orac</p></blockquote> <p>After that, there's only one last thing to do: <a href=""><img alt="giphy" class="aligncenter size-full wp-image-49575" data-entity-type="" data-entity-uuid="" height="211" src="" width="400" /></a></p> </div> <span><a title="View user profile." href="/author/oracknows">oracknows</a></span> <span>Sun, 10/08/2017 - 21:36</span> <div class="field field--name-field-blog-categories field--type-entity-reference field--label-inline"> <div class="field--label">Categories</div> <div class="field--items"> <div class="field--item"><a href="/channel/social-sciences" hreflang="en">Social Sciences</a></div> </div> </div> Mon, 09 Oct 2017 01:36:38 +0000 oracknows 22638 at Torturing more mice in the name of antivaccine pseudoscience, 2017 aluminum edition <span>Torturing more mice in the name of antivaccine pseudoscience, 2017 aluminum edition</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><div class="featured-image"><img alt="" class="attachment-post-thumbnail size-post-thumbnail wp-post-image" data-entity-type="" data-entity-uuid="" height="344" sizes="(max-width: 590px) 100vw, 590px" src="" srcset=" 590w, 450w, 154w, 596w, 343w, 150w, 600w" width="590" /><div class="caption" style="width:590px;"> </div> <div class="caption" style="width:590px;">"Why, oh, why do I have to die in the cause of such crappy science?"</div> </div> <p>For antivaxers, aluminum is the new mercury.</p> <p>Let me explain, for the benefit of those not familiar with the antivaccine movement. For antivaxers, it is, first and foremost, always about the vaccines. Always. Whatever the chronic health issue in children, vaccines must have done it. Autism? It’s the vaccines. Sudden infant death syndrome? Vaccines, of course. Autoimmune diseases? Obviously it must be the vaccines causing it. Obesity, diabetes, ADHD? Come on, you know the answer!</p> <p>Because antivaxers will never let go of their obsession with vaccines as The One True Cause Of All Childhood Health Problems, the explanation for how vaccines supposedly cause all this harm are ever morphing in response to disconfirming evidence. Here’s an example. Back in the late 1990s and early 2000s, antivaxers in the US (as opposed to in the UK, where the MMR vaccine was the bogeyman) focused on mercury in vaccines as the cause of autism. That’s because many childhood vaccines contained thimerosal, a preservative that contains mercury. In an overly cautious bit of worshiping at the altar of the precautionary principle, in 1999 the CDC recommended removing the thimerosal from childhood vaccines, and as a result it was removed from most vaccines by the end of 2001. (Some flu vaccines continued to contain thimerosal for years after that, but no other childhood vaccine did, and these days it’s uncommon for thimerosal-containing vaccines of any kind.)</p> <p>More importantly, the removal of thimerosal from childhood vaccines provided a natural experiment to test the hypothesis that mercury causes or predisposes to autism. After all, if mercury in vaccines caused autism, the near-complete removal of that mercury from childhood vaccines in a short period of time should have resulted in a decline in autism prevalence beginning a few years after the removal. Guess what happened? Autism prevalence didn’t decline. It continued to rise. To scientists, this observation was a highly convincing falsification of the hypothesis through a convenient natural experiment, although those who belong to the strain of antivaccine movement sometimes referred to as the mercury militia still flog mercury as a cause of autism even now. Robert F. Kennedy, Jr. is perhaps the most famous mercury militia member, although of late he’s been sounding more and more like a run-of-the-mill antivaxer.</p> <p>Which brings us to aluminum.</p> <p>With mercury in vaccines pretty definitively eliminated as The One True Cause Of Autism, antivaxers started looking for other ingredients to blame for autism because, as I said before, it’s first, foremost, and always all about the vaccines. So naturally they shifted their attention to the aluminum adjuvants in many vaccines. Adjuvants are compounds added to vaccine in order to boost the immune response to the antigen used, and aluminum salts <a href="">have been used</a> as <a href="">effective adjuvants</a> for <a href="">many years now</a> and <a href="">have an excellent safety record</a>. None of that has stopped antivaxers from trying to make aluminum the new mercury by blaming aluminum-containing vaccines for autism. I was reminded by this earlier this week when my e-mail was flooded with messages about new study being <a href="" rel="nofollow">flogged by antivaxers</a> in spectacularly ignorant ways, including three—yes, three—identical messages from a certain antivaxer with a severe case of Dunning-Kruger and delusions of grandeur basically challenging me to review this study and assuring me that antivaxers would be citing it for a long time. Well, whenever I receive messages like that, particularly annoying repetition, my answer is: Be very careful what you wish for.</p> <p>Also: Challenge accepted.</p> <p>Which brings us to the study itself. It’s by antivaccine “researchers” whose <a href="">previous studies</a> and <a href="">review articles</a> I’ve <a href="">discussed before</a>. Yes, I’m referring to Christopher Shaw and Lucija Tomljenovic in the Department of Ophthalmology at the University of British Columbia. Both have a long history of publishing antivaccine “research,” mainly falsely blaming the aluminum adjuvants in vaccines for autism and, well, just about any health problem children have and <a href="">blaming Gardasil for premature ovarian failure</a> and all manner of woes <a href="">up to and including death</a>. Shaw was even prominently featured in the rabidly antivaccine movie <a href="">The Greater Good</a>. Not surprisingly, they’ve <a href="">had a paper retracted</a>, as well..</p> <p>This time around, they’ve gone back to their old stomping grounds, the <em>Journal of Inorganic Biochemistry</em>, and, along with two other co-authors, published <a href="">Subcutaneous injections of aluminum at vaccine adjuvant levels activate innate immune genes in mouse brain that are homologous with biomarkers of autism</a>. It’s where they published review article in 2011 <a href="">full of antivaccine misinformation and distortions</a>. So, given Shaw and Tomljenovic’s history, it is not unreasonable to be suspicious of this study as well. But, hey, you never know. Maybe it’s a good study that sheds light on an important aspect of the pathogenesis of autism…Ah, who’m I kidding? It’s nothing of the sort. It’s yet another study designed to imply that aluminum adjuvants cause autism.</p> <p>Before we look at the study itself, specifically the experiments included in it, let’s consider the hypothesis being tested, because experiments in any study should be directed at falsifying the hypothesis. Unfortunately, there is no clear statement of hypothesis where it belongs, namely in the introduction. Instead, what we get is this:</p> <blockquote><p>Given that infants worldwide are regularly exposed to Al adjuvants through routine pediatric vaccinations, it seemed warranted to reassess the neurotoxicity of Al in order to determine whether Al may be considered as one of the potential environmental triggers involved in ASD.</p> <p>In order to unveil the possible causal relationship between behavioral abnormalities associated with autism and Al exposure, we initially injected the Al adjuvant in multiple doses (mimicking the routine pediatric vaccine schedule) to neonatal CD-1 mice of both sexes.</p> </blockquote> <p>This is basically a fishing expedition in which the only real hypothesis is that “aluminum in vaccines is bad and causes bad immune system things to happen in the brain.” “Fishing expeditions” in science are studies in which the hypothesis is not clear and the investigators are looking for some sort of effect that they suspect they will find. In fairness, fishing expeditions are not a bad thing in and of themselves—indeed, they are often a necessary first step in many areas of research—but they are hypothesis-generating, not hypothesis confirming. After all, there isn’t a clear hypothesis to test; otherwise it wouldn’t be a fishing expedition. The point is that this study does not confirm or refute any hypothesis, much less provide any sort of slam-dunk evidence that aluminum adjuvants cause autism.</p> <p>Moving along, I note that this is a mouse experiment, and somehow antivaxers are selling this as compelling evidence that vaccines cause autism through their aluminum adjuvants causing an inflammatory reaction in the brain. Now, seriously. Mouse models can be useful for a lot of things, but, viewed critcally, for the most part autism is not really one of them. After all, autism is a human neurodevelopmental disorder diagnosed entirely by behavioral changes, and correlating mouse behavior with human behavior is very problematic. Indeed, correlating the behavior of any animal, even a primate, with human behavior is fraught with problems. Basically, there is no well-accepted single animal model of autism, and autism research has been littered with mouse models of autism that were found to be very much wanting. (<a href="">“Rain mouse,” anyone?</a>) Basically, despite the <a href="">existence of many mouse strains</a> touted to be relevant to autism, almost none of them are truly relevant because:</p> <blockquote><p>A good animal model satisfies three fundamental criteria. The first, called face validity, requires sufficient similarities between the phenotype of the mice and symptoms of the human disorder. The second, called construct validity, is achieved if the biological cause of the human disease is replicated in the mouse — for example, when an autism-associated gene is mutated in mice. Finally, a mouse model has predictive validity if treatments improve both the human symptoms of the disorder and the mouse phenotype.</p> <p>Diagnosis of autism is purely behavioral and requires clearly defined symptoms in each of three core categories: abnormal social interactions, impaired communication and repetitive behavior. One of the challenges in studying mouse models is determining which behaviors from the mouse repertoire could be considered analogous to these symptoms.</p> </blockquote> <p>And:</p> <blockquote><p>So far, very few of these mouse models display behavioral phenotypes relevant to all three core domains of autism. What’s more, in some cases, physical problems such as poor general health following seizures, or low exploratory activity, produce false positives that prevent the interpretation of more complex, autism-relevant phenotypes.</p> </blockquote> <p>Pay particular attention to the part about construct validity. The assumption behind this study is that immune changes in the brain of mice will be relevant to immune activation in the brains of autistic humans. That is an assumption that hasn’t yet been confirmed with sufficient rigor to view this study’s results as any sort of compelling evidence that aluminum adjuvants cause autism. Yes, the authors include this important-looking diagram describing how they think immune system activation causes autism (click to embiggen):</p> <p><a href=""><img alt="" class="aligncenter size-medium wp-image-11064" data-entity-type="" data-entity-uuid="" height="184" sizes="(max-width: 450px) 100vw, 450px" src="" srcset=" 450w, 768w, 1024w, 220w, 590w, 596w, 950w, 489w, 150w, 1297w" width="450" /></a></p> <p>In the end, though, as impressive as it is, the relevance of this chart to autism is questionable at best, as is the relevance of this study. So let’s look at the mouse strain chosen by the investigators, <a href="">CD-1 mice</a>. Basically, there’s nothing particularly “autistic” (even in terms of existing mouse models purported to be relevant to autism) about these mice, which are described in most catalogues of companies selling them as “general purpose.” Basically, the authors used them because they had used them before in previous studies in which they reported that aluminum injections caused <a href="">motor neuron degeneration</a> (nope, no autism) and another crappy paper in the same journal from 2013 purporting to <a href="">link aluminum with adverse neurological outcomes</a>. That’s it.</p> <p>As for the experiment itself, neonatal mice were divided into two groups, a control group that received saline injections and the experimental group received injections of aluminum hydroxide in doses timed such that they that purportedly mimicked the pediatric vaccine schedule. Looking over the schedule used, I can’t help but note that there’s a huge difference between human infant development and mouse development. Basically, the mice received aluminum doses claimed to be the same as what human babies get by weight six times in the first 17 days of life. By comparison, in human babies these doses are <a href="">separated by months</a>. In addition, in human babies, vaccines are injected intramuscularly (in a muscle). In this study, the mice were injected subcutaneously (under the skin). This difference immediately calls into question applicability and construct validity. The authors stated that they did it because they wanted to follow previously utilized protocols in their laboratory. In some cases, that can be a reasonable rationale for an experimental choice, but in this case the original choice was questionable in the first place. Blindly sticking with the same bad choice is just dumb.</p> <p>So what were the endpoints examined in the mice injected with aluminum hydroxide compared to saline controls? After 16 weeks, the mice were euthanized and their brains harvested to measure gene expression and the levels of the proteins of interest. Five males and five females from each group were “randomly paired” for “gene expression profiling.” Now, when I think of gene expression profiling, I usually think of either cDNA microarray experiments, in which the levels of thousands of genes are measured at the same time, or next generation sequencing, in which the level of every RNA transcript in the cell can be measured simultaneously. That doesn’t appear to be what the authors did. Instead, they used a technique known as PCR to measure the messenger RNA levels of a series of cytokines. Basically, they examined the amount of RNA coding for various immune proteins in the brain chosen by the authors as relevant to inflammation. The authors also did Western blots for many of those proteins, which is a test in which proteins are separated on a gel, blotted to a filter, and then probed with specific antibodies, resulting in bands that can be measured by a number of techniques, including autoradiography or chemiluminescence, both of which can be recorded on film on which the relevant bands can be visualized. Basically, what the authors did wasn’t really gene expression profiling. It was measuring a bunch of genes and proteins and hoping to find a difference.</p> <p>There’s an even weirder thing. The authors didn’t use quantitative real time reverse transcriptase PCR, which has been the state-of-the-art for measuring RNA message levels for quite some time. Rather, they used a very old, very clunky form of PCR that can only produce—at best—semiquantitative results. (That’s why we used to call it semiquantitative PCR.) Quite frankly, in this day and age, there is absolutely zero excuse for choosing this method for quantifying gene transcripts. If I were a reviewer for this article, I would have recommended not publishing it based on this deficiency alone. Real time PCR machines, once very expensive and uncommon, are widely available. (Hell, I managed to afford very simple one in my lab nearly 15 years ago.) Any basic or translational science department worth its salt has at least one available to its researchers.</p> <p>The reason that this semiquantitative technique is considered inadequate is that the amount of PCR product grows exponentially, roughly doubling with every cycle of PCR, asymptotically approaching a maximum as the primers are used up.<br /> It usually takes around 30-35 cycles before everything saturates and the differences observed in the intensity of the DNA bands when they are separated on a gel become indistinguishable. That’s why PCR was traditionally and originally primarily considered a “yes/no” test. Either the RNA being measured was there and produced a PCR band, or it didn’t. In this case, the authors used 30 cycles, which is more than enough to result in saturation. (Usually semiquantitative PCR stops around 20-25 cycles or even less.) And I didn’t even (yet) mention how the authors didn’t use DNAse to eliminate the small amounts of DNA that contaminate nearly all RNA isolations. Basically, the primers used for PCR pick up DNA as well as any any RNA, and DNA for the genes of interest will be guaranteed to contaminate the specimens without DNAse treatment. Yes, you molecular biologists out there, I know that’s simplistic, but my audience doesn’t consist of molecular biologists.</p> <p>Now, take a look at Figures 1A and 1B as well as Figures 2A and 2B. (<a href="">You can do it if you want</a>. The article is open access.) Look at the raw bands in the A panels of the figures. Do you see much difference, except for IFNG (interferon gamma) in Figure 1A? I don’t. What I see are bands of roughly the same intensity, even the ones that are claimed to vary by three-fold. In other words, I basically am very skeptical that the investigators saw much of difference in gene expression between controls and the aluminum-treated mice. In fairness, for the most part, the protein levels as measured by Western blot did correlate with what was found on PCR, but there’s another odd thing. The investigators didn’t do Western blots for all the same proteins whose gene expression they measured by PCR. Of course, they present primers for 27 genes, but only show blots for 18 (17 inflammatory genes plus beta actin, which was used as a standard to normalize the values for the other 17 genes).</p> <p>I also question the statistical tests chosen by the authors. Basically, they examined each gene separately and used Student’s t-test to assess statistical significance. However, in reality they did many comparisons, at least 17, and there’s no evidence that the authors controlled for multiple comparisons. If one chooses statistical significance to occur at p &lt; 0.05 and compares 20 samples, by random chance alone at least one will be different. Add to that the fact that there is no mention of whether the people performing the assays were blinded to experimental group, and there's a big problem. Basic science researchers often think that blinding isn't necessary in their work, but there is a potential for unconscious bias that they all too often don't appreciate. For example, the authors used Image J, free image processing software developed by the NIH. I've used Image J before. It's a commonly used app used to quantify the density of bands on gels, even though it's old software and hasn't been updated in years. Basically, it involves manually drawing outlines of the bands, setting the background, and then letting the software calculate the density of the bands. The potential for bias shows up in how you draw the lines around the bands and set the backgrounds. As oblivious as they seem to be to this basic fact, basic scientists are just as prone to unconscious bias as the rest of us, and, absent blinding, in a study like this there is definitely the potential for unconscious bias to affect the results. In fairness, few basic science researchers bother to blind whoever is quantifying Western blots or ethidium bromide-stained DNA gels of PCR products, but that's just a systemic problem in biomedical research that I not infrequently invoke when I review papers. Shaw and Tomljenovic are merely making the same mistake that at least 90% of basic scientists make.</p> <p>But let’s step back and take the authors’ results at face value for a moment. Let’s assume that what is reported is a real effect. In the rest of the paper, the authors present evidence of changes in gene expression that suggest the activation of a molecular signaling pathway controlled by a molecule called NF-κB and that male mice were more susceptible to this effect than females. (Just like autism!) Funny, but I know NF-κB. I’ve <a href="">published on NF-κB</a>. I had an NIH R01 grant to study how my favorite protein affected NF-κB. True, I ended up abandoning that line of research because I hit some dead ends. True, I’m not as familiar with NF-κB as I used to be. But I do know enough to know that NF-κB is easy to activate and very nonspecific. I used to joke that just looking at my cells funny would activate NF-κB signaling. Also, NF-κB activation is indeed associated with inflammation, but so what? What we have is an artificial model in which the mice are dosed much more frequently with aluminum than human infants. Does this have any relevance to the human brain or to human autism? who knows? Probably not. No, almost certainly not.</p> <p>Also, the mouse immune system is <a href="">different</a> from the <a href="">human</a> <a href="">immune system</a>. None of this stops the authors from concluding:</p> <blockquote><p>Based on the data we have obtained to date, we propose a tentative working hypothesis of a molecular cascade that may serve to explain a causal link between Al and the innate immune response in the brain. In this proposed scheme, Al may be carried by the macrophages via a Trojan horse mechanism similar to that described for the human immunodeficiency virus (HIV) and hepatitis C viruses, travelling across the blood-brain-barrier to invade the CNS. Once inside the CNS, Al activates various proinflammatory factors and inhibits NF-κB inhibitors, the latter leading to activation of the NF-κB signaling pathway and the release of additional immune factors. Alternatively, the activation of the brain’s immune system by Al may also occur without Al traversing the blood-brain barrier, via neuroimmuno-endocrine signaling. Either way, it appears evident that the innate immune response in the brain can be activated as a result of peripheral immune stimuli. The ultimate consequence of innate immune over-stimulation in the CNS is the disruption of normal neurodevelopmental pathways resulting in autistic behavior.</p> </blockquote> <p>That’s what we call in the business conclusions not supported by the findings in a study. On a more “meta” level, it’s not even clear whether the markers of inflammation observed in autistic brains are causative or an epiphenomenon. As Skeptical Raptor noted. It could be that the inflammation reported is caused by whatever the primary changes in the brain that result in autism. Cause and effect are nowhere near clear. One can’t help but note that many of the infections vaccinated against cause way more activation of the immune system and cytokines than vaccination.</p> <p>So what are we left with?</p> <p>Basically, what we have is yet another mouse study of autism. The study purports to show that aluminum adjuvants cause some sort of “neuroinflammation,” which, it is assumed, equals autism. By even the most charitable interpretation, the best that can be said for this study is that it might show increased levels of proteins associated with inflammation in the brains of mice who had been injected with aluminum adjuvant way more frequently than human babies ever would be. Whether this has anything to do with autism is highly questionable. At best, what we have here are researchers with little or no expertise in very basic molecular biology techniques using old methodology that isn’t very accurate overinterpreting the differences in gene and protein levels that they found. At worst, what we have are antivaccine “researchers” who are not out for scientific accuracy but who actually want to promote the idea that vaccines cause autism. (I know, I know, it’s hard not to ask: Why not both?) If this were a first offense, I’d give Shaw and Tomljenovic the benefit of the doubt, but this is far from their first offense. Basically, this study adds little or nothing to our understanding of autism or even the potential effects of aluminum adjuvants. It was, as so many studies before, the torture of mice in the name of antivax pseudoscience. <a href="">The mice used in this study died in vain</a> in a study supported by the <a href="">profoundly antivaccine Dwoskin Foundation</a>.</p> <p>Also, I’ll tell my antivax admirer the same thing I once told J.B. Handley when he taunted me to examine a study that he viewed as “slam dunk” evidence for a vaccine-autism link: <a href="">You don’t tug on Superman’s cape</a>. And, no, <a href="">your name isn’t Slim</a>. You’re not an exception.</p> <p><strong>ADDENDUM 9/27/2017</strong>: Apparently I wasn’t…Insolent…enough with this paper. On PubPeer there is a big discussion about whether the images in this paper were manipulated and whether the authors self-plagiarized Figure 1 from another paper. <a href="">It looks bad</a>.</p> </div> <span><a title="View user profile." href="/author/oracknows">oracknows</a></span> <span>Thu, 09/21/2017 - 01:00</span> <div class="field field--name-field-blog-categories field--type-entity-reference field--label-inline"> <div class="field--label">Categories</div> <div class="field--items"> <div class="field--item"><a href="/channel/brain-and-behavior" hreflang="en">Brain and Behavior</a></div> </div> </div> Thu, 21 Sep 2017 05:00:11 +0000 oracknows 22627 at Comments of the Week #175: From future technology to the cause of dark energy <span>Comments of the Week #175: From future technology to the cause of dark energy</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><blockquote><p>“There will be days when we lose faith. Days when our allies turn against us...but the day will never come that we forsake this planet and its people.” ―Optimus Prime</p></blockquote> <p>There was too much to simply keep it to a single article a day this week here at <a href="">Starts With A Bang!</a> The dynamic duo of Megan Watzke and Kimberly Arcand published a delightful contribution on scale, and we're gearing up for a month where we'll highlight some of the telescopes of the 2020s (and maybe beyond) that will help shape the future of astronomy. In the meantime, those of you who caught totality from the eclipse have affirmed to me that it was, in fact, one of the greatest experiences of your lifetime. Want to know exactly what it was like? Well, check out our <a href="">latest episode</a> of the <a href="">Starts With A Bang podcast</a>, where we highlight exactly that!</p> <p></p><center> <iframe frameborder="no" height="450" scrolling="no" src=";color=ff5500&amp;auto_play=false&amp;hide_related=false&amp;show_comments=true&amp;show_user=true&amp;show_reposts=false&amp;visual=true" width="100%"></iframe><p></p></center> <p>Thanks to our generous <a href="">Patreon supporters</a> (including some of you), we've got some fantastic ideas in the pipeline that I can't wait for you to read. In the meantime, though, let's take a look back as to what we've covered over this past week:</p> <ul><li><a href="" rel="noopener noreferrer" target="_blank">What science experiments will open the door to the future?</a> (for Ask Ethan),</li> <li><a href="">The ‘Eye Of Creation’ Holds The Secrets To Cosmic Life And Death</a> (for Mostly Mute Monday),</li> <li><a href="" rel="noopener noreferrer" target="_blank">How Hurricane Harvey’s Record-Setting Rainfall Is Happening Right Now</a>,</li> <li><a href="" rel="noopener noreferrer" target="_blank">No, Neil deGrasse Tyson, Squashing Curiosity And Wonder Is Never Okay</a>,</li> <li><a href="" rel="noopener noreferrer" target="_blank">Why understanding scale is vital, not just for science, but for everyone</a> (by Kimberly Arcand and Megan Watzke),</li> <li><a href="" rel="noopener noreferrer" target="_blank">5 Facts We Can Learn If LIGO Detects Merging Neutron Stars</a>, and</li> <li><a href="" rel="noopener noreferrer" target="_blank">A new explanation for dark energy: the matter in our Universe</a>.</li> </ul><p>I just received word that we're six weeks away from the publication of <a href="">Treknology</a>, and that enough preorders have happened that they're <em>already</em> going to have to do a second printing of the book! (That's good news, probably.) But you're not here to get book updates; you're here for the bonus science. With that said, let's get right to it, and into our <a href="">comments of the week</a>!</p> <div style="width: 610px;display:block;margin:0 auto;"><a href="/files/startswithabang/files/2017/05/Ev059HR_3D-1200x954.jpg"><img alt="" class="size-medium wp-image-36211" data-entity-type="" data-entity-uuid="" height="477" src="/files/startswithabang/files/2017/05/Ev059HR_3D-1200x954-600x477.jpg" width="600" /></a> The particle tracks emanating from a high energy collision at the LHC in 2014. Although these collisions are plentiful and incredibly energetic, they have not yet yielded any compelling evidence of physics beyond the Standard Model. Image credit: Wikimedia Commons user Pcharito. <p> </p> </div> <blockquote><p>From <a href="">Elle H.C.</a> on nuclear reactions and energy conservation: "On the mass-energy conversion, so why do they say there’s no energy released during particle collisions, like in a fission reaction for instance, or is this something I misunderstood?"</p></blockquote> <p>So there's an important starting point that I want to make sure gets emphasized: in every particle-particle, particle-photon, antiparticle-particle, etc., reaction that's ever been observed, energy and momentum both are always 100% conserved. If you add up the energy of the rest mass plus the kinetic energy of the initial reactants, and compare it to the energy of the rest mass plus the kinetic energy of the products, energy is always conserved. Those two numbers will balance one another out. Now, that doesn't mean that the masses are going to balance! In fact, in pretty much every nuclear reaction, they don't; either you have fusion (where energy is released, bringing you up closer to iron-56), or fission (where energy is released, bringing you down closer to iron-56), and so there's more <em>kinetic</em> energy available at the end. That's what normally happens. So overall, energy is usually liberated in a nuclear reaction, but it's just being converted from one form (mass) to another (kinetic energy).</p> <blockquote><div style="width: 610px;display:block;margin:0 auto;"><a href="/files/startswithabang/files/2015/10/fig_four8.jpg"><img alt="" class="size-full wp-image-33629" data-entity-type="" data-entity-uuid="" height="181" src="/files/startswithabang/files/2015/10/fig_four8.jpg" width="600" /></a> The only way to 'disrupt' a proton, or any particle, is via a collision, interaction, or decay involving another external particle. Image credit: Ned Wright / Sean Carroll, via <a href=""></a>. <p> </p> </div> <p>And from <a href="">Elle H.C.</a> again, on what may be the root of all these misconceptions: "I am only focusing on the idea of how vibrations might change the energy/mass levels of a Proton, and if that may lead to the disruption of a Proton. Please do explain to us what’s so ‘misleading’ about this question."</p></blockquote> <p>What's misleading is that "vibration" is a completely unrelated classical concept that has no business in the quantum world. It's not related and the question makes no sense, as nuclei don't vibrate, energy levels don't vibrate, and nothing of the sort causes the disruption or disintegration of a proton. For what seems like ages, you've been going on about this, and I couldn't for the life of me figure out why you wouldn't take "this makes no sense" for an answer. But now I think I see. For clarification, you also <a href="">provided a link</a> to where this idea of vibration comes from: <a href="">Sean Carroll's blog</a>. And Sean, like many, talks about how a particle can be viewed as a vibration, or excitation, of a fundamental field. For example, he calls the Higgs boson a vibration of the Higgs field. So I think this is where your misconception arises, because you are picturing the field as an underlying, static thing, permeating all of space, and that it's vibrating in one place, creating a particle there, and so if you make that field vibrate in one spot over and over, perhaps you can make something interesting happen. I <em>think</em> that's where your mind is. And if so, here's why it's wrong.</p> <div style="width: 610px;display:block;margin:0 auto;"><a href="/files/startswithabang/files/2017/09/zhIUh.jpg"><img alt="" class="size-medium wp-image-36585" data-entity-type="" data-entity-uuid="" height="451" src="/files/startswithabang/files/2017/09/zhIUh-600x451.jpg" width="600" /></a> The vibrating modes of a guitar string. Image credit: Mark Peterson / Mt. Holyoke. <p> </p> </div> <p>Sure, for a physical string, it makes sense to talk about different vibrational modes, and how they correspond to different sounds or frequencies. But for fields and particles, they're only called:</p> <ul><li>modes,</li> <li>or vibrations,</li> <li>or energy levels,</li> <li>or excitations,</li> </ul><p>because the different allowable states obey an analogous set of mathematical rules. But <em>nothing is vibrating</em>, and <em>nothing is excited</em>, and <em>nothing is physically at a different level</em>, and so on. The proton does not vibrate; space does not vibrate; even fields do not vibrate. Particles don't exist (or not exist) because a field is (or isn't) vibrating; particles exist (or not) with a particular configuration because of the quantum state that a quanta of energy occupies (or doesn't occupy). I hope this clears up your "vibration" questions once and for all! You have misinterpreted an analogy to mean something other than what it means, and have been talking about physical impossibilities as though they had validity because of it. But that's not the end of the world! It just means that you have an opportunity, so long as you're humble before the laws of nature, to learn about where your misconception is. You can learn about the way the Universe actually works, revise your picture of it, and begin drawing more valid conclusions and asking better questions. If you can do that, you're well on your way to a satisfying life that's rooted in the physical reality we all inhabit.</p> <blockquote><div style="width: 610px;display:block;margin:0 auto;"><a href="/files/startswithabang/files/2017/08/max_7841-1200x801.jpg"><img alt="The ALPHA collaboration has come the closest of any experiment to measuring the behavior of neutral antimatter in a gravitational field. Depending on the results, this could open the door to incredible new technologies. Image credit: Maximilien Brice/CERN." class="size-medium wp-image-36545" data-entity-type="" data-entity-uuid="" height="401" src="/files/startswithabang/files/2017/08/max_7841-1200x801-600x401.jpg" width="600" /></a> The ALPHA collaboration has come the closest of any experiment to measuring the behavior of neutral antimatter in a gravitational field. Depending on the results, this could open the door to incredible new technologies. Image credit: Maximilien Brice/CERN. <p> </p> </div> <p>From <a href="">Frank</a> on what is and isn't possible: "Basically, we don’t really know many big ideas in science-fiction are really theoretically/practically possible or not. And that means our knowledge of physics is incomplete. And that means we should try to answer those questions by doing more theoretical research, as well as more experiments and observations."</p></blockquote> <p>Here's the important thing, to be totally transparent: Everything that we can draw conclusions about is based only in our current understanding of physics and the laws that govern the Universe. But it's fun, as a theorist, to play the game of "what if?" What if all we know isn't all there is to physics? What if there are some new things? And if X or Y or Z is a new thing, what are the consequences that arise? That was the point of <a href="" rel="noopener noreferrer" target="_blank">last week's Ask Ethan article</a>: what could possibly occur to bring some of our "science fiction" dream technologies into reality? And if antimatter has a negative gravitational mass (we haven't made a sensitive enough test), or dark matter can be harnessed and turned/amplified into energy via <em>E = mc^2</em> (it may be possible), or if the Universe rotates at the right rate to allow closed timelike curves (it probably doesn't, but it isn't ruled out), some very interesting consequences arise. In particular, some presently thought-to-be-impossible ideas become possible. And that's worth remembering, as we continue to experiment.</p> <blockquote><div style="width: 610px;display:block;margin:0 auto;"><a href="/files/startswithabang/files/2017/08/1280px-Antimatter_Rocket-1200x960.jpg"><img alt="" class="size-medium wp-image-36546" data-entity-type="" data-entity-uuid="" height="480" src="/files/startswithabang/files/2017/08/1280px-Antimatter_Rocket-1200x960-600x480.jpg" width="600" /></a> All rockets ever envisioned require some type of fuel, but if a dark matter engine were created, new fuel is always to be found simply by traveling through the galaxy. Image credit: NASA / MSFC. <p> </p> </div> <p>From <a href="">CFT</a> on loss and behavior: "My last few posts were very upset and angry, I made the mistake of drinking after receiving a phone call about the death of someone very dear to me."</p></blockquote> <p>Well all the best to you in these troubling times. May you make peace with what has happened and come out okay with yourself, your life, and the world without your loved one on the other side of your grief. Thank you, also, to <a href="">rich r</a> for being a model of kindness in his compassion to CFT. Kindness, remember, costs us nothing.</p> <blockquote><div style="width: 610px;display:block;margin:0 auto;"><a href="/files/startswithabang/files/2017/08/Hurricane-Harvey.jpg"><img alt="From the International Space Station on August 25, 2017, 250 miles above Earth, a NASA astronaut captured photos of Hurricane Harvey. Image credit: NASA." class="size-medium wp-image-36569" data-entity-type="" data-entity-uuid="" height="337" src="/files/startswithabang/files/2017/08/Hurricane-Harvey-600x337.jpg" width="600" /></a> From the International Space Station on August 25, 2017, 250 miles above Earth, a NASA astronaut captured photos of Hurricane Harvey. Image credit: NASA. <p> </p> </div> <p>From <a href="">John</a> on the physics of hurricanes: "It’s notable to read here of a science that appears essentially the same as was presented to me in primary school many moons ago!"</p></blockquote> <p>This is very much the case! The basics of hurricane science and tropical storm formation, in general, has changed very little in perhaps the past 40+ years. Once we began launching Earth-monitoring satellites to watch how these storms form over the ocean, we learned very quickly what the mechanisms at play were. Air blowing rapidly over a warm ocean (typically, at least 80 degrees Fahrenheit or 27 degrees Celsius) will result in that air collecting water, rising, cooling, forming clouds, and then the air dropping again, while additional warm, wet air continuing to rise beneath it. The faster the winds and the warmer the water, the more devastating this can get. People with a variety of political persuasions are going to argue about what the finer points of this one event -- Hurricane Harvey -- means, but the previous paragraph, about the basic science behind hurricane formation, will not change, no matter what is legislated.</p> <blockquote><div style="width: 610px;display:block;margin:0 auto;"><a href="/files/startswithabang/files/2017/08/globe_inset_v3.jpg"><img alt="" class="size-medium wp-image-36562" data-entity-type="" data-entity-uuid="" height="600" src="/files/startswithabang/files/2017/08/globe_inset_v3-600x600.jpg" width="600" /></a> The entire path of totality across Earth's surface, for the August 21, 2017 eclipse. Only 0.26% of the surface experienced totality. Image credit: NASA's Scientific Visualization Studio. <p> </p> </div> <p>From <a href="">Sean T</a> on Neil deGrasse Tyson's wonder-crushing statements: "Most people will only experience an eclipse when it is relatively close to home, as this one was for Americans (as will, of course the 2024 one be as well). Let people just wonder at and enjoy it when they can."</p></blockquote> <p>Do you see the above image? See that "giant" swath where the eclipse falls? That quarter-of-a-percent of Earth's surface? According to Neil, that's what "not rare" looks like. Now, there was misinformation out there -- and it's always good to correct misinformation -- but it's important to do it in a way that's inclusive, that doesn't talk down to people, and that amplifies the wonder and awe at the natural Universe. At least, that's what I try to have be my <em>modus operandi</em>. But I have gotten, particularly on Twitter and Tumblr, a lot of hate mail about the piece I wrote about Neil. This is one of the dangers of a personality cult: if you deify someone, you lose the ability to recognize their flaws, no matter how egregious they are. And if you believe it about yourself, you lose the ability to self-improve. May we all never fall into that trap here!</p> <blockquote><div style="width: 610px;display:block;margin:0 auto;"><a href="/files/startswithabang/files/2017/08/Jangle-Joe-Sexton.jpg"><img alt="The eclipsed Sun, the visible corona, and the reddish hues around the edges of the Moon's shadow — along with human beings rapt with awe — were among the most spectacular sights of the total eclipse. Image credit: Joe Sexton / Jesse Angle." class="size-medium wp-image-36531" data-entity-type="" data-entity-uuid="" height="450" src="/files/startswithabang/files/2017/08/Jangle-Joe-Sexton-600x450.jpg" width="600" /></a> The eclipsed Sun, the visible corona, and the reddish hues around the edges of the Moon's shadow — along with human beings rapt with awe — were among the most spectacular sights of the total eclipse. Image credit: Joe Sexton / Jesse Angle. <p> </p> </div> <p>From <a href="">jvj</a> on another eclipse experience: "I spent 45 minutes explaining how an eclipse happens to a young person, with a HS education, who didn’t know what the Milky Way is. He spent 1 1/2 hours watching the eclipse with his family with a pair of Celestron 2X eclipse glasses I gave him. (We had 80% totality in our location). No doubt hundreds of thousands of folks who haven’t given “science” a second thought in a long time also joined my friend in experiencing the eclipse."</p></blockquote> <p>Part of the reason, I think, that so many people don't engage with science is that it feels so foreign to them. It feels as though it's divorced from their day-to-day experience. What made this eclipse special is that there were literally <strong>200,000,000 people</strong> who lived within a 1-day drive of the path of totality. This was a very rare opportunity for people to experience a cosmic event that only occurs over any particular location on Earth, on average, once every 400 years or so. Yes, eclipses <em>anywhere</em> aren't rare, but you don't get to be everywhere on Earth at once. Relating science to what people experience and understand is one of the biggest challenges of science communication. Yes, Neil correctly stated a fact, achieving McLovin levels of communication.</p> <p></p><center> <iframe allowfullscreen="allowfullscreen" frameborder="0" height="315" src="" width="560"></iframe><p></p></center> <p>But I think everyone who demands more isn't being unreasonable. In fact, people who think Neil should be immune from criticism or improvements because of the good he does are missing the point of learning, of self-improvement, and of knowledge entirely. But that's just my opinion, and you're entitled to your own as well.</p> <blockquote><div style="width: 610px;display:block;margin:0 auto;"><a href="/files/startswithabang/files/2017/08/bennu_size_comparison.jpg"><img alt="" class="size-medium wp-image-36571" data-entity-type="" data-entity-uuid="" height="287" src="/files/startswithabang/files/2017/08/bennu_size_comparison-600x287.jpg" width="600" /></a> Comparing the size of unrelated objects, such as a 'familiar' one with an 'unfamiliar' one, can help people get a feel for scale in a uniquely powerful way. Image credit: NASA’s Goddard Space Flight Center Conceptual Image Lab. <p> </p> </div> <p>From <a href="">symball</a> on visualizations for scale: "Here in the UK we have a more standard unit scale, for areas it is the size of Wales, and for volume either olympic swimming pools or Wembley Stadium. For height we use double decker buses, or occasionally Nelsons Column."</p></blockquote> <p>I personally propose that we begin using a single, standard unit for areas, volumes, heights, and weights.</p> <div style="width: 610px;display:block;margin:0 auto;"><a href="/files/startswithabang/files/2012/07/GodzillaRSC.jpeg"><img alt="Godzilla munching on a train" class="size-medium wp-image-18669" data-entity-type="" data-entity-uuid="" height="432" src="/files/startswithabang/files/2012/07/GodzillaRSC-600x432.jpg" width="600" /></a> Image credit: Godzilla the motion picture, by Ishirō Honda, image retrieved from Will Dodson. <p> </p> </div> <p>How do you feel about units of "Godzillas"?</p> <blockquote><div style="width: 610px;display:block;margin:0 auto;"><a href="/files/startswithabang/files/2017/08/dietrich_bin_neutron_star_mgr_01.jpg"><img alt="3D rendering of the gravitational waves emitted from a binary neutron star system at merger. The central region (in density) is stretched by a factor of ~5 for better visibility. Image credit: AEI Potsdam-Golm." class="size-medium wp-image-36567" data-entity-type="" data-entity-uuid="" height="351" src="/files/startswithabang/files/2017/08/dietrich_bin_neutron_star_mgr_01-600x351.jpg" width="600" /></a> 3D rendering of the gravitational waves emitted from a binary neutron star system at merger. The central region (in density) is stretched by a factor of ~5 for better visibility. Image credit: AEI Potsdam-Golm. <p> </p> </div> <p>From <a href="">Anadish Kumar Pal</a> on whether LIGO could have detected merging neutron stars or not: "There might be some astronomical observation of gravitational waves produced by neutron stars; although, I think, this time it is quite improbable, looking at the sheer fortuitousness of the so-called detection makes it untenable — the VIRGO run was too short (just 25 days), LIGO never found any orbiting neutron stars’ gravitational waves in the last 3 years, while there are too many neutron stars nearby to have slipped LIGO’s notice."</p></blockquote> <p>Remember, please, how probability works. And combine that with how gravitational wave events work. The amplitude of gravitational waves increase tremendously in the final moments, as the distance between two objects reaches a minimum. The known neutron star pairs are far too distant to have their gravitational wave amplitudes detected. In fact, it's only during the final seconds, at most, that inspiraling binaries will be at the appropriate frequencies and amplitudes to be seen by LIGO.</p> <div style="width: 610px;display:block;margin:0 auto;"><a href="/files/startswithabang/files/2017/06/f5.jpg"><img alt="" class="size-medium wp-image-36298" data-entity-type="" data-entity-uuid="" height="475" src="/files/startswithabang/files/2017/06/f5-600x475.jpg" width="600" /></a> The sensitivities of a variety of gravitational wave detectors, old, new, and proposed. Note, in particular, Advanced LIGO (in orange), LISA (in dark blue), and BBO (in light blue). Image credit: Minglei Tong, Class.Quant.Grav. 29 (2012) 155006. <p> </p> </div> <p>So saying "we didn't see anything in years" is like buying a lottery ticket every second for a few years (it was months, actually, but whatever), and not winning, and drawing the conclusion that <em>therefore</em><em>, I won't win if I play for another few weeks</em>. But maybe you will! No one expected LIGO would detect its first black hole-black hole merger after turning on for just a few days in September of 2015, but it happened. Merging neutron stars -- with or without VIRGO observing it, too -- could have happened. Of course, it could <em>not</em> have happened, too. It's just speculation at this point. But don't say "too many neutron stars nearby to have slipped LIGO’s notice" as though that's a fact. Until we know the merger rate and the local population of neutron star binaries, that's not a valid conclusion.</p> <blockquote><div style="width: 610px;display:block;margin:0 auto;"><a href="/files/startswithabang/files/2017/04/LQCD1.jpg"><img alt="" class="size-medium wp-image-36034" data-entity-type="" data-entity-uuid="" height="424" src="/files/startswithabang/files/2017/04/LQCD1-600x424.jpg" width="600" /></a> As computational power and Lattice QCD techniques have improved over time, so has the accuracy to which various quantities about the proton, such as its component spin contributions, can be computed. Image credit: Laboratoire de Physique de Clermont / ETM Collaboration. <p> </p> </div> <p>And finally, from <a href="">Frank</a> on analogous experiments: "If physical Black Hole analogue(s) possible, then maybe we should try to find physical analogue(s) for expansion of the universe/Dark Energy."</p></blockquote> <p>You must be <em>very</em> precise if you want to create an analogue system. Most people, when they talk about building a system as an analogy for a system that we cannot physically study in a lab, misunderstand what's going on entirely. It's very tempting to try and create a visualization in your head for what an analogous system would look like, to set that system up, and then run experiments. But that is <em>not</em> what an "analogue system" as you call it actually is. Rather, it's a system that is governed by the same equations, which may or may not look anything like the original system you're trying to model. You know how we build black hole analogs? We create a low-temperature, condensed matter system with a rapidly flowing fluid, where it flows so fast it exceeds the speed of sound in that medium. These <a href="">sonic black holes</a> are called this because sound waves cannot escape from the fluid. It's a mathematical analogy. We can try to find a physical analogue for an expanding Universe or dark energy, but that's a tall order that won't be easily accomplished by a conventional, positive-pressure fluid or gas. It's important to be open-minded, but when you confront your idea with physical reality, it's reality that shall always be the victor and the arbiter of what's right. Thanks for a great week, everyone, and I'll see you back here tomorrow for more Starts With A Bang!</p> </div> <span><a title="View user profile." href="/author/esiegel">esiegel</a></span> <span>Sun, 09/03/2017 - 02:04</span> <div class="field field--name-field-blog-categories field--type-entity-reference field--label-inline"> <div class="field--label">Categories</div> <div class="field--items"> <div class="field--item"><a href="/channel/physical-sciences" hreflang="en">Physical Sciences</a></div> </div> </div> Sun, 03 Sep 2017 06:04:11 +0000 esiegel 37089 at NASA team provides free satellite public health data to researchers and communities <span>NASA team provides free satellite public health data to researchers and communities</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><p>by Dominika Heusinkveld, MD, MPH Researchers at NASA and the University of Arizona, among others, are hoping to make real-time air quality forecasting a reality in the next few years. The <a href="">NASA Health and Air Quality Applied Sciences Team</a>, or HAQAST, is collaborating with health departments, county and state agencies, and university researchers to get the word out about its satellite data. The data, available for free online, can help track air quality indicators, heavy metals in air, dust, and other atmospheric components which can affect human health.</p> <div style="width: 310px;display:block;margin:0 auto;"><a href="/files/thepumphandle/files/2017/08/photo.png"><img alt="" class="wp-image-11937 size-medium" data-entity-type="" data-entity-uuid="" height="197" src="" width="300" /></a> Photo courtesy of NASA Image Library <p> </p> </div> <p>NASA satellites have been collecting data for years on nitrogen dioxide, ozone, particulate matter, and sulfur dioxide. The time period of available data depends on when the individual satellite was launched. The HAQAST team hopes to encourage local stakeholders to make use of it. NASA HAQAST Team Leader Dr. Tracey Holloway says,  “Hopefully when [agencies] see that satellite data and other NASA resources can answer their [public health] questions, they will take advantage of all the amazing satellite and other data available.” A past NASA project, the <a href="">Air Quality Applied Sciences Team</a> (AQAST), was the genesis of the current HAQAST project. AQAST aimed to increase the utility of satellite data to researchers and public agencies while improving communication with stakeholders such as the public and government officials. “We publish papers in journals but it’s not really percolating into policy,” said <a href="">Avelino Arellano, Jr.</a>, Associate Professor of Data Assimilation and Atmospheric Chemistry at the University of Arizona’s Department of Hydrology and Atmospheric Sciences. The AQAST project was an important way to connect the data to stakeholders. One of the AQAST projects resulted in a brief <a href="">video</a> with President Obama explaining how satellite data has been helpful in tracking nitrogen dioxide, a common air pollutant. Arellano sees the video as one of the success stories of AQAST.  Another was improving communication and relationships between agencies like NASA, the EPA, and NOAA. “AQAST was instrumental in showing how satellites can ‘see’ trends in air pollution, even in areas where no other monitors exist. As a result, the EPA used satellite data in their <a href="">public report</a> on clean air trends for the first time in 2016,” says Holloway. HAQAST plans to build on those successes with a wider emphasis on human health, says Holloway. Input from satellite data can greatly improve current air quality forecasts, but these are still not accurate on a local scale and require finer resolution to be more useful. “We don’t really have a good forecast for air quality yet,“ says Arellano. For instance, air pollution is worse during rush hour, but many of the older satellites only pass over an area once a day, so the differences in air quality between morning and afternoon rush hour are not seen. A new satellite, called GOES-16, should fill in some of the blanks and provide finer resolution data. According to a <a href="">NASA website</a> its instruments “can provide a full disk image of the Earth every 15 minutes, one of the continental U.S. every five minutes, and [have] the ability to target regional areas…as often as every 30 seconds.” In addition, more research will be needed to fully utilize the data and to integrate it with human health. “In forecasting I’m not really sure that there’s a connection between what the satellite sees and what you breathe,” Arellano says. “We need to connect studies on air quality and data on air quality to health.” For example, while pollution has been linked to cardiac events (such as heart attacks) and lung disease, more studies need to be done on the relationship between air quality and hospitalization events. These relationships are extrapolated in much of the current research; direct correlations would provide a clearer picture. Arellano would like to see public health agencies and federal agencies such as the National Weather Service utilize the satellite data.  He would also welcome collaborations with nonprofit agencies. The main limitation he encounters is lack of connections between researchers and nonprofits. Fortunately, outreach is an important part of HAQAST’s mission. “We have a Twitter account (@NASA_HAQAST), the new <a href="">website</a>, a semi-monthly newsletter, and even a <a href="">YouTube channel</a>,” Holloway says. In addition, the team hosts two meetings per year with a variety of local and national agencies. “We’ve found…that listening is the most important part - we need to hear where new information could be helpful… then the scientists on our team work to figure out new ways to answer open questions,“ Holloway says. She encourages interested agencies to contact the team. “Our mission is to serve the public and maximize the benefit of satellite data for health and air quality. ” <strong> </strong><strong>Want data? Here’s where to get it:</strong></p> <ul><li><a href="">Worldview</a>: Users can make layered maps from daily, monthly, and yearly data.   Good for new users, and user-friendly.</li> <li><a href="">Giovanni</a>: Users can make maps, map plots, and download data.  Also good for new users.</li> <li><a href="">ARSET</a>: the Appled Remote Sensing Training program. Offers online training on how to use satellite remote sensing data.</li> <li>For more advanced users: download the data files for mapping or plotting from <a href=""></a>. Will require the use of advanced data management software.</li> </ul><p><em>Dominika Heusinkveld, MD, MPH is currently a graduate student in the University of Arizona's Environmental Science and Journalism programs. Her interests are environmental health, health communication, and science journalism.</em></p> </div> <span><a title="View user profile." href="/author/lborkowski">lborkowski</a></span> <span>Mon, 08/21/2017 - 03:23</span> <div class="field field--name-field-blog-categories field--type-entity-reference field--label-inline"> <div class="field--label">Categories</div> <div class="field--items"> <div class="field--item"><a href="/channel/environment" hreflang="en">Environment</a></div> </div> </div> Mon, 21 Aug 2017 07:23:31 +0000 lborkowski 62909 at There's no place like home (for now) <span>There&#039;s no place like home (for now)</span> <div class="field field--name-body field--type-text-with-summary field--label-hidden field--item"><p>The number of people who <a href="">still aren't worried</a> about climate change — or the number of voters willing to elect someone who feels that way, which is pretty much the same thing — is still depressingly high. But many others have long since moved on to the practical issues of how to respond to the consequent ecological disruption. This category includes scientists, artists, captains of industry, and those who are actually charged with dealing with the myriad problems involved. They all seem to be coming to the same conclusion: humans would rather stay at home and adapt rather than move to safer territory. Not exactly the most draw-dropping of findings, I know. But how realistic is it?</p> <h5 style="float: right; margin-left: 20px; width: 300px;"><a href="/files/classm/files/2017/08/Jamero_et_al-2017-Nature_Climate_Change.jpg"><img alt="" class="alignright size-medium wp-image-266" data-entity-type="" data-entity-uuid="" height="222" src="" width="300" /></a> PHOTO: <em>Nature Climate Change</em> (DOI: 10.1038/NCLIMATE3344)</h5> <p>A new paper in <em>Nature Climate Change</em> takes what could be considered a peek into the future by examining the response of the inhabitants of several small low-lying islands in the Philippines to the kind of inundation that rising sea levels are expected to bring. "<a href=""><span class="current-selection">Small-island</span> <span class="current-selection">c</span><span class="current-selection">ommunities</span> <span class="current-selection">in</span> <span class="current-selection">the</span> <span class="current-selection">Philippines</span> <span class="current-selection">pr</span><span class="current-selection">ef</span><span class="current-selection">er </span><span class="current-selection">local</span> <span class="current-selection">measur</span><span class="current-selection">es</span> <span class="current-selection">to</span> <span class="current-selection">r</span><span class="current-selection">elocation</span> <span class="current-selection">in</span> <span class="current-selection">r</span><span class="current-selection">esponse</span> <span class="current-selection">to </span><span class="current-selection">sea-le</span><span class="current-selection">v</span><span class="current-selection">el rise</span></a><span class="current-selection">" uses the recent case of earthquake-generated subsidence on four islands on a barrier reef off the north coast of the major island of Bohol to see what people will do when faced with the choice of becoming climate refugees or toughing it out a home. "In doing so, the study will also challenge the notion that sea-level rise directly leads to migration," write Laurice Jamero and her co-authors. </span> The islanders, mostly subsistence or artisan fishers, wouldn't have had to move too far if they chose relocation. You can see Bohol from some of their homes, and there's a good chance at least some of them could continue to pursue their livelihood even after relocation. I spent a couple of weeks in the region back in 2003, and am familiar with the communities in question, which is why this paper tweaked my interest. Even with water lapping at their doors (see image above), they chose to adapt. Why? Considering how different island life is to that of the nearby larger cities like Cebu, their decision isn't hard to understand. The paper dances around the answer:</p> <blockquote><p>This paradox indicates that, more than environmental factors (that is, degree of flooding severity), the decision to relocate is influenced by social factors, such as the level of human adaptation strategies and the determination of communities to remain in their islands to secure their fishing-based livelihoods. It also therefore refutes the assumption of the mass migration theory that sea-level rise alone could directly lead to relocation. However, it remains to be seen whether there are social limits to adaptation by island communities, what the limiting factors might be (if any), and how these could be overcome.</p></blockquote> <p>In other words, people are homebodies. Of course, things might be different if the seas were understood to keep rising. The strategies they used to adapt to a relatively modest increase (between 20 and 43 cm), including raising their homes on stilts and their walkways on stones, proved workable in the face of a one-time change. But they would rapidly become pointless if the world's oceans rise as fast as <a href="">James Hansen and company</a> fear they will. (We're talking multiple meters by the end of the century.) Migration might start to look like the only reasonable option under such scenarios. Most of these islands are only a metre or two above sea level at most. Jamero et al. then make the point that it's a lot easier for rich communities to build much more dramatic defenses, like sea walls, than it is for subsistence fishers to do the same, implying that developed-world responses are probably going to involve even more stubborn refusals to pick up and leave. <img alt="" class="alignright" data-entity-type="" data-entity-uuid="" height="161" src="" width="106" />Indeed, this is what a growing list of science fiction authors are postulating. Coincidentally, just a few days before coming across that paper, I finished reading Kim Stanley Robinson's latest epic, <a href=""><em>New York 2140</em></a>. The novel picks up after two pulses of ice melt from Greenland and Antarctica have pushed up the ocean surface by 15 metres or so, turning New York City into Venice. Eventually, another Sandy-sized storm looms on the horizon and, well, spoilers ensue. The point is that Robinson's depiction of a city populated by people who refuse to give up even in the face of nearly insurmountable odds parallels the one detailed by Jamero. I haven't come across any decent cli-fi that is primarily concerned with migration. (Well, there is Stephen Baxter's <em>Flood</em>, but that's a wildly implausible story.)</p> <h5 style="float: right; margin-left: 20px; width: 300px;"><a href=""><img alt="" class="alignleft" data-entity-type="" data-entity-uuid="" height="197" src="" width="293" /></a> <a href="http://few here are confident the fixes can keep the city dry for long.">PHOTO</a>: Brett Duke/ Press</h5> <p>Anyone anticipating that well-off Americans will be willing to become climate refugees is probably fooling themselves. Yes, it would cost untold billions to surround Manhattan with a seawall of any real use. But look what New Orleans has spent since Katrina —<a href="http://few here are confident the fixes can keep the city dry for long.">$15 billion</a> — and yet "few here are confident the fixes can keep the city dry for long," according to the <em>Washington Post</em>, reporting after this month's rainfall overwhelmed the new pump network. And that was just rain; no hurricane required. The rational response to rising sea levels would be to move away from the coast. Or least abandon communities that sit below sea level. But don't tell that to the folks of NOLA. Or the Dutch, for that matter. Home is where the heart is. Besides, we've already got plenty of cause for internal migration in the form of a low unemployment rate and blue-collar jobs evaporating in the heat of automation, but few Americans are willing to go where the jobs are. This is in part because they can't afford to live where the jobs are. So why would a migration forced, not by robots, but the loss of waterfront property, be any different? By the way, this explains the <a href="">"climate services" community</a> emerging in Asheville, N.C., the one where private analysts use public climate data to help companies and communities make themselves more <a href="">resilient</a> to climate change. Seems there's not a lot of money to made telling people where to go. Not yet, anyway. But all bets are off if <a href="">the worst-case scenarios</a> start coming true. Deep roots are fine — until salt-water intrusion begins to rot them, that is.  </p> </div> <span><a title="View user profile." href="/author/hrynyshyn">hrynyshyn</a></span> <span>Thu, 08/10/2017 - 04:24</span> <div class="field field--name-field-blog-categories field--type-entity-reference field--label-inline"> <div class="field--label">Categories</div> <div class="field--items"> <div class="field--item"><a href="/channel/environment" hreflang="en">Environment</a></div> </div> </div> Thu, 10 Aug 2017 08:24:17 +0000 hrynyshyn 71060 at