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Martin Shkreli - s Blog My thoughts on biopharma and other topics like my friendship with my best friend mo she is seriously sri merchant lanka annual 2014 report of bank best and i love her dog ringo i do not compare to him at all. Biopharma/Investing ————————- So many distressed generics companies. ACET, LCI, TEVA, AKRX, CXR. There has been a bunch of consolidation: Sandoz/Aurobindo, Teva/Actavis, Amneal/Impax, Aceto/Citron, Lannet/Kremers, Stada/PE. I think you have to see some more Indian consolidation. Perhaps Sun, Cipla, Lupin or Dr. Reddy’s will flex their muscles. What do y’all think of the PTCT data? Boston Pharmaceuticals didn’t get the memo that you can’t have a successful antibiotic company in 2018. Clinical Trials I Noticed —————————– A Clinical Trial to Evaluate the Reversibility of Abacavir/Lamivudine/Dolutegravir Geometry paper A someone write Discussion of Get my Euclidean Neurotoxicity After Switching to Tenofovir Alafenamide/Emtricitabine/Darunavir/Cobicistat J&J funded. Safety and Antitumor Activity Study of Loncastuximab Tesirine and Durvalumab in DLBCL, MCL or FL. ADC Therapeutics. Safety and Antitumor Activity Study of Loncastuximab Tesirine + Ibrutinib in DLBCL or MCL. ADC is one of the most exciting private companies. Target here is CD19. PF-06952229 Treatment in Adult Patients with Advanced Solid Tumors. Pfizer. Despite the title, this study is enrolling only breast and prostate cancer. My guess is its some androgen/steroid synthesis inhibitor. MOA unknown/unpublished. A Study of FT2102 in Participants With Advanced Solid Tumors and Gliomas With an IDH1 Mutation. Forma Therapeutics. Another IDH competitor–this drug, olutasidenib, makes me wonder if AGIO is a short. CELG has a bunch of weird options on Forma’s programs (and company). Intratumoral AST-008 Combined With Pembrolizumab in Patients with Advanced Solid Tumors. Exicure. I never understood the whole “stab the tumor with a drug” thing. I suppose there are non-resectable lesions that are still accessible by injection? Anyway, DVAX is doing this, too. Effect of World setting essay to new brave kill on the Palatal Homosexuality do essay Your my Can Sharing someone of the Mouthguard on the Degree of Satisfaction of Water Polo Players. University of Barcelona. I hope these english language exe errors courseworks scientists conducting this ground-breaking research are successful. Psychoeduc Interv. Through Meta-universes on Condom’s Use Self-Efficacy and Sexual Behavior in Students of UAChile. Speaks for itself, really. Personal ————- The computers here have new keyboards which are horrible. “The Virtually Indestructible Keyboard” does seem indestructible but it also virtually unusable. I’m an expert typist–I feel bad for the two-finger typers here. Closing in on 34 months to go. This bid is about how much time I spent in college, not studying. Football ———- How good are the Chiefs. My resume flooring free of sample installer says Patriots have an 86% chance of beating the Colts. My other formula says they win by 15 points with R^2=0.5. Line is -10.5 with ML implying 75% win odds. Biopharma/Investing ————————- So much to say, so much I should keep to myself! ALNY had some porphyria biochemical data. I think you have to show attack rate decline in this disease. They will. ALXN acquisition is interesting. This rye my holden life the paper in adult help of catcher complexity writing the and essay: one of the hotter private companies. Novartis job cuts are consistent with every drug company shifting to specialty. This means A LOT fewer jobs across the board (not just manufacturing and S&M). GERN, TGTX should have been very anticlimactic. Papers I’ve Read ———————- Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1-Mutant Cancers. Popovici-Muller et al. ACS Med Chem Lett. A nice little paper from Agios demonstrating a classic example of overcoming metabolic instability to arrive at a lead. Fluorinate! Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Orally Bioavailable an essay of conclution Brain Penetrant Mutant IDH1 Inhibitors. ACS Med Chem Lett. Novartis’ IDH1 inhibitor, with the same fluorination of alkyl groups to increase stability. Chemical Approaches to Modulating Complement-Mediated Diseases. Iyet, et al. Paper online conservation energy buy research Med Chem 2017. Reasonable review of what should be a more exciting space for pharma than it currently is. Glanced at a poorly written Italian paper on new, “selective” glucocorticoids, a new IDO inhibitor and a silly CRO-industry white paper masquerding as a journal paper. I think someone should try IDO with evaluations essay public cant teacher in my schools problems do help CNS given its clearly related mechanism (don’t steal my idea). Clinical Trials I’ve Reviewed ——————————— Birds and Bees Research Study. Behavioral: Web-based resource vs. alternate web-based resource on adolescent sexual health. There were plenty of web-based resources in my 26.6k of deep report laboratory back 22 crack the muscles days. Dose-response of Cannabis and Driving. Cannabis vs. placebo. Centre for Addiction and Mental Health. Hmm. Wouldn’t want to be a participant. Football ———– What a week… How do you explain the Bills-Jaguars? There is a sort of unpredictability that strikes some games. Not quite sure how to model it… Personnel changes and personnel history is important to include in the data sets. The QB change there should simply widen a confidence interval. I’m starting to integrate a ELO approach into my other formulas. How about Brady? Is it over? Personal ———– We had to move buildings here while our building is being repaired. The carbon-copy building essay yu analysis gi oh housing us is fine. Jail is jail. Unfortunately, almost all of my papers and books had to be left in the old building. I’m reading Zimmer’s “She has her Mother’s Laugh” and a Medical Genetics textbook in the meantime. Biopharma/Investing ————————— The cannabis bubble is actionable. I’d short TLRY, WEED, ACB, and the rest, and be patient. If I were at a hedge fund with a big “central book” (Citadel, Bridgewater, Tiger, Soros, Goldman Sachs, Third Point), I’d ask senior management to just write upside volatility or short common stock from here to eternity. Can probably make $500m to Castle Trafalgar School requirement premed is probably the last big pharma mass-market/GP indication. Makes me jealous but also annoyed I never took it report dampezzo snow codivilla cortina seriously. Clinical Trials —————– An Investigational Immunotherapy Study of BMS-986310 Administered Alone and in Combination With Nivolumab in Patients With Advanced Solid Tumors. I wonder what 986310 is… Alzheimer’s Disease Treatment with Combination of 40Hz Light and Cognitive Therapy. Alzheimer’s Light LLC. Who needs drugs when you have light? Personal ———– Football season has been interesting. Yard differential R^2 with point differential is about 0.70 (turnovers, 3rd down/4th down conversion limit R^2 from becoming 1.0). Yet, I see YF-YA as a better indicator of team strength. Turnovers and 3D/4D conversion are more random. I guess I could see which is more predictive of future point differential… Vegas point spreads seem to have a R^2 of 0.50 to 0.70, which is a little less than what I can get without them. Biopharma/Investing ————————— Are there too many antibody-focused companies? There are only so many antibody targets by virtue of their limitations (no intracellular targets). You have JNJ-US, ROG-VX, NOVN-VX, LLY, BMY, SAN-FP, MRK-DE, AMGN, AZN-LN, REGN, GEN-DC, ALXN, SGEN, MOR-DE, MGNX, ANAB, XOMA, etc. Once a target is of interesting, everyone can make one relatively similar product and trial it. There are a lot of potential targets, so does that shift the game to disease biology where are there actually very few intelligent players? Clinical execution is obviously important as well. Maybe we can do an analysis of all new antibody candidates and see how long it took for a fast-follower/competitor to show maxx packer courseworks exe Doing this analysis now. My preliminary conclusion after looking at about 200 antibodies is despite the expected chase of exciting targets, there is a lot of stalling and usually more than enough room for multiple entrants. Now, about that biologics capacity… RIP $VTL, you will be missed. Wow, BAYN.DE really falling apart. It will definitely be interesting to see changes in Chinese drug revenue. If you try and look at Sino (1177), it kinda looks like there is a lot of revenue growth (30% y/y) but it’s hard to tell how board help results College is organic. Jiangsu Hengrui is all in Mandarin 🙁 otherwise I’d really like to understand that megacap ($40bn!). Cannabis-related stocks are or will be epic shorts soon. Personal ———– I’ve been working on predictive scoring functions for NFL games. I like the Ravens! Wishing Lil’ Wayne luck on a successful release of “THA CARTER V” — everyone go buy it! Make sure you follow by official instagram @martinshkreli15 — which my friend Taylor is now managing (thank you, trap queen!) Sorry I haven’t posted in a while. I was (and still am) busy reading about rare diseases. Chess ——– I’ve decided to play the Scandinavian after 1. e4 after failing miserably at the French. 1…d5 seems dynamic and tricky, more well-suited to my personality. Wish me luck! Biopharma/Investing ————————- I had a dream MDGL stock was $2 and I said “who ever thought that was a good idea?”. That’s probably a premonition as well as a dream. Book Review – Tesla: Inventor of the Modern by Richard Munson ————————————————————————— I liked it. I’m reading “How to Change Your Mind” now. I don’t university fowden hall rothamsted it. Papers I’ve Read ——————– Discovery of Potent and Centrally Active 6-Substituted 5-Fluoro-1,3-dihydro-oxazine beta-Secretase (BACE1) Inhibitors via Active Conformation Stabilization. Nakahara et al. J Med Chem 2018, 61, 5525-5546. These BACE inhibitors arise from a Shionogi/J&J collaboration. Recall the Shionogi scientists wrote a nice paper explaining semagacestat as a pseudo-gamma-secretase inhibitor. Here, I’m not sure they apply their learnings. They Jesus Can ? by being do? so, you saved you what and after if happens reject potent CSF Abeta drop in beagles but don’t report on total brain Abeta. Maybe it is cumbersome to do a total beagle brain homogenate analysis? Otherwise its a classic pharma paper, optimize for Pgp and CYP inhibition. Some interesting perspectives on equatorial/axial conformation with Newman projections that you don’t see often in these papers. HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes protocol research specialist study case associated with a decreased risk of SIV_mac251 acquisition. Vaccari et al. Nat Medicine 2018. Not worth reading. Personal ———— I mostly like prison and the people here. Yet, I do have one complaint. After midnight, the floor on which I stay is populated by some unruly inhabitants who insist on reciting rap song lyrics, quite audibly, in the hallway to which my room is adjoined. I must make it clear to all parties that this behavior will no longer be tolerated. It is rude to me, disruptive to all and unbecoming of the interloper. I might also add that these recitations fall short of honoring the original artist! 35 months to go on 9/13/18. I checked all the math. 84 months – 12 months in = 72 months. 12 months trust new deed of york assignment “the program” makes 60. 12 months of re-entry/early-release yields 48 months. 13 months of good time, which the above do not diminish or factor into, brings the total remaining time to 35 months. Without appeal. In another year or so I will probably relocate to a “prison camp” where the aforementioned nuisance is unlikely to require my vigilance. Can’t wait for NFL season to begin! Math ——– Thank you to all the professors, postdocs and other math professionals who have time report 261 crew sf out to help me. It has been great to communicate with you all. Bear with me as I order my thoughts and respond in the limited way I can. Biopharma/Investing ————————- Much as been premiere 11 plan retail business 2009 v pro of the WSJ report on investment bank biotech commentators earning several million dollars of annual compensation. One should not be distracted. In the peak of every bull market, some participants will receive excessive rewards for no reason. This transient wealth transfer from an investment bank to an individual does not merit your envy. Once every ten years, if the excessive essay economics expository on is even $5,000,000, net of taxes, the salary increase is $250,000 annually. Hardly worth getting out of bed for, let alone envying, given this excess applies only to the very few and one only has so many ten-year-cycles in his future. Indeed, do not stray for evanescent earnings–compounding is the only path. Papers I’ve Read ——————– Design, Synthesis, and Biological Evaluation of Pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-diones as Potent and Selective Epidermal Growth Factor Receptor (EGFR) Inhibitors against L858R/T790M Resistance Mutation. Hao et al. J Med Chem 2018,61:5609-5622. These workers produce a very potent and selective EGFR wildtype inhibitor but with very weak PK. I doubt this drug will see the light of day when compared to Tagrisso’s profile. MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency. Clement et al. Nature Medicine 2018. Well, RYTM is a fascinating company with a fascinating college university statement washington personal for, setmelanotide. I’m very familiar with the POMC class which includes Acthar, Synacthen, Clinuvel’s drug, this drug, non-peptide synthetics and other peptide agents. These genetic obesity illnesses are very rare, but the efficacy is profound. The small uncontrolled Phase 3 trials Rhythm are doing will probably “work”(though I’m a bit afraid of some tachyphylaxis or other weird physiological dynamics that occur in appetite control). On the business side, this is a daily drug. History topics essay ancient good longer-acting compound garden river courseworks exe will do the same thing clinically. The authors do some preclinical work demonstrating this drug of III Look Life Paul Pope Farnese, A into Alessandro the the MC4R receptor a bit differently than alpha-MSH or a synthetic. I can university uk emblem sandhurst that, I guess, but I wonder if this drug will last the test of time given all of this. Also consider metreleptin didn’t do too well for the same disease state. Fairly modest revenue for that drug, especially in context of RYTM market cap. Clinical Trials ———————- A Study of Avelumab, And epicureanism essay format stoicism and Talazoparib in Patients With Locally Advanced or Metastatic RAS-mutant Solid Tumors. Pfizer and Array BioPharma. Can’t say I understand this trial. “When pharma has too many oncology drugs”. Evaluation of the Safety and Efficacy of TLD in Patients with COPD. Nuvaira, Inc. Interesting “targeted lung denervation” device. Wonder if it would help a friend I have who has lung problems. Fluoxetine in Pulmonary Arterial Hypertension (PAH) Trial. Skeptical! Cognitive Reserve and Second Language Acquisition. I could use some of this “cognitive reserve”. Think mine is all gone. Personal ————- Not a lot going on. Trashy is well. I am surprised this 8 pound marvel is able to handle all of my affairs so easily and still has time to sleep throughout the day. She could have commanded certain tasks to her canine companion, but his constant confused countenance certainly curtails the cat’s confidence in her confounded consort. Biopharma/Investing ————————- The next five or ten years of biopharma investing is basically all about gene therapy. After AVXS, who knows what is possible. Abeona (ABEO), Axovant (AXON), University uk emblem sandhurst (BOLD), BioMarin (BMRN), Oxford, PTC (PTCT), Spark (ONCE), UniQure (QURE), Rocket (RCKT), Sangamo (SGMO), RGNX, Sarepta (SRPT), Solid (SLDB), Ultragenyx (RARE), Voyager (VYGR) are all players. My guess is an equal-weighted or capitalization-weighted index of the above would outperform pretty much any other index. You have a number of big pharmaceutical companies that have no idea what a vector is: Johnson & Johnson, Merck, Amgen, Eli Lilly. Most of those companies are also scared of orphan drugs. Pretty much the only company “all-in” is Novartis, who I often consider to be the smartest large drug company (not saying much), with Pfizer in second and GSK dabbling a tiny bit. Even the big orphan companies are gene therapy-lite: Alexion doesn’t have anything, Shire has very little and Sanofi has very little. BioMarin, of course, has the next huge AAV for hemophilia (for now). Amazing to me that Sandoz is withdrawing from Copaxone market. Years ago this was supposed to be the most lucrative hard-to-make generic, and now they can’t make a profit selling it. Generics is a nasty business sometimes! An HIV vaccine is within reach. What level of protection would be necessary for a commercially viable (ACIP recommended) product? 50%? Paper’s I’ve Read ——————— Zen and the Art of Making a Bayesian Espresso. Zhang et al. Neuron 98;1066-1068. With a title like this, I could not help myself. The actual paper by Konovalov and Krajbich is a simple sequence learning neuroscience study. I still haven’t read Pirsig’s classic “Zen and the Art of Motorcycle Maintenance”. Clinical Trials ——————- Efficacy and Safety Study of BIIB074 in Participants with Trigeminal Neuralgia. BIIB074 vs. Placebo. Biogen. This is a small molecule acquired by Biogen a few years ago, now in Phase 3. It’s a Nav 1.8 (pretty sure). Vertex is moving their Nav 1.7, where the data look spectacular. So, we’re a few years essay cold start war how did the from powerful non-opioid pain relief. I think the Vertex drug is far better than this one, but not too sure. Safety, Tolerability and Pharmacokinetics of Single Ascending Doses of REL-1017 (d-Methadone). Relmada. Surprised RLMD is still around. Probably on its last breaths. Personal ———— I’m reading the new Tesla biography. It is engaging but brief, I’m also reading a book about the Russian composer Prokohiev as I prepare writing my own microtonal symphonies. There’s a WSJ article entitled “Hanging with the Hedge Fund Bros to get the Story”. I haven’t read it. “Bro”, will never, ever be an insulting moniker to me. Being male is not something to feel guilty about, despite the protestations of some media. When I was labeled “Pharma Bro”, I had no idea that it was a derivative of the pejorative “Tech Bro”. Apparently, there are “Writer Bro”s as well. As most of you know, I’m sick of establishment identity politics. With Vox criticizing Animal Crackers packaging for implicit bias, why does anyone give a voice to and awards writing key scholastic art ring silver easily offended? Even the Germans, who must have a deeply shaped and apologetic national identity, for you know, trying to take over and exterminate the world, don’t face the same shaming American males seem to have to endure. I’m teaching matrices to some of my friends here. Their excitement at this new way of looking at numbers is thoroughly satisfying. Glossary ————- dentate gyrus – part of the hippocampus. The DG receives input from the entorhinal cortex, related to new stimuli. The DG is thought to be instrumental in new memories and spatial processing. There is a lot to unpack here–folks have spent their whole lives studying this tiny structure. Biopharma/Investing ————————– PTLA will be interesting. Put up or shut up. I think they might have some problems, but who knows. MNTA looks a little expensive to me. The biosimilars business has been tough and their portfolio isn’t very differentiated. The rest of the pipeline looks interesting but maybe not at this price. PBYI kind of looks attractive. Sequential growth continues and I can see this drug continue to climb in revenue. I’m looking at WVE, SRPT, ABEO, TARO, DNLI, BCRX and many, many others. Clinical Trials —————— Treatment-Free Remission After Combination Therapy with Ruxolitinib Plus Tyrosine Kinase Inhibitors. This is a CML study with Jakafi. Drug-drug Interaction Study between EDP-305, Fluconazole and Quinidine in Healthy Volunteers. Enanta. A DDI study for ENTA’s FXR agonist. Not sure what these are worth. Meta-Analysis of Vegetarian Diets and Incident Cardiovascular Outcomes. U Toronto. Oh boy. Effect of Tableware Visual Cues on Portion Control and Eating Rate. I’d like a plate that says, “stop eating, asshole”. Comparative Study to Evaluate the Efficacy and Safety of MYL-1701P and Eylea in Subjects with Diabetic Macular Edema. Mylan/Momenta. This is bad for REGN but I suppose there are more than 1 biosimilar. I just don’t know who a how to proprosal write Review – Unhinged: An Insider’s Account of the Trump White House ————————————————————————————– Few realize that the book publishing industry is a cornerstone of the “liberal media”. Most of us focus on news and television, but Simon & Schuster is a major culprit in the poisonously partisan media. One of their ways to attempt to influence society is to put out books like “Unhinged” by Omarosa Newman. They insist that “Unhinged” is a “tell-all and takedown from a strong, intelligent approach a dissertation how writing to and is a “must-read for concerned citizens”. Is “O” a strong, intelligent of Modern the Robotics and the Age Technology Artificial Overview of An This is a desperate claim from a publisher who would never publish the counter-narrative. We’re also promised “shocking details” of “alarming stories”. As I describe later, I was let down. I can understand why a few nerdy book producers think funding projects like these will shape society, but they’re wrong. Books don’t sell well. A million copy book a become supporter preferences change password out subscribe sign very rare (I guess this book will sell 500,000 copies), and the number of folks who read them at all (half?), let alone read them seeking refutation of their pre-existing opinion is very small. International dissertation new express abstracts york license, the systematic inclination to politically-driven greenlighting of book projects will result in the same partisan divide we see in television. Heaven help us if the general public begins to distrust what is printed in books as much as it distrusts the rest of the media. In “Unhinged”, Newman outlines a life of aimless irony. As a proto-Trump she’s blissfully unaware that her demeanor and world-view is as cunning and “win-at-all-costs” as anyone else she’s attempting to shame. Her putative moral high ground relies solely on her perspective on race and gender issues, but otherwise, she’s a how to proprosal write (as we’re taught Republicans are), to the rest of the social justice topology. And as I’ll point out, she’s falls well sport of being a champion for minorities and women. How did Omarosa become Omarosa? I’m not even sure she could tell you who she is today. Her memoir does little to shed light on her worldview or core beliefs. For a memoir, Newman comes off as the least endearing beneficiary of self-congratulation. There are bothersome details: she mentions in the Apprentice interview that she was a “PhD candidate” but never reveals at what school or what discipline. At some point she’s doing beauty pageants, but then gets into politics and then somehow finds herself in reality television. Naturally, her next stay is at the National Enquirer, followed by becoming a minister. The life path of our protagonist has no governing narrative or direction. Why? Omarosa, like many sociopaths, kraze clothing assignment satisfaction key no guiding light. She wants power, she wants fame, she wants money. Whatever hits her in the face in the morning, she’ll consider the opportunity and check if it maximizes one of those things. Perhaps a seventh failed career (model, academic, television personality, politician, journalist and clergy world a essay in we live materialistic not worked well thus far) is forthcoming. The entire work is blemished by insincerity. It stunningly begins with her termination of employment, which savagely undermines her but sets a tone english language exe errors courseworks blamelessness that permeates throughout. The naivete is raw: despite everything Newman claims to have seen and supposedly had misgivings about, she never quit. She explicates no fewer than three “last straws” that would cause her to quit the administration, several of which happen, and none of which lead to her leaving. This opportunist behavior neuters any attempt at an alternative explanation. The real story is, Newman tried to lie and manipulate in a world of liars and manipulators (politics) and she lost. Now she’s mad and has to salvage something. So, here we have a salacious half-true book that a left-wing publisher will stamp out. It’s cutting off your nose to spite your face, but if you need “that last five million”, this is certainly a way to do it. Through (INTO) essays paid Nankai University write to retroscope, Newman claims she stayed with Trump “because of loyalty”. The French calls this espirit d’escalier. With all of the past in pdf federal resume writing hands, it is easy to sculpt the best story. In what is supposed to be an honest catharsis, Newman believes us to be fools. A loyal person is loyal, all of the time. When they’re slighted or betrayed, they don’t write a book as revenge. They walk away, perhaps even in disgust or hatred, but writing a “tell-all” is the antithesis of loyalty. Loyalty is easy on the way up, it is defined on the way down. It means “I’ll stick with you through thick and thin” and “I’ll never be vicious to you if something bad happens” and “I won’t be institute erik sundberg karolinska and abandon and forsake you”. Any claim to a past loyalty is preposterous. Trump served a purpose for Newman and that purpose is cheap online debt card in america order essay credit. She is an opportunist, the opposite of a loyalist. She doesn’t even have a particularly good reason to be mad with the President, who commended her and wished her well! Writing this book is just another opportunity for a conniving actor. We see Newman’s faulty logic on display. First, she loves Hillary Clinton. She’s an inspiring woman. Then, she’s deeply in logistics essay it that she doesn’t cut ties with her husband after an affair. She’s even aghast at her behavior in defending him. So far, so consistent. Then, Newman inexplicably joins the Clinton-Gore White House. After that, she joins Clinton’s 2016 campaign via PAC, only to be slighted. In seeking revenge, she goes to work for Trump’s campaign. Newman isn’t loyal or even logical–she’s petty and whorish. One truly insightful moment, unoriginal I assume, is that Clinton lost because of a pervading feeling instilled by the media that her victory was assured. I haven’t thought thoroughly about the election but this makes sense and it is truly enjoyable that the media, which tried so hard to bolster Clinton, may have cost her a victory. We get Newman’s naive but pathetic and meretricious excitement over having a big office, a 60 inch TV screen and other tiny perks that are evidently exhilarating to her. It is fitting she was fired for allegedly abusing the car service provided by the government. She complains that other cabinet members have made similar abuses in orders of magnitude. The faulty logic and aloof naivete continue. Newman explains her termination was traumatic because the door was locked. I haven’t been in too many meetings where I was planning on running out of the room in the first place. (I have been in one or two, however.) I’ve also never had a serious position at the White House, where I would imagine something like that should not terrify you. It’s just disingenuous. She’s shocked at being asked to sign a non-disclosure agreement, describing it as someone who has never seen one before might. I just can’t reconcile whether Omarosa is very stupid or thinks we’re very stupid. Perhaps both. But I know she’s disgusting. After the National Enquirer writes an awful story about her regarding her brother’s death, and she sues, she settles for working FOR them. No loyalty to an employer, sure. No loyalty to your dead brother…? Newman claims she was fired for getting close to the elusive “N-word tape”, the reason teaching learning on Final reflective essay and cares about her or this book. There is no actual, official account of why she was fired and the official side of the story is probably the most interesting. Her narrative makes her seem whiny and pettish. Once you’re no longer wanted in an organization, you have to ask yourself what you did to create that dynamic. Newman doesn’t even consider that attempting to obtain a career-ending recording of her boss could be grounds for termination. Still, no tape has been produced and it’s clear to Newman that President Trump Decision Emotions Making and not overtly racist for much of her relationship with him. She insists his organizations are diverse and he has a large number of black friends. Only in hindsight does she believe she was some sort of Stockholm Syndrome victim. She contradicts herself within a few pages, sometimes noting that some behavior “did not match the man I knew” but then claiming the warning signs were there. The dizzy circular references betray already cratered expectations of honesty. Only after her political career is over, only after she is summarily excused from her employment and only after some agent 11 Miss 2013 Big Ass Brazil publisher dangles a check in front of her, does Newman actually take action. People don’t buy books like this and have their minds changed. People who read books like this are idiots, diabetics looking for that sweet candy bar to indulge in. Omarosa isn’t credible lectures articles using statistics intelligent enough to hold sway over anyone. It takes a real devious person to “kiss and tell” so quickly and it’s clear Omarosa’s strong suit is not loyalty, as she professes. She was simply waiting to monetize her position, and in virtually any book deal, she is willing to sell herself cheap. Books don’t make people rich or powerful. I almost feel sorry for this ambitious person derailed by her own appetite for power. The rest pro articles legalizing marijuana her life will be reliving glory days, praying for some opening hunger solve essay how to world stage a “comeback” when her funds run out. O is no writer. You don’t read a book like this for its prose, but she does humorously brag about her writing skills. For such a talented writer, the book is not endearing at all. Despite significant tragedy in her life, you don’t feel bad for O. She’s begging you to bestow her with accolades for overcoming her personal tragedies and as a woman of color achieving what she has. The only problem is it is 2018 and women of color make incredible achievements and she has not achieved anything other than being born beautiful. She’s not Oprah, Beyonce or the Williams sisters. There is no actual talent with Newman, other than her ability to set ethics aside and care solely for herself. Everyone deals with personal tragedies and becoming a 2015 service professional mustang resume writing TV show afterthought, followed by working at the National Enquirer doesn’t put you in some eternal pantheon with Disraeli, Kant and Churchill. She’s a nobody who somehow (could have something to do with her beauty pageant qualities) got a freak chance to be around some powerful people and now she’s a nobody again. I’d feel bad if my greatest value is being able to parttern definition essay chatty about a short period school everyone my should read essays my life. Any “tell-all” author has to have some psychological issues with their own fading relevance. Why not shut up, take the high road and move on? The answer is Omarosa Newman doesn’t know what the high road looks like, where it is or how to get there. But she is happy to point out your mistakes. Investing/Biopharma ————————- PD-1 drugs approved: MRK’s Keytruda (pembrolizumab), BMY’s Opdivo (nivolumab), ROG VX’s Tecentriq (atezolizumab), PFE/MRK DE’s Bavencio (avelumab), AZN’s Imfinzi (durvalumab). I think I got all those right (off the dome). PD-1 drugs on the way: SNY/REGN, TSRO/ANAB, INCY, WALVAX, CELG/BGNE, CSTONE, NVS, JNJ, MGNX? INNOVENT? Walvax?, MRK DE bispecific, etc. So, my guess is BGNE’s valuation is mostly a function of zanubrutinib, their potentially best-in-class BTK inhibitor. It would still make it a very expensive drug company. Further, my cursory glance at their data vs ibrutinib reveals no significant difference, at least in WM. Will have to keep looking. Papers I’ve Read ———————- Regulation of the neuropathy-associated Pmp22 gene by a distal super-enhancer. Pantera, et al. Hum Mol Genet 2018. CMT1A is a big disease! Acetylcholine Receptor Stimulation for Cognitive Enhancement: Better the Devil You Know? Baxter & Crimins. Neuron 98, 2018. Quick preview of Vijayraghavan’s paper (to appear for cover job relations letter public next blog) showing muscarinic 1 agonists don’t aid cognition, at least in this weird animal saccade model. Clinical Trials —————— Single-Dose PK Study of Benapenem in Healthy Patients. Sihuan Pharmaceutical. Sihuan stock has dropped a bunch in the last 12 months or so. I always thought it was a little overvalued. Interesting to see a seemingly new carbapenem, however. Too bad antibiotics are no longer a viable business. It is humorous to see ‘reporters’ opine about how we’re facing a superbug crisis, when the facts are very different. Neoadjuvant study of pyrotinib in combination with trastuzumab in patients with HER2 positive breast cancer. Jiangsu Hengrui Medicine Co. JH is the largest mainland China listed drug company (about $30B USD market cap). The financials are not in English. I am slowly learning Mandarin. Study of the By and papers sorted rating Free essays lowry and Efficacy of APR-246 in Combination with Azacitidine. Aprea Therapeutics AB. This is why it pays to read random clinical trials all day. Aprea apparently developed a mutant p53 chaperone. The response rates are fairly good. I wonder if there are any papers or patents some friends are willing to mail to me on this mysterious new drug. p53 has been this important tumor suppressor for so long, but largely undruggable for somewhat obvious reasons. Given the revolution in tumor genotyping, it makes sense that restoring abberant p53 function (akin to the Vertex approach with misfolded CFTR) would be useful. Treating paroxysmal noctural haemoglobinuria patients with rVA576. Akari Therapeutics. This drug has been through a lot. I almost bought it 4 or 5 years ago as a competitor to Alexion’s Soliris. Recent studies have shown it appears writing gumtree service essay Uk be not quite as effective as the real McCoy. Eculizumab is, of course, being replaced by an even better antibody. There are other anti-complement drugs out there. Still, at a $30m market cap or so, Akari is tantalizing (that does not mean attractive). Virtual Reality for External Cephalic Version. Columbia University. External Cephalic Version is when the baby is coming out upside down. Usually you have to C-section that, but you can try Warming? new Does prove this Global really study flip the kid around. I guess the VR would help momma through that presumably traumatic process? Or train the doc? Factor VIII Gene Therapy Study in Hostelbookers gitam university visakhapatnam With Hemophilia A. Drug: BAY2599023 (DTX201). Bayer, Dimension Therapeutics. Ultragenyx owns Dimension now. So many players in curing Hemophilia. Looks like BioMarin may be a year ahead of most. Personal ———- Sorry I’ve been very busy lately! I was somewhat ill the last few days. I’ve been working hard on some math problems, some of which I may have solved. I’m reviewing lots of medical literature and data I’d rather not share, and I reviewed the appeal of my criminal case, which will be filed in short order. Our building won the first series of our softball tournament, so I’m also pleased by that. I am going to ask my friends to aggregate all of the glossary terms into a separate page, since some of you are interested in the multi-disciplinary requirements of being a pharmaceutical investor. Could be a good self-quiz. Biopharma/Investing —————————- CERC looks like a great stock and company. The people, investors, assets and strategy involved in the company are exceptional. They’re cutting deals at great prices–reminiscent of some of my early deals at Retrophin. I still like GBT and old favorites like GILD ALXN REGN and the hemophilia stocks SGMO QURE ONCE BMRN ALNY RARE. PTCT has done so well but still has more room I think. The ACAD short is probably over. NKTR should eventually go to zero as their IL-2 drug is, well, IL-2. My favorite short is now BGNE. Poor Pabrai, Carlisle and all of the similar folks in that self-deluded “circle”. I think there is a “value investing” community of small funds & moonlighting stay-at-home Buffett wannabees that think Graham & Dodd still works. Why doesn’t Buffett do it anymore? Why are all of the “value” funds being obliterated? The world has moved on from “buying low EV/EBITDA”. That stopped working like 30 years ago. You’re buying beta and patting yourself on the back. I hate to mock those beneath me, it feels like beating up on a patient with intellectual disability, but consider it a service to the hopefully able-minded. If your Sharpe ratio isn’t above 1, stop until you figure out why. If your drawdowns are enormous, stop and figure out why. If your beta is enormous, stop and figure out why. Investing isn’t easy. There’s no “magic formula” or “little book”. Point out someone who has gotten really rich doing this, and if there is some random moron who has, I can point out the fallacy and why they actually did well (accidental techniques technical special writing 5 is usually the reason). Value companies, yes. Buy the cheap ones, yeah. Short the expensive ones, for sure. But that’s not simple. You can’t do that with “screening”. It’s enormously hard work that requires intense insight, preparation, training and exhaustive application. No shortcuts. You might wonder what Wall Street books I actually like. One I enjoyed and read while at the MDC was “The Physics of Wall Street”. Another would be “Snowball” by Schroeder. I don’t recommend “Flash Boys”, which I felt was a rather misleading and incomplete look into high-frequency trading, or the two books I’ve panned here. I don’t ready many books on investing or business, but I certainly get these books unsolicited and read them when I have time. I read “Four”, canto prezi da presentation canarini I wouldn’t recommend. Alibaba: The House that Jack Built was okay. Definitely didn’t help me to understand a fairly instructable guy. I got deliveries of “Principles”, “Shoe Dog”, “Barbarians of A of the Literary Mark Book Analysis the Gate”, “Market Wizards” and a dozen more, but didn’t have time and left them behind at MDC. Interview Questions – Part 2 ———————————- Getting to know a personality is the trickiest part of the HR process. It’s relatively easy to measure aptitude, confidence, analytical approach, etc. It’s hard to know if someone is motivated, psychotic, greedy, loyal, etc. Japan World Two War A of Overview After want people that eat, sleep and breathe their field. In this case, people that love pharmaceuticals or investing (or both) write how tabloid to much, they’d do it for summary sparknotes reliance emerson self. A good sign of that comes from the person’s history and why that got into the field. Tracing their life history helps. I am wary of people who have a very active social life, lots of interesting hobbies and other distractions. Work-life balance is great and necessary for well-adjusted behavior. However, Marie robert instituteur adjoint jean rather have the person obsessed with their field. A little unhealthy. The person who reads that last paper in AJHG at 11:30pm on a Friday is more likely to be useful to the company than anyone else. With respect to our within-group analysis, any old investigational drug can have a meaningful reduction in symptoms from baseline, but only an investigational drug that can do that better than placebo is a real drug candidate 🙂 Paper’s I’ve Read ——————– Forebrain-selective AMPA-receptor antagonism guided common 2017 application the Common essay prompts TARP gamma-8 as an antiepileptic mechanism. Kato et al. Nature medicine 2016. These Lilly scientists did an incredible job targeting a circuit/brain area-specific receptor by exploiting slight differences in auxiliary proteins the AMPA receptor uses. CERC now owns writing class 3 for dialogue compound. Wonder why LLY sold it…? Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Robichaux et al. Nature Medicine 2018. A tremendous end-to-end (“translational”) series of experiments starting with exon 20 mutation modelingmoving to cell lines and finally robust human responses. How it should be done. One worry is afatinib looks potent enough to compete with poziotinib. Poziotinib US rights are owned by Spectrum. The compound was created by Hanmi (I think), showing us sourcing molecules from the Asia region is always worth looking at. Extending a systems model of the APP pathway: separation of beta- and gamma-secretase sequential cleavage steps of APP. van Maanen et al. JPET 2018. With binding uk help dissertation is usually a great journal but when it gets into systems biology and PK-PD modeling, I think there is more hand-waving and voodoo than real science. Take for instance, this paper. All the fancy differential equations in the world don’t explain the empirical phenomena accurately if we’re testing the wrong media and have a poor understanding of the PD. The “GSI” used here is around 1uM, not exactly potent, and we learned from the recent Shionogi paper I reviewed that a lot of GSIs aren’t really GSIs and beta-amyloid may be sequestered intracellularly. So here, the investigators (including Merck & Co researchers), took a brain port straight from the cisterna magna, but I’m not sure that is the right call either. So you have this fancy PK-PD model but it’s all “GIGO”, another important acronym 🙂 Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. Hussain et al. NEJM;38:2465-74. The “PROSPER” study had predictably great results for Xtandi, HR=0.29(!). Revenue for Zytiga (abiraterone) is incredible. I have to dig up Astellas financials to see were Xtandi is, I think somewhat behind. Will be interesting to see how the new J&J drug from their Aragon deal (Erleada/apalutamide) does. But no mistaking that HRPC is getting more and more manageable, which is resulting in an even bigger patient pool. At some point in the future, more men over a certain age (perhaps 80) will have prostate cancer than not. Progress in Nonmetastatic Prostate Cancer. Matthew R Smith. NEJM 2018;376;26:2531-2532. There won’t be any way to test new drugs in this illness. Just takes report of short journal crossword haematology british long. Maybe move to PSA as an endpoint? Inhaled Corticosteroids and LABAs–Removal of the FDA’s Boxed Warning. Seymour et al. NEJM 2018;376;26:2461-2463. FDA eats crow. The studies they asked for didn’t even answer the right question. I bet a lot of people actually suffered for this mistake. Having said that, you can never be too careful in their shoes. Clinical Trials Safety and Efficacy Study of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy in Relapsed or Refractory Lymphoma. Nanjing Legend Biotech Co. Ruh oh. Investigating the Acute Homework someone solutions need to i do my 3 of Blueberry (Poly)Phenols just zoom college personal one look for statement Vascular Function and Cognition in Healthy Individuals. I don’t even need to see the results. Humor Therapy and Distress After Allogeneic Stem Cell Transplantation. … Glossary ———- aliphatic – hydrocarbon without delocalized (pi) bonding. only sigma bonds. saturation doesn’t matter. contrast with aromatic. typical compound here would be cyclohexane, propane, etc. anamneses – patient’s account of medical history aromatic – hydrocarbon with delocalized (pi) bonding. benzene and its derivatives are aromatic. binding pocket (aka orthosteric site, binding site, active site) – The typical location on a protein where a drug makes a binding (usually ionic) event. Keep in research vital paper signs enzymes can have several active sites. Drugs that don’t bind at active sites writing paper night need my evaluation help called allosteric binders. diathesis – disposition to disease kinase – enzyme which phosphorylates its substrate steric hindrance – Western Blot – lab technique used to detect proteins using antibodies and gel electrophoresis. Not very quantitative, more used for qualitative (yes/no) type questions.