tbuckley/cabot-search huggingface dataset:
Preventing RhD haemolytic disease of the newborn
Authors: R. Fox, I. R McFadyen, V. J Martlew, H. L Howard, C. A Clarke, A. Saha, C. Everett, J. Wray
Journal: BMJ (1998)

Many climate change scientists do not agree that global warming is happeningEditor-The apocalyptic tone that Smith adopted in relation to the environment bears little relation to reality. 1 In his editorial Smith asserts, "virtually all scientists agree that global warming is happening."Global warming is now joining the list of "what everyone knows."Whether most scientists outside climatology believe that global warming is happening is less relevant than whether the climatologists do.A letter signed by over 50 leading members of the American Meteorological Society warned about the policies promoted by environmental pressure groups."The policy initiatives derive from highly uncertain scientific theories.They are based on the unsupported assumption that catastrophic global warming follows from the burning of fossil fuel and requires immediate action.We do not agree." 2 Those who have signed the letter represent the overwhelming majority of climate change scientists in the United States, of whom there are about 60.McMichael and Haines quote the 1995 report of the Intergovernmental Panel on Climate Change (IPCC), which is widely believed to "prove" that climate change induced by humans has occurred. 3 The original draft document did not say this.What happened was that the policymakers' summary (which became the "take home message" for politicians) altered the conclusions of the scientists.This led Dr Frederick Seitz, former head of the United States National Academy of Sciences, to write, "In more than sixty years as a member of the American scientific community . . .I have never witnessed a more disturbing corruption of the peer-review process than the events that led to this IPCC report." 4 Policymaking should be guided by proved fact, not speculation.Most members of the Intergovernmental Panel on Climate Change believe that current climate models do not accurately portray the atmosphereocean system.Measurements made by means of satellites show no global warming but a cooling of 0.13°C between 1979 and 1994. 5Furthermore, since the theory of global warming assumes maximum warming at the poles, why have average temperatures in the Arctic dropped by 0.88°C over the past 50 years? 5
Safety of Recombinant Activated Factor VII in Randomized Clinical Trials
Authors: Marcel Levi, Jerrold H. Levy, Henning Friis Andersen, David Truloff
Journal: New England Journal of Medicine (2010)

The use of recombinant activated factor VII (rFVIIa) on an off-label basis to treat life-threatening bleeding has been associated with a perceived increased risk of thromboembolic complications. However, data from placebo-controlled trials are needed to properly assess the thromboembolic risk. To address this issue, we evaluated the rate of thromboembolic events in all published randomized, placebo-controlled trials of rFVIIa used on an off-label basis.We analyzed data from 35 randomized clinical trials (26 studies involving patients and 9 studies involving healthy volunteers) to determine the frequency of thromboembolic events. The data were pooled with the use of random-effects models to calculate the odds ratios and 95% confidence intervals.Among 4468 subjects (4119 patients and 349 healthy volunteers), 401 [corrected] had thromboembolic events (9.0%). [corrected] Rates of arterial thromboembolic events among all 4468 subjects were higher among those who received rFVIIa than among those who received placebo (5.5% vs. 3.2%, P=0.003). Rates of venous thromboembolic events were similar among subjects who received rFVIIa and those who received placebo (5.3% vs. 5.7%). Among subjects who received rFVIIa, 2.9% had coronary arterial thromboembolic events, as compared with 1.1% of those who received placebo (P=0.002). Rates of arterial thromboembolic events were higher among subjects who received rFVIIa than among subjects who received placebo, particularly among those who were 65 years of age or older (9.0% vs. 3.8%, P=0.003); the rates were especially high among subjects 75 years of age or older (10.8% vs. 4.1%, P=0.02).In a large and comprehensive cohort of persons in placebo-controlled trials of rFVIIa, treatment with high doses of rFVIIa on an off-label basis significantly increased the risk of arterial but not venous thromboembolic events, especially among the elderly. (Funded by Novo Nordisk.).
Effects of particle size on the triboelectrification phenomenon in pharmaceutical excipients: Experiments and multi-scale modeling
Authors: Raj Mukherjee, Vipul Gupta, Shivangi Naik, Saurabh Sarkar, Vinit Sharma, Prasad Peri, Bodhisattwa Chaudhuri
Journal: Asian Journal of Pharmaceutical Sciences (2016)

Particle sizes play a major role to mediate charge transfer, both between identical and different material surfaces. The study probes into the probable mechanism that actuates opposite polarities between two different size fractions of the same material by analyzing the charge transfer patterns of two different sizes of microcrystalline cellulose (MCC). Quantum scale calculations confirmed alteration of charge transfer capacities due to variation of moisture content predicted by multiple surface and bulk analytical techniques. Discrete Element Method (DEM) based multi-scale computational models pertinent to predict charge transfer capacities were further implemented, and the results were in accordance to the experimental charge profiles.
Social Determinants of Racial Disparities in CKD
Authors: Jenna M. Norton, Marva M. Moxey-Mims, Paul W. Eggers, Andrew S. Narva, Robert A. Star, Paul L. Kimmel, Griffin P. Rodgers
Journal: Journal of the American Society of Nephrology (2016)

Significant disparities in CKD rates and outcomes exist between black and white Americans. Health disparities are defined as health differences that adversely affect disadvantaged populations, on the basis of one or more health outcomes. CKD is the complex result of genetic and environmental factors, reflecting the balance of nature and nurture. Social determinants of health have an important role as environmental components, especially for black populations, who are disproportionately disadvantaged. Understanding the social determinants of health and appreciating the underlying differences associated with meaningful clinical outcomes may help nephrologists treat all their patients with CKD in an optimal manner. Altering the social determinants of health, although difficult, may embody important policy and research efforts, with the ultimate goal of improving outcomes for patients with kidney diseases, and minimizing the disparities between groups.
Prognostic model for patients (pts) with advanced pancreatic cancer (aPC) receiving first-line modified FOLFIRINOX (mFOLFIRINOX)
Authors: C. Vivaldi, E. Vasile, L. Fornaro, G. Pasquini, S. Catanese, C. Caparello, G. Musettini, M. Lencioni, S. Ricci, A. Falcone
Journal: Annals of Oncology (2015)
Further Studies on the Frequency of Achlorhydria Among Mexicans in Los Angeles
Authors: George Drake, Jr., M.D., Charles M. Carpenter, M.D., John E. Dunn, Jr., M.D.
Journal: JNCI Journal of the National Cancer Institute (1962)

A previous report (Grinspoon, L., and Dunn, J. E., Jr., J. Nat. Cancer Inst. 22: 617–631, 1959) of tubeless gastric analysis indicated that an excess of achlorhydria was not found among Japanese as might have been expected because of the high rate of gastric cancer in this racial group. An unexpected observation was an excess of achlorhydria among Mexican controls as compared to Caucasian controls. The additional data in this report support the finding of excess achlorhydria among Mexicans as compared to Caucasians, and also show that the Japanese have a significant deficiency. The latter condition may reflect a bias resulting from the fact that the Caucasians and Mexicans in the study largely come from a hospital population, while a large proportion of the Japanese are from an ambulatory-patient and well population.
Abstract 14288: ReAssessment of Anti-Platelet Therapy Using an Individualized Strategy Based on Genetic Evaluation Facilitated by a Point-Of-Care Genetic Test (RAPID GENE): A Randomized Proof-Of-Concept Study
Authors: Derek So, Jason Roberts, Alexandre Stewart, Sandro Goncalves, Michel Le May, Chris Glover, Alexander Dick, Michael Froeschl, Edward O'Brien, Jean-Francois Marquis, Marino Labinaz
Journal: Circulation (2011)

Background: Increased rates of major adverse cardiovascular events following percutaneous coronary intervention (PCI) in individuals receiving clopidogrel have been associated with the CYP2C19*2 allele. Ultra rapid identification of CYP2C19*2 carriers with subsequent alteration of anti-platelet therapy would be integral for development of pharmacogenomic strategies. To date, there has been no prospective evaluation of this strategy. Methods: We developed and validated a point-of-care genetic test for the CYP2C19*2 allele and then evaluated its feasibility in the clinical setting through a prospective proof-of-concept randomized controlled trial designed to examine the potential efficacy of a pharmacogenomic approach following PCI. Patients were randomized to either a strategy of rapid genotyping with selective administration of prasugrel 10mg daily to CYP2C19*2 carriers or to standard therapy with clopidogrel 75 mg daily. Efficacy of the treatment strategies was evaluated using platelet function testing w...
Embrace scientific rhetoric for its power
Authors: D. Junger
Journal: BMJ (1995)

referrals may well have reversed since 1991 because of the NHS reforms, which have seen so many radical changes in both general practice and the hospital sector.Until more up to date national data are available, Armstrong and Nicoll's argument, which is based on historical trends, may not be applicable.In addition, our figures show a small decrease in the number of patients followed up during the period.This is contrary to Armstrong and Nicoll's suggestion that the problem of recycling patients has become worse in recent years and has resulted in access for new outpatient referrals being blocked.
Perspectives in Oncology Drug Pricing—Reply
Authors: Daniel A. Goldstein, David H. Howard, Christopher R. Flowers
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Laboratory Diagnosis and Clinical Profile of Anti-p200 Pemphigoid
Authors: Joost M. Meijer, Gilles F. H. Diercks, Enno Schmidt, Hendri H. Pas, Marcel F. Jonkman
Journal: JAMA Dermatology (2016)

Anti-p200 pemphigoid is a rare subepidermal autoimmune blistering disease characterized by autoantibodies against a 200-kDa protein in the basement membrane zone. Anti-p200 pemphigoid is probably often misdiagnosed because of low availability of diagnostic assays and expertise and classified as bullous pemphigoid or epidermolysis bullosa acquisita.To clinically characterize patients with anti-p200 pemphigoid, identified by using indirect immunofluorescence microscopy on skin substrates deficient in type VII collagen and laminin-332 (knockout analysis), to validate this technique by immunoblot with dermal extract, and to incorporate direct immunofluorescence serration pattern analysis in the diagnostic algorithm.This was a retrospective study performed from January 2014 to June 2015 with biobank patient materials and clinical data for the period 1998 to 2015 from the single national referral center on autoimmune bullous diseases. Patients were selected based on a dermal side binding on 1-mol/L salt (sodium chloride)-split human skin substrate by indirect immunofluorescence microscopy, not diagnosed epidermolysis bullosa acquisita or anti-laminin-332 mucous membrane pemphigoid.Indirect immunofluorescence microscopy knockout analysis was performed and diagnosis of anti-p200 confirmed by immunoblot with dermal extract. Clinical, histological, and immunological findings were registered. Autoantibodies against laminin γ1 were determined by immunoblot.Twelve patients with anti-p200 pemphigoid (7 male and 5 female; mean age, 66.6 years) were identified using the indirect immunofluorescence microscopy knockout analysis. Direct immunofluorescence microscopy showed a linear n-serrated IgG deposition pattern along the basement membrane zone in 9 of 11 patients. The diagnosis was confirmed by immunoblot showing autoantibodies against 200-kDa protein in dermal extract in 12 of 12 patients. Autoantibodies against recombinant laminin γ1 were detected by immunoblot in 8 of 12 patients. Remarkable similarities were seen in clinical features with predominantly tense blisters on hands and feet, resembling dyshidrosiform pemphigoid. Mucosal involvement was seen in 6 (50%) of the patients.Predominance of blisters on hands and feet may be a clinical clue to the diagnosis of anti-p200 pemphigoid. Direct immunofluorescence microscopy serration pattern analysis and indirect immunofluorescence microscopy knockout analysis are valuable additional techniques to facilitate the diagnosis of anti-p200 pemphigoid.
Evolution of Vertebrate Phototransduction: Cascade Activation
Authors: Trevor D. Lamb, Hardip Patel, Aaron Chuah, Riccardo C. Natoli, Wayne I. L. Davies, Nathan S. Hart, Shaun P. Collin, David M. Hunt
Journal: Molecular Biology and Evolution (2016)

We applied high-throughput sequencing to eye tissue from several species of basal vertebrates (a hagfish, two species of lamprey, and five species of gnathostome fish), and we analyzed the mRNA sequences for the proteins underlying activation of the phototransduction cascade.The molecular phylogenies that we constructed from these sequences are consistent with the 2R WGD model of two rounds of whole genome duplication.Our analysis suggests that agnathans retain an additional representative (that has been lost in gnathostomes) in each of the gene families we studied; the evidence is strong for the G-protein a subunit (GNAT) and the cGMP phosphodiesterase (PDE6), and indicative for the cyclic nucleotide-gated channels (CNGA and CNGB).Two of the species (the hagfish Eptatretus cirrhatus and the lamprey Mordacia mordax) possess only a single class of photoreceptor, simplifying deductions about the composition of cascade protein isoforms utilized in their photoreceptors.For the other lamprey, Geotria australis, analysis of the ratios of transcript levels in downstream and upstream migrant animals permits tentative conclusions to be drawn about the isoforms used in four of the five spectral classes of photoreceptor.Overall, our results suggest that agnathan rod-like photoreceptors utilize the same GNAT1 as gnathostomes, together with a homodimeric PDE6 that may be agnathanspecific, whereas agnathan cone-like photoreceptors utilize a GNAT that may be agnathan-specific, together with the same PDE6C as gnathostomes.These findings help elucidate the evolution of the vertebrate phototransduction cascade from an ancestral chordate phototransduction cascade that existed prior to the vertebrate radiation.
IV. Septic Shock–Pathogenesis and Treatment
Authors: Louis Weinstein, Albert S. Klainer
Journal: New England Journal of Medicine (1966)

SEPTIC shock is a dynamic syndrome induced by infections of varying type in which inadequate perfusion of tissues with blood develops. Although the microcirculation of the capillary loop is the final determinant of the events that occur in this condition, multiple factors are involved in the genesis and persistence of progressive decompensation of the capillary circulation and the cells that it supports. Effective therapy of septic shock requires knowledge of its pathogenesis, anticipation and recognition of the clinical picture, the use of available bedside and laboratory technics for assessing the nature and degree of the derangements and rapid initiation of . . .
Analytic Validation of RNA <i>In Situ</i> Hybridization (RISH) for AR and AR-V7 Expression in Human Prostate Cancer
Authors: Liana B. Guedes, Carlos L. Morais, Fawaz Almutairi, Michael C. Haffner, Qizhi Zheng, John T. Isaacs, Emmanuel S. Antonarakis, Changxue Lu, Harrison Tsai, Jun Luo, Angelo M. De Marzo, Tamara L. Lotan
Journal: Clinical Cancer Research (2016)

RNA expression of androgen receptor splice variants may be a biomarker of resistance to novel androgen deprivation therapies in castrate-resistant prostate cancer (CRPC). We analytically validated an RNA in situ hybridization (RISH) assay for total AR and AR-V7 for use in formalin-fixed paraffin-embedded (FFPE) prostate tumors.
The Antibody-Drug Conjugate (ADC) IMGN779 Is Highly Active in Vitro and in Vivo Against Acute Myeloid Leukemia (AML) with FLT3-ITD Mutations
Authors: Kathleen R Whiteman, Paul Noordhuis, Russell Walker, Krystal Watkins, Yelena Kovtun, Lauren Harvey, Alan Wilhelm, Holly Johnson, Gerrit Jan Schuurhuis, Gert J Ossenkoppele, Robert J. Lutz
Journal: Blood (2014)
Studies on &lt;italic&gt;Fused&lt;/italic&gt;, a Mutant Gene Producing Ovarian Tumors in &lt;italic&gt;Drosophila melanogaster&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Patricia A. Smith, R. C. King
Journal: JNCI Journal of the National Cancer Institute (1966)

Flies homozygous for the mutant gene fused (fu) are characterized by fused wing veins, a maternal effect upon embryogenesis, and ovarian tumors. A number of mutant alleles have been studied and all exhibit this same syndrome. The rate at which ovarian tumors develop is characteristic for each allele. This rate was shown to be independent of modifying genes and unaffected by the maternal cytoplasm. The rate is also temperature-sensitive, tumors appearing more slowly at 18 than at 25° C. Females heterozygous for all possible combinations of these alleles were produced, and, in all 21, tumors were observed in the compound females. Cases of dominance, complementarity, and interference were observed with reference to certain allelic combinations. A model is proposed to explain the diverse effects on development of the fused gene and also the interaction of the alleles in ovarian development. Females homozygous for fused and either heterozygous or homozygous for the second chromosomal recessive gene female-sterile (fes) were also studied. The les gene was shown to be epistatic to fu in fu/fu; fes/fes females, and the rate of tumor production was greater in fu/fu; fes/+ females than in fu/fu;+/+ females. A mechanism for the action of fu and fes in controlling cell division is presented.
Supporting young people in their transition to adults’ services: summary of NICE guidance
Authors: Swaran P Singh, Beth Anderson, Kristin Liabo, Thines Ganeshamoorthy
Journal: BMJ (2016)

#### What you need to know

In spite of a wealth of guidance,1 young people making the transition from children’s to adults’ services are often inadequately or inconsistently supported.2 3 4 This can lead to disrupted care.5 It can also mean they disengage from services, which can be costly, both for them and for care providers.

Transition is a process and should not be conflated with transfer, which is a discrete event. Simple transfer may result in poor understanding of the young person’s treatment needs by the new adult team. Healthcare transition is a gradual, purposeful, and goal oriented process. It can be difficult and often coincides with other transitions such as development into adulthood, which adds complexity. Transition should start well before transfer and enable patients to understand the service changes they can expect. See linked infographic on supporting young people in their transition to adults’ services.

We summarise the most recent recommendations from the Institute for Health and Care Excellence (NICE) aimed at improving the transition process and outcomes across health and social care.6

NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the guideline committee’s experience and expert opinion of …
PWE-063 Local experience of using tacrolimus as rescue therapy in resistant ibd
Authors: K Lithgo, T Price, MW Johnson
Journal: Gut (2015)

<h3>Introduction</h3> Tacrolimus is a macrolide immunosuppressant. By inhibiting the transcription of interleukins (ILs) such as IL-2, tumour necrosis factor-α (TNF) and interferon-gamma, it exerts a powerful and selective suppression of T-cell function. Oral Tacrolimus has been used in patients with refractory ulcerative colitis, but its role in Crohn’s disease has not yet been determined, especially when compared with alternative approaches such as anti TNFs.<sup>1</sup>We reviewed the clinical outcomes of a small but growing cohort of resistant IBD patients where Tacrolimus was started as rescue therapy. <h3>Method</h3> The National IBD Registry was used to identify all IBD patients at the Luton and Dunstable University Hospital presently being treated on Tacrolimus. A retrospective review of these patients was then performed using data held on our National IBD Registry, Evolve (in-house hospital electronic records system) and ICE (hospital results system). A comparison was made of the data collected pre and post Tacrolimus therapy e.g. ESR, CRP, faecal calprotectin, Harvey Bradshaw Index (HBI) for Crohn’s patients and modified UC Disease Activity Index (UCDAI) for ulcerative colitis patients. <h3>Results</h3> The Luton and Dunstable University Hospital IBD Registry and Patient Management System now contains the clinical details of 3002 IBD patients. Of these a total of 10 patients had been started on Tacrolimus, 2 had Crohn’s and 8 had ulcerative colitis (3 Pan UC, 1 left sided UC and 4 distal UC). These patients had been started on Tacrolimus for a range of reasons including; failure of a range of standard therapies, multiple drug sensitivities, patients refusing biological therapy, failure of biological therapy, biological funding issues, steroid dependancy, steroid contraindications and refusing admission for IV steroids. All patients improved on Tacrolimus, with reductions seen in the average HBI from 7.5 to 4.5, and in the average mUCDAI scores from 7.9 to 3.5. A decrease was also seen with the average CRP pre and post Tacrolimus therapy decreasing from 24.4 to 9.7, and with the ESRs from 30.2 to 7.8. No adverse reactions have been experienced to date. <h3>Conclusion</h3> Our results suggest that Tacrolimus is a highly effective immunomodulator therapy, and a useful addition to the IBD therapeutic armoury, particularly in those with difficult or resistant UC or Crohn’s disease. We have been impressed with its speed of action and ease of dose adjustment. Further studies are required to assess its longterm safety profile and use in Crohn’s disease. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Landy J, Wahed M, Peake ST, Hussein M, Ng SC, Lindsay JO, Hart AL. Oral tacrolimus as maintenance therapy for refractory ulcerative colitis-an analysis of outcomes in two London tertiary centres. <i>J Crohns Colitis</i>. 2013;<b>7</b>(11):e516–21. doi: 10.1016/j.crohns.2013.03.008. Epub 2013 Apr 25