tbuckley/cabot-search huggingface dataset:
Use of genomics in toxicology and epidemiology: findings and recommendations of a workshop.
Authors: Carol J Henry, Richard Phillips, Francis Carpanini, J Christopher Corton, Katherine Craig, Koichi Igarashi, Robert Leboeuf, Gary Marchant, Kimberly Osborn, William D Pennie, Lewis L Smith, M Jane Teta, Vanessa Vu
Journal: Environmental Health Perspectives (2002)

The sequencing of the human genome has revolutionized biology and led to an astounding variety of technologies and bioinformatics tools, enabling researchers to study expression of genes, the function of proteins, metabolism, and genetic differences within populations and between individuals. These scientific advances are making an impact in the medical research community and hold great promise for prevention, diagnosis, and treatment of diseases. This developing field also holds great promise for improving the scientific basis for understanding the potential impacts of chemicals on health and the environment. A workshop sponsored by the International Council of Chemical Associations was held to review the state of the science in the application of genomics technologies in toxicology and epidemiology. Further, consideration was given to the ethical, legal, and regulatory issues and their influence on the direction and application of genomics technologies to environmental health research. Four overarching themes emerged from the workshop: Genomics technologies should be used within a framework of toxicology and epidemiology principles and applied in a context that can be used in risk assessment; effective application of these technologies to epidemiology will require suitable biologic samples from large and diverse population groups at the relevant period of exposure; ethical, legal, and social perspectives require involvement of all stakeholder communities; and a unified research agenda for genomics technologies as applied to toxicology, epidemiology, and risk assessment is urgently needed for the regulatory and scientific communities to realize the potential power and benefits of these new technologies.
Natural killer cell activity in untreated systemic lupus erythematosus
Authors: K. Oshimi, M. Sumiya, N. Gonda, S. Kano, F. Takaku
Journal: Annals of the Rheumatic Diseases (1982)

With strictly selected controls natural killer cell activity was evaluated in 10 untreated patients with systemic lupus erythematosus. Natural killer levels of the patients were significantly lower than those of the age- and sex-matched normal controls. Natural killer levels, however, did not correlate with disease activity.
Overflow, access, and attention
Authors: Ned Block
Journal: Behavioral and Brain Sciences (2007)

Abstract In this response to 32 commentators, I start by clarifying the overflow argument. I explain why the distinction between generic and specific phenomenology is important and why we are justified in acknowledging specific phenomenology in the overflow experiments. Other issues discussed are the relations among report, cognitive access, and attention; panpsychic disaster; the mesh between psychology and neuroscience; and whether consciousness exists.
Periurethral Bacterial Flora in Women
Authors: Calvin M. Kunin
Journal: JAMA (1980)

To determine whether the periurethral flora of women with recurrent urinary infections differ from that of women without infection, a prospective study was conducted of matched premenopausal women. Daily or alternate-day urine cultures in patients and control subjects were obtained for six months to one year, as were daily records of sexual intercourse. Periurethral colonization with the same organism preceded 29 of 31 and six of seven episodes of significant bacteriuria in patients and control subjects, respectively. Prolonged periods of intermittent colonization with the same Escherichia coli serotype were observed in both patients and control subjects. Proportion of days of colonization of E coli or other Gram-negative bacteria was not significantly different between cases and controls and was not influenced by rates of sexual intercourse. Spontaneous cure occurred despite continued sexual intercourse.
Auranofin or D-Penicillamine in the Treatment of Rheumatoid Arthritis
Authors: MARC C. HOCHBERG
Journal: Annals of Internal Medicine (1986)

Ninety patients were entered into a randomized, controlled, double-blind trial lasting 12 months to compare auranofin (6 mg/d), and D-penicillamine (250 mg/d for 4 weeks, 500 mg/d for 4 weeks, then 750 mg/d thereafter) in the treatment of rheumatoid arthritis. Most patients in both groups completed the trial with significant improvement in all quantitative measures of efficacy. Patients treated with D-penicillamine were more likely to have "important improvement" in physician global assessment, swollen joint count, and score and grip strength. The overall frequency of side effects was similar between the two groups; however, more patients were withdrawn for adverse effects from the D-penicillamine group, and proteinuria (> 2+) and thrombocytopenia (< 100 000 mm3) occurred significantly more frequently with D-penicillamine than auranofin (p = 0.028). These results suggest that in the dosage regimen used, auranofin is safer than D-penicillamine but that D-penicillamine tends to show greater clinical effectiveness in patients with rheumatoid arthritis.
Parental Consent for Abortion
Authors: Kevin E. Glancy
Journal: JAMA (1993)

To the Editor.  —I wish to raise several objections to the opinions expressed by the Council on Ethical and Judicial Affairs 1 regarding parental consent for abortion.  I do not believe that the conclusions reached by the Council are consistent with their own arguments. Repeatedly throughout the Council Report, parents are noted to be the persons from whom a minor will most often receive appropriate counseling. And further, they point out that minors frequently have erroneous preconceptions regarding negative responses from their parents regarding pregnancy, which will (despite physician encouragement to the contrary) most likely not allow helpful parental involvement. Thus, in order to deal with the remaining minority, the Council concludes that parental involvement should not be required and ignores legal mechanisms already in place protecting abused minors.  The Council also places consent for abortion in a totally different category from all other consents for medical procedures. The Council
Oral administration of protease inhibits enterotoxigenic Escherichia coli receptor activity in piglet small intestine.
Authors: T L Mynott, R K Luke, D S Chandler
Journal: Gut (1996)

The virulence of enterotoxigenic Escherichia coli (ETEC) is attributed to their ability to adhere via fimbrial adhesins to specific receptors located on the intestinal mucosa. A novel approach to preventing ETEC induced diarrhoea would be to prevent attachment of ETEC to intestine by proteolytically modifying the receptor attachment sites. This study aimed to examine the effect of bromelain, a proteolytic extract obtained from pineapple stems, on ETEC receptor activity in porcine small intestine. Bromelain was administered orally to piglets and K88+ ETEC attachment to small intestine was measured at 50 cm intervals using an enzyme immunoassay. K88+ ETEC attachment to intestinal sections that were not treated with bromelain varied appreciably between sampling sites. Variability in receptor activity along the intestinal surface is though to be caused by the localised effects of endogenous proteases. Oral administration of exogenous protease inhibited K88+ ETEC attachment to pig small intestine in a dose dependent manner (p &lt; 0.05). Attachment of K88+ ETEC was negligible after treatment, resembling the levels of attachment of K88 to piglets of the genetically determined non-adhesive phenotype, which are resistant to K88+ ETEC infection. Serum biochemical analysis and histopathological examination of treated piglets showed no adverse effects of the bromelain treatment. It is concluded that administration of bromelain can inhibit ETEC receptor activity in vivo and may therefore be useful for prevention of K88+ ETEC induced diarrhoea.
England's NHS is struggling to boost productivity despite drive for efficiency, finds analysis
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Doctors may be the key factor to increasing productivity in the health service, shows an analysis that found that NHS activity in England was “stubbornly stagnant” last year. 

The analysis, by the Nuffield Trust, an independent health policy think tank, found that activity at hospital trusts in England fell by 1% in 2011-12 after increasing by 4.8% a year between 2006-7 and 2010-11.1 

But an in-depth look at the factors influencing England’s NHS output found that organisations with a higher proportion of doctors and other medical staff were associated with higher productivity. 

The analysis also suggests that competition between NHS providers drives down productivity, raising questions about whether the coalition government’s changes to the NHS, which centre on increasing marketisation, will achieve what they set out to—deliver the health services needed to …
Excretory Rates in Posttransplant Cystinuric Patient
Authors: Edward P. Nolan
Journal: JAMA (1978)

<h3>To the Editor.—</h3> While studying phenotypes of cystinuria, we measured the daily excretion rates of a 28-year-old man with a nine-year history of cystine stone formation and who, during the course of our study, received a kidney transplant at a nearby hospital because of "end-stage kidney failure." Our measurements of his cystine and dibasic amino acid excretion are of interest since they are, to our knowledge, the first record of a surgical "cure" of the disease. The patient's genetic constitution, predicted from the phenotype expressions of his obligate carrier daughter and mother, respectively, is compound heterozygous for the types I and III of cystinuria.<sup>1,2</sup>A brother, furthermore, expressed the type III heterozygous phenotype. The pretransplant excretion rates are clearly abnormal (Table) but lessso than those of other stone-forming patients in our experience. We attribute the milder biochemical expression to his renal failure, a characteristic of severely affected cystinuric
THE MANAGEMENT OF IMPETIGO CONTAGIOSA IN MATERNITY HOSPITALS
Authors: J. HARPER BLAISDELL
Journal: JAMA (1924)

"Impetigo contagiosa is breaking out on Baby C. in the nursery." To the hospital superintendent who has been through a previous epidemic of impetigo contagiosa, such an announcement brings immediate anxiety and fear, for she is confronted at that moment by the instant necessity for a change of routine in the nursery, a doubling or more in that part of the nursing personnel, and a ceaseless vigilance in the coming days, if this contagious disease is to be spared the other babies and even death warded off. And yet, in spite of the frequent occurrence of this important problem, the minutiae of treatment, so essential for the intelligent handling of these situations, are almost entirely lacking in the literature and the textbooks alike. Knowles and Munson<sup>1</sup>review the literature on epidemics in institutions, and add to the series the details of three small outbreaks of impetigo in two hospitals
Targeting Tumor Endothelial Marker 8 in the Tumor Vasculature of Colorectal Carcinomas in Mice
Authors: Stephen Fernando, Bradley S. Fletcher
Journal: Cancer Research (2009)

Tumor endothelial marker 8 (TEM8) is a recently described protein that is preferentially expressed within tumor endothelium. We have developed a fusion protein that targets TEM8 and disrupts tumor vasculature by promoting localized thrombosis. Fusion protein specificity and function were evaluated using Western blot analysis, ELISA, and enzymatic assays. A xenograft model of colorectal carcinoma was used to test the efficacy of targeted and control fusion proteins. Mice treated with the gene encoding anti-TEM8/truncated tissue factor exhibited a 53% reduction in tumor volume when compared with the untreated animals (P < 0.0001; n = 10) and achieved a 49% increase in tumor growth delay by Kaplan-Meier analysis (P = 0.0367; n = 6). Immunohistochemistry confirmed tumor endothelial expression of TEM8, fusion protein homing to tumor vasculature, decrease in vessel density, and localized areas of thrombosis. These data support the hypothesis that targeting TEM8 can be an effective approach to influence tumor development by disrupting tumor vasculature.
Homogeneous neural networks cannot provide complex cognitive functions
Authors: Alexey M. Ivanitsky, Andrey R. Nikolaev
Journal: Behavioral and Brain Sciences (1999)

Within the Hebbian paradigm the mechanism for integrating cell assemblies oscillating with different frequencies remains unclear. We hypothesize that such an integration may occur in cortical “interaction foci” that unite synchronously oscillated assemblies through hard-wired connections, synthesizing the information from various functional systems of the brain.
Purpura fulminans due to protein S deficiency following chickenpox
Authors: W.G. PHILLIPS, J.R. MARSDEN, F.G. HILL
Journal: British Journal of Dermatology (1992)

Journal Article Purpura fulminans due to protein S deficiency following chickenpox Get access W.G. PHILLIPS, W.G. PHILLIPS Departments of Dermatology, Birmingham Children's Hospital, Ladywood Middleway, Birmingham B16 8ET, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.R. MARSDEN, J.R. MARSDEN Departments of Dermatology, Birmingham Children's Hospital, Ladywood Middleway, Birmingham B16 8ET, U.K. Dr J.R. Marsden Search for other works by this author on: Oxford Academic Google Scholar F.G. HILL F.G. HILL Departments of Haematology, Birmingham Children's Hospital, Ladywood Middleway, Birmingham B16 8ET, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue 1, 1 July 1992, Pages 30–32, https://doi.org/10.1111/j.1365-2133.1992.tb14821.x Published: 01 July 1992
Outbreak of hepatitis A infection associated with the consumption of frozen berries, Ireland, 2013 - linked to an international outbreak
Authors: M Fitzgerald, L Thornton, J O'Gorman, L O’Connor, P Garvey, M Boland, A M Part, J Rogalska, H Coughlan, J MacDiarmada, J Heslin, M Canny, P Finnegan, J Moran, D O’Flanagan, Collective on behalf of the Hepatitis A Outbreak Control Team
Journal: Eurosurveillance (2014)

In May 2013, a European alert was issued regarding a hepatitis A virus (HAV) outbreak in Italy. In June 2013, HAV subgenotype IA with an identical sequence was identified in Ireland in three cases who had not travelled to Italy. The investigation consisted of descriptive epidemiology, a case-control study, microbiological testing of human and food specimens, molecular typing of positive specimens and food traceback. We identified 21 outbreak cases (14 confirmed primary cases) with symptom onset between 31 January and 11 October 2013. For the case-control study, we recruited 11 confirmed primary cases and 42 matched controls. Cases were more likely than controls to have eaten berry cheesecake (matched odds ratio (mOR): 12; 95% confidence interval (CI): 1.3-114), whole frozen berries (mOR: 9.5; 95% CI: 1.0-89), yoghurt containing frozen berries (mOR: 6.6, 95% CI: 1.2-37) or raw celery (mOR: 4; 95% CI: 1.2-16). Among cases, 91% had consumed at least one of four products containing frozen berries (mOR: 12; 95% CI: 1.5-94). Sixteen food samples tested were all negative for HAV. As products containing frozen berries were implicated in the outbreak, the public were advised to heat-treat frozen berries before consumption.
Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths
Authors: Amy S. B. Bohnert
Journal: JAMA (2011)

<h3>Context</h3>The rate of prescription opioid–related overdose death increased substantially in the United States over the past decade. Patterns of opioid prescribing may be related to risk of overdose mortality.<h3>Objective</h3>To examine the association of maximum prescribed daily opioid dose and dosing schedule (“as needed,” regularly scheduled, or both) with risk of opioid overdose death among patients with cancer, chronic pain, acute pain, and substance use disorders.<h3>Design</h3>Case-cohort study.<h3>Setting</h3>Veterans Health Administration (VHA), 2004 through 2008.<h3>Participants</h3>All unintentional prescription opioid overdose decedents (n = 750) and a random sample of patients (n = 154 684) among those individuals who used medical services in 2004 or 2005 and received opioid therapy for pain.<h3>Main Outcome Measure</h3>Associations of opioid regimens (dose and schedule) with death by unintentional prescription opioid overdose in subgroups defined by clinical diagnoses, adjusting for age group, sex, race, ethnicity, and comorbid conditions.<h3>Results</h3>The frequency of fatal overdose over the study period among individuals treated with opioids was estimated to be 0.04%.The risk of overdose death was directly related to the maximum prescribed daily dose of opioid medication. The adjusted hazard ratios (HRs) associated with a maximum prescribed dose of 100 mg/d or more, compared with the dose category 1 mg/d to less than 20 mg/d, were as follows: among those with substance use disorders, adjusted HR = 4.54 (95% confidence interval [CI], 2.46-8.37; absolute risk difference approximation [ARDA] = 0.14%); among those with chronic pain, adjusted HR = 7.18 (95% CI, 4.85-10.65; ARDA = 0.25%); among those with acute pain, adjusted HR = 6.64 (95% CI, 3.31-13.31; ARDA = 0.23%); and among those with cancer, adjusted HR = 11.99 (95% CI, 4.42-32.56; ARDA = 0.45%). Receiving both as-needed and regularly scheduled doses was not associated with overdose risk after adjustment.<h3>Conclusion</h3>Among patients receiving opioid prescriptions for pain, higher opioid doses were associated with increased risk of opioid overdose death.
Estimation of the Residual Volume of the Right Ventricle of the Dog's Heart
Authors: J. P. HOLT, J. ALLENSWORTH, J. Diana, D. Collins, H. Kines
Journal: Circulation Research (1957)

The measurement of right ventricular end-diastolic volume, end-systolic volume, and stroke volume by means of the electric conductivity technic is described. The right ventricle empties in a "fractional" manner, as does the left ventricle, and on the average 39 per cent of its end-diastolic volume is ejected with each stroke, leaving a residual volume of 61 per cent.
IMPACT OF APPROPRIATE USE CRITERIA BASED PERCUTANEOUS CORONARY INTERVENTIONS ON LONG TERM CLINICAL OUTCOMES OF PATIENTS: A LARGE VOLUME, SINGLE CENTER EXPERIENCE
Authors: Nagendra Boopathy Senguttuvan, Jason Kovacic, Usman Baber, Swathi Roy, Annapoorna Kini, Samin Sharma
Journal: Journal of the American College of Cardiology (2014)
The Lancet's two days to bury bad news
Authors: B. Deer
Journal: BMJ (2011)

In the third part of a special BMJ series, Brian Deer reveals what happened when he reported misconduct in Andrew Wakefield’s MMR research to the medical journal that published it

Preparing to give evidence in London to a UK General Medical Council fitness to practise panel, Richard Horton, editor of the Lancet , nodded in turn to three accused doctors, seated among their lawyers to his left. First, Simon Murch, almost close enough to touch. Next, John Walker-Smith, more distant. Finally, Andrew Wakefield, at the far end of the hearing room. Each smiled thinly and nodded back.

The four had last met together three and a half years before, at the Lancet ’s offices, nearly two miles north. There they had begun the journey that now brought their reunion in this, the longest medical disciplinary inquiry ever. Running for 217 days, between July 2007 and May 2010, it would probe the research and a paper that launched the MMR vaccine scare, and would lead to Wakefield and Walker-Smith being struck off.1 2

Their previous encounter was in 2004, on the afternoon of Wednesday 18 February. They had gathered in Horton’s office to deal with an approach from me concerning a four month Sunday Times investigation. For five hours that morning, I had briefed the Lancet ’s senior staff about a now notorious 1998 paper in their journal.3 It reported on 12 children seen at the Royal Free hospital, north London, and claimed to have discovered a possible “new syndrome” involving regressive autism, inflammatory bowel disease, and MMR.

Mostly I had stood, occasionally pulling documents, as Horton, with five editors, took notes. I told them that the paper’s first author, Wakefield, was retained by a lawyer and was funded to help sue vaccine manufacturers. Admissions criteria for the study …
Reconstructing the heart: a challenge for integrative physiology
Authors: D. Noble, G. Bett
Journal: Cardiovascular Research (1993)

Journal Article Reconstructing the heart: a challenge for integrative physiology Get access Denis Noble, Denis Noble University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, United Kingdom: D Noble, G Bett. Correspondence to Professor Noble. Search for other works by this author on: Oxford Academic PubMed Google Scholar Glenna Bett Glenna Bett University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, United Kingdom: D Noble, G Bett. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 10, October 1993, Pages 1701–1712, https://doi.org/10.1093/cvr/27.10.1701 Published: 01 October 1993 Article history Received: 09 February 1993 Accepted: 17 May 1993 Published: 01 October 1993
Phosphorylation of Ribosomal Protein S6 Attenuates DNA Damage and Tumor Suppression during Development of Pancreatic Cancer
Authors: Abed Khalaileh, Avigail Dreazen, Areej Khatib, Roy Apel, Avital Swisa, Norma Kidess-Bassir, Anirban Maitra, Oded Meyuhas, Yuval Dor, Gideon Zamir
Journal: Cancer Research (2013)

The signaling pathways that mediate the development of pancreatic ductal adenocarcinoma (PDAC) downstream of mutant Kras remain incompletely understood. Here, we focus on ribosomal protein S6 (rpS6), an mTOR effector not implicated previously in cancer. Phosphorylation of rpS6 was increased in pancreatic acinar cells upon implantation of the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) or transgenic expression of mutant Kras. To examine the functional significance of rpS6 phosphorylation, we used knockin mice lacking all five phosphorylatable sites in rpS6 (termed rpS6(P-/-) mice). Strikingly, the development of pancreatic cancer precursor lesions induced by either DMBA or mutant Kras was greatly reduced in rpS6(P-/-) mice. The rpS6 mutants expressing oncogenic Kras showed increased p53 along with increased staining of γ-H2AX and 53bp1 (Trp53bp1) in areas of acinar ductal metaplasia, suggesting that rpS6 phosphorylation attenuates Kras-induced DNA damage and p53-mediated tumor suppression. These results reveal that rpS6 phosphorylation is important for the initiation of pancreatic cancer.