tbuckley/cabot-search huggingface dataset:
Book: A Mind So Rare: The Evolution of Human Consciousness
Authors: B. Charlton
Journal: BMJ (2001)

Merlin Donald W W Norton, £22.95, pp 371 ISBN 0 393 04950 7 Rating: ![Graphic][1]</img> ![Graphic][2]</img> ![Graphic][3]</img> There has been tremendous progress over the past few decades in understanding the nature and functioning of human consciousness. Although this knowledge has not yet settled into an explicit consensus, and details are lacking, nevertheless all the necessary elements are in place. A theory of human consciousness is here or hereabouts. From the evidence of this book, Donald is one of those who substantially understand consciousness—which is to say that he can give a … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Every breath you take
Authors: Sanjay Kumar
Journal: BMJ (2004)

Indoor stoves and a boom in diesel cars are contributing to dangerous levels of air pollution in South Asia. Sanjay Kumar reports 

Simple neglected public health issues, not exotic ones, dominate the agenda for environmental health in the South Asian region.

“Lack of safe sanitation, water, and hygiene are the biggest cause of infection and the key issues for environmental health in the region,” says Gourisankar Ghosh, executive director of the Water Supply and Sanitation Collaborative Council, the Geneva based UN mandated body for water and sanitation goals. The council calls this inadequacy “one of the biggest scandals of the last 50 years.”

South Asian countries are among the countries whose hygiene levels are “disastrous,” says the council. In India alone, 519 500 children die every year from poor hygiene; the equivalent figures in neighbouring Pakistan and in Afghanistan are 135 000 and 48 000 respectively.

The primary cause of this is unsafe disposal of human excreta: 72% of human excreta in India is disposed of in an unsafe way. The amounts of excreta disposed of in an unsafe way in other countries in the region are 72% in Nepal, 88% in Afghanistan, 52% in Bangladesh, 38% in Pakistan, and 30% in Bhutan. These figures are given by the Water Supply and Sanitation Collaborative Council in a new report called Listening (www.wsscc.org/listening/).

Frequent …
Kinome Profiling of Clinical Cancer Specimens
Authors: Kaushal Parikh, Maikel P. Peppelenbosch
Journal: Cancer Research (2010)

Over the past years novel technologies have emerged to enable the determination of the transcriptome and proteome of clinical samples. These data sets will prove to be of significant value to our elucidation of the mechanisms that govern pathophysiology and may provide biological markers for future guidance in personalized medicine. However, an equally important goal is to define those proteins that participate in signaling pathways during the disease manifestation itself or those pathways that are made active during successful clinical treatment of the disease: the main challenge now is the generation of large-scale data sets that will allow us to define kinome profiles with predictive properties on the outcome-of-disease and to obtain insight into tissue-specific analysis of kinase activity. This review describes the current techniques available to generate kinome profiles of clinical tissue samples and discusses the future strategies necessary to achieve new insights into disease mechanisms and treatment targets.
Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears β-amyloid in a mouse model of Alzheimer disease
Authors: Dan Frenkel, Ruth Maron, David S. Burt, Howard L. Weiner
Journal: Journal of Clinical Investigation (2005)

Amyloid beta-peptide (Abeta) appears to play a key pathogenic role in Alzheimer disease (AD). Immune therapy in mouse models of AD via Abeta immunization or passive administration of Abeta antibodies markedly reduces Abeta levels and reverses behavioral impairment. However, a human trial of Abeta immunization led to meningoencephalitis in some patients and was discontinued. Here we show that nasal vaccination with a proteosome-based adjuvant that is well tolerated in humans plus glatiramer acetate, an FDA-approved synthetic copolymer used to treat multiple sclerosis, potently decreases Abeta plaques in an AD mouse model. This effect did not require the presence of antibody, as it was observed in B cell-deficient (Ig mu-null) mice. Vaccinated animals developed activated microglia that colocalized with Abeta fibrils, and the extent of microglial activation correlated strongly with the decrease in Abeta fibrils. Activation of microglia and clearing of Abeta occurred with the adjuvant alone, although to a lesser degree. Our results identify a novel approach to immune therapy for AD that involves clearing of Abeta through the utilization of compounds that have been safely tested on or are currently in use in humans.
Digitalis Toxicity, Calcium, and Pronethalol
Authors: S. R. Kottegoda
Journal: BMJ (1964)

great surprise that she was getting so much for her 2s.I wonder if some way could not be found to indicate to patients when they receive drugs the cost they would have to meet if they met the cost out of their own pocket.From a different point of view, however, bearing in mind my article on "On not taking P.A.
Book Review Diseases of the Thyroid (Contemporary Endocrinology.) Edited by Lewis E. Braverman. 393 pp. Totowa, N.J., Humana Press, 1997. $125. 0-896-03414-3 Thyroid Disease: Endocrinology, surgery, nuclear medicine, and radiotherapy Second edition. Edited by Stephen A. Falk. 768 pp., illustrated. Philadelphia, Lippincott–Raven, 1997. $139. 0-397-51705-X
Authors: Anthony D. Toft
Journal: New England Journal of Medicine (1997)
Outcomes of screening to prevent cancer: Authors' reply
Authors: A E Raffle
Journal: BMJ (2003)

Editor—We agree that screening can be thought of like insurance. It is not the likelihood of a house fire that makes you pay your premiums, it is the seriousness.

We believe numbers screened are valuable. Policy about screening is unsatisfactory in that support for, or dismissal of, the worth of screening programmes is dominated by advocacy rather than scientific debate.1 Part of the reason this situation persists is that the literature is so hard to understand. It is full of statistical jargon, opaque terminology, and flawed concepts. We need to present complete information about all consequences of screening in an easily understandable way. People understand numbers and explanations in plain English, far better than probabilities, percentages, or sensitivity and specificity.2

Sasieni questions our estimates of cases and deaths. Our adjustment for “without screening” is as shown in figures 6.6 and 6.8 of page 51 of the reference we gave.3 We are happy to share our calculations, and without access to the age breakdown of our cohort we are unsure how alternative estimates can be derived.

We tested varying assumptions for mortality reduction after 1996. Even if 75% of deaths in our study population are prevented after 1996, our conclusion is still that screening is very labour intensive, with 790 women screened for 35 years to prevent one death, involving 6098 tests. We view case-control studies with caution.4

We can all hope that future benefits will be substantial, but we cannot let this divert us from the sobering finding that before 1996 there were 57 000 tests and 1955 women with abnormal results for each death prevented. Misguided media campaigns are already causing a repetition of this situation with prostate cancer screening. Invasive investigations and treatments for 2000, in the hope of possibly helping one, will seriously damage men's health.
Comparison of Ductal Lavage and Random Periareolar Fine Needle Aspiration as Tissue Acquisition Methods in Early Breast Cancer Prevention Trials
Authors: Banu Arun, Vicente Valero, Catherine Logan, Kristine Broglio, Edgardo Rivera, Abenaa Brewster, Guosheng Yin, Marjorie Green, Henry Kuerer, Yun Gong, Doris Browne, Gabriel N. Hortobagyi, Nour Sneige
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Short-term phase I and phase II breast cancer prevention trials require tissue acquisition at baseline and after intervention to evaluate modulation of potential biomarkers. Currently used tissue acquisition methods include ductal lavage (DL), random periareolar fine needle aspiration (RPFNA), and core needle biopsy. The optimum method to retrieve adequate samples and the most accepted method by study participants is not known. Experimental Design: We compared RPFNA and DL as breast tissue acquisition methods for short-term breast cancer prevention trials by evaluating sample adequacy and tolerability in subjects who participated in two prospective phase II breast cancer prevention trials. Eighty-six women at increased risk for breast cancer were included in this study and underwent baseline DL and RPFNA. High risk was defined as having a 5-year Gail score of &amp;gt;1.67% or a history of atypical hyperplasia (AH), lobular carcinoma, or breast cancer. Results: Median age was 54.5 years (range, 39-75 years); 75% of the women were postmenopausal. About 51% of the women yielded nipple aspiration fluid, and breast fluid samples via DL were retrieved in 73% of these subjects. Of these samples, 71% were adequate samples (greater than 10 epithelial cells). However, when the entire cohort was considered, only 31% of the subjects had adequate samples. RPFNA was also attempted in all subjects, and sample retrieval rate was 100%. Out of these, 96% of the subjects had adequate samples. In DL samples, AH rate was 3.7% was and hyperplasia (H) rate was 11.1%. In RPFNA samples, AH rate was 12.9%, and H rate was 24.7%. Cytology findings in RPFNA samples correlated with age, menopausal status, and breast cancer risk category (previous history of lobular carcinoma in situ). Both procedures were well tolerated, and no complications occurred among participants. Conclusions: Considering that the main end point for short-term prevention trials is the modulation of biomarkers, it is important to optimize adequate sample acquisition; therefore, RPFNA is a more practical option for future phase I and II breast cancer prevention trials compared with DL.
Efficacy and safety of the angiotensin II receptor blocker losartan for hypertrophic cardiomyopathy: the INHERIT randomised, double-blind, placebo-controlled trial
Authors: Anna Axelsson, Kasper Iversen, Niels Vejlstrup, Carolyn Ho, Jakob Norsk, Lasse Langhoff, Kiril Ahtarovski, Pernille Corell, Ole Havndrup, Morten Jensen, Henning Bundgaard
Journal: The Lancet Diabetes & Endocrinology (2014)
Viruses and Other Environmental Factors as Possible Sources of Phenotypic Heterogeneity in Familial Dilated Cardiomyopathy
Authors: Wolfgang Poller, Heinz-Peter Schultheiss, Uwe Kühl
Journal: Journal of the American College of Cardiology (2006)

In their interesting and recent state-of-the-art study, Burkett and Hershberger ([1][1]) stated that “familial dilated cardiomyopathy (DCM) demonstrates incomplete penetrance, variable expression, and significant locus and allelic heterogeneity, making clinical and genetic diagnosis complex.”
Abstract 2351: Identification of somatic mutations in esophageal squamous cell carcinoma and corresponding xenograft by next-generation sequencing
Authors: Douglas D. Fang, Yibo Gao, Qiang Xu, Hongye Sun, Bin Zhang, Zhaoli Chen, Chi-Chung Chan, Jie He
Journal: Cancer Research (2012)

Abstract The genomes of all cancer cells carry somatic mutations, including both passenger and driver mutations. Driver mutations, which are implicated in oncogenesis, are most likely preserved in xenografted tumor cells in immunedeficient mice. Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas in the gastrointenstinal tract. It is prevalent in the developing world and associated with substantial morbidity and mortality. Molecular mechanisms contributing to initiation and progression of ESCC are still poorly understood. Systematic identification of genetic variations and putative driver mutations may lead to understanding of pathogenesis of the disease. In this study, using next-generation sequencing we performed exome sequencing of eight paired Chinese esophageal squamous cell carcinoma and xenograft. Comparing with control genomes obtained from case-matched peripheral blood cells, we identified a wide variety of somatic variations in both primary and xenograft tumors, including TP53, RGMA, MUC4, TCEAL6, PRSS3, etc. Moreover, we found that mouse sequences accounted for a significant fraction of sequence reads from xenograft samples. Excluding these mouse sequences significantly improved the accuracy of mutation detection in xenograft samples. Overall, our findings shed a light on important somatic mutations involved in ESCC. In addition, comparison between primary and xenograft tumors may lead to identification of driver mutations that confer growth advantage. These mutations represent therapeutic opportunities for development of targeted therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2351. doi:1538-7445.AM2012-2351
Modification of Human Left Ventricular Relaxation by Small-Amplitude, Phase-Controlled Mechanical Vibration on the Chest Wall
Authors: Yoshiro Koiwa, Hideyuki Honda, Takehiko Takagi, Jun-ichi Kikuchi, Nobuo Hoshi, Tamotsu Takishima
Journal: Circulation (1997)

Background Direct clinical manipulation to improve an impairment of left ventricular (LV) relaxation has not been reported. We investigated whether the LV relaxation rate in humans could be modulated by phase-controlled mechanical vibration applied to the patient's anterior chest wall and whether there are some quantitative differences in the responses of normal (N), hypertrophied (H), and failing (F) ventricle. Methods and Results In 46 patients (N, 10; H, 18 [hypertrophic cardiomyopathy]; F, 18 [heart failure]), the vibrator was attached to the precordium and a 50-Hz, 2-mm sinusoidal mechanical vibration was applied, with the timing restricted from the onset of isovolumic relaxation to end-diastole during cardiac catheterization. Heart rate and peak LV pressure showed no difference with vibration. However, in all patients, precordial vibration caused an acceleration of the LV pressure fall. The magnitude of the induced reduction of the time constant of LV pressure decay (ΔT) was larger ( P &lt;.01) in H and F than in N (4.6±2.3, 4.0±1.6, and 0.6±1.5 ms for H, F, and N, respectively). ΔT correlated strongly with the magnitude of impaired relaxation and the magnitude of transmitted vibration to the ventricle. Conclusions Phase-controlled, small-amplitude vibration on the chest wall can directly modulate LV relaxation rate, especially in those with hypertrophy or failing ventricle.
Control of Japanese Encephalitis — Within Our Grasp?
Authors: Tom Solomon
Journal: New England Journal of Medicine (2006)

The second half of 2005 saw one of the largest outbreaks of Japanese encephalitis that has occurred in northern India in recent years. Cases were first reported in the state of Uttar Pradesh in July 2005; by November, there had been nearly 5000 cases and 1300 deaths, as well as outbreaks in neighboring Nepal. At the height of the outbreak, some hospitals had no beds available, and even their corridors were full of patients.1 Although the number of cases was especially high for this part of India, for Asia as a whole, the outbreak was nothing new. Unusual outbreaks of . . .
Most clinical trials fail to meet FDA requirement to publish results within a year
Authors: S. Mayor
Journal: BMJ (2015)

Nearly nine in 10 clinical trials fail to meet the US Food and Drug Administration requirement to make summary results publicly available within a year of completion, a study reported in the New England Journal of Medicine has found.1

Researchers identified 13 327 clinical trials that were completed or terminated from 1 January 2008 to 31 August 2012. All were covered by the FDA Amendments Act of 2007, which requires …
The Effect of Portal Diversion on the Early Stages of Liver Carcinogenesis in the Rat
Authors: Lorne E. Rotstein, Leonard Makowka, George Lee, Emmanuel Farber
Journal: Hepatology (1982)

The effect of portal diversion by ameroid constriction was studied in the carcinogenic process in the rat after initiation of foci by diethylnitrosamine and after the establishment of putative preneoplastic nodules. Portal diversion or portal diversion plus partial hepatectomy did not act to promote or select for the development of nodules. Furthermore, portal diversion did not alter the natural history of established nodules. These results suggest that vascular factors are not important at these early stages of the carcinogenic process in the rat liver.
Migraine Headache
Authors: Adrian M. Ostfeld
Journal: JAMA (1960)

<h3>Definition.—</h3> Migraine may be defined as periodic recurrent headache, one-sided in origin, commonly associated with anorexia and nausea, often affecting several members of the same family, and intimately related to cranial vasodilatation. Roughly 10% of the United States' population exhibits the syndrome. It has been stated that the disorder occurs more frequently in women than in men and affects those who work with their minds rather than muscles. However, women, the better educated, and the white collar worker seem more readily to admit to illness and to visit physicians than do men, the poorly educated, and the blue collar worker. Therefore, sampling errors in the population studied may have accounted for some of these findings. <h3>Physiology.—</h3> The vasodilatation of migraine occurs primarily in extracranial arteries, arterioles, venules, and possibly veins.<sup>1</sup>The arteries usually involved are the superficial temporal, supraorbital, posterior auricular, and occipital. Unlike the intracranial vessels, these arteries
Tumoral calcinosis: a pathological study of fifty-six cases
Authors: P.H. McKEE, N.G. LIOMBA, M.S.R. HUTT
Journal: British Journal of Dermatology (1982)

Journal Article Tumoral calcinosis: a pathological study of fifty‐six cases Get access P.H. McKEE, P.H. McKEE Department of Histopathology, St Thomas's Hospital Medical School, London SE1 7EH Dr Phillip H.McKee Search for other works by this author on: Oxford Academic Google Scholar N.G. LIOMBA, N.G. LIOMBA Department of Tropical Pathology, St Thomas's Hospital Medical School, London SE1 7EH Search for other works by this author on: Oxford Academic Google Scholar M.S.R. HUTT M.S.R. HUTT Department of Tropical Pathology, St Thomas's Hospital Medical School, London SE1 7EH Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 107, Issue 6, 1 December 1982, Pages 669–674, https://doi.org/10.1111/j.1365-2133.1982.tb00526.x Published: 01 December 1982 Article history Accepted: 03 March 1982 Published: 01 December 1982
Analysis of the effects of overexpression of metallothionein-I in transgenic mice on the reproductive toxicology of cadmium.
Authors: T Dalton, K Fu, G C Enders, R D Palmiter, G K Andrews
Journal: Environmental Health Perspectives (1996)

Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis is highly sensitive to cadmium, whereas in females the peri-implantation period of pregnancy is sensitive. To examine the potential roles of the cadmium-binding protein, metallothionein (MT), in the reproductive toxicology of cadmium, we examined a transgenic mouse strain that overexpresses metallothionein-I (MT-I). These mice had dramatically increased steady-state levels of MT-I mRNA and MT in the testes and in the female reproductive tract during the peri-implantation period of pregnancy, and this overexpression occurred in a cell-specific and temporally regulated manner similar to that of the endogenous MT-I gene. Transgenic and control males were injected with cadmium, and the histology of the testes was examined. An injection of 7.5 mumol Cd/kg had no effect on histology of the testes in either transgenic or control mice. In contrast, an injection of 10 mumol Cd/kg caused rapid changes in the histology of the testes and resulted in pronounced testicular necrosis in both control and transgenic mice. Female transgenic and control mice were mated and then injected with cadmium (30-45 mumol Cd/kg) on the day of blastocyst implantation (day 4). In both of these groups, injection of cadmium reduced pregnancy rate, and no dramatic protection was afforded by maternal and/or embryonic overexpression of MT. Thus, overexpression of MT-I does not significantly protect against either of these cadmium-induced effects on fertility.
Idiopathic immune-mediated acquired von Willebrand's disease in a patient with angiodysplasia: Demonstration of an unusual inhibitor causing a functional defect and rapid clearance of von Willebrand factor
Authors: Salah A. Alhumood, Dana V. Devine, Laurie Lawson, Stephen H. Nantel, Cedric J. Carter
Journal: American Journal of Hematology (1999)

A case of idiopathic immune-mediated von Willebrand's disease (AvWD) associated angiodysplasia and recurrent lower gastrointestinal bleeding is reported. Coagulation parameters at presentation were activated partial thromboplastin time of 41 sec, bleeding time >15 min, factor VIII procoagulant activity, 5%; von Willebrand factor antigen (WF:Ag) 5%, and vWF:ristocetirn cofactor activity 11% sodium dodecyl sulfate-agarose gel electrophoresis pattern of plasma vWF showed a pattern similar to type II vWD. An in vitro inhibitor against vWF in the immunoglobulin (Ig)G fraction of the patient's plasma was demonstrated vWF parameters showed a short-lived increase after 1-deamino-8-D-arginine vasopressin (DDAVP) administration. The patient's bleeding episodes were initially managed adequately with cryoprecipitate replacement therapy and DDAVP, to which she became refractory. No significant improvement was achieved following the institution of immunosuppressive therapy in the form of high-dose steroids and cyclophosphamide. She was then treated with intravenous immunoglobulin (IvIg) to which she showed an adequate response in terms of her clinical situation and her hemostatic parameters. The patient is on maintenance treatment with repeated courses of IvIg based on vWF parameter monitoring. To our knowledge, this is the third reported association between idiopathic immune-mediated AvWD and angiodysplasia. Am. J. Hematol. 60:151–157, 1999. © 1999 Wiley-Liss, Inc.
Listening to patients' narratives can help improve quality of psychosis care
Authors: J. Feinmann
Journal: BMJ (2011)

Doctors have been urged to go back to basics in mental health care and listen to the narratives of people with experience of psychosis as a foundation for improving treatment and services and bringing hope of recovery to those in crisis.

The call came at the launch of a new section of the health website Healthtalkonline. The section on psychosis is based on in depth interviews with a cross section of 34 people, including three carers, talking about their experience of persecutory voices. It covers issues such as what to expect from medication and emergency treatment as well as ways of coping—with a mix of trenchant criticisms of mental health services alongside examples of splendid care.

Listening to experiences was held up as a way forward from the current situation where “schizophrenia is the ninth leading …