tbuckley/cabot-search huggingface dataset:
Law enforcement duties and sudden cardiac death among police officers in United States: case distribution study
Authors: V. Varvarigou, A. Farioli, M. Korre, S. Sato, I. J. Dahabreh, S. N. Kales
Journal: BMJ (2014)

To assess the association between risk of sudden cardiac death and stressful law enforcement duties compared with routine/non-emergency duties. Case distribution study (case series with survey information on referent exposures). United States law enforcement. Summaries of deaths of over 4500 US police officers provided by the National Law Enforcement Officers Memorial Fund and the Officer Down Memorial Page from 1984 to 2010. Observed and expected sudden cardiac death counts and relative risks for sudden cardiac death events during specific strenuous duties versus routine/non-emergency activities. Independent estimates of the proportion of time that police officers spend across various law enforcement duties obtained from surveys of police chiefs and front line officers. Impact of varying exposure assessments, covariates, and missing cases in sensitivity and stability analyses. 441 sudden cardiac deaths were observed during the study period. Sudden cardiac death was associated with restraints/altercations (25%, n=108), physical training (20%, n=88), pursuits of suspects (12%, n=53), medical/rescue operations (8%, n=34), routine duties (23%, n=101), and other activities (11%, n=57). Compared with routine/non-emergency activities, the risk of sudden cardiac death was 34-69 times higher during restraints/altercations, 32-51 times higher during pursuits, 20-23 times higher during physical training, and 6-9 times higher during medical/rescue operations. Results were robust to all sensitivity and stability analyses. Stressful law enforcement duties are associated with a risk of sudden cardiac death that is markedly higher than the risk during routine/non-emergency duties. Restraints/altercations and pursuits are associated with the greatest risk. Our findings have public health implications and suggest that primary and secondary cardiovascular prevention efforts are needed among law enforcement officers.
Discovery of gene expression-based pharmacodynamic biomarker for a p53 context-specific anti-tumor drug Wee1 inhibitor
Authors: Shinji Mizuarai, Kazunori Yamanaka, Hiraku Itadani, Tsuyoshi Arai, Toshihide Nishibata, Hiroshi Hirai, Hidehito Kotani
Journal: Molecular Cancer (2009)

Abstract Background Wee1 is a tyrosine kinase regulating S-G2 cell cycle transition through the inactivating phosphorylation of CDC2. The inhibition of Wee1 kinase by a selective small molecule inhibitor significantly enhances the anti-tumor efficacy of DNA damaging agents, specifically in p53 negative tumors by abrogating S-G2 checkpoints, while normal cells with wild-type p53 are not severely damaged due to the intact function of the G1 checkpoint mediated by p53. Since the measurement of mRNA expression requires a very small amount of biopsy tissue and is highly quantitative, the development of a pharmacodynamic (PD) biomarker leveraging mRNA expression is eagerly anticipated in order to estimate target engagement of anti-cancer agents. Results In order to find the Wee1 inhibition signature, mRNA expression profiling was first performed in both p53 positive and negative cancer cell lines treated with gemcitabine and a Wee1 inhibitor, MK-1775. We next carried out mRNA expression profiling of skin samples derived from xenograft models treated with the Wee1 inhibitor to identify a Wee1 inhibitor-regulatory gene set. Then, the genes that were commonly modulated in both cancer cell lines and rat skin samples were extracted as a Wee1 inhibition signature that could potentially be used as a PD biomarker independent of p53 status. The expression of the Wee1 inhibition signature was found to be regulated in a dose-dependent manner by the Wee1 inhibitor, and was significantly correlated with the inhibition level of a direct substrate, phosphorylated-CDC2. Individual genes in this Wee1 inhibition signature are known to regulate S-G2 cell cycle progression or checkpoints, which is consistent with the mode-of-action of the Wee1 inhibitor. Conclusion We report here the identification of an mRNA gene signature that was specifically changed by gemcitabine and Wee1 inhibitor combination treatment by molecular profiling. Given the common regulation of expression in both xenograft tumors and animal skin samples, the data suggest that the Wee1 inhibition gene signature might be utilized as a quantitative PD biomarker in both tumors and surrogate tissues, such as skin and hair follicles, in human clinical trials.
Human rheumatoid factor crossidiotypes. I. WA and BLA are heat-labile conformational antigens requiring both heavy and light chains.
Authors: V Agnello, J L Barnes
Journal: The Journal of Experimental Medicine (1986)

Evidence was obtained that both the WA and BLA crossidiotype (XId) groups are conformational antigens requiring both L and H chains and that with heat denaturation the antigens that define the XIds and antigen-binding activity are lost in parallel. In contrast, the primary structure-dependent crossreactive idiotype (CRI), PSL2, which is only weakly detected on native Wa and Bla monoclonal rheumatoid factors (mRFs), became prominently detected on the heated Wa and Bla mRFs. Heat denaturation may provide a simple method for distinguishing Ids determined by conformational antigen from primary structure-dependent Ids. In addition to heat denaturation, some acid conditions commonly used for preparation of RFs were also found to cause marked loss of Id antigen. The finding of PSL2-CRI on Bla mRF indicates that this Id is not unique to the WA XId.
Prognostic power of proadrenomedullin in community-acquired pneumonia is independent of aetiology
Authors: Salvador Bello, Ana B. Lasierra, Elisa Mincholé, Sergio Fandos, Maria Angeles Ruiz, Elisabeth Vera, Francisco de Pablo, Miguel Ferrer, Rosario Menendez, Antoni Torres
Journal: European Respiratory Journal (2011)

Biomarkers are useful in community-acquired pneumonia (CAP). Recently, midregional (MR) proadrenomedullin (proADM) has been shown to be of potential prognostic use. We sought to determine whether this prognostic role depends on the cause of CAP. We conducted a prospective cohort study of immunocompetent patients with CAP. Pneumonia Severity Index (PSI) and CURB-65 score (confusion (abbreviated mental test score of ≤ 8), urea ≥ 7 mol · L(-1), respiratory rate ≥ 30 breaths · min(-1), blood pressure <90 mmHg systolic or <60 mmHg diastolic, and age ≥ 65 yrs), blood C-reactive protein, procalcitonin, MR-proADM, and microbiological studies were systematically performed. Patients were grouped as bacterial, viral/atypical and mixed CAP, and were followed up at 30, 90 and 180 days, and 1 yr. We recruited 228 CAP patients. Identification of at least one pathogen was achieved in 155 (68%) patients. MR-proADM levels closely correlated with increasing severity scores, and showed an important predictive power for complications and short- and long-term mortality (1 yr). Its addition to PSI and CURB-65 significantly improved their prognostic accuracy. A MR-proADM cut-off of 0.646 nmol · L(-1) identified 92% of patients scored as PSI classes IV and V as high risk. MR-proADM outcome prediction power was not affected by different aetiologies. MR-proADM has high short- and long-term prognostic accuracy, and increases the accuracy of clinical scores. The prognostic value of MR-proADM is not modified by different possible CAP aetiologies.
Effect of highly active antiretroviral therapy (HAART) on pharmacokinetics and pharmacodynamics of doxorubicin in patients with HIV-associated non-Hodgkin's lymphoma
Authors: G. Toffoli, G. Corona, G. Cattarossi, M. Boiocchi, G. Di Gennaro, U. Tirelli, E. Vaccher
Journal: Annals of Oncology (2004)
The Population of India
Authors: A. W. M. Brown
Journal: BMJ (1946)

Antibody titres for <i>Bordetella pertussis</i> in paired sera from 223 children with suspected whooping cough showed good correlation by complement fixation and agglutination techniques. The patient9s age was related to serological responses and in a different way to <i>B. pertussis</i> isolations: in 73 children under 6 months of age <i>B. pertussis</i> was isolated from nasopharyngeal secretions in 42% and serological findings were positive in 19%; in 11 patients over 1 year of age serological tests were positive in 65% and cultures in 19%. <i>B. pertussis</i> was isolated from 59 out of 210 patients, while rising antibody titres were found in a further 43 from whom no isolations were made; thus 102 (49%) out of 210 showed evidence of infection with <i>B. pertussis</i>. Serotype 1,3 was the commonest serotype isolated from both immunized and unimmunized children. Previous immunization appeared to reduce the chances of isolating <i>B. pertussis</i>.
Electrical events during gamete maturation and fertilization in animals and humans
Authors: E. Tosti
Journal: Human Reproduction Update (2004)

Gamete cells are electrogenic, i.e. capable of responding to electrical stimuli and modifying their electrical properties during the crucial periods of maturation and fertilization.Ion channels have been widely demonstrated on the plasma membrane of the oocyte and spermatozoon in all animals studied, and electrical modi®cations in gametes are due to ion currents that are modulated via these ion channels.The modi®cation of intracellular calcium levels in gametes has been extensively studied, and these modi®cations are recognized to be a second messenger system for gamete maturation and fertilization.Other ions also move through the plasma membrane, either in association with or independent of calcium, and these generate typical features such as fertilization currents and oscillation of resting potential.These modi®cations were ®rst studied in marine invertebrates, and the observations subsequently compared with mammalian systems, including human.The precise role played by these currents in the processes of maturation and fertilization is still poorly understood; however, recent research opens new frontiers for their clinical and technological application.
Ethical and clinical issues in the use of home non-invasive mechanical ventilation for the palliation of breathlessness in motor neurone disease
Authors: M. I Polkey, R. A Lyall, A C. Davidson, P N. Leigh, J. Moxham
Journal: Thorax (1999)

Motor neurone disease (MND) is a devastating and progressive neurological disorder in which degeneration of motor neurones results in weakness and wasting of the dependent muscles. The prevalence of MND is approximately five per 100 000 and approximately 30% of patients have primary bulbar symptoms.1 Half of the patients die within 36 months of experiencing the first symptom.

Presentation with ventilatory failure is recognised but uncommon,2 occurring in less than 5% of cases3; however, abnormalities of respiratory muscle function are frequently detectable.4 5 As the condition progresses respiratory muscle strength diminishes4 6; indeed, the rate of change in respiratory function is the only measurable parameter which predicts survival.1 When the load placed on the respiratory muscle pump exceeds the capacity of the respiratory muscles, then the patient is at risk of ventilatory failure. Initially abnormalities may be present only in sleep7 or on exercise8 but, frequently, established ventilatory failure ensues. Ventilatory failure is usually manifest by dyspnoea which may be worse on lying flat (if diaphragm weakness is prominent) or sitting upright (if expiratory muscle weakness predominates). More commonly there is generalised weakness and then there are no clear cut postural symptoms. Direct questioning may elicit symptoms suggestive of disordered sleep architecture—for example, daytime somnolence, difficulty concentrating, or “respiratory” nightmares—or carbon dioxide retention—for example, morning headache. Examination may show paradoxical abdominal motion during respiration. This indicates substantial diaphragm weakness9 combined with preservation of enough upper thoracic musculature to generate sufficient negative intrathoracic pressure to cause inward abdominal motion. In more advanced disease paradoxical motion may be difficult to elicit and the patient may simply appear tachypnoeic without useful rib cage movement. In established MND patients may also complain of choking symptoms; most commonly this represents swallowing difficulties. However, if unrelated …
Subgroup Analyses Based on Liver Metastases and the Number of Metastatic Sites from the Mpact Phase III Trial of Nab-Paclitaxel Plus Gemcitabine Vs Gemcitabine Alone for Metastatic Pancreatic Cancer
Authors: Weekes Colin, Parnis Francis, Thaler Josef, Prenen Hans, Letourneau Richard, Raymond Eric, Santoro Armando, Garcia-Carbonero Rocio, Weis John, Romano Alfredo, McGovern Desmond, Penenberg Darryl, Von Hoff Daniel
Journal: Annals of Oncology (2014)
Jagged-1 and Notch3 Juxtacrine Loop Regulates Ovarian Tumor Growth and Adhesion
Authors: Jung-Hye Choi, Joon T. Park, Ben Davidson, Patrice J. Morin, Ie-Ming Shih, Tian-Li Wang
Journal: Cancer Research (2008)

Abstract Notch3 gene amplification and pathway activation have been reported in ovarian serous carcinoma. However, the primary Notch3 ligand that initiates signal transduction in ovarian cancer remains unclear. In this report, we identify Jagged-1 as the highest expressed Notch ligand in ovarian tumor cells as well as in peritoneal mesothelial cells that are in direct contact with disseminated ovarian cancer cells. Cell-cell adhesion and cellular proliferation were reduced in Notch3-expressing ovarian cancer cells that were cocultured with Jagged-1 knockdown mesothelial and tumor feeder cells. Interaction of Notch3-expressing ovarian cancer cells with Jagged-1–expressing feeder cells activated the promoter activity of candidate Notch3 target genes, and this activity was attenuated by Notch3 siRNA. Constitutive expression of the Notch3 intracellular domain significantly suppressed the Jagged-1 shRNA–mediated growth inhibitory effect. In Notch3-expressing ovarian cancer cells, Jagged-1–stimulating peptides enhanced cellular proliferation, which was suppressed by γ-secretase inhibitor and Notch3 siRNA. Taken together, our results show that Jagged-1 is the primary Notch3 ligand in ovarian carcinoma and Jagged-1/Notch3 interaction constitutes a juxtacrine loop promoting proliferation and dissemination of ovarian cancer cells within the intraperitoneal cavity. [Cancer Res 2008;68(14):5716–23]
Microstructural White Matter Abnormalities and Cognitive Functioning in Type 2 Diabetes
Authors: Yael D. Reijmer, Manon Brundel, Jeroen de Bresser, L. Jaap Kappelle, Alexander Leemans, Geert Jan Biessels
Journal: Diabetes Care (2012)

To examine whether type 2 diabetes is associated with microstructural abnormalities in specific cerebral white matter tracts and to relate these microstructural abnormalities to cognitive functioning.
Acute propranolol administration effectively decreases portal pressure in patients with TIPS dysfunction
Authors: L Bellis
Journal: Gut (2002)

<b>Background and aims:</b> Up to 60% of patients treated with transjugular intrahepatic portosystemic shunt (TIPS) require angioplasty or restenting during the first year of follow up because of TIPS dysfunction (stenosis of the intrahepatic shunt increasing the portal pressure gradient above the 12 mm Hg threshold). We hypothesised that in patients with TIPS stenosis, propranolol administration, by decreasing portal inflow, would markedly decrease portal pressure. <b>Patients and methods:</b> Eighteen patients with TIPS dysfunction were investigated by measuring portal pressure gradient before and after acute propranolol administration (0.2 mg/kg intravenously; n=18). <b>Results:</b> Propranolol markedly reduced the portal pressure gradient (from 16.6 (3.5) to 11.9 (4.8) mm Hg; p&lt;0.0001), cardiac index (−26 (7)%), and heart rate (−18 (7)%) (p&lt;0.0001). Portal pressure gradient decreased to less than 12 mm Hg in nine patients, more frequently in those with moderate dysfunction (portal pressure gradient 16 mm Hg) than in patients with severe dysfunction (portal pressure gradient &gt;16 mm Hg) (8/10 <i>v</i> 1/8; p=0.015). <b>Conclusions:</b> Propranolol therapy may delay the increase in portal pressure and reduce the need for reintervention in patients with TIPS dysfunction.
Reconciling managers, doctors, and patients: the role of clear communication
Authors: Conor Farrington
Journal: Journal of the Royal Society of Medicine (2011)

If jargon were a disease, managers in the National Health Service would be among its most prominent victims. The leading symptom is a notorious fondness for buzzwords, with phrases such as ‘blue-sky thinking’ and ‘joined-up working’ becoming increasingly prominent in both policy documents and everyday working discourse.1 Secondary symptoms include corporate-style slogans such as ‘Choose Well’, mission and vision statements for every NHS Trust, and a relentless tendency to describe healthcare as the NHS's ‘core business’. Whether these symptoms are the by-products of a broader trend towards managerialism (and increasing use of management consultancy services) in the delivery of public services,2,3 or the result of an attempt to establish management as a bona fide profession with its own terminology and area of expertise,4 their prevalence is undeniable in the contemporary NHS.

Managers are not the only culprits, however, and it has long been acknowledged that healthcare professionals, and doctors in particular, have a tendency to indulge in medical jargon when communicating with patients.5 As one group of commentators noted, ‘[t]he voice of medicine is characterised by medical terminology, objective descriptions of physical symptoms, and the classification of these within a reductionist biomedical model’.6 Since doctors typically have more power than other stakeholders in healthcare contexts, the same commentators argue, this biomedical model of communication frequently prevails, to the detriment of other voices.6

From one point of view, the use of managerial and medical jargon in healthcare is simply a reflection of managers' and doctors' areas of expertise – an epiphenomenon that accompanies healthcare provision without fundamentally altering it. It can also be argued, however, that NHS jargon actively generates obstacles to effective healthcare delivery by raising unnecessary barriers to doctor–patient communication and obstructing the clear definition and comprehension of healthcare policy and practice, with negative implications for Public and Patient Involvement (PPI) initiatives.a More fundamentally, the prevalence of corporate jargon can be read as the side-effect of an increasingly managerial culture in the NHS, with political targets and excessive administrative regulation leading both managers and clinicians to write patients out of healthcare (with frequently catastrophic results). In response, this paper advocates clear communication on the part of all healthcare stakeholders, links clear communication to a strong focus on patient-centred (rather than target-centred) care, and suggests some ways in which the NHS can eschew ‘jargonese’ and embrace plain English.
The dysgonic form of <i>Microsporum canis</i> in N. W. London
Authors: W. D. L. TUCKER
Journal: British Journal of Dermatology (1980)

SUMMARY An account is given of the occurrence in N. W. London of ringworm due to the dysgonic form of Microsporum canis in cats, dogs, and humans. The unusual morphology of the dysgonic strain is described as is the extraordinary lability of the fungus in culture. The distribution of cases in man and animals in the area is mapped. The clinical and epidemiological behaviour of the fungus, as illustrated by four family outbreaks, differs little from that of the typical strain. The origin of the dysgonic strain is unknown.
Calcium, sodium, and the calcium paradox.
Authors: W G Nayler, S E Perry, J S Elz, M J Daly
Journal: Circulation Research (1984)

The effect of "sodium loading," of verapamil and of nifedipine on the gain in calcium and sodium, and on the loss of myoglobin, during the calcium paradox in adult rat hearts was examined. Raising cell sodium from 56.5 +/- 2.6 to 129.5 +/- 10.2 mumol sodium/gram dry weight did not alter the degree or rate of calcium gain or myoglobin release during calcium repletion after long periods (greater than 2 minutes) of calcium-free perfusion; under these conditions, and in the presence of 10 micrograms/liter verapamil, calcium gain was enhanced. However, after shorter periods (0.5-1.5 minutes), of calcium-free perfusion, calcium gain was enhanced in "sodium-loaded" hearts, even in the absence of verapamil, and particularly during the early stages of repletion. The presence of 1 and 10 mumol/liter dl-verapamil and 1 mumol/liter nifedipine before, during, and after 10 minutes of calcium-free perfusion significantly (P less than 0.01) slowed the early (up to 1 minute for verapamil and 2 minutes for nifedipine) but not the late gain in calcium. When verapamil was present, the late gain in calcium was actually enhanced. These agents also abolished the early (45 seconds) but not the late (greater than 2 minutes) gain in sodium that occurs during repletion. We propose that the gain in calcium that occurs during calcium repletion after a period of calcium-free perfusion can be divided into at least two phases (early and late), and that the early phase contains a verapamil/nifedipine-sensitive component and a verapamil/nifedipine-insensitive component, the latter probably involving sodium-calcium exchange.
Manifestations of pulmonary tuberculosis on computed tomography in patients with HIV infection, depending on the degree of immunosuppression
Authors: Anna Lazareva, Pavel Gavrilov, Eugeniya Reshetneva, Eugenii Malashenkov, Petr Yablonskiy
Journal: European Respiratory Journal (2013)

Diagnosis of TB in patients with HIV infection is often difficult because of the low frequency allocation MBT in the sputum, and not the typical radiographic manifestations.

Material and methods. Analyzed by CT in detecting pulmonary disease in 64 patients with HIV infection and TB. 54 people have been confirmed TB detection MBT in sputum, 10 by biopsy. The patients were divided into 4 groups. group 1 - with a CD4 - > 500, (n = 16), group 2 -200-499 (n = 24), group 3 -100-199 (n = 10), 4-group - <100 (n = 14).

Results. Depending on the level of CD4 pulmonary manifestations of TB changed

View this table:

Manifestations of pulmonary tuberculosis on CT





For a moderate decrease in immunity in CT picture is dominated well- defined nodules and alveolar infiltration (> 80%), cavities- only 50%. With a decrease in CD4 stated reduce the frequency of alveolar infiltration (up 14.3%), and the cavities. Increasing the frequency of interstitial changes (up 57.1%) and ground-glass nodules (up 42.8%). In all groups, the high frequency of adenopathy (> 80%).

Conclusion: With the decline of immunity in HIV-infected TB patients were significantly more manifest atypical CT features.