tbuckley/cabot-search huggingface dataset:
Genetic analysis of families of patients with Behcet's syndrome: data incompatible with autosomal recessive inheritance.
Authors: J A Bird Stewart
Journal: Annals of the Rheumatic Diseases (1986)

Data on families with Behçet's syndrome were analysed to test a hypothesis of autosomal recessive inheritance. Fifteen families from the UK and nine from Turkey were included. There were 27 individuals with Behçet's syndrome according to the Japanese criteria and 119 unaffected individuals. There were no affected parents in the families. The 'goodness of fit' test of Elandt-Johnson was applied to the distribution of affected individuals in these families, and the data were found to be incompatible with autosomal recessive inheritance. HLA associations were also examined in patients and relatives, and this led to re-examination of previously published data on HLA associations with Behçet's syndrome.
Longitudinal Study of Human Papillomavirus Persistence and Cervical Intraepithelial Neoplasia Grade 2/3: Critical Role of Duration of Infection
Authors: A. C. Rodriguez, M. Schiffman, R. Herrero, A. Hildesheim, C. Bratti, M. E. Sherman, D. Solomon, D. Guillen, M. Alfaro, J. Morales, M. Hutchinson, H. Katki, L. Cheung, S. Wacholder, R. D. Burk
Journal: JNCI Journal of the National Cancer Institute (2010)

The natural history of human papillomavirus (HPV) infections in older women is critical for preventive strategies, including vaccination and screening intervals, but is poorly understood. In a 7-year population-based cohort study in Guanacaste, Costa Rica, we examined whether women's age and the duration of carcinogenic HPV infections influenced subsequent persistence of infection and risk of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse disease. At enrollment, of the 9466 participants eligible for pelvic examination, 9175 were screened for cervical neoplasia using multiple methods; those with CIN 2 or worse disease were censored and treated. Participants at low risk of CIN 2 or worse (n = 6029) were rescreened at 5–7 years (passively followed), whereas higher-risk participants (n = 2115) and subsets of low-risk women (n = 540) and initially sexually inactive women (n = 410) were rescreened annually or semiannually (actively followed) for up to 7 years. HPV testing was done using a polymerase chain reaction–based method. We determined, by four age groups (18–25, 26–33, 34–41, and ≥42 years), the proportion of prevalent infections (found at baseline) and newly detected infections (first found during follow-up) that persisted at successive 1-year time points and calculated absolute risks of CIN 2 and CIN grade 3 (CIN 3) or worse during follow-up. P values are two-sided. Regardless of the woman's age, newly detected infections were associated with very low absolute risks of persistence, CIN 2, or worse disease. For newly detected infections, the rate of progression to CIN 2+ (or CIN 3+), after 3 years of follow-up, was not higher for women aged 34 years and older than for younger women. Moreover, rates of newly detected infections declined sharply with age (in the actively followed group, at ages 18–25, 26–33, 34–41, and ≥42 years, rates were 35.9%, 30.6%, 18.1%, and 13.5%, respectively; P < .001). Among prevalent infections, persistent infections among older women (≥42 years) was higher than that among younger age groups or new infections at any age ( P < .01 for comparison of eight groups). Most (66 of 85) CIN 2 or worse detected during follow-up was associated with prevalent infections. Only a small subset (25 of 1128) of prevalent infections persisted throughout follow-up without apparent CIN 2 or worse. The rate of new infections declines with age, and new infections typically do not progress to CIN 2 or worse disease in older women; thus, overall potential benefit of prophylactic vaccination or frequent HPV screening to prevent or detect new carcinogenic HPV infections at older ages is low.
Frontier migration fosters ethos of independence: Deconstructing the climato-economic theory of human culture
Authors: Stephanie de Oliveira Chen, Shinobu Kitayama
Journal: Behavioral and Brain Sciences (2013)

Abstract Evidence Van de Vliert draws on is more consistent with the idea that settlement in the frontier encourages independent mentality and individualistic social institutions. This cultural system can sometimes flourish, generating both wealth and power, but clearly not always. In our view, wealth is, for the most part, a measure of success of any given cultural group, and climate is important to the extent that it plays a role in creating rugged lands of frontier.
Feasibility, Yield, and Cost of Active Tuberculosis Case Finding Linked to a Mobile HIV Service in Cape Town, South Africa: A Cross-sectional Study
Authors: Katharina Kranzer, Stephen D. Lawn, Gesine Meyer-Rath, Anna Vassall, Eudoxia Raditlhalo, Darshini Govindasamy, Nienke van Schaik, Robin Wood, Linda-Gail Bekker
Journal: PLoS Medicine (2012)

Katharina Kranzer and colleagues investigate the operational characteristics of an active tuberculosis case-finding service linked to a mobile HIV testing unit that operates in underserviced areas in Cape Town, South Africa.
Immune response to RB1-regulated senescence limits radiation-induced osteosarcoma formation
Authors: Maya Kansara, Huei San Leong, Dan Mei Lin, Sophie Popkiss, Puiyi Pang, Dale W. Garsed, Carl R. Walkley, Carleen Cullinane, Jason Ellul, Nicole M. Haynes, Rod Hicks, Marieke L. Kuijjer, Anne-Marie Cleton-Jansen, Philip W. Hinds, Mark J. Smyth, David M. Thomas
Journal: Journal of Clinical Investigation (2013)

Ionizing radiation (IR) and germline mutations in the retinoblastoma tumor suppressor gene (RB1) are the strongest risk factors for developing osteosarcoma. Recapitulating the human predisposition, we found that Rb1+/– mice exhibited accelerated development of IR-induced osteosarcoma, with a latency of 39 weeks. Initial exposure of osteoblasts to carcinogenic doses of IR in vitro and in vivo induced RB1-dependent senescence and the expression of a panel of proteins known as senescence-associated secretory phenotype (SASP), dominated by IL-6. RB1 expression closely correlated with that of the SASP cassette in human osteosarcomas, and low expression of both RB1 and the SASP genes was associated with poor prognosis. In vivo, IL-6 was required for IR-induced senescence, which elicited NKT cell infiltration and a host inflammatory response. Mice lacking IL-6 or NKT cells had accelerated development of IR-induced osteosarcomas. These data elucidate an important link between senescence, which is a cell-autonomous tumor suppressor response, and the activation of host-dependent cancer immunosurveillance. Our findings indicate that overcoming the immune response to senescence is a rate-limiting step in the formation of IR-induced osteosarcoma.
De Subitaneis Mortibus
Authors: THOMAS N. JAMES, NINA A. J. CARSON, PETER FROGGATT
Journal: Circulation (1974)

Conspicuous abnormalities of the coronary arteries and veins and of the sinus node, atrioventricular (A-V) node and His bundle are described in the heart of a boy dying with congenital homocystinuria. The unproven possibility of transient disturbances of cardiac rhythm or conduction is discussed relative to the pathogenesis of the bouts of unconsciousness with and without convulsions characteristic of the disease. Factual information on the stability or instability of electrical activity of the heart in such patients is particularly needed because of the possibility of treatable aspects of an otherwise seemingly inexorable process.
Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease
Authors: W. Szafranski, A. Cukier, A. Ramirez, G. Menga, R. Sansores, S. Nahabedian, S. Peterson, H. Olsson
Journal: European Respiratory Journal (2003)

The efficacy and safety of budesonide/formoterol in a single inhaler compared with placebo, budesonide and formoterol were evaluated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). In a 12-month, randomised, double-blind, placebo-controlled, parallel-group study in 812 adults (mean age 64 yrs, mean forced expiratory volume in one second (FEV 1 ) 36% predicted normal), patients received two inhalations twice daily of either budesonide/formoterol (Symbicort®) 160/4.5 µg (delivered dose), budesonide 200 µg (metered dose), formoterol 4.5 µg or placebo. Severe exacerbations and FEV 1 (primary variables), peak expiratory flow (PEF), COPD symptoms, health-related quality of life (HRQL), mild exacerbations, use of reliever β 2 ‐agonist and safety variables were recorded. Budesonide/formoterol reduced the mean number of severe exacerbations per patient per year by 24% versus placebo and 23% versus formoterol. FEV 1 increased by 15% versus placebo and 9% versus budesonide. Morning PEF improved significantly on day 1 versus placebo and budesonide; after 1 week, morning PEF was improved versus placebo, budesonide and formoterol. Improvements in morning and evening PEF versus comparators were maintained over 12 months. Budesonide/formoterol decreased all symptom scores and use of reliever β 2 ‐agonists significantly versus placebo and budesonide, and improved HRQL versus placebo. All treatments were well tolerated. These results suggest a role for budesonide/formoterol in the long-term management of moderate-to-severe chronic obstructive pulmonary disease.
Comparison of the Soluble Basal Insulin Analog Insulin Detemir With NPH Insulin
Authors: Kjeld Hermansen, Sten Madsbad, Hans Perrild, Allan Kristensen, Mads Axelsen
Journal: Diabetes Care (2001)

OBJECTIVE— Insulin detemir (NN304) is a soluble basal insulin analog developed to cover basal insulin requirements. This trial aimed to compare the blood glucose—lowering effect of insulin detemir with that of NPH insulin (NPH) and to evaluate the two treatments with regard to intrasubject variation of fasting blood glucose, incidence of hypoglycemia,dose requirements, and safety. RESEARCH DESIGN AND METHODS— This multicenter open randomized crossover trial in 59 type 1 diabetic subjects comprised a 2-week run-in period on a basal-bolus regimen with NPH insulin once daily, followed by two 6-week periods of optimized basal-bolus therapy with either once-daily insulin detemir or NPH insulin. RESULTS— The area under the curve, in the time interval 23:00-8:00, derived from 24-h serum glucose profiles, was not statistically significantly different for the two treatment periods (insulin detemir:NPH ratio 89.2:83.5, P = 0.59). The intrasubject variation in fasting blood glucose during the last 4 days of treatment was lower for insulin detemir compared with NPH (P &amp;lt; 0.001). Mean dose requirements of insulin detemir were 2.35 times higher (95% CI 2.22-2.48) compared with NPH. During the last week of treatment, fewer subjects experienced hypoglycemic episodes on insulin detemir (60%) compared with NPH treatment (77%)(P = 0.049). CONCLUSIONS— Insulin detemir was as effective as NPH in maintaining glycemic control when administered at a higher molar dose. The results indicate that insulin detemir may provide more predictable fasting blood glucose with lower intrasubject variation and reduced risk of hypoglycemia compared with NPH.
Selective angiography in acute mid-gut ischaemia.
Authors: D R Harper, T A Buist
Journal: Gut (1978)

Acute mesenteric ischaemia has a high mortality. Early diagnosis and treatment appropriate to the type and extent of vascular insufficiency are essential. Selective angiography can establish the diagnosis and distinguish patients with acute vascular occlusion who require urgent surgery from those with non-occlusive ischaemia for which early surgery is contraindicated.
Using the lower limit of normal for the FEV1/FVC ratio reduces the misclassification of airway obstruction
Authors: M P Swanney, G Ruppel, P L Enright, O F Pedersen, R O Crapo, M R Miller, R L Jensen, E Falaschetti, J P Schouten, J L Hankinson, J Stocks, P H Quanjer
Journal: Thorax (2008)

<h3>Aim:</h3> The prevalence of airway obstruction varies widely with the definition used. <h3>Objectives:</h3> To study differences in the prevalence of airway obstruction when applying four international guidelines to three population samples using four regression equations. <h3>Methods:</h3> We collected predicted values for forced expiratory volume in 1 s/forced vital capacity (FEV<sub>1</sub>/FVC) and its lower limit of normal (LLN) from the literature. FEV<sub>1</sub>/FVC from 40 646 adults (including 13 136 asymptomatic never smokers) aged 17–90+years were available from American, English and Dutch population based surveys. The prevalence of airway obstruction was determined by the LLN for FEV<sub>1</sub>/FVC, and by using the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society/European Respiratory Society (ATS/ERS) or British Thoracic Society (BTS) guidelines, initially in the healthy subgroup and then in the entire population. <h3>Results:</h3> The LLN for FEV<sub>1</sub>/FVC varied between prediction equations (57 available for men and 55 for women), and demonstrated marked negative age dependency. Median age at which the LLN fell below 0.70 in healthy subjects was 42 and 48 years in men and women, respectively. When applying the reference equations (Health Survey for England 1995–1996, National Health and Nutrition Examination Survey (NHANES) III, European Community for Coal and Steel (ECCS)/ERS and a Dutch population study) to the selected population samples, the prevalence of airway obstruction in healthy never smokers aged over 60 years varied for each guideline: 17–45% of men and 7–26% of women for GOLD; 0–18% of men and 0–16% of women for ATS/ERS; and 0–9% of men and 0–11% of women for BTS. GOLD guidelines caused false positive rates of up to 60% when applied to entire populations. <h3>Conclusions:</h3> Airway obstruction should be defined by FEV<sub>1</sub>/FVC and FEV<sub>1</sub> being below the LLN using appropriate reference equations.
Somatic hypermutation as a generator of antinuclear antibodies in a murine model of systemic autoimmunity
Authors: Wenzhong Guo, Diana Smith, Katja Aviszus, Thiago Detanico, Ryan A. Heiser, Lawrence J. Wysocki
Journal: The Journal of Experimental Medicine (2010)

Systemic lupus erythematosus (SLE) is characterized by high-avidity IgG antinuclear antibodies (ANAs) that are almost certainly products of T cell–dependent immune responses. Whether critical amino acids in the third complementarity-determining region (CDR3) of the ANA originate from V(D)J recombination or somatic hypermutation (SHM) is not known. We studied a mouse model of SLE in which all somatic mutations within ANA V regions, including those in CDR3, could be unequivocally identified. Mutation reversion analyses revealed that ANA arose predominantly from nonautoreactive B cells that diversified immunoglobulin genes via SHM. The resolution afforded by this model allowed us to demonstrate that one ANA clone was generated by SHM after a VH gene replacement event. Mutations producing arginine substitutions were frequent and arose largely (66%) from base changes in just two codons: AGC and AGT. These codons are abundant in the repertoires of mouse and human V genes. Our findings reveal the predominant role of SHM in the development of ANA and underscore the importance of self-tolerance checkpoints at the postmutational stage of B cell differentiation.
Nobel Laureates in Neuroscience: 1904-1981
Authors: H H Jasper, T L Sourkes
Journal: Annual Review of Neuroscience (1983)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Drosophila are protected from Pseudomonas aeruginosa lethality by transgenic expression of paraoxonase-1
Authors: David A. Stoltz, Egon A. Ozer, Peter J. Taft, Marilyn Barry, Lei Liu, Peter J. Kiss, Thomas O. Moninger, Matthew R. Parsek, Joseph Zabner
Journal: Journal of Clinical Investigation (2008)

Pseudomonas aeruginosa uses quorum sensing, an interbacterial communication system, to regulate gene expression. The signaling molecule N-3-oxododecanoyl homoserine lactone (3OC12-HSL) is thought to play a central role in quorum sensing. Since 3OC12-HSL can be degraded by paraoxonase (PON) family members, we hypothesized that PONs regulate P. aeruginosa virulence in vivo. We chose Drosophila melanogaster as our model organism because it has been shown to be a tractable model for investigating host-pathogen interactions and lacks PONs. By using quorum-sensing–deficient P. aeruginosa, synthetic acyl-HSLs, and transgenic expression of human PON1, we investigated the role of 3OC12-HSL and PON1 on P. aeruginosa virulence. We found that P. aeruginosa virulence in flies was dependent upon 3OC12-HSL. PON1 transgenic flies expressed enzymatically active PON1 and thereby exhibited arylesterase activity and resistance to organophosphate toxicity. Moreover, PON1 flies were protected from P. aeruginosa lethality, and protection was dependent on the lactonase activity of PON1. Our findings show that PON1 can interfere with quorum sensing in vivo and provide insight into what we believe is a novel role for PON1 in the innate immune response to quorum-sensing–dependent pathogens. These results raise intriguing possibilities about human-pathogen interactions, including potential roles for PON1 as a modifier gene and for PON1 protein as a regulator of normal bacterial florae, a link between infection/inflammation and cardiovascular disease, and a potential therapeutic modality.
High incidence of pulmonary bacterial co-infection in children with severe respiratory syncytial virus (RSV) bronchiolitis
Authors: K Thorburn
Journal: Thorax (2006)

Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTI). Viral LRTI is a risk factor for bacterial superinfection, having an escalating incidence with increasing severity of respiratory illness. A study was undertaken to determine the incidence of pulmonary bacterial co-infection in infants and children with severe RSV bronchiolitis, using paediatric intensive care unit (PICU) admission as a surrogate marker of severity, and to study the impact of the co-infection on morbidity and mortality.A prospective microbiological analysis was made of lower airways secretions on all RSV positive bronchiolitis patients on admission to the PICU during three consecutive RSV seasons.One hundred and sixty five children (median age 1.6 months, IQR 0.5-4.6) admitted to the PICU with RSV bronchiolitis were enrolled in the study. Seventy (42.4%) had lower airway secretions positive for bacteria: 36 (21.8%) were co-infected and 34 (20.6%) had low bacterial growth/possible co-infection. All were mechanically ventilated (median 5.0 days, IQR 3.0-7.3). Those with bacterial co-infection required ventilatory support for longer than those with only RSV (p<0.01). White cell count, neutrophil count, and C-reactive protein did not differentiate between the groups. Seventy four children (45%) received antibiotics prior to intubation. Sex, co-morbidity, origin, prior antibiotics, time on preceding antibiotics, admission oxygen, and ventilation index were not predictive of positive bacterial cultures. There were 12 deaths (6.6%), five of which were related to RSV.Up to 40% of children with severe RSV bronchiolitis requiring admission to the PICU were infected with bacteria in their lower airways and were at increased risk for bacterial pneumonia.
Promoting physical activity in general practice: a controlled trial of written advice and information materials
Authors: Ben J Smith, Adrian E Bauman, Fiona C Bull, Michael L Booth, Mark F Harris
Journal: British Journal of Sports Medicine (2000)

Objective —To investigate the impact of a simple written prescription for physical activity given by a general practitioner and the effect of supplementing this with mailed information materials about physical activity. Methods —A controlled trial was conducted in 27 general practices in New South Wales, Australia. Subjects were sequential routine care patients between 25 and 65 years old. Controls (n = 386) were recruited first, and intervention subjects two weeks later. Intervention subjects were randomised to receive a prescription only (n = 380) or a prescription plus a mailed booklet (n = 376). Self reported physical activity levels were measured by interview at baseline, 6–10 weeks, and seven to eight months. Results —By intention to treat, the average changes in minutes of total physical activity did not differ significantly between the groups. Inactive people in the prescription plus supplementary booklet group were significantly more likely than controls to report an increase in their physical activity by at least 60 min/week after 6–10 weeks (odds ratio 1.58, 95% confidence interval 1.06 to 2.35). No significant short term improvements in self reported activity were shown in the prescription only group. In the supplemented group, the proportion reporting an increase in physical activity to 3344 kJ/week at 6–10 weeks was not significant, and neither intervention group showed significant increases in any of the outcome measures at seven to eight months by intention to treat. Treatment received analysis showed greater improvements in intervention groups, especially the prescription plus booklet group, in which the odds of inactive people in this group reporting increased activity became significant at seven to eight months. Conclusions —A prescription for physical activity from a general practitioner, supplemented by additional written materials, can lead to modest short term improvements in self reported physical activity levels among inactive patients. A prescription alone was found not to be effective.
Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age
Authors: Keith T. Jones
Journal: Human Reproduction Update (2007)

Mammalian oocytes begin meiosis in the fetal ovary, but only complete it when fertilized in the adult reproductive tract. This review examines the cell biology of this protracted process: from entry of primordial germ cells into meiosis to conception. The defining feature of meiosis is two consecutive cell divisions (meiosis I and II) and two cell cycle arrests: at the germinal vesicle (GV), dictyate stage of prophase I and at metaphase II. These arrests are spanned by three key events, the focus of this review: (i) passage from mitosis to GV arrest during fetal life, regulated by retinoic acid; (ii) passage through meiosis I and (iii) completion of meiosis II following fertilization, both meiotic divisions being regulated by cyclin-dependent kinase (CDK1) activity. Meiosis I in human oocytes is associated with an age-related high rate of chromosomal mis-segregation, such as trisomy 21 (Down's syndrome), resulting in aneuploid conceptuses. Although aneuploidy is likely to be multifactorial, oocytes from older women may be predisposed to be becoming aneuploid as a consequence of an age-long decline in the cohesive ties holding chromosomes together. Such loss goes undetected by the oocyte during meiosis I either because its ability to respond and block division also deteriorates with age, or as a consequence of being inherently unable to respond to the types of segregation defects induced by cohesion loss.