tbuckley/cabot-search huggingface dataset:
Age- and Sex-Specific Prevalences of Diabetes and Impaired Glucose Regulation in 13 European Cohorts
Journal: Diabetes Care (2003)

OBJECTIVE—To report the age- and sex-specific prevalences of diabetes and impaired glucose regulation (IGR) according to the revised 1999 World Health Organization criteria for diabetes in Europe. RESEARCH DESIGN AND METHODS—A total of 13 studies from nine European countries with 7,680 men and 9,251 women aged 30–89 years were included in the data analysis. RESULTS—In most of the study populations, the age-specific prevalences of diabetes were &amp;lt;10% in subjects younger than 60 years and between 10 and 20% at 60–79 years of age. Mean 2-h plasma glucose (2hPG) concentration increased linearly with age, but fasting plasma glucose (FPG) concentration did not. The increase in the prevalence of undiagnosed diabetes and IGR in the elderly was mainly a result of the large increase in 2hPG rather than FPG. Diabetes and impaired fasting glycemia defined by isolated fasting hyperglycemia was more common in men than in women 30–69 years of age, whereas the prevalence of isolated postload hyperglycemia, particularly impaired glucose tolerance, was higher in women than in men, especially in the elderly (individuals &amp;gt;70 years of age). More than half of the diabetes was undiagnosed in subjects younger than 50 years of age. CONCLUSIONS—Most European populations have a moderate to low prevalence of diabetes and IGR. Diabetes and IGR will be underestimated in Europe, particularly in women and in elderly men, if diagnoses are based on fasting glucose determination alone.
Cytotoxic T cells recognize male antigen and H-2 as distinct entities.
Authors: H von Boehmer, W Haas, H Pohlit
Journal: The Journal of Experimental Medicine (1978)

XX cells from XX/XY hemopoietic chimeras do not express male determinants in a way to render them either stimulators or targets for male-specific cytotoxic lymphocytes. XX- but not XY-responder T cells from chimeras can be activated to lyse allogeneic male target cells; T cells from normal XX mice depleted of alloreactive T cells, however, cannot be sensitized to lyse allogeneic XY targets. The results imply that T cells recognize the Y-antigen and H-2 as distinct entities, and that in chimeras, they acquire the potential to react against allogeneic XY cells.
Identification and characterization of high-flux-control genes of yeast through competition analyses in continuous cultures
Authors: Daniela Delneri, David C Hoyle, Konstantinos Gkargkas, Emma J M Cross, Bharat Rash, Leo Zeef, Hui-Sun Leong, Hazel M Davey, Andrew Hayes, Douglas B Kell, Gareth W Griffith, Stephen G Oliver
Journal: Nature Genetics (2007)
Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up
Authors: Lorraine Harper, Matthew D Morgan, Michael Walsh, Peter Hoglund, Kerstin Westman, Oliver Flossmann, Vladimir Tesar, Phillipe Vanhille, Kirsten de Groot, Raashid Luqmani, Luis Felipe Flores-Suarez, Richard Watts, Charles Pusey, Annette Bruchfeld, Niels Rasmussen, Daniel Blockmans, Caroline O Savage, David Jayne
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Introduction</h3> The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were combined with the same glucocorticoid protocol (CYCLOPS study (Randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis published de groot K, harper L <i>et al</i> Ann Int Med 2009)). The study had limited power to detect a difference in relapse. This study describes the long-term outcomes of patients in the CYCLOPS study. <h3>Methods</h3> Long-term outcomes were ascertained retrospectively from 148 patients previously recruited to the CYCLOPS Trial. Data on survival, relapse, immunosuppressive treatment, cancer incidence, bone fractures, thromboembolic disease and cardiovascular morbidity were collected from physician records retrospectively. All patients were analysed according to the group to which they were randomised. <h3>Results</h3> Median duration of follow-up was 4.3 years (IQR, 2.95–5.44 years). There was no difference in survival between the two limbs (p=0.92). Fifteen (20.8%) DO and 30 (39.5%) pulse patients had at least one relapse. The risk of relapse was significantly lower in the DO limb than the pulse limb (HR=0.50, 95% CI 0.26 to 0.93; p=0.029). Despite the increased risk of relapse in pulse-treated patients, there was no difference in renal function at study end (p=0.82). There were no differences in adverse events between the treatment limbs. <h3>Discussion</h3> Pulse cyclophosphamide is associated with a higher relapse risk than DO cyclophosphamide. However, this is not associated with increased mortality or long-term morbidity. Although the study was retrospective, data was returned in 90% of patients from the original trial.
Progranulin and cholangiocarcinoma: another bad boy on the block!
Authors: Domenico Alvaro
Journal: Gut (2011)

Cholangiocarcinoma (CCA) is a cancer that may develop in any portion of the biliary tree and is characterised by a bad prognosis and virtually no response to chemotherapy.1 2 In Western countries the incidence of intrahepatic CCA is progressively growing while that of extrahepatic CCA is stable or slightly decreasing.3 A number of recent studies have investigated the agents and mechanisms modulating the proliferation of CCA cells including growth factors, cytokines, neuropeptides and hormones.4 In their paper published in Gut , Frampton et al 5 provide compelling evidence that progranulin (PGRN) represents a new growth factor for CCA. The expression and secretion of PGRN is upregulated in CCA cell lines and human CCA biopsies, and this is in part occurs via interleukin 6 (IL-6)-mediated activation of the ERK1/2/RSK1/C/EBPβ pathway. Knockdown of PGRN expression in CCA cells decreased the expression of proliferating cellular nuclear antigen, a marker of cell proliferation, and slowed tumour growth in vivo. The authors suggest that PGRN may be a potential target for the development of novel therapeutic strategies for CCA.5

PGRN is a secreted glycoprotein consisting of tandem repeats of a 12-cysteine module called granulin or epithelin domain. It is proteolytically degraded by elastase with the release of 6 kDa peptides corresponding to granulin modules …
Intravenous golimumab is effective in patients with active rheumatoid arthritis despite methotrexate therapy with responses as early as week 2: results of the phase 3, randomised, multicentre, double-blind, placebo-controlled GO-FURTHER trial
Authors: Michael E Weinblatt, Clifton O Bingham, Alan M Mendelsohn, Lilianne Kim, Michael Mack, Jiandong Lu, Daniel Baker, Rene Westhovens
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> Evaluate the efficacy of intravenous golimumab 2 mg/kg+methotrexate (MTX) in patients with active rheumatoid arthritis (RA) receiving MTX. <h3>Methods</h3> Patients (n=592) with active disease (≥6/66 swollen, ≥6/68 tender joints, C-reactive protein ≥1.0 mg/dl, rheumatoid factor positive and/or anticyclic citrullinated protein antibody positive at screening) despite MTX (15–25 mg/week) participated in this double-blind, placebo-controlled, phase 3 study. Patients were randomised (2:1) to receive intravenous golimumab 2 mg/kg, or placebo infusions at weeks 0 and 4 and every (q) 8 weeks; patients continued MTX. Placebo patients with &lt;10% improvement in combined swollen/tender joint counts at week 16 could early escape to intravenous golimumab 2 mg/kg. The primary endpoint was week 14 American College of Rheumatology 20% (ACR20) response. Analyses employed non-responder imputation and last-observation-carried-forward. <h3>Results</h3> At week 14, significantly (p&lt;0.001) larger proportions of golimumab+MTX than placebo+MTX patients achieved ACR20 response (59% vs 25%, respectively), a disease activity score of good/moderate (EULAR) response (81% vs 40%), and greater median improvement in health assessment questionnaire scores (0.500 vs 0.125). Improvements versus placebo+MTX were observed by week 2. Similar proportions of patients receiving golimumab+MTX and placebo+MTX, respectively, reported adverse events through week 16 (47% and 44%) and week 24 (53% and 49%). Serious adverse events were reported by more golimumab+MTX (4.1%) than placebo+MTX (2%) patients at week 24. <h3>Conclusion</h3> The addition of intravenous golimumab rapidly and significantly improved signs and symptoms in patients with active RA despite ongoing MTX, in some patients by week 2.
Linkage Analysis of Markers on Chromosome 11q13 with Asthma and Atopy in a United Kingdom Population
Authors: N. SIMON THOMAS, JANE WILKINSON, CHRISTINE LONJOU, NEWTON E. MORTON, STEPHEN T. HOLGATE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Previous studies have suggested that atopy is linked to the beta chain of the high affinity IgE receptor (Fc ɛ R1- β ) on chromosome 11q13. Fc ɛ R1- β polymorphisms, I181L, V183L, and E237G, are reported to be associated with asthma and atopy. The aim of this study was to investigate linkage to Fc ɛ R1- β in a UK population and to assess the frequency of the polymorphisms and their association with asthma and atopy. A sample of 131 families was recruited at random with a sample of 109 families ascertained via an asthmatic proband. Each subject completed a written and video-assisted questionnaire and underwent bronchial challenge and skin prick testing. Serum total and specific IgE levels were measured. Quantitative scores were derived for asthma and atopy using principal component analysis. Four microsatellite markers were genotyped, including Fc ɛ R1- β . The frequency of the I181L and V183L polymorphisms were determined by sequencing, and the E237G polymorphism was determined using the amplification refractory mutation system. We found no evidence for linkage to Fc ɛ R1- β and only weak evidence for linkage to the less informative marker E237G. We found no examples of the I181L/V183L polymorphism in our population sample. Our study has failed to strengthen the evidence for a candidate gene on chromosome 11q13.
X-ray interpretation: A self-assessment survey
Authors: Manish Pagaria, Premnath Balakrishnan, Arun Dev Vellore
Journal: European Respiratory Journal (2012)

AIM: To assess the confidence of hospital based doctors in reviewing plain radiographs.

METHODS: An online e-survey tool collected responses from 600 doctors from the West Midlands area, UK. They were asked to rate their confidence as: not confident, will always need senior help; somewhat confident; confident in interpreting some conditions; confident of routine and common conditions; very confident, seek radiology advice occasionally; highly confident, almost never seek radiology advice. We also asked them to self assess their confidence in identifying some common findings on x-rays; and collected data on any formal or informal training they had received.

RESULTS: 241(40%) responses were received; of these 165 were from medical and 76 from non-medical specialities. The level of confidence expressed by medical doctors in interpreting chest x-rays (48.5%) was significantly higher than abdominal (17.4%) and skeletal x-rays (6.2%). Doctors in non-medical specialties were better with skeletal x-rays (22.5%).

Of the 241, 70 had been to a radiology course, 127 had some form of formal and 57 had only informal training. 11 (9 medical trainees) did not have any form of training. 177/241 felt that there should be radiology training for all doctors, and it should be a compulsory part of the training portfolio.

CONCLUSION: There was variability in confidence amongst hospital doctors in interpreting x-rays across training grades and clinician groups. Basic radiology training as a separate competency may need to be considered in the training programmes and e-portfolio of hospital doctors. Training in chest radiograph interpretation should merit focused attention in the respiratory specialty training as well as the HERMES curricula.
THE GENERAL PRACTITIONER AND THE PSYCHIATRIST
Authors: FREDERICK LEMERE, AUSTIN B. KRAABEL
Journal: American Journal of Psychiatry (1959)

1. Sixty percent of 416 general practitioner respondents felt that their psychiatric training was reasonably adequate. A desire for more presentations and informal discussions of office-type cases was expressed. 2. Generalists are in need of more instruction in counseling techniques. 3. Twenty-four percent of general practice was considered to be primarily psychiatric in nature. The respondents estimated that they could take care of 78% of their psychiatric patients themselves. The main complaint about psychiatric patients was that they take too much time and are often difficult to help. 4. The main difficulties with referring patients to a psychiatrist were the expense to the patient (72%), resistance on the part of the patient (43%) and lack of available psychiatrists (32%). 5. The main complaints of these generalists about psychiatrists were their lack of availability and the inadequate nature of psychiatric reports to the referring doctor. 6. That progress is being made was indicated by the fact that the younger general practitioners were better satisfied with their psychiatric training, and felt that they could and wished to take care of more of their psychiatric patients as compared to the older practitioners. Some suggestions are made for improving the help that the psychiatrist can give to the generalist in this important area of medical practice.
IκBα glutathionylation and reduced histone H3 phosphorylation inhibit eotaxin and RANTES
Authors: P. Seidel, M. Roth, Q. Ge, I. Merfort, C.T. S’ng, A.J. Ammit
Journal: European Respiratory Journal (2011)

Airway smooth muscle cells (ASMCs) secrete eotaxin and RANTES (regulated on activation, normal T-cell expressed and secreted) in response to tumour necrosis factor (TNF)-α, which is inhibited by the nuclear factor (NF)-κB inhibitor dimethylfumarate (DMF). NF-κB/IκB (inhibitor of NF-κB) glutathionylation and changes in chromatin remodelling can inhibit NF-κB activity. In this study, we determined whether NF-κB/IκB glutathionylation and reduced histone H3 phosphorylation might underlie the inhibitory effect of DMF on NF-κB activity, and eotaxin and RANTES secretion. Primary human ASMCs were treated with DMF, diamide and/or glutathione (GSH) ethylester (OEt) prior to TNF-α stimulation and were subsequently analysed by ELISA, electrophoretic mobility shift assay, immunofluorescence, co-immunoprecipitation or immunoblotting. DMF reduced intracellular GSH and induced IκBα glutathionylation (IκBα-SSG), which inhibited IκBα degradation, NF-κB p65 nuclear entry and NF-κB/DNA binding. In addition, DMF inhibited the phosphorylation of histone H3, which was possibly mediated by the inhibitory effect of DMF on mitogen- and stress-activated protein kinase (MSK)-1. However, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase MAPK and MAPK phosphatase-1, upstream of MSK-1, were not inhibited by DMF. Importantly, DMF-mediated effects on NF-κB, histone H3, eotaxin and RANTES were reversed by addition of GSH-OEt. Our data suggest that DMF inhibits NF-κB-dependent eotaxin and RANTES secretion by reduction of GSH with subsequent induction of IκBα-SSG and inhibition of histone H3 phosphorylation. Our findings offer new potential drug targets to reduce airway inflammation in asthma.
Risk of non-fatal cardiac failure and ischaemic heart disease with long acting beta 2 agonists
Authors: R. M Martin, N. R Dunn, S. N Freemantle, R. D Mann
Journal: Thorax (1998)

<h3>BACKGROUND</h3> The long term safety of β agonists, particularly in patients with heart disease, has not been fully established. <h3>METHODS</h3> This study accessed the results of three cohort studies involving: 12 294 patients receiving at least one prescription for nedocromil between November 1986 and September 1988; 15 407 patients prescribed salmeterol between December 1990 and May 1991; and 8098 patients prescribed bambuterol between February 1993 and December 1995. Details of all dispensed prescriptions for these drugs prescribed by general practitioners in England soon after their launch were provided in confidence by the Prescription Pricing Authority. Questionnaires were sent to the prescriber asking for details of events occurring after the first prescription (prescription event monitoring). Rates and relative risks of non-fatal cardiac failure and ischaemic heart disease were calculated, comparing bambuterol and salmeterol with the reference drug nedocromil. <h3>RESULTS</h3> The age and sex adjusted relative risk of non-fatal cardiac failure associated with bambuterol was 3.41 (95% confidence limits (CL) 1.99 to 5.86) when compared with nedocromil. When salmeterol was compared with nedocromil the adjusted relative risk of non-fatal cardiac failure was 1.10 (95% CL 0.63 to 1.91). The adjusted relative risk of non-fatal ischaemic heart disease was 1.23 (95% CL 0.73 to 2.08) and 1.07 (95% CL 0.69 to 1.66) for bambuterol and salmeterol, compared with nedocromil, respectively. However, in the first month of exposure the adjusted relative risk of non-fatal ischaemic heart disease was 3.95 (95% CL 1.38 to 11.31) when bambuterol was compared with nedocromil. <h3>CONCLUSIONS</h3> Caution should be exercised when prescribing long acting oral β agonists to patients at risk of cardiac failure. More definitive evidence would come from prospective randomised trials.
Update in Pulmonary Infections 2010
Authors: Richard G. Wunderink, Grant W. Waterer
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

It is difficult to discuss the year in review for pulmonary infections without starting with the 2009 novel H1N1 influenza pandemic. Although excess deaths were reported for pediatric (1) and pregnant patients (2) from the prior year, the most surprising thing about the year 2010 is actually the lack of clinical infection with influenza. This resulted from a combination of factors. The first is that the novel 2009 H1N1 strain was the only circulating influenza strain during the 2009 to 2010 influenza season. The second is the dramatic effect of large-scale immunization against this particular strain. As can be seen in Figure 1, shortly after the vaccine became available, the rate of positive cultures reported to the CDC dropped dramatically (3). A similar pattern was seen with pediatric deaths, another CDC marker of influenza severity. The combination of vaccination and prior exposure during the spring of 2009 resulted in sufficient herd immunity to almost completely block new cases of influenza. Despite the ominous start, the 2009 to 2010 influenza season was actually associated with fewer deaths than in nonpandemic years. One of the lasting effects of this pandemic is a change in the standards of the Advisory Committee on Immunization Practices regarding eligibility for influenza vaccination; the committee now recommends seasonal influenza vaccination or all persons 6 months of age or older (4). The lung pathology of fatal cases of the novel H1N1 infections was reviewed by Mauad and colleagues (5). They describe three distinct pathologic findings: diffuse alveolar damage, necrotizing tracheobronchitis, and diffuse alveolar damage with diffuse alveolar hemorrhage. A subsequent letter suggests that most of the patients who had purulent tracheobronchitis also had concomitant bacterial pneumonia (6). This association supports the concept that viral damage to the airway mucosa may be important in the pathogenesis of secondary pneumonia. Documented bacterial pneumonia at onset of the H1N1 infection is uncommon, but ventilatorassociated pneumonia (VAP) often occurs as a consequence of the severe acute lung injury and prolonged mechanical ventilation (7). Therefore, the purulent tracheobronchitis may be part of the spectrum of VAP previously described in other autopsy series (8). COMMUNITY-ACQUIRED PNEUMONIA
Revised Tumor and Node Categorization for Rectal Cancer Based on Surveillance, Epidemiology, and End Results and Rectal Pooled Analysis Outcomes
Authors: Leonard L. Gunderson, John Milburn Jessup, Daniel J. Sargent, Frederick L. Greene, Andrew Stewart
Journal: Journal of Clinical Oncology (2009)

Purpose The sixth edition of the American Joint Committee on Cancer (AJCC) rectal cancer staging subdivided stage II into IIA (T3N0) and IIB (T4N0) and stage III into IIIA (T1-2N1M0), IIIB (T3-4N1M0), and IIIC (anyTN2M0). Subsequent analyses supported revised substaging of stage III as a result of improved survival with T1-2N2 versus T3-4N2 and survival of T4N1 more similar to T3-4N2 than T3N1. The AJCC Hindgut Taskforce sought population-based validation that depth of invasion interacts with nodal status to affect survival. Methods Surveillance, Epidemiology, and End Results (SEER) population-based data from January 1992 to December 2004 for 35,829 patients with rectal cancer were compared with rectal pooled analysis data (3,791 patients). T4N0 cancers were stratified by tumors that perforate visceral peritoneum (T4a) versus tumors that invade or are adherent to adjacent organs or structures (T4b). N1 and N2 were stratified by number of positive nodes as follows: N1a/N1b (one v two to three nodes) and N2a/N2b (four to six v ≥ seven nodes). Five-year observed and relative survival rates were obtained for each TN category. Results SEER rectal cancer analyses confirm that T1-2N2 cancers have better prognosis than T3-4N2, T4bN1 have similar prognosis to T4N2, T1-2N1 have similar prognosis to T2N0/T3N0, and T1-2N2a have similar prognosis to T2N0/T3N0 (T1N2a) or T4aN0 (T2N2a). Prognosis for T4a lesions is better than T4b by N category. The number of positive nodes affects prognosis. Conclusion This SEER population-based rectal cancer analysis validates the rectal pooled analyses and supports the shift of T1-2N2 lesions from IIIC to IIIA or IIIB and T4bN1 from IIIB to IIIC. SEER outcomes support subdividing T4, N1, and N2 and revised substaging of stages II and III. Survival by TN category suggests a complex biologic interaction between depth of invasion and nodal status.
More data needed on injury risk among young elite athletes
Authors: Kathrin Steffen, Lars Engebretsen
Journal: British Journal of Sports Medicine (2010)

Injuries can counter the beneficial effects of sports participation at a young age if a child or adolescent is unable to continue to participate because of residual effects of injury. Independent of activity level, injuries represent a considerable problem for the athlete and can result in an increased potential for future disability and inactivity. Injuries are also referred to as one of the major reasons for athletes to drop out of sports. Systematic injury registrations at the youth and adolescent level have been performed in recreational sports to gain knowledge on injury risk, as well as on the most common and most severe sport specific injuries. However, information on injury risk of the young athlete competing in high level sports seems less available or unknown. This paper reviews the current knowledge on injury risk of the youth and adolescent elite athlete participating in sports presented in the Youth Olympic Games 2010. Apart from football, little is known on injury epidemiology among young elite athletes. Systematic injury surveillance of this highly competitive population is needed to monitor injuries, identify high risk sports, and ensure new knowledge on injury trends, which can form the basis for further research on injury risk factors, mechanisms, and in the final step, on injury prevention.