A High Statistics Search for Ultra-High Energy Gamma-Ray Emission from Cygnus X-3 and Hercules X-1

We have carried out a high statistics (2 Billion events) search for ultra-high energy gamma-ray emission from the X-ray binary sources Cygnus X-3 and Hercules X-1. Using data taken with the CASA-MIA detector over a five year period (1990-1995), we find no evidence for steady emission from either source at energies above 115 TeV. The derived upper limits on such emission are more than two orders of magnitude lower than earlier claimed detections. We also find no evidence for neutral particle or gamma-ray emission from either source on time scales of one day and 0.5 hr. For Cygnus X-3, there is no evidence for emission correlated with the 4.8 hr X-ray periodicity or with the occurrence of large radio flares. Unless one postulates that these sources were very active earlier and are now dormant, the limits presented here put into question the earlier results, and highlight the difficulties that possible future experiments will have in detecting gamma-ray signals at ultra-high energies.Comment: 26 LaTeX pages, 16 PostScript figures, uses psfig.sty to be published in Physical Review

SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

Hamsters (cricetus cricetus) and camera - use of a camera for collecting biological data about number of litters and the gain of weight of young in the first two months.

Contains fulltext : 91876.pdf (publisher's version ) (Open Access)4 p

Empirical treatment followed by a test-and-treat strategy is more cost-effective in comparison with prompt endoscopy or radiography in patients with dyspeptic symptoms: a randomized trial in a primary care setting.

Contains fulltext : 58548.pdf (publisher's version ) (Closed access)OBJECTIVE: Management of patients with dyspepsia remains controversial. No consensus has yet been reached concerning diagnostic and medical strategies. We conducted a randomized trial to assess the effectiveness of three management strategies for patients with uninvestigated persistent dyspeptic symptoms. METHODS: A total of 199 patients presenting in primary care with dyspeptic symptoms (age 18-65 years, no alarming symptoms) were randomized to either empirical treatment with omeprazole and, in the case of symptomatic relapse, serological Helicobacter pylori infection testing plus eradication therapy (treat-and-test group), prompt upper gastrointestinal endoscopy (endoscopy group) or prompt upper gastrointestinal radiography (radiography group) followed by directed medical treatment. Symptoms, patients' satisfaction and use of resources were recorded during 6 months of follow-up. RESULTS: Sixty-nine patients were assigned to the treat-and-test group, 64 to the radiography group and 66 to the endoscopy group. The median age was 44 years; 104 patients were male and 37% were H.pylori infected. A total of 170 patients (85%) returned the 6 months questionnaire. The numbers of patients with complete symptom relief in the treat-and-test group, endoscopy group and radiography group were 21, 16 and 15, respectively, at 3 months (P = 0.59), and 23, 13 and 12, respectively, at 6 months (P = 0.05). Twenty-two patients in the treat-and-test group underwent endoscopy or radiography. Two patients in the endoscopy group and four patients in the radiography group underwent more than one diagnostic test. The average medical cost per patient for the treat-and-test group was euro 276, for the endoscopy group euro 426 and for the radiography group euro 321, respectively. CONCLUSION: Empirical treatment followed by a test-and-eradicate strategy resulted in fewer diagnostic tests, more symptom relief and lower medical costs compared with prompt upper gastrointestinal radiography or endoscopy in the management of uninvestigated patients with persistent dyspeptic symptoms

Predominant symptom behavior in patients with persistent dyspepsia during treatment.

Contains fulltext : 57155.pdf (publisher's version ) (Closed access)BACKGROUND: Grouping of patients based on a predominant dyspeptic symptom is frequently employed in management strategies for dyspepsia. Such subdivision, however, suggests that dyspeptic symptom patterns are constant over time. OBJECTIVE: To investigate the behavior of symptoms over time and to study the effects of diagnostic procedures and treatment on the pattern and severity of dyspeptic symptoms. METHODS: Patients with persistent dyspeptic symptoms completed a validated questionnaire at regular time intervals as part of a clinical trial in primary care. Based on predominant symptoms, patients were classified into ulcer-like dyspepsia, reflux-like dyspepsia, dysmotility-like dyspepsia, and unspecific dyspepsia according to the Rome II criteria. RESULTS: Questionnaires were returned at baseline, 1, 3, and 6 months by 185, 172, 169, and 170 patients, respectively. At baseline, 35% of patients reported predominantly reflux-like dyspepsia, 34% had ulcer-like dyspepsia, 16% had dysmotility-like dyspepsia, and in 15% symptoms were not specific. During the 6-month follow-up period, only 35% of patients kept the same predominant symptom. Symptom (in)stability was not dependent on diagnostic procedures or on therapy with proton pump inhibitors, H2-receptor antagonists, prokinetics, or antacids. CONCLUSION: In the majority of dyspeptic patients, symptoms change continuously as time goes on. Symptom instability is not influenced by diagnostic procedures or therapy. Thus, there is little sense in symptom-based management of dyspepsia in primary care

Evaluation of p16/Ki-67 dual-stained cytology as triage test for high-risk human papillomavirus-positive women

The aim of this study was to evaluate the clinical utility of p16/Ki-67 dual staining, for the identification of CIN in high-risk HPV-positive women from a non-responder screening cohort. P16/Ki-67 dual staining, Pap cytology, and HPV16/18 genotyping were performed on physician-taken liquid-based samples from 495 women who tested high-risk HPV positive on self-sampled material (PROHTECT-3B study). Different triage strategies involving p16/Ki-67 dual staining were evaluated for sensitivity, specificity, and predictive value for ≥CIN2 and ≥CIN3, and compared to Pap cytology with a threshold of atypical cells of undetermined significance. Centrally revised histology or an adjusted endpoint with combined high-risk HPV negative and cytology negative follow-up at 6 months was used as gold standard. Pap cytology (threshold atypical cells of undetermined significance) triage of high-risk HPV-positive samples showed a sensitivity of 93% (95% confidence interval: 85-98) with a specificity of 49% (95% confidence interval: 41-56) for ≥CIN3. Three triage strategies with p16/Ki-67 showed a significantly increased specificity with similar sensitivity. P16/Ki-67 triage of all high-risk HPV-positive samples had a sensitivity of 92% (95% confidence interval: 84-97) and a specificity of 61% (95% confidence interval: 54-69) for ≥CIN3. Applying p16/Ki-67 triage to only high-risk HPV-positive women with low-grade Pap cytology showed a similar sensitivity of 92% (95% confidence interval: 84-97), with a specificity for ≥CIN3 of 64% (95% confidence interval: 56-71). For high-risk HPV-positive women with low-grade and normal Pap cytology, triage with p16/Ki-67 showed a sensitivity of 96% (95% confidence interval: 89-99), and a specificity of 58% (95% confidence interval: 50-65). HPV16/18 genotyping combined with Pap cytology showed a sensitivity and specificity for ≥CIN3 similar to Pap cytology with an atypical cells of undetermined significance threshold. Because the quality of Pap cytology worldwide varies, and differences in sensitivity and specificity are limited between the three selected strategies, p16/Ki-67 triage of all high-risk HPV-positive samples would be the most reliable strategy in triage of high-risk HPV-positive women with an increased specificity and similar sensitivity compared with Pap cytology triage