Simulating regimes of chemical disturbance and testing impacts in the ecosystem using a novel programmable dosing system

File replaced (incorrect version) on 16/8/2022 by KT (LDS)

XMM–Newton campaign on ultraluminous X-ray source NGC 1313 X-1: wind versus state variability

Most ultraluminous X-ray sources (ULXs) are thought to be powered by neutron stars and black holes accreting beyond the Eddington limit. If the compact object is a black hole or a neutron star with a magnetic field ≲1012 G, the accretion disc is expected to thicken and launch powerful winds driven by radiation pressure. Evidence of such winds has been found in ULXs through the high-resolution spectrometers onboardXMM–Newton, but several unknowns remain, such as the geometry and launching mechanism of these winds. In order to better understand ULX winds and their link to the accretion regime, we have undertaken a major campaign with XMM–Newton to study the ULX NGC 1313 X-1, which is known to exhibit strong emission and absorption features from a mildly relativistic wind. The new observations show clear changes in the wind with a significantly weakened fast component (0.2c) and the rise of a new wind phase which is cooler and slower (0.06–0.08c). We also detect for the first time variability in the emission lines which indicates an origin within the accretion disc or in the wind. We describe the variability of the wind in the framework of variable super-Eddington accretion rate and discuss a possible geometry for the accretion disc

Developing a preference-based utility scoring algorithm for the Psoriasis Area Severity Index (PASI)

Introduction It is challenging to identify health state utilities associated with psoriasis because generic preference-based measures may not capture the impact of dermatological symptoms. The Psoriasis Area Severity Index (PASI) is one of the most commonly used psoriasis rating scales in clinical trials. The purpose of this study was to develop a utility scoring algorithm for the PASI. Methods Forty health states were developed based on PASI scores of 40 clinical trial patients. Health states were valued in time trade-off interviews with UK general population participants. Regression models were conducted to crosswalk from PASI scores to utilities (e.g., OLS linear, random effects, mean, robust, spline, quadratic). Results A total of 245 participants completed utility interviews (51.4% female; mean age =45.3y). Models predicting utility based on the four PASI location scores (head, upper limbs, trunk, lower limbs) had better fit/accuracy (e.g., R2, mean absolute error [MAE]) than models using the PASI total score. Head/upper limb scores were more strongly associated with utility than trunk/lower limb. The recommended model is the OLS linear model based on the four PASI location scores (R2 = 0.13; MAE =0.03). An alternative is recommended for situations when it is necessary to estimate utility based on the PASI total score. Conclusions The recommended scoring algorithm may be used to estimate utilities based on PASI scores of any treatment group with psoriasis. Because the PASI is commonly used in psoriasis clinical trials, this scoring algorithm greatly expands options for quantifying treatment outcomes in cost-effectiveness analyses of psoriasis therapies. Results indicate that psoriasis of the head/upper limbs could be more important than trunk/lower limbs, suggesting reconsideration of the standard PASI scoring approach

Medicinal herb use among asthmatic patients attending a specialty care facility in Trinidad

BACKGROUND: There is an increasing prevalence of asthma in the Caribbean and patients remain non-compliant to therapy despite the development of guidelines for management and prevention. Some patients may self-medicate with medicinal herbs for symptomatic relief, as there is a long tradition of use for a variety of ailments. The study assessed the prevalence of use and the factors affecting the decision to use herbs in asthmatic patients attending a public specialty care clinic in Trinidad. METHODS: A descriptive, cross-sectional study was conducted at the Chest Clinic in Trinidad using a de novo, pilot-tested, researcher-administered questionnaire between June and July 2003. RESULTS: Fifty-eight out of 191 patients (30.4%) reported using herbal remedies for symptomatic relief. Gender, age, ethnicity, and asthma severity did not influence the decision to use herbs; however, 62.5% of patients with tertiary level schooling used herbs, p = 0.025. Thirty-four of these 58 patients (58.6%) obtained herbs from their backyards or the supermarket; only 14 patients (24.1%) obtained herbs from an herbalist, herbal shop or pharmacy. Relatives and friends were the sole source of information for most patients (70.7%), and only 10.3% consulted an herbalist. Ginger, garlic, aloes, shandileer, wild onion, pepper and black sage were the most commonly used herbs. CONCLUSIONS: Among patients attending the Chest Clinic in Trinidad the use of herbal remedies in asthma is relatively common on the advice of relatives and friends. It is therefore becoming imperative for healthcare providers to become more knowledgeable on this modality and to keep abreast with the latest developments

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives

Distinct regulation of c-myb gene expression by HoxA9, Meis1 and Pbx proteins in normal hematopoietic progenitors and transformed myeloid cells

The proto-oncogenic protein c-Myb is an essential regulator of hematopoiesis and is frequently deregulated in hematological diseases such as lymphoma and leukemia. To gain insight into the mechanisms underlying the aberrant expression of c-Myb in myeloid leukemia, we analyzed and compared c-myb gene transcriptional regulation using two cell lines modeling normal hematopoietic progenitor cells (HPCs) and transformed myelomonocytic blasts. We report that the transcription factors HoxA9, Meis1, Pbx1 and Pbx2 bind in vivo to the c-myb locus and maintain its expression through different mechanisms in HPCs and leukemic cells. Our analysis also points to a critical role for Pbx2 in deregulating c-myb expression in murine myeloid cells cotransformed by the cooperative activity of HoxA9 and Meis1. This effect is associated with an intronic positioning of epigenetic marks and RNA polymerase II binding in the orthologous region of a previously described alternative promoter for c-myb. Taken together, our results could provide a first hint to explain the abnormal expression of c-myb in leukemic cells