A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients

Forty-eight patients who provided 2 consecutive blood samples that tested positive for cytomegalovirus DNA by polymerase chain reaction (PCR) were randomized to receive either full-dose ganciclovir ( 5 mg/kg intravenously [iv] twice daily) or half-dose ganciclovir (5 mg/kg iv once daily) plus half-dose foscarnet (90 mg/kg iv once daily) for 14 days. In the ganciclovir arm, 17 (71%) of 24 patients reached the primary end point of being CMV negative by PCR within 14 days of initiation of therapy, compared with 12 (50%) of 24 patients in the ganciclovir-plus-foscarnet arm (P = .12). Toxicity was greater in the combination-therapy arm. In patients who failed to reach the primary end point, baseline virus load was 0.77 log(10) higher, the replication rate before therapy was faster (1.5 vs. 2.7 days), and the viral decay rate was slower (2.9 vs. 1.1 days) after therapy. Bivariable logistic regression models identified baseline virus load, bone-marrow transplantation, and doubling time and half-life of decay as the major factors affecting response to therapy within 14 days. This study did not support a synergistic effect of ganciclovir plus foscarnet in vivo

Hummingbirds Budget Energy Flexibly in Response to Changing Resources

A key component of individual fitness is the ability to manage energy stores in response to variable resource availability, but because directly measuring energy budgets is difficult, daily energy management is rarely measured. Hummingbirds\u27 energy management is relatively simple to model compared to other endotherms because they have high mass‐specific metabolic rates and store little fat. We determined which aspects of the hummingbird daily energy budget (i.e. thermoregulation, daytime activity costs, night‐time costs) change at the individual level in response to environmental variation. We found that daily energy expenditure varied threefold in two populations of broad‐billed hummingbirds (Cynanthus latirostris). Our model indicated the energy budget was distributed in the following proportions: daytime activity, 59% (range 22%–84%); thermoregulation, 23% (11%–32%); basal metabolism, 7% (3%–16%); and night‐time energy, 17% (6%–37%). Activity costs were higher at the hotter, homogeneous site and during the early‐wet season at both sites. Increased daily energy expenditure was related to decreased nectar availability and not significantly related to temperature or bird mass. With climate change, the indirect energetic costs of shifting resources could have greater impacts on endotherm energy budgets than direct costs such as thermoregulation. Increased foraging and activity costs could decrease the energy available to birds for somatic repair and reproduction, potentially causing differential fitness across seasons and sites

Longitudinal Examination of Which Married Young Women Use Contraception to Delay a First Pregnancy in Bihar and Uttar Pradesh, India

Early marriage and childbearing put young women and their babies at risk of poor health and well-being. This study uses two rounds of longitudinal data from young women ages 15–19 in 2015–2016 and followed in 2018–2019 to determine factors associated with contraceptive use before a first pregnancy among young, married women in Bihar and Uttar Pradesh, India. Discrete time hazard models were used to analyze time to first use starting from the month of marriage. Overall, use of contraception prior to a first pregnancy was low in this sample (between 12 to 20% used before a first pregnancy). Young women who reported that someone discussed the importance of delaying a first birth at the time of marriage were significantly more likely to have used a method of family planning (FP) before a first pregnancy than those who did not receive this information. Further, women who discussed FP with their husband before a first pregnancy were more likely to use contraception. Finally, among recently married young women, those who experienced pressure to have a child were less likely to use before a first pregnancy. As young women recognize the advantages of delaying a first birth and adopt FP to meet their needs, social norms around early childbearing will slowly adjust and early use to delay a first pregnancy will become more normative

High efficacy and low toxicity of weekly docetaxel given as first-line treatment for metastatic breast cancer

Background: Docetaxel is one of the most effective antitumor agents currently available for the treatment of metastatic breast cancer (MBC). This phase II multicenter study prospectively analyzed the efficacy and toxicity of docetaxel given on a weekly schedule as first-line treatment of metastatic breast cancer. Patients and Methods: All patients received docetaxel, 35 mg/m(2) weekly for 6 weeks, followed by 2 weeks of rest. Subsequent cycles ( 3 weeks of treatment, 2 weeks of rest) were given until a maximum of 5 cycles or disease progression. Premedication consisted of 8 mg dexamethasone intravenously 30 min prior to the infusion of docetaxel. Results: Fifty-four patients at a median age of 58 years with previously untreated MBC were included in the study. A median of 10 doses ( median cumulative dose 339 mg/m(2)) was administered ( range: 2 - 18). The overall response rate was 48.1% ( 95% CI: 34 - 61%, intent-to-treat). Median survival was 15.8 months and median time to progression was 5.9 months ( intent-to-treat). Hematological toxicity was mild with absence of neutropenia-related complications. Grade 3 neutropenia was observed in 3.7% of patients and grade 3 and 4 anemia was observed in 5.6 and 1.9% of patients, respectively. Conclusion: The weekly administration of docetaxel is highly efficient and safe as first-line treatment for MBC and may serve as an important treatment option specifically in elderly patients and patients with a reduced performance status. Copyright (C) 2005 S. Karger AG, Basel

Caregiving in multiple sclerosis and quality of life: a meta-synthesis of qualitative research

Objective: The lack of adequate conceptualisation and operationalisation of quality of life (QoL) limits the ability to have a consistent body of evidence to improve QoL research and practice in informal caregiving for people with multiple sclerosis (MS). Thus, we conducted a meta-synthesis of qualitative research to improve the conceptual understanding of the experiences of MS carers and to identify factors that affect carers' QoL. Design: Systematic searches of five electronic databases yielded 17 qualitative studies which were synthesised using the principles of meta-ethnography. Results: The synthesis resulted in nine inter-linking themes: Changes and losses; challenges revolving around MS; caregiving demands; burden of care; future concerns; external stressors; experiences of support; strategies used in managing the caregiving role; and motivating factors. Our findings suggest that MS carers can have both positive and negative experiences which may bring challenges and rewards to the carers. Conclusion: We present a proposed QoL model for MS caregiving which can be used to inform the development of interventions for MS carers to improve their QoL. However, further empirical research is needed to examine the utility of this model and to explore the concept of QoL in MS carers in more detail

Successful long-term monotherapy with rituximab in a patient with chronic lymphocytic leukemia of the B-cell-lineage: a case report

<p>Abstract</p> <p>Introduction</p> <p>Treatment of chronic lymphocytic leukemia of the B-cell-lineage is strongly based upon clinical staging because of the heterogeneous clinical course of this disease.</p> <p>Case presentation</p> <p>We describe a 62-year-old patient with newly diagnosed chronic lymphocytic leukemia of the B-cell-lineage who did not respond to several chemotherapy regimens including chlorambucil, fludarabine and cyclophosphamide, developing a marked neutropenia and thrombocytopenia with life-threatening infections. Further chemotherapy appeared not feasible because of bone marrow toxicity. The patient was treated with 600 mg/m²rituximab weekly followed by eight courses of biweekly therapy and then by long-term maintenance therapy, achieving almost complete remission of the symptoms and disease control.</p> <p>Conclusion</p> <p>After resistance to standard chemotherapy with chlorambucil and fludarabine, a patient with chronic lymphocytic leukemia of the B-cell-lineage was successfully treated with rituximab.</p

Fantasies of subjugation: a discourse theoretical account of British policy on the European Union

The decision by the UK government to hold a referendum on Britain’s membership of the European Union (EU) marks an important development in policy towards the EU. Policy changes of this kind must be understood in the historical and political context in which they occur. This includes the framing of the policy issues within public discourse. In the UK, policies are formed in a discursive environment which is overwhelmingly hostile towards the EU. Debates are structured by a predominantly Euroskeptic discourse which emphasizes the UK’s separation and heterogeneity from the rest of the EU. Drawing on the logics of critical explanation, this article examines the structure and affective power of Euroskeptic discourses which dictate the terms of the EU debate. It presents a case study of the recent EU treaty revision process, culminating in the Treaty of Lisbon. In so doing, it enables a deeper understanding of recent policy developments

Survey of the quality of experimental design, statistical analysis and reporting of research using animals

For scientific, ethical and economic reasons, experiments involving animals should be appropriately designed, correctly analysed and transparently reported. This increases the scientific validity of the results, and maximises the knowledge gained from each experiment. A minimum amount of relevant information must be included in scientific publications to ensure that the methods and results of a study can be reviewed, analysed and repeated. Omitting essential information can raise scientific and ethical concerns. We report the findings of a systematic survey of reporting, experimental design and statistical analysis in published biomedical research using laboratory animals. Medline and EMBASE were searched for studies reporting research on live rats, mice and non-human primates carried out in UK and US publicly funded research establishments. Detailed information was collected from 271 publications, about the objective or hypothesis of the study, the number, sex, age and/or weight of animals used, and experimental and statistical methods. Only 59% of the studies stated the hypothesis or objective of the study and the number and characteristics of the animals used. Appropriate and efficient experimental design is a critical component of high-quality science. Most of the papers surveyed did not use randomisation (87%) or blinding (86%), to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods described their methods and presented the results with a measure of error or variability. This survey has identified a number of issues that need to be addressed in order to improve experimental design and reporting in publications describing research using animals. Scientific publication is a powerful and important source of information; the authors of scientific publications therefore have a responsibility to describe their methods and results comprehensively, accurately and transparently, and peer reviewers and journal editors share the responsibility to ensure that published studies fulfil these criteria

Effects of anisotropic interactions on the structure of animal groups

This paper proposes an agent-based model which reproduces different structures of animal groups. The shape and structure of the group is the effect of simple interaction rules among individuals: each animal deploys itself depending on the position of a limited number of close group mates. The proposed model is shown to produce clustered formations, as well as lines and V-like formations. The key factors which trigger the onset of different patterns are argued to be the relative strength of attraction and repulsion forces and, most important, the anisotropy in their application.Comment: 22 pages, 9 figures. Submitted. v1-v4: revised presentation; extended simulations; included technical results. v5: added a few clarification