Social impact bonds: a wolf in sheep’s clothing?

This article provides a rounded critique of social impact bonds (SIBs): a newly developed and innovative financial investment model, developed in the UK and starting to spread internationally that could transform the provision of social services. Although SIBs have the potential to influence delivery by all providers, this article raises three concerns about their possible effects – in relation to their potential outcomes, unintended consequences for the UK third sector, and governance – and then reflects on SIBs as the latest manifestation of the ideological shift which the UK third sector is undergoing.</jats:p

Clinical review: Influenza pandemic – physicians and their obligations

An influenza pandemic threatens to be the most lethal public health crisis to confront the world. Physicians will have critical roles in diagnosis, containment and treatment of influenza, and their commitment to treat despite increased personal risks is essential for a successful public health response. The obligations of the medical profession stem from the unique skills of its practitioners, who are able to provide more effective aid than the general public in a medical emergency. The free choice of profession and the societal contract from which doctors derive substantial benefits affirm this commitment. In hospitals, the duty will fall upon specialties that are most qualified to deal with an influenza pandemic, such as critical care, pulmonology, anesthesiology and emergency medicine. It is unrealistic to expect that this obligation to treat should be burdened with unlimited risks. Instead, risks should be minimized and justified against the effectiveness of interventions. Institutional and public cooperation in logistics, remuneration and psychological/legal support may help remove the barriers to the ability to treat. By stepping forward in duty during such a pandemic, physicians will be able to reaffirm the ethical center of the profession and lead the rest of the healthcare team in overcoming the medical crisis

Enhanced heterogeneity of rpoB in Mycobacterium tuberculosis found at low pH.

OBJECTIVES: The aim of this study was to gain an insight into the molecular mechanisms of the evolution of rifampicin resistance in response to controlled changes in the environment. METHODS: We determined the proportion of rpoB mutants in the chemostat culture and characterized the sequence of mutations found in the rifampicin resistance-determining region of rpoB in a steady-state chemostat at pH 7.0 and 6.2. RESULTS: The overall proportion of rpoB mutants of strain H37Rv remained constant for 37 days at pH 7.0, ranging between 3.6 x 10(-8) and 8.9 x 10(-8); however, the spectrum of mutations varied. The most commonly detected mutation, serine to leucine mutation at codon 531 (S531L), increased from 40% to 89%, while other mutations (S531W, H526Y, H526D, H526R, S522L and D516V) decreased over the 37 day sampling period. Changing the pH from 7.0 to 6.2 did not significantly alter the overall proportion of mutants, but resulted in a decrease in the percentage of strains harbouring S531L (from 89% to 50%) accompanied by an increase in the range of different mutations from 4 to 12. CONCLUSIONS: The data confirm that the fitness of strains with the S531L mutation is greater than that of strains containing other mutations. We also conclude that at low pH the environment is permissive for a wider spectrum of mutations, which may provide opportunities for a successful mutant to survive

Sinonasal undifferentiated carcinoma and esthesioneuroblastoma recurring as nonintestinal adenocarcinoma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97478/1/lary23746.pd

Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis

Supported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership, U.S. Agency for International Development, U.K. Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and National Institutes of Health, AIDS Clinical Trials Group and by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636, and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426); Bayer Healthcare for the donation of moxifloxacin; and Sanofi for the donation of rifampin.Background: Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis. Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The primary end point was treatment failure or relapse within 18 months after randomization. Results: Of the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%) than in the control group (92%), for a difference favoring the control group of 6.1 percentage points (97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points (97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group, ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or 4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the ethambutol group, and 123 (19%) in the control group. Conclusions: The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load, as compared with the control group. However, noninferiority for these regimens was not shown, which indicates that shortening treatment to 4 months was not effective in this setting. (Funded by the Global Alliance for TB Drug Development and others; REMoxTB ClinicalTrials.gov number, NCT00864383.)Publisher PDFPeer reviewe

Endemic Sexual Violence and Abuse: Contexts and Dispositions

Endemic sexual violence and abuse has been observed in a number of specific circumstances, most notably conflict zones, remote and marginalised communities, and religious and state institutions. In this article we examine several documented examples and argue that a similar set of causal processes are at work in all of these otherwise apparently disparate circumstances. Rather than construing the problem as ‘organised’ sexual abuse, we present the problem in terms of the breakdown (or disorganisation) of usual individual, situational and ecological constraints

Avoiding Irrational NeuroLaw Exuberance: A Plea for Neuromodesty

In a 2002 editorial published in The Economist, the following warning was given: Genetics may yet threaten privacy, kill autonomy, make society homogeneous and gut the concept of human nature. But neuroscience could do all of these things first. The genome was fully sequenced in 2001, and there has not been one resulting major advance in therapeutic medicine since. Thus, even in its most natural applied domain-medicine-genetics has not had the far-reaching consequences that were envisioned. The same has been true for various other sciences that were predicted to revolutionize the law, including behavioral psychology, sociology, psychodynamic psychology, and others. This will also be true of neuroscience, which is simply the newest science on the block. Neuroscience is not going to do the terrible things The Economist fears, at least not for the foreseeable future. Neuroscience has many things to say but not nearly as much as people would hope, especially in relation to law. At most, in the near to intermediate term, neuroscience may make modest contributions to legal policy and case adjudication. Nonetheless, there has been irrational exuberance about the potential contribution of neuroscience, an issue I have addressed previously and referred to as Brain Overclaim Syndrome. I first consider the law\u27s motivation and the motivation of some advocates to turn to science to solve the very hard normative problems that law addresses. Part III discusses the law\u27s psychology and its concepts of the person and responsibility. The next Part considers the general relation of neuroscience to law, which I characterize as the issue of translation. Part V canvasses various distractions that have bedeviled clear thinking about the relation of scientific, causal accounts of behavior to responsibility. The following Part examines the limits of neurolaw and Part VII considers why neurolaw does not pose a genuinely radical challenge to the law\u27s concepts of the person and responsibility. Part VIII makes a case for cautious optimism about the contribution neuroscience may make to law in the near and intermediate term. A brief conclusion follows..

Neuromuscular responses to mild-muscle damaging eccentric exercise in a low glycogen state.

The aim of this study was to examine the effect of low muscle glycogen on the neuromuscular responses to maximal eccentric contractions. Fourteen healthy men (22±3years) performed single-leg cycling (20min at ∼75% maximal oxygen uptake (V̇O2 max); eight 90 s sprints at a 1:1 work-to-rest ratio (5% decrements from 90% to 55% V̇O2 max until exhaustion) the evening before 100 eccentric (1.57rads(-1)) with reduced (RED) and normal glycogen (NORM). Neuromuscular responses were measured during and up to 48h after with maximal voluntary and involuntary (twitch, 20Hz and 50Hz) isometric contractions. During eccentric contractions, peak torque decreased (RED: -16.1±2.5%; NORM: -6.2±5.1%) and EMG frequency increased according to muscle length. EMG activity decreased for RED only. After eccentric contractions, maximal isometric force was reduced up to 24h for NORM (-13.5±5.8%) and 48h for RED (-7.4±10.9%). Twelve hours after eccentric contractions, twitch force and the 20:50Hz ratio were decreased for RED but not for NORM. Immediate involuntary with prolonged voluntary force loss suggests that reduced glycogen is associated with increased susceptibility to mild muscle-damaging eccentric exercise with contributions of peripheral and central mechanisms to be different during recovery