Clinical use of HIV integrase inhibitors : a systematic review and meta-analysis

Background: Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods: MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results: 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion: In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment

Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline

Menu labelling and food choice in obese adults: a feasibility study.

BACKGROUND: To date research examining the benefits of menu labelling in the UK is sparse. The aim of the present study was to examine the impact of menu labelling in a UK obese population. METHODS: Using a repeated measures design, 61 patients at a tier 3 weight management service completed four questionnaires to assess their food choice (control) and behaviour change when presented with 3 menu labelling formats (calorie content; nutrient content; and energy expenditure). RESULTS: All three forms of labelling increased participants weight control concerns compared to the control condition. There was a significant difference in content of food ordered in the three menu labelling formats compared to the control condition. The calorie condition had the largest percentage decrease in calories selected followed by energy expenditure and nutrient content. However, no difference was observed between the three conditions in the desire for menu labelling in restaurants to be introduced in the UK. CONCLUSIONS: The findings suggest that menu labelling should be enforced in the UK as it is both beneficial to promoting healthy eating and in demand. This study is the first to examine menu labelling in a UK obese population using energy expenditure equivalents to provide nutritional information

Myelination induces axonal hotspots of synaptic vesicle fusion that promote sheath growth

Myelination of axons by oligodendrocytes enables fast saltatory conduction. Oligodendrocytes are responsive to neuronal activity, which has been shown to induce changes to myelin sheaths, potentially to optimize conduction and neural circuit function. However, the cellular bases of activity-regulated myelination in vivo are unclear, partly due to the difficulty of analyzing individual myelinated axons over time. Activity-regulated myelination occurs in specific neuronal subtypes and can be mediated by synaptic vesicle fusion, but several questions remain: it is unclear whether vesicular fusion occurs stochastically along axons or in discrete hotspots during myelination and whether vesicular fusion regulates myelin targeting, formation, and/or growth. It is also unclear why some neurons, but not others, exhibit activity-regulated myelination. Here, we imaged synaptic vesicle fusion in individual neurons in living zebrafish and documented robust vesicular fusion along axons during myelination. Surprisingly, we found that axonal vesicular fusion increased upon and required myelination. We found that axonal vesicular fusion was enriched in hotspots, namely the heminodal non-myelinated domains into which sheaths grew. Blocking vesicular fusion reduced the stable formation and growth of myelin sheaths, and chemogenetically stimulating neuronal activity promoted sheath growth. Finally, we observed high levels of axonal vesicular fusion only in neuronal subtypes that exhibit activity-regulated myelination. Our results identify a novel "feedforward" mechanism whereby the process of myelination promotes the neuronal activity-regulated signal, vesicular fusion that, in turn, consolidates sheath growth along specific axons selected for myelination

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Preference for novel faces in male infant monkeys predicts cerebrospinal fluid oxytocin concentrations later in life

The ability to recognize individuals is a critical skill acquired early in life for group living species. In primates, individual recognition occurs predominantly through face discrimination. Despite the essential adaptive value of this ability, robust individual differences in conspecific face recognition exist, yet its associated biology remains unknown. Although pharmacological administration of oxytocin has implicated this neuropeptide in face perception and social memory, no prior research has tested the relationship between individual differences in face recognition and endogenous oxytocin concentrations. Here we show in a male rhesus monkey cohort (N = 60) that infant performance in a task used to determine face recognition ability (specifically, the ability of animals to show a preference for a novel face) robustly predicts cerebrospinal fluid, but not blood, oxytocin concentrations up to five years after behavioural assessment. These results argue that central oxytocin biology may be related to individual face perceptual abilities necessary for group living, and that these differences are stable traits

Control of bovine mastitis: old and recent therapeutic approaches

Mastitis is defined as the inflammatory response resulting of the infection of the udder tissue and it is reported in numerous species, namely in domestic dairy animals. This pathology is the most frequent disease of dairy cattle and can be potentially fatal. Mastitis is an economically important pathology associated with reduced milk production, changes in milk composition and quality, being considered one of the most costly to dairy industry. Therefore, the majority of research in the field has focused on control of bovine mastitis and many efforts are being made for the development of new and effective anti-mastitis drugs. Antibiotic treatment is an established component of mastitis control programs; however, the continuous search for new therapeutic alternatives, effective in the control and treatment of bovine mastitis, is urgent. This review will provide an overview of some conventional and emerging approaches in the management of bovine mastitis infections.F. Gomes acknowledge the financial support of the Portuguese Foundation for Science and Technology through the Grant SFRH/BPD/84488/2012 and for financial support to the CEB research center

New Caledonian crows rapidly solve a collaborative problem without cooperative cognition

There is growing comparative evidence that the cognitive bases of cooperation are not unique to humans. However, the selective pressures that lead to the evolution of these mechanisms remain unclear. Here we show that while tool-making New Caledonian crows can produce collaborative behavior, they do not understand the causality of cooperation nor show sensitivity to inequity. Instead, the collaborative behavior produced appears to have been underpinned by the transfer of prior experience. These results suggest that a number of possible selective pressures, including tool manufacture and mobbing behaviours, have not led to the evolution of cooperative cognition in this species. They show that causal cognition can evolve in a domain specific manner-understanding the properties and flexible uses of physical tools does not necessarily enable animals to grasp that a conspecific can be used as a social tool

Benefits of a ball and chain: simple environmental enrichments improve welfare and reproductive success in farmed American mink (Neovison vison)

Can simple enrichments enhance caged mink welfare? Pilot data from 756 sub-adults spanning three colour-types (strains) identified potentially practical enrichments, and suggested beneficial effects on temperament and fur-chewing. Our main experiment started with 2032 Black mink on three farms: from each of 508 families, one juvenile male-female pair was enriched (E) with two balls and a hanging plastic chain or length of hose, while a second pair was left as a non-enriched (NE) control. At 8 months, more than half the subjects were killed for pelts, and 302 new females were recruited (half enriched: ‘late E’). Several signs of improved welfare or productivity emerged. Access to enrichment increased play in juveniles. E mink were calmer (less aggressive in temperament tests; quieter when handled; less fearful, if male), and less likely to fur-chew, although other stereotypic behaviours were not reduced. On one farm, E females had lower cortisol (inferred from faecal metabolites). E males tended to copulate for longer. E females also weaned more offspring: about 10% more juveniles per E female, primarily caused by reduced rates of barrenness (‘late E’ females also giving birth to bigger litters on one farm), effects that our data cautiously suggest were partly mediated by reduced inactivity and changes in temperament. Pelt quality seemed unaffected, but E animals had cleaner cages. In a subsidiary side-study using 368 mink of a second colour-type (‘Demis’), similar temperament effects emerged, and while E did not reduce fur-chewing or improve reproductive success in this colour-type, E animals were judged to have better pelts. Overall, simple enrichments were thus beneficial. These findings should encourage welfare improvements on fur farms (which house 60-70 million mink p.a.) and in breeding centres where endangered mustelids (e.g. black-footed ferrets) often reproduce poorly. They should also stimulate future research into more effective practical enrichments

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta