Exploring aspects of scientific publishing in astrophysics and cosmology: the views of scientists

Abstract Scientists in astrophysics and cosmology make much use of the arXiv repository. Concerns raised by scientists in those fields about publication costs and delays, and the transparency and validity of the peer review process, raised questions about levels of satisfaction with existing publishing models. This paper discusses the results from a community survey in the fields of astrophysics and cosmology, conducted as part of an investigation into the feasibility of an "overlay journal" model in these disciplines. Six hundred and eighty three (683) researchers provided information about their academic/research background, their research practices, and their attitudes, both as producers and consumers of information, to the traditional journal publishing system, and gave their reaction to the overlay publication model. The survey results indicate that scientists in these disciplines are, in general, favourably disposed towards new publishing models, although some important caveats and concerns, particularly regarding quality, were highlighted

UCL Press: The UK’s first fully open access university press

Delivered at the University of Cambridge as part of Open Access Week 201

NGX-4010, a capsaicin 8% patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: integrated analysis of two phase III, randomized, controlled trials

BACKGROUND HIV-associated distal sensory polyneuropathy (HIV-DSP) is the most frequently reported neurologic complication associated with HIV infection. NGX-4010 is a capsaicin 8% dermal patch with demonstrated efficacy in the treatment of HIV-DSP. Data from two phase III, double-blind studies were integrated to further analyze the efficacy and safety of NGX-4010 and explore the effect of demographic and baseline factors on NGX-4010 treatment in HIV-DSP. METHODS Data from two similarly designed studies in which patients with HIV-DSP received NGX-4010 or a low-concentration control patch (capsaicin 0.04% w/w) for 30 or 60 minutes were integrated. Efficacy assessments included the mean percent change from baseline in Numeric Pain Rating Scale (NPRS) scores to Weeks 2-12. Safety and tolerability assessments included adverse events (AEs) and pain during and after treatment. RESULTS Patients (n = 239) treated with NGX-4010 for 30 minutes demonstrated significantly (p = 0.0026) greater pain relief compared with controls (n = 100); the mean percent change in NPRS scores from baseline to Weeks 2-12 was -27.0% versus -15.7%, respectively. Patients who received a 60-minute application of NGX-4010 (n = 243) showed comparable pain reductions (-27.5%) to patients treated for 30 minutes, but this was not statistically superior to controls (n = 115). NGX-4010 was effective regardless of gender, baseline pain score, duration of HIV-DSP, or use of concomitant neuropathic pain medication, although NGX-4010 efficacy was greater in patients not receiving concomitant neuropathic pain medications. NGX-4010 was well tolerated; the most common AEs were application-site pain and erythema, and most AEs were mild to moderate. The transient increase in pain associated with NGX-4010 treatment decreased the day after treatment and returned to baseline by Day 2. CONCLUSIONS A single 30-minute application of NGX-4010 provides significant pain relief for at least 12 weeks in patients with HIV-DSP and is well tolerated. TRIAL REGISTRATION C107 = NCT00064623; C119 = NCT00321672

Associations between facial expressions and observational pain in residents with dementia and chronic pain

AimTo identify specific facial expressions associated with pain behaviors using the PainChek application in residents with dementia.DesignThis is a secondary analysis from a study exploring the feasibility of PainChek to evaluate the effectiveness of a social robot (PARO) intervention on pain for residents with dementia from June to November 2021.MethodsParticipants experienced PARO individually five days per week for 15 min (once or twice) per day for three consecutive weeks. The PainChek app assessed each resident's pain levels before and after each session. The association between nine facial expressions and the adjusted PainChek scores was analyzed using a linear mixed model.ResultsA total of 1820 assessments were completed with 46 residents. Six facial expressions were significantly associated with a higher adjusted PainChek score. Horizontal mouth stretch showed the strongest association with the score, followed by brow lowering parting lips, wrinkling of the nose, raising of the upper lip and closing eyes. However, the presence of cheek raising, tightening of eyelids and pulling at the corner lip were not significantly associated with the score. Limitations of using the PainChek app were identified.ConclusionSix specific facial expressions were associated with observational pain scores in residents with dementia. Results indicate that automated real-time facial analysis is a promising approach to assessing pain in people with dementia. However, it requires further validation by human observers before it can be used for decision-making in clinical practice.ImpactPain is common in people with dementia, while assessing pain is challenging in this group. This study generated new evidence of facial expressions of pain in residents with dementia. Results will inform the development of valid artificial intelligence-based algorithms that will support healthcare professionals in identifying pain in people with dementia in clinical situations.Reporting MethodThe study adheres to the CONSORT reporting guidelines.Patient or Public ContributionOne resident with dementia and two family members of people with dementia were consulted and involved in the study design, where they provided advice on the protocol, information sheets and consent forms, and offered valuable insights to ensure research quality and relevance

High Levels of Genetic Divergence Detected in Sacramento Perch Suggests Two Divergent Translocation Sources

Translocation has been used to conserve imperiled fishes and create new fisheries. One species for which translocation has played a significant role is the Sacramento Perch Archoplites interruptus. Extirpated from its native range, the Sacramento Perch has been introduced throughout California and Nevada through multiple translocation events, though historical records are incomplete. Recent assessments of eight previously uncharacterized Sacramento Perch populations have prompted reevaluation of range-wide population structure to inform a genetic management plan for long-term resiliency of this species. We examined Sacramento Perch genetic diversity and population structure across the current range of the species using 12 microsatellite markers. We analyzed samples from the eight uncharacterized populations and seven populations previously studied by Schwartz and May (2008). Bayesian clustering supported two distinct clusters of Sacramento Perch herein designated as A and B. Within these two clusters we detected hierarchical substructure, likely due to genetic drift after population founding. Genetic differentiation among populations within the same cluster was relatively low (FST = 0.023–0.176), while differentiation among populations from different clusters was higher (FST = 0.190–0.320). The existence of two strongly divergent genetic clusters in Sacramento Perch suggests two distinct translocation sources, and we recommend that these clusters be treated as genetic management units (GMUs). The B GMU populations had fairly low levels of genetic diversity relative to the A GMU populations. All populations showed evidence of past bottlenecks, and most had effective population sizes placing them at risk for inbreeding depression. Human-facilitated gene flow is recommended to prevent further genetic diversity loss. Due to uncertainty surrounding Sacramento Perch translocation history and strong levels of divergence between the two GMUs, translocations should be facilitated only between populations within the same GMU

Effects of estrogens and estrogenic disrupting compounds on fish mineralized tissues

Estrogens play well-recognized roles in reproduction across vertebrates, but also intervene in a wide range of other physiological processes, including mineral homeostasis. Classical actions are triggered when estrogens bind and activate intracellular estrogen receptors (ERs), regulating the transcription of responsive genes, but rapid non-genomic actions initiated by binding to plasma membrane receptors were recently described. A wide range of structurally diverse compounds from natural and anthropogenic sources have been shown to interact with and disrupt the normal functions of the estrogen system, and fish are particularly vulnerable to endocrine disruption, as these compounds are frequently discharged or run-off into waterways. The effect of estrogen disruptors in fish has mainly been assessed in relation to reproductive endpoints, and relatively little attention has been given to other disruptive actions. This review will overview the actions of estrogens in fish, including ER isoforms, their expression, structure and mechanisms of action. The estrogen functions will be considered in relation to mineral homeostasis and actions on mineralized tissues. The impact of estrogenic endocrine disrupting compounds on fish mineralized tissues will be reviewed, and the potential adverse outcomes of exposure to such compounds will be discussed. Current lacunae in knowledge are highlighted along with future research priorities.Foundation for Science and Technology of Portugal (FCT) [PTDC/AAG-GLO/4003/2012, PEst-C/MAR/LA0015/2011, SFRH/BPD/25247/2005]info:eu-repo/semantics/publishedVersio

Cobicistat Versus Ritonavir as a Pharmacoenhancer of Atazanavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-Naive HIV Type 1-Infected Patients: Week 48 Results

Background. Cobicistat (COBI) is a pharmacoenhancer with no antiretroviral activity in vitro. Methods. An international, randomized, double-blind, double-dummy, active-controlled trial was conducted to evaluate the efficacy and safety of COBI versus ritonavir (RTV) as a pharmacoenhancer of atazanavir (ATV) in combination with emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) in treatment-naive patients. The primary end point was a human immunodeficiency virus type 1 (HIV-1) RNA load of 100 000 copies/mL, rates were similar (86% vs 86%). Similar percentages of patients in both groups had serious adverse events (10% of COBI recipients vs 7% of RTV recipients) and adverse events leading to discontinuation of treatment with the study drug (7% vs 7%). Median increases in the serum creatinine level were 0.13 and 0.09 mg/dL, respectively, for COBI and RTV recipients. Conclusions. COBI was noninferior to RTV in combination with ATV plus FTC/TDF at week 48. Both regimens achieved high rates of virologic success. Safety and tolerability profiles of the 2 regimens were comparable. Once-daily COBI is a safe and effective pharmacoenhancer of the protease inhibitor ATV. Clinical Trials Registration. NCT0110851

Weight evolution in HIV-1 infected women in Rwanda after stavudine substitution due to lipoatrophy: comparison of zidovudine with tenofovir/abacavir.

This cohort study was conducted amongst female patients manifesting lipoatrophy while receiving stavudine-containing first-line antiretroviral treatment regimens at two urban health centres in Rwanda. The objectives were to assess weight evolution after stavudine substitution and to describe any significant difference in weight evolution when zidovudine or tenofovir/abacavir was used for substitution. All adult patients on stavudine-containing first-line regimens who developed lipoatrophy (diagnosed using a lipodystrophy case definition study-based questionnaire) and whose treatment regimen was changed were included (n=114). In the most severe cases stavudine was replaced with tenofovir or abacavir (n=39), and in the remainder with zidovudine (n=75). For patients changed to zidovudine a progressive weight loss was seen, while those on tenofovir/abacavir showed a progressive weight increase from six months. The between-group difference in weight evolution was significant from nine months (difference at 12 months: 2.3kg, P=0.02). These differences were confirmed by follow-up lipoatrophy scores. In multivariate analysis, substitution with tenofovir/abacavir remained significantly associated with weight gain. This is the first study in Africa assessing weight gain as a proxy for recovery after stavudine substitution due to lipoatrophy, providing supporting evidence that tenofovir/abacavir is superior to zidovudine. The weight loss with zidovudine might justify earlier substitution and access to better alternatives like tenofovir/abacavir

Persistence of lipoatrophy after a four-year long interruption of antiretroviral therapy for HIV1 infection: case report

BACKGROUND: HIV-infected patients on long-term highly active antiretroviral therapy often present peculiar patterns of fat redistribution, referred to as lipodystrophy. In spite of recent investigations, it is not known whether and to what extent the main features of lipodystrophy – that is lipoatrophy of peripheral fat at face, limbs and buttocks, as well as fat accumulation at breasts, abdomen and the dorso-cervical region – can be reversible once clinically manifest. CASE PRESENTATION: A 35 year old Caucasian HIV infected female developed severe diffuse lipodystrophy while on highly active antiretroviral therapy. A remarkable increase of breast size, fat accumulation at waist, and a fat pad on her lumbar spine were paralleled by progressive and disfiguring lipoatrophy of face, limbs and buttocks. The patient decided to interrupt her therapy after 20 months, with a stably suppressed viremia and a CD4 lymphocyte count >500/μL. She could carry on a safe treatment interruption for longer than 4 years. Most sites of fat accumulation switched to nearly normal appearance, whereas lipoatrophy was substantially unchanged at all affected sites. CONCLUSION: our observation provides pictorial evidence that lipoatrophy may not be reversible even under ideal circumstances. Therefore, strategies to prevent lipoatrophy should be considered when defining therapeutic regimens for HIV infected patients, especially those at high risk