Pharmacotherapies for Obesity: Past, Current, and Future Therapies

Past therapies for the treatment of obesity have typically involved pharmacological agents usually in combination with a calorie-controlled diet. This paper reviews the efficacy and safety of pharmacotherapies for obesity focusing on drugs approved for long-term therapy (orlistat), drugs approved for short-term use (amfepramone [diethylpropion], phentermine), recently withdrawn therapies (rimonabant, sibutamine) and drugs evaluated in Phase III studies (taranabant, pramlintide, lorcaserin and tesofensine and combination therapies of topiramate plus phentermine, bupropion plus naltrexone, and bupropion plus zonisamide). No current pharmacotherapy possesses the efficacy needed to produce substantial weight loss in morbidly obese patients. Meta-analyses support a significant though modest loss in bodyweight with a mean weight difference of 4.7 kg (95% CI 4.1 to 5.3 kg) for rimonabant, 4.2 kg (95% CI 3.6 to 4.8 kg) for sibutramine and 2.9 kg (95% CI 2.5 to 3.2 kg) for orlistat compared to placebo at ≥12 months. Of the Phase III pharmacotherapies, lorcaserin, taranabant, topiramate and bupropion with naltrexone have demonstrated significant weight loss compared to placebo at ≥12 months. Some pharmacotherapies have also demonstrated clinical benefits. Further studies are required in some populations such as younger and older people whilst the long term safety continues to be a major consideration and has led to the withdrawal of several drugs

Microscopy with ultraviolet surface excitation for rapid slide-free histology.

Histologic examination of tissues is central to the diagnosis and management of neoplasms and many other diseases, and is a foundational technique for preclinical and basic research. However, commonly used bright-field microscopy requires prior preparation of micrometre-thick tissue sections mounted on glass slides, a process that can require hours or days, that contributes to cost, and that delays access to critical information. Here, we introduce a simple, non-destructive slide-free technique that within minutes provides high-resolution diagnostic histological images resembling those obtained from conventional haematoxylin-and-eosin-histology. The approach, which we named microscopy with ultraviolet surface excitation (MUSE), can also generate shape and colour-contrast information. MUSE relies on ~280-nm ultraviolet light to restrict the excitation of conventional fluorescent stains to tissue surfaces, and it has no significant effects on downstream molecular assays (including fluorescence in situ hybridization and RNA-seq). MUSE promises to improve the speed and efficiency of patient care in both state-of-the-art and low-resource settings, and to provide opportunities for rapid histology in research

Wind Ensemble

Kennesaw State University School of Music presents Wind Ensemble.https://digitalcommons.kennesaw.edu/musicprograms/1626/thumbnail.jp

Comparative Population Genomics of African Montane Forest Mammals Support Population Persistence across a Climatic Gradient and Quaternary Climatic Cycles

The Eastern Afromontane biodiversity hotspot (EABH) has the highest concentration of biodiversity in tropical Africa, yet few studies have investigated recent historical diversification processes in EABH lineages. Herein, we analyze restriction-site associated DNA-sequences (RAD-Seq) to study recent historical processes in co-distributed mouse (Hylomyscus) and shrew (Sylvisorex) species complexes, with an aim to better determine how historical paleoenvironmental processes might have contributed to the EABH’s high diversity. We analyzed complete SNP matrices of \u3e 50,000 RAD loci to delineate populations, reconstruct the history of isolation and admixture, and discover geographic patterns of genetic partitioning. These analyses demonstrate that persistently unsuitable habitat may have isolated multiple populations distributed across montane habitat islands in the Itombwe Massif and Albertine Rift to the west as well as Mt Elgon and Kenyan Highlands to the east. We detected low genetic diversity in Kenyan Highland populations of both genera, consistent with smaller historical population sizes in this region. We additionally tested predictions that Albertine Rift populations are older and more persistently isolated compared to the Kenyan Highlands. Phylogenetic analyses support greater historical isolation among Albertine Rift populations of both shrews and mice compared to the Kenyan Highlands and suggest that there are genetically isolated populations from both focal genera in the Itombwe Massif, Democratic Republic of Congo. The Albertine Rift ecoregion has the highest mammalian tropical forest species richness per unit area on earth. Our results clearly support accelerating efforts to conserve this diversity

Fenitrothion: toxicokinetics and toxicologic evaluation in human volunteers.

An unblinded crossover study of fenitrothion 0.18 mg/kg/day [36 times the acceptable daily intake (ADI)] and 0.36 mg/kg/day (72 X ADI) administered as two daily divided doses for 4 days in 12 human volunteers was designed and undertaken after results from a pilot study. On days 1 and 4, blood and urine samples were collected for analysis of fenitrothion and its major metabolites, as well as plasma and red blood cell cholinesterase activities, and biochemistry and hematology examination. Pharmacokinetic parameters could only be determined at the higher dosage, as there were insufficient measurable fenitrothion blood levels at the lower dosage and the fenitrooxone metabolite could not be measured. There was a wide range of interindividual variability in blood levels, with peak levels achieved between 1 and 4 hr and a half-life for fenitrothion of 0.8-4.5 hr. Although based on the half-life, steady-state levels should have been achieved; the area under the curve (AUC)(0-12 hr) to AUC(0-(infinity) )ratio of 1:3 suggested accumulation of fenitrothion. There was no significant change in plasma or red blood cell cholinesterase activity with repeated dosing at either dosage level of fenitrothion, and there were no significant abnormalities detected on biochemical or hematologic monitoring

Gravitational Waves and Gamma-Rays from a Binary Neutron Star Merger: GW170817 and GRB 170817A

On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory. The probability of the near-simultaneous temporal and spatial observation of GRB 170817A and GW170817 occurring by chance is 5.0 × 10 -8 . We therefore confirm binary neutron star mergers as a progenitor of short GRBs. The association of GW170817 and GRB 170817A provides new insight into fundamental physics and the origin of short GRBs. We use the observed time delay of (+1.74±0.05)between GRB 170817A and GW170817 to: (i) constrain the difference between the speed of gravity and the speed of light to be between -3 × 10 -15 and +7 × 10 -16 times the speed of light, (ii) place new bounds on the violation of Lorentz invariance, (iii) present a new test of the equivalence principle by constraining the Shapiro delay between gravitational and electromagnetic radiation. We also use the time delay to constrain the size and bulk Lorentz factor of the region emitting the gamma-rays. GRB 170817A is the closest short GRB with a known distance, but is between 2 and 6 orders of magnitude less energetic than other bursts with measured redshift. A new generation of gamma-ray detectors, and subthreshold searches in existing detectors, will be essential to detect similar short bursts at greater distances. Finally, we predict a joint detection rate for the Fermi Gamma-ray Burst Monitor and the Advanced LIGO and Virgo detectors of 0.1-1.4 per year during the 2018-2019 observing run and 0.3-1.7 per year at design sensitivity

Participation as Post-Fordist Politics: Demos, New Labour, and Science Policy

In recent years, British science policy has seen a significant shift ‘from deficit to dialogue’ in conceptualizing the relationship between science and the public. Academics in the interdisciplinary field of Science and Technology Studies (STS) have been influential as advocates of the new public engagement agenda. However, this participatory agenda has deeper roots in the political ideology of the Third Way. A framing of participation as a politics suited to post-Fordist conditions was put forward in the magazine Marxism Today in the late 1980s, developed in the Demos thinktank in the 1990s, and influenced policy of the New Labour government. The encouragement of public participation and deliberation in relation to science and technology has been part of a broader implementation of participatory mechanisms under New Labour. This participatory program has been explicitly oriented toward producing forms of social consciousness and activity seen as essential to a viable knowledge economy and consumer society. STS arguments for public engagement in science have gained influence insofar as they have intersected with the Third Way politics of post-Fordism

Tweet valence, volume of abuse, and observers’ dark tetrad personality factors influence victim-blaming and the perceived severity of Twitter cyberabuse

Previous research into Twitter cyberabuse has yielded several findings: victim-blaming (VB) was influenced by victims’ initial tweet-valence; perceived severity (PS) was influenced independently by tweet valence and abuse volume; VB and PS were predicted by observer narcissism and psychopathy. However, this previous research was limited by its narrow focus on celebrity victims, and lack of consideration of observer sadism. The current study investigated 125 observers’ VB and PS perceptions of lay-user cyberabuse, and influence of observers’ Dark Tetrad scores (psychopathy, narcissism, Machiavellianism, sadism). We manipulated initial-tweet valence (negative, neutral, positive) and received abuse volume (low, high). Our results indicated that VB was highest following negative initial tweets; VB was higher following high-volume abuse. PS did not differ across initial-tweet valences; PS was greater following a high abuse volume. Regression analyses revealed that observer sadism predicted VB across initial-tweet valences; psychopathy predicted PS when initial tweets were ‘emotive’ (negative, positive), whereas Machiavellianism predicted PS when they were neutral. Our results show that perceptions of lay-user abuse are influenced interactively by victim-generated content and received abuse volume. Our current results contrast with perceptions of celebrity-abuse, which is mostly determined by victim-generated content. Findings are contextualised within the Warranting Theory of impression formation

Search for High-energy Neutrinos from Binary Neutron Star Merger GW170817 with ANTARES, IceCube, and the Pierre Auger Observatory

The Advanced LIGO and Advanced Virgo observatories recently discovered gravitational waves from a binary neutron star inspiral. A short gamma-ray burst (GRB) that followed the merger of this binary was also recorded by the Fermi Gamma-ray Burst Monitor (Fermi-GBM), and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory (INTEGRAL), indicating particle acceleration by the source. The precise location of the event was determined by optical detections of emission following the merger. We searched for high-energy neutrinos from the merger in the GeV-EeV energy range using the Antares, IceCube, and Pierre Auger Observatories. No neutrinos directionally coincident with the source were detected within ± 500 s around the merger time. Additionally, no MeV neutrino burst signal was detected coincident with the merger. We further carried out an extended search in the direction of the source for high-energy neutrinos within the 14 day period following the merger, but found no evidence of emission. We used these results to probe dissipation mechanisms in relativistic outflows driven by the binary neutron star merger. The non-detection is consistent with model predictions of short GRBs observed at a large off-axis angle

Childhood in Sociology and Society: The US Perspective

The field of childhood studies in the US is comprised of cross-disciplinary researchers who theorize and conduct research on both children and youth. US sociologists who study childhood largely draw on the childhood literature published in English. This article focuses on American sociological contributions, but notes relevant contributions from non-American scholars published in English that have shaped and fueled American research. This article also profiles the institutional support of childhood research in the US, specifically outlining the activities of the ‘Children and Youth’ Section of the American Sociological Association (ASA), and assesses the contributions of this area of study for sociology as well as the implications for an interdisciplinary field.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline