Eight weeks of supplementation with a multi-ingredient weight loss product enhances body composition, reduces hip and waist girth, and increases energy levels in overweight men and women

Background: Numerous natural products are marketed and sold claiming to decrease body weight and fat, but few undergo finished product-specific research demonstrating their safety and efficacy. Objective: To determine the safety and efficacy of a multi-ingredient supplement containing primarily raspberry ketone, caffeine, capsaicin, garlic, ginger and Citrus aurantium (Prograde Metabolism™ [METABO]) as an adjunct to an eight-week weight loss program. Methods: Using a randomized, placebo-controlled, double-blind design, 70 obese but otherwise healthy subjects were randomly assigned to METABO or a placebo and underwent 8 weeks of daily supplementation, a calorie restricted diet, and exercise training. Subjects were tested for changes in body composition, serum adipocytokines (adiponectin, resistin, leptin, TNF-α, IL-6) and markers of health including heart rate and blood pressure. Results: Of the 45 subjects who completed the study, significant differences were observed in: body weight (METABO -2.0% vs. placebo -0.5%, P < 0.01), fat mass (METABO -7.8 vs. placebo -2.8%, P < 0.001), lean mass (METABO +3.4% vs. placebo +0.8%, P < 0.03), waist girth (METABO -2.0% vs. placebo -0.2%, P < 0.0007), hip girth (METABO -1.7% vs. placebo -0.4%, P < 0.003), and energy levels per anchored visual analogue scale (VAS) (METABO +29.3% vs. placebo +5.1%, P < 0.04). During the first 4 weeks, effects/trends for maintaining elevated serum leptin (P < 0.03) and decreased serum resistin (P < 0.08) in the METABO group vs. placebo were also observed. No changes in systemic hemodynamics, clinical blood chemistries, adverse events, or dietary intake were noted between groups. Conclusions: METABO administration is a safe and effective adjunct to an eight-week diet and exercise weight loss program by augmenting improvements in body composition, waist and hip girth. Adherence to the eight-week weight loss program also led to beneficial changes in body fat in placebo. Ongoing studies to confirm these results and clarify the mechanisms (i.e., biochemical and neuroendocrine mediators) by which METABO exerts the observed salutary effects are being conducted. Keywords: Dietary supplement; Raspberry ketone; Adipokine; Body composition; Fat loss; Capsaici

Measurement of the directional sensitivity of Dark Matter Time Projection Chamber detectors

The Dark Matter Time Projection Chamber (DMTPC) is a direction-sensitive detector designed to measure the direction of recoiling $^{19}$F and $^{12}$C nuclei in low-pressure CF$_4$ gas using optical and charge readout systems. In this paper, we employ measurements from two DMTPC detectors, with operating pressures of 30-60 torr, to develop and validate a model of the directional response and performance of such detectors as a function of recoil energy. Using our model as a benchmark, we formulate the necessary specifications for a scalable directional detector with sensitivity comparable to that of current-generation counting (non-directional) experiments, which measure only recoil energy. Assuming the performance of existing DMTPC detectors, as well as current limits on the spin-dependent WIMP-nucleus cross section, we find that a 10-20 kg scale direction-sensitive detector is capable of correlating the measured direction of nuclear recoils with the predicted direction of incident dark matter particles and providing decisive (3$\sigma$) confirmation that a candidate signal from a non-directional experiment was indeed induced by elastic scattering of dark matter particles off of target nuclei.Comment: 13 pages, 10 figures. Accepted for publication in Phys. Rev. D. Added color figures, switched to more compact layout, and fixed some reference

Dark Matter Time Projection Chamber : Recent R&D Results

The Dark Matter Time Projection Chamber collaboration recently reported a dark matter limit obtained with a 10 liter time projection chamber filled with CF[subscript 4] gas. The 10 liter detector was capable of 2D tracking (perpendicular to the drift direction) and 2D fiducialization, and only used information from two CCD cameras when identifying tracks and rejecting backgrounds. Since that time, the collaboration has explored the potential benefits of photomultiplier tube and electronic charge readout to achieve 3D tracking, and particle identification for background rejection. The latest results of this effort is described here

Comparative UAV and field phenotyping to assess yield and nitrogen use efficiency in hibrid and conventional barley

With the commercialization and increasing availability of Unmanned Aerial Vehicles (UAVs) multiple rotor copters have expanded rapidly in plant phenotyping studies with their ability to provide clear, high resolution images. As such, the traditional bottleneck of plant phenotyping has shifted from data collection to data processing. Fortunately, the necessarily controlled and repetitive design of plant phenotyping allows for the development of semi-automatic computer processing tools that may sufficiently reduce the time spent in data extraction. Here we present a comparison of UAV and field based high throughput plant phenotyping (HTPP) using the free, open-source image analysis software FIJI (Fiji is just ImageJ) using RGB (conventional digital cameras), multispectral and thermal aerial imagery in combination with a matching suite of ground sensors in a study of two hybrids and one conventional barely variety with ten different nitrogen treatments, combining different fertilization levels and application schedules. A detailed correlation network for physiological traits and exploration of the data comparing between treatments and varieties provided insights into crop performance under different management scenarios. Multivariate regression models explained 77.8, 71.6, and 82.7% of the variance in yield from aerial, ground, and combined data sets, respectively

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Association of Gangrenous, Suppurative, and Exudative Findings With Outcomes and Resource Utilization in Children With Nonperforated Appendicitis.

IMPORTANCE: The clinical significance of gangrenous, suppurative, or exudative (GSE) findings is poorly characterized in children with nonperforated appendicitis. OBJECTIVE: To evaluate whether GSE findings in children with nonperforated appendicitis are associated with increased risk of surgical site infections and resource utilization. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study used data from the Appendectomy Targeted Database of the American College of Surgeons Pediatric National Surgical Quality Improvement Program, which were augmented with operative report data obtained by supplemental medical record review. Data were obtained from 15 hospitals participating in the Eastern Pediatric Surgery Network (EPSN) research consortium. The study cohort comprised children (aged ≤18 years) with nonperforated appendicitis who underwent appendectomy from July 1, 2015, to June 30, 2020. EXPOSURES: The presence of GSE findings was established through standardized, keyword-based audits of operative reports by EPSN surgeons. Interrater agreement for the presence or absence of GSE findings was evaluated in a random sample of 900 operative reports. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day postoperative surgical site infections (incisional and organ space infections). Secondary outcomes included rates of hospital revisits, postoperative abdominal imaging, and postoperative length of stay. Multivariable mixed-effects regression was used to adjust measures of association for patient characteristics and clustering within hospitals. RESULTS: Among 6133 children with nonperforated appendicitis, 867 (14.1%) had GSE findings identified from operative report review (hospital range, 4.2%-30.2%; P \u3c .001). Reviewers agreed on presence or absence of GSE findings in 93.3% of cases (weighted κ, 0.89; 95% CI, 0.86-0.92). In multivariable analysis, GSE findings were associated with increased odds of any surgical site infection (4.3% vs 2.2%; odds ratio [OR], 1.91; 95% CI, 1.35-2.71; P \u3c .001), organ space infection (2.8% vs 1.1%; OR, 2.18; 95% CI, 1.30-3.67; P = .003), postoperative imaging (5.8% vs 3.7%; OR, 1.70; 95% CI, 1.23-2.36; P = .002), and prolonged mean postoperative length of stay (1.6 vs 0.9 days; rate ratio, 1.43; 95% CI, 1.32-1.54; P \u3c .001). CONCLUSIONS AND RELEVANCE: In children with nonperforated appendicitis, findings of gangrene, suppuration, or exudate are associated with increased surgical site infections and resource utilization. Further investigation is needed to establish the role and duration of postoperative antibiotics and inpatient management to optimize outcomes in this cohort of children

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Exoplanet Science Priorities from the Perspective of Internal and Surface Processes for Silicate and Ice Dominated Worlds

The geophysics of extrasolar planets is a scientific topic often regarded as standing largely beyond the reach of near-term observations. This reality in no way diminishes the central role of geophysical phenomena in shaping planetary outcomes, from formation, to thermal and chemical evolution, to numerous issues of surface and near-surface habitability. We emphasize that for a balanced understanding of extrasolar planets, it is important to look beyond the natural biases of current observing tools, and actively seek unique pathways to understand exoplanet interiors as best as possible during the long interim prior to a time when internal components are more directly accessible. Such pathways include but are not limited to: (a) enhanced theoretical and numerical modeling, (b) laboratory research on critical material properties, (c) measurement of geophysical properties by indirect inference from imprints left on atmospheric and orbital properties, and (d) the purpose-driven use of Solar System object exploration expressly for its value in comparative planetology toward exoplanet-analogs. Breaking down barriers that envision local Solar System exploration, including the study of Earth's own deep interior, as separate from and in financial competition with extrasolar planet research, may greatly improve the rate of needed scientific progress for exoplanet geophysics. As the number of known rocky and icy exoplanets grows in the years ahead, we expect demand for expertise in 'exogeoscience' will expand at a commensurately intense pace. We highlight key topics, including: how water oceans below ice shells may dominate the total habitability of our galaxy by volume, how free-floating nomad planets may often attain habitable subsurface oceans supported by radionuclide decay, and how deep interiors may critically interact with atmospheric mass loss via dynamo-driven magnetic fields

DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency.

During genome replication, polymerase epsilon (Pol ε) acts as the major leading-strand DNA polymerase. Here we report the identification of biallelic mutations in POLE, encoding the Pol ε catalytic subunit POLE1, in 15 individuals from 12 families. Phenotypically, these individuals had clinical features closely resembling IMAGe syndrome (intrauterine growth restriction [IUGR], metaphyseal dysplasia, adrenal hypoplasia congenita, and genitourinary anomalies in males), a disorder previously associated with gain-of-function mutations in CDKN1C. POLE1-deficient individuals also exhibited distinctive facial features and variable immune dysfunction with evidence of lymphocyte deficiency. All subjects shared the same intronic variant (c.1686+32C>G) as part of a common haplotype, in combination with different loss-of-function variants in trans. The intronic variant alters splicing, and together the biallelic mutations lead to cellular deficiency of Pol ε and delayed S-phase progression. In summary, we establish POLE as a second gene in which mutations cause IMAGe syndrome. These findings add to a growing list of disorders due to mutations in DNA replication genes that manifest growth restriction alongside adrenal dysfunction and/or immunodeficiency, consolidating these as replisome phenotypes and highlighting a need for future studies to understand the tissue-specific development roles of the encoded proteins