In an increasing number of states and countries, cannabis now stands poised to join alcohol and tobacco as a legal drug. Quantifying the relative adverse and beneficial effects of cannabis and its ...constituent cannabinoids should therefore be prioritized. Whereas newspaper headlines have focused on links between cannabis and psychosis, less attention has been paid to the much more common problem of cannabis addiction. Certain cognitive changes have also been attributed to cannabis use, although their causality and longevity are fiercely debated. Identifying why some individuals are more vulnerable than others to the adverse effects of cannabis is now of paramount importance to public health. Here, we review the current state of knowledge about such vulnerability factors, the variations in types of cannabis, and the relationship between these and cognition and addiction.
We present a high-performance event reconstruction algorithm: an Image Pixel-wise fit for Atmospheric Cherenkov Telescopes (ImPACT). The reconstruction algorithm is based around the likelihood ...fitting of camera pixel amplitudes to an expected image template. A maximum likelihood fit is performed to find the best-fit shower parameters. A related reconstruction algorithm has already been shown to provide significant improvements over traditional reconstruction for both the CAT and H.E.S.S. experiments. We demonstrate a significant improvement to the template generation step of the procedure, by the use of a full Monte Carlo air shower simulation in combination with a ray-tracing optics simulation to more accurately model the expected camera images. This reconstruction step is combined with an MVA-based background rejection.
Examples are shown of the performance of the ImPACT analysis on both simulated and measured (from a strong VHE source) gamma-ray data from the H.E.S.S. array, demonstrating an improvement in sensitivity of more than a factor two in observation time over traditional image moments-fitting methods, with comparable performance to previous likelihood fitting analyses. ImPACT is a particularly promising approach for future large arrays such as the Cherenkov Telescope Array (CTA) due to its improved high-energy performance and suitability for arrays of mixed telescope types.
ABSTRACT
The use of acoustic Doppler current profilers (ADCP) for discharge measurements and three‐dimensional flow mapping has increased rapidly in recent years and has been primarily driven by ...advances in acoustic technology and signal processing. Recent research has developed a variety of methods for processing data obtained from a range of ADCP deployments and this paper builds on this progress by describing new software for processing and visualizing ADCP data collected along transects in rivers or other bodies of water. The new utility, the Velocity Mapping Toolbox (VMT), allows rapid processing (vector rotation, projection, averaging and smoothing), visualization (planform and cross‐section vector and contouring), and analysis of a range of ADCP‐derived datasets. The paper documents the data processing routines in the toolbox and presents a set of diverse examples that demonstrate its capabilities. The toolbox is applicable to the analysis of ADCP data collected in a wide range of aquatic environments and is made available as open‐source code along with this publication. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
A total of 360 Ross 708 male broiler chicks were used in an 8 treatment and 9 replicate cage study to explore the influence of day-old chick weight on the efficacy of exogenous phytase. Treatments ...were arranged as a 2 × 4 factorial with the factors being diet (a positive (PC) and negative control (NC) varying in nutrient density fed without or with 2 concentrations of exogenous phytase) and chick weight (light; <38.5 g or heavy; >42 g). Chicks were sourced from the same breeder flock, with light and heavy chicks being selected from the naturally occurring heterogeneity in the population. The diets were corn-soybean meal based and the PC was formulated to meet the nutrient requirements of male broiler chicks. The NC was formulated to contain 120 kcal/kg, 0.5, 0.18, and 0.18% less apparent metabolizable energy (AME), crude protein (CP), calcium (Ca), and phosphorus (P), respectively, than the PC. Amino acid (AA) density in the NC was also reduced in line with the reduction in CP and the manufacturers’ recommendations for the effect of phytase on amino acid digestibility. Phytase at either 1,000 FYT/kg or 3,000 FYT/kg was added only to the NC to create a total of 4 diets. Water and mash feed were available ad libitum and were offered to 8 replicate cages, each containing 5 chicks. The experiment was conducted over a period of 3 wk and diets were offered in 2 phases (starter from d 1 to 10 and grower from d 11 to 21). Growth performance was monitored at the end of each diet phase and on d 21 ileal digesta were collected for estimation of apparent digestibility of energy (DE), nitrogen (N), Ca, P, dry matter (DM), and AA. There were no statistically significant interactions between diet and day-old chick weight for any of the measured parameters. Light chicks had significantly lower weight gain (approx. 5%) at both d 10 and d 21 compared with heavy chicks. This effect was principally associated with reduced feed intake and there was no significant effect of chick weight on feed conversion ratio (FCR). Chick weight had no effect on ileal nutrient digestibility. The reduction in nutrient density from the PC to the NC generated a significant reduction in weight gain (around 12%) and a significant increase in FCR (1.68 vs. 1.83). This effect was associated with a significant reduction in ileal DE (approximately 150 kcal/kg) and in the digestibility of several AA. Exogenous phytase significantly increased weight gain, reduced FCR and generated a significant increase in the ileal digestibility of energy, N, P, and several AA. Although chick weight and diet did not interact statistically, heavy chicks benefited more than light chicks from high doses of exogenous phytase across almost all measured end points which was confirmed by regression analysis. In conclusion, light chicks have inferior performance outcomes than heavy chicks principally because of reduced feed intake, but putatively not in digestive capacity per se. Exogenous phytase is effective in improving performance and nutrient digestibility in nutrient deficient diets. The effect of chick weight per se, and also breeder flock age, on the utility of supra-nutritional inclusion concentrations of exogenous phytase warrants further study.
Abstract The DNA Commission of the International Society of Forensic Genetics (ISFG) regularly publishes guidelines and recommendations concerning the application of DNA polymorphisms to the question ...of human identification. Previous recommendations published in 2000 addressed the analysis and interpretation of mitochondrial DNA (mtDNA) in forensic casework. While the foundations set forth in the earlier recommendations still apply, new approaches to the quality control, alignment and nomenclature of mitochondrial sequences, as well as the establishment of mtDNA reference population databases, have been developed. Here, we describe these developments and discuss their application to both mtDNA casework and mtDNA reference population databasing applications. While the generation of mtDNA for forensic casework has always been guided by specific standards, it is now well-established that data of the same quality are required for the mtDNA reference population data used to assess the statistical weight of the evidence. As a result, we introduce guidelines regarding sequence generation, as well as quality control measures based on the known worldwide mtDNA phylogeny, that can be applied to ensure the highest quality population data possible. For both casework and reference population databasing applications, the alignment and nomenclature of haplotypes is revised here and the phylogenetic alignment proffered as acceptable standard. In addition, the interpretation of heteroplasmy in the forensic context is updated, and the utility of alignment-free database searches for unbiased probability estimates is highlighted. Finally, we discuss statistical issues and define minimal standards for mtDNA database searches.
Persistency of organic chemicals is a key property in their environmental risk assessment. Information on persistency is often derived from the results of biodegradability screening tests such as the ...ready biodegradability tests (RBTs). RBTs are, however, not designed for this purpose and suffer from several problems that lead to a high variability of the results and, hence, to difficulties in their interpretation. The origin and exposure history of the inocula used for biodegradability testing can lead to highly variable outcomes. Microbial adaptation to chemicals and its impact on biodegradation needs further investigation in order to have a better understanding of their effects on persistency assessments of chemicals. It is well described that microbial adaptation stimulates biodegradation of organic chemicals. Several mechanisms responsible for these phenomena have been described, amongst which are i) shifts in community composition or abundances, ii) mutations within populations, iii) horizontal gene transfer or iv) recombination events. These adaptation processes may well be mimicked under laboratory conditions, but the outcome remains difficult to predict as we lack a fundamental understanding of the adaptive responses. This review aims to bring together our current knowledge regarding microbial adaptation and its implication for the testing of biodegradation of chemicals.
Abstract Background Patients with potentially curative oesophago-gastric cancer typically undergo neo-adjuvant chemotherapy prior to surgery. The majority of anti-cancer drugs have a narrow ...therapeutic index. The aim of this study was to determine if features of body composition, assessed using computed tomography (CT) scans, may be predictive of dose-limiting toxicity (DLT) in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer. The influence of sarcopenia and DLT on overall survival was also evaluated. Methods 89 Patients having potentially curative oesophago-gastric cancer surgery were studied. Patients studied had histologically confirmed oesophago-gastric cancer with no evidence of distant metastasis on pre-operative staging. CT scan was performed in all cases at diagnosis. DLT was defined as toxicity leading to postponement of treatment, a drug dose reduction or definitive interruption of drug administration. Results DLT occurred in 37 out of 89 patients (41.6%) undergoing chemotherapy. Sarcopenia (odds ratio, 2.95; 95% confidence interval, 1.23–7.09; p = 0.015) was associated with DLT on multivariate analysis. Median overall survival for patients who were sarcopenic was 569 days (IQ range: 357–1230 days) vs. 1013 days (IQ range: 496–1318 days) for patients who were not sarcopenic ( p = 0.04). There was no significant difference in overall survival in patients who experienced DLT compared with those that did not ( p = 0.665). Conclusions Sarcopenia is a significant predictor of DLT in oesophago-gastric cancer patients undergoing neo-adjuvant chemotherapy. These results raise the potential for use of assessment of skeletal muscle mass using CT scans to predict toxicity and individualize chemotherapy dosing.
Human activity is drastically altering the habitat use of natural populations. This has been documented as a driver of phenotypic divergence in a number of wild animal populations. Here, we show that ...urban and rural populations of red foxes (
Vulpes vulpes
) from London and surrounding boroughs are divergent in skull traits. These changes are primarily found to be involved with snout length, with urban individuals tending to have shorter and wider muzzles relative to rural individuals, smaller braincases and reduced sexual dimorphism. Changes were widespread and related to muscle attachment sites and thus are likely driven by differing biomechanical demands of feeding or cognition between habitats. Through extensive sampling of the genus
Vulpes
, we found no support for phylogenetic effects on skull morphology, but patterns of divergence found between urban and rural habitats in
V. vulpes
quantitatively aligned with macroevolutionary divergence between species. The patterns of skull divergence between urban and rural habitats matched the description of morphological changes that can occur during domestication. Specifically, urban populations of foxes show variation consistent with ‘domestication syndrome’. Therefore, we suggest that occurrences of phenotypic divergence in relation to human activity, while interesting themselves, also have the potential to inform us of the conditions and mechanisms that could initiate domestication. Finally, this also suggests that patterns of domestication may be developmentally biased towards larger patterns of interspecific divergence.
Despite successful control efforts in China over the past 60 years, zoonotic schistosomiasis caused by Schistosoma japonicum remains a threat with transmission ongoing and the risk of localised ...resurgences prompting calls for a novel integrated control strategy, with an anti-schistosome vaccine as a core element. Anti-schistosome vaccine development and immunisation attempts in non-human mammalian host species, intended to interrupt transmission, and utilising various antigen targets, have yielded mixed success, with some studies highlighting variation in schistosome antigen coding genes (ACGs) as possible confounders of vaccine efficacy. Thus, robust selection of target ACGs, including assessment of their genetic diversity and antigenic variability, is paramount. Tetraspanins (TSPs), a family of tegument-surface antigens in schistosomes, interact directly with the host's immune system and are promising vaccine candidates. Here, for the first time to our knowledge, diversity in S. japonicum TSPs (SjTSPs) and the impact of diversifying selection and sequence variation on immunogenicity in these protiens were evaluated.
SjTSP sequences, representing parasite populations from seven provinces across China, were gathered by baiting published short-read NGS data and were analysed using in silico methods to measure sequence variation and selection pressures and predict the impact of selection on variation in antigen protein structure, function and antigenic propensity.
Here, 27 SjTSPs were identified across three subfamilies, highlighting the diversity of TSPs in S. japonicum. Considerable variation was demonstrated for several SjTSPs between geographical regions/provinces, revealing that episodic, diversifying positive selection pressures promote amino acid variation/variability in the large extracellular loop (LEL) domain of certain SjTSPs. Accumulating polymorphisms in the LEL domain of SjTSP-2, -8 and -23 led to altered structural, functional and antibody binding characteristics, which are predicted to impact antibody recognition and possibly blunt the host's ability to respond to infection. Such changes, therefore, appear to represent a mechanism utilised by S. japonicum to evade the host's immune system.
Whilst the genetic and antigenic geographic variability observed amongst certain SjTSPs could present challenges to vaccine development, here we demonstrate conservation amongst SjTSP-1, -13 and -14, revealing their likely improved utility as efficacious vaccine candidates. Importantly, our data highlight that robust evaluation of vaccine target variability in natural parasite populations should be a prerequisite for anti-schistosome vaccine development.
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