A real-time, quantitative PCR method using hydrolysis probes for the monitoring of Plasmodium falciparum load in experimentally infected human volunteers

Background: The accurate quantification of Plasmodium falciparum parasite numbers by PCR is an important tool for monitoring growth kinetics in subjects infected and subsequently treated with anti-malarial agents

Genome of the house fly, <i>Musca domestica</i> L., a global vector of diseases with adaptations to a septic environment

Background: Adult house flies, Musca domestica L., are mechanical vectors of more than 100 devastating diseases that have severe consequences for human and animal health. House fly larvae play a vital role as decomposers of animal wastes, and thus live in intimate association with many animal pathogens. Results: We have sequenced and analyzed the genome of the house fly using DNA from female flies. The sequenced genome is 691 Mb. Compared with Drosophila melanogaster, the genome contains a rich resource of shared and novel protein coding genes, a significantly higher amount of repetitive elements, and substantial increases in copy number and diversity of both the recognition and effector components of the immune system, consistent with life in a pathogen-rich environment. There are 146 P450 genes, plus 11 pseudogenes, in M. domestica, representing a significant increase relative to D. melanogaster and suggesting the presence of enhanced detoxification in house flies. Relative to D. melanogaster, M. domestica has also evolved an expanded repertoire of chemoreceptors and odorant binding proteins, many associated with gustation. Conclusions: This represents the first genome sequence of an insect that lives in intimate association with abundant animal pathogens. The house fly genome provides a rich resource for enabling work on innovative methods of insect control, for understanding the mechanisms of insecticide resistance, genetic adaptation to high pathogen loads, and for exploring the basic biology of this important pest. The genome of this species will also serve as a close out-group to Drosophila in comparative genomic studies

The governance of justice and internal security in Scotland: Between the Scottish independence referendum and British decisions on the EU

This article examines how the governance of justice and internal security in Scotland could be affected by the outcome of the Scottish independence referendum in September 2014. The article argues that it is currently impossible to equate a specific result in the referendum with a given outcome for the governance of justice and internal security in Scotland. This is because of the complexities of the current arrangements in that policy area and the existence of several changes that presently affect them and are outside the control of the government and of the people of Scotland. This article also identifies an important paradox. In the policy domain of justice and internal security, a ‘no’ vote could, in a specific set of circumstances, actually lead to more changes than a victory of the ‘yes’ camp

Population genomics of the critically endangered kākāpō

Summary The kākāpō is a flightless parrot endemic to New Zealand. Once common in the archipelago, only 201 individuals remain today, most of them descending from an isolated island population. We report the first genome-wide analyses of the species, including a high-quality genome assembly for kākāpō, one of the first chromosome-level reference genomes sequenced by the Vertebrate Genomes Project (VGP). We also sequenced and analyzed 35 modern genomes from the sole surviving island population and 14 genomes from the extinct mainland population. While theory suggests that such a small population is likely to have accumulated deleterious mutations through genetic drift, our analyses on the impact of the long-term small population size in kākāpō indicate that present-day island kākāpō have a reduced number of harmful mutations compared to mainland individuals. We hypothesize that this reduced mutational load is due to the island population having been subjected to a combination of genetic drift and purging of deleterious mutations, through increased inbreeding and purifying selection, since its isolation from the mainland ∼10,000 years ago. Our results provide evidence that small populations can survive even when isolated for hundreds of generations. This work provides key insights into kākāpō breeding and recovery and more generally into the application of genetic tools in conservation efforts for endangered species

Mutations in CRADD Result in Reduced Caspase-2-Mediated Neuronal Apoptosis and Cause Megalencephaly with a Rare Lissencephaly Variant.

Lissencephaly is a malformation of cortical development typically caused by deficient neuronal migration resulting in cortical thickening and reduced gyration. Here we describe a "thin" lissencephaly (TLIS) variant characterized by megalencephaly, frontal predominant pachygyria, intellectual disability, and seizures. Trio-based whole-exome sequencing and targeted re-sequencing identified recessive mutations of CRADD in six individuals with TLIS from four unrelated families of diverse ethnic backgrounds. CRADD (also known as RAIDD) is a death-domain-containing adaptor protein that oligomerizes with PIDD and caspase-2 to initiate apoptosis. TLIS variants cluster in the CRADD death domain, a platform for interaction with other death-domain-containing proteins including PIDD. Although caspase-2 is expressed in the developing mammalian brain, little is known about its role in cortical development. CRADD/caspase-2 signaling is implicated in neurotrophic factor withdrawal- and amyloid-β-induced dendritic spine collapse and neuronal apoptosis, suggesting a role in cortical sculpting and plasticity. TLIS-associated CRADD variants do not disrupt interactions with caspase-2 or PIDD in co-immunoprecipitation assays, but still abolish CRADD's ability to activate caspase-2, resulting in reduced neuronal apoptosis in vitro. Homozygous Cradd knockout mice display megalencephaly and seizures without obvious defects in cortical lamination, supporting a role for CRADD/caspase-2 signaling in mammalian brain development. Megalencephaly and lissencephaly associated with defective programmed cell death from loss of CRADD function in humans implicate reduced apoptosis as an important pathophysiological mechanism of cortical malformation. Our data suggest that CRADD/caspase-2 signaling is critical for normal gyration of the developing human neocortex and for normal cognitive ability

Implantable loop recorders can detect paroxysmal atrial fibrillation in Standardbred racehorses with intermittent poor performance

BACKGROUND: Limited information is available on paroxysmal atrial fibrillation (PAF) in the horse. Indeed, undiagnosed PAF could result in poor performance. Due to the intermittent occurrence, PAF is difficult to diagnose. However, implanting a small ECG device (implantable loop recorder, ILR) subcutaneously, allows the continuous and automatic detection of PAF. OBJECTIVES: The aim was to investigate the potential of ILRs as a tool for diagnosing PAF in horses with poor performance. STUDY DESIGN: Prospective field study. METHODS: Twelve racing Standardbred trotters with intermittent reduced performance (mean age: six years) were enrolled prospectively. The ILR was implanted subcutaneously at the fifth or sixth left intercostal space and data from the ILR was collected during the study period in which the horses were followed for a median duration of 7.5 month (range 6‐28). RESULTS: The ILR was able to detect PAF in four out of twelve racehorses. The ILR also detected sustained atrial fibrillation (AF) in one horse during the study. The ILRs rely on RR detection and R waves were correctly identified in 96%. One hundred episodes were categorised as AF by the ILRs and subsequently visual ECG inspection categorised 12 as sinus rhythm (SR), 28 as sinus arrhythmia (SA), 14 as other arrhythmias and 46 as AF episodes. The Root Mean Square of the Successive Differences (RMSSD) values were significantly increased for AF compared to SR and SA. MAIN LIMITATIONS: Few horses included and duration of study period varied among the horses. Further it was not possible to assess the sensitivity of the device in the current study and the ILRs proved to have a high rate of false positive misclassifications. CONCLUSIONS: This study indicates that ILRs can be used for detection of PAF episodes and could be a useful ECG tool for horses presenting with poor performance. This methodology provides a platform to facilitate the long‐term assessment of AF development and quantification of AF burden in horses. Further studies including both healthy and poor performing horses are needed in order to learn more about PAF prevalence in racehorses

Subterranean movement inferred by temporary emigration in Barton Springs salamanders (Eurycea sosorum)

Movement behavior is an important aspect of animal ecology but is challenging to study in species that are unobservable for some portion of their lives, such as those inhabiting subterranean environments. Using four years of robust-design capture-recapture data, we examined the probability of movement into subterranean habitat by a population of endangered Barton Springs salamanders (Eurycea sosorum), a species that inhabits both surface and subterranean groundwater habitats. We tested the effects of environmental variables and body size on survival and temporary emigration, using the latter as a measure of subterranean habitat use. Based on 2,046 observations of 1,578 individuals, we found that temporary emigration was higher for larger salamanders, 79% of which temporarily emigrated into subterranean habitat between primary sampling intervals, on average. Body size was a better predictor of temporary emigration and survival compared to environmental covariates, although coefficients from lower ranked models suggested turbidity and dissolved oxygen may influence salamander movement between the surface and subsurface. Surface population dynamics are partly driven by movement below ground and therefore surface abundance estimates represent a fraction of the superpopulation. As such, while surface habitat management remains an important conservation strategy for this species, periodic declines in apparent surface abundance do not necessarily indicate declines of the superpopulation associated with the spring habitat

The role of pharmacists in opioid stewardship: A scoping review

Background: The opioid epidemic is an international public health concern. Pharmacists are in a strategic position to promote and implement effective opioid stewardship due to both their central role on health care teams and frequent interaction with patients. Despite this integral role, pharmacists do not have harmonized scopes of practice in opioid stewardship.Objectives: This scoping review was conducted to identify and critically review the role of pharmacists in opioid stewardship and identify future areas of study.Methods: The scoping review was conducted according to the methodological framework proposed by Arksey and O'Malley, which was further modified by the Joanna Briggs Institute. Six databases were searched for original, peer-reviewed research; PubMed (MEDLINE), Ovid Embase, Ovid International Pharmaceutical Abstracts, Scopus, Cochrane Library, and APA PsycInfo.Results: In 92% of the included studies (n = 77), opioid stewardship interventions led by either a pharmacist or in an interdisciplinary team resulted in improvements in at least one outcome measure, with education and medication therapy adjustments being the most predominant activities. Other areas supported by evidence include community stakeholder education, policy and guideline setting, and risk assessment.Conclusion: This scoping review provides valuable insight into the various roles pharmacists can have in opioid stewardship. The findings from this review identified opioid stewardship activities that can make significant contributions towards reducing the impact of the opioid crisis. This review informs future research and has the potential to influence pharmacy practice on a national and international scale