Overdose risk perceptions and experience of overdose among heroin users in Cork, Ireland. Preliminary results from a pilot overdose prevention study

Background. Opioid overdose is the primary cause of death among injecting drug users (IDU). Overdose is generally not sudden, occurs over one to three hours, and often in the presence of bystanders. This presents a unique window of opportunity to intervene. Aim. Successful overdose prevention training includes appropriate clinical and non-clinical responses. The study aimed to investigate Irish IDU experience of overdose, and need for education and resuscitation skills programming. We report on pilot findings. Methods. Phase One assessed service user experience of overdose, substances used, setting for overdose, and awareness of appropriate non-clinical responses (n=52). Phase two implemented an educational intervention at two Cork addiction service sites. This involved assessing service user awareness of appropriate non-clinical methods to manage overdose and their interest in receiving resuscitation training (n=26). Phase three piloted a resuscitation skills training intervention for staff, family and IDU consisting of instruction on how to recognise and prevent overdose, appropriate response techniques; rescue breathing, and calling emergency services (n=26). Results. The findings illustrated the majority had experienced overdose, described the main substances involved, the settings, the responses employed, and the perceptions of risk. The need for education equipping IDU with overdose prevention and management skills was identified. Awareness of appropriate responses (correct emergency numbers, recovery and resuscitation skills) improved following the educational and skills training interventions Conclusions. Continued efforts in Ireland to integrate culturally specific overdose prevention into agonist opioid treatment services, prison discharge, homeless primary health and needle and syringe exchange are warranted

Oral tolerance to cancer can be abrogated by T regulatory cell inhibition

Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut

Prevalence and determinants of the use of self-tests by members of the public: a mixed methods study

Background Self-tests can be used by members of the public to diagnose conditions without involving a doctor, nurse or other health professional. As technologies to design and manufacture diagnostic tests have developed, a range of self-tests have become available to the public to buy over-the-counter and via the Internet. This study aims to describe how many people have used self-tests and identify factors associated with their use. Methods A postal questionnaire will elicit basic information, including sociodemographic characteristics, and whether the person has used or would use specified self-tests. Consent will be sought to recontact people who want to participate further in the study, and interviews and focus groups will be used to develop hypotheses about factors associated with self-test use. These hypotheses will be tested in a case-control study. An in-depth questionnaire will be developed incorporating the identified factors. This will be sent to: people who have used a self-test (cases); people who have not used a self-test but would use one in the future (controls); and people who have not used and would not use a self-test (controls). Logistic regression analysis will be used to establish which factors are associated with self-test use. Discussion Self-tests do have potential benefits, for example privacy and convenience, but also potential harms, for example delay seeking treatment after a true negative result when the symptoms are actually due to another condition. It is anticipated that the outcomes from this study will include recommendations about how to improve the appropriate use of self-tests and existing health services, as well as information to prepare health professionals for patients who have used self-tests

In Vivo Measurement of Hippocampal GABAA/cBZR Density with [18F]-Flumazenil PET for the Study of Disease Progression in an Animal Model of Temporal Lobe Epilepsy

PURPOSE: Imbalance of inhibitory GABAergic neurotransmission has been proposed to play a role in the pathogenesis of temporal lobe epilepsy (TLE). This study aimed to investigate whether [(18)F]-flumazenil ([(18)F]-FMZ) PET could be used to non-invasively characterise GABA(A)/central benzodiazepine receptor (GABA(A)/cBZR) density and affinity in vivo in the post-kainic acid status epilepticus (SE) model of TLE. METHODS: Dynamic [(18)F]-FMZ -PET scans using a multi-injection protocol were acquired in four male wistar rats for validation of the partial saturation model (PSM). SE was induced in eight male Wistar rats (10 weeks of age) by i.p. injection of kainic acid (7.5–25 mg/kg), while control rats (n = 7) received saline injections. Five weeks post-SE, an anatomic MRI scan was acquired and the following week an [(18)F]-FMZ PET scan (3.6–4.6 nmol). The PET data was co-registered to the MRI and regions of interest drawn on the MRI for selected structures. A PSM was used to derive receptor density and apparent affinity from the [(18)F]-FMZ PET data. KEY FINDINGS: The PSM was found to adequately model [(18)F]-FMZ binding in vivo. There was a significant decrease in hippocampal receptor density in the SE group (p<0.01), accompanied by an increase in apparent affinity (p<0.05) compared to controls. No change in cortical receptor binding was observed. Hippocampal volume reduction and cell loss was only seen in a subset of animals. Histological assessment of hippocampal cell loss was significantly correlated with hippocampal volume measured by MRI (p<0.05), but did not correlate with [(18)F]-FMZ binding. SIGNIFICANCE: Alterations to hippocampal GABA(A)/cBZR density and affinity in the post-kainic acid SE model of TLE are detectable in vivo with [(18)F]-FMZ PET and a PSM. These changes are independent from hippocampal cell and volume loss. [(18)F]-FMZ PET is useful for investigating the role that changes GABA(A)/cBZR density and binding affinity play in the pathogenesis of TLE

Binary orbits as the driver of γ-ray emission and mass ejection in classical novae

Classical novae are the most common astrophysical thermonuclear explosions, occurring on the surfaces of white dwarf stars accreting gas from companions in binary star systems. Novae typically expel �10,000 solar masses of material at velocities exceeding 1,000 km/s. However, the mechanism of mass ejection in novae is poorly understood, and could be dominated by the impulsive flash of the thermonuclear runaway, prolonged optically thick winds, or binary interaction with the nova envelope. Classical novae are now routinely detected in GeV gamma-rays, suggesting that relativistic particles are accelerated by strong shocks in nova ejecta. Here we present high-resolution imaging of the gamma-ray-emitting nova V959 Mon at radio wavelengths, showing that its ejecta were shaped by binary motion: some gas was expelled rapidly along the poles as a wind from the white dwarf, while denser material drifted out along the equatorial plane, propelled by orbital motion. At the interface between the equatorial and polar regions, we observe synchrotron emission indicative of shocks and relativistic particle acceleration, thereby pinpointing the location of gamma-ray production. Binary shaping of the nova ejecta and associated internal shocks are expected to be widespread among novae, explaining why many novae are gamma-ray emitters

Reducing bias in auditory duration reproduction by integrating the reproduced signal

Duration estimation is known to be far from veridical and to differ for sensory estimates and motor reproduction. To investigate how these differential estimates are integrated for estimating or reproducing a duration and to examine sensorimotor biases in duration comparison and reproduction tasks, we compared estimation biases and variances among three different duration estimation tasks: perceptual comparison, motor reproduction, and auditory reproduction (i.e. a combined perceptual-motor task). We found consistent overestimation in both motor and perceptual-motor auditory reproduction tasks, and the least overestimation in the comparison task. More interestingly, compared to pure motor reproduction, the overestimation bias was reduced in the auditory reproduction task, due to the additional reproduced auditory signal. We further manipulated the signal-to-noise ratio (SNR) in the feedback/comparison tones to examine the changes in estimation biases and variances. Considering perceptual and motor biases as two independent components, we applied the reliability-based model, which successfully predicted the biases in auditory reproduction. Our findings thus provide behavioral evidence of how the brain combines motor and perceptual information together to reduce duration estimation biases and improve estimation reliability

The Dawn of Open Access to Phylogenetic Data

The scientific enterprise depends critically on the preservation of and open access to published data. This basic tenet applies acutely to phylogenies (estimates of evolutionary relationships among species). Increasingly, phylogenies are estimated from increasingly large, genome-scale datasets using increasingly complex statistical methods that require increasing levels of expertise and computational investment. Moreover, the resulting phylogenetic data provide an explicit historical perspective that critically informs research in a vast and growing number of scientific disciplines. One such use is the study of changes in rates of lineage diversification (speciation - extinction) through time. As part of a meta-analysis in this area, we sought to collect phylogenetic data (comprising nucleotide sequence alignment and tree files) from 217 studies published in 46 journals over a 13-year period. We document our attempts to procure those data (from online archives and by direct request to corresponding authors), and report results of analyses (using Bayesian logistic regression) to assess the impact of various factors on the success of our efforts. Overall, complete phylogenetic data for ~60% of these studies are effectively lost to science. Our study indicates that phylogenetic data are more likely to be deposited in online archives and/or shared upon request when: (1) the publishing journal has a strong data-sharing policy; (2) the publishing journal has a higher impact factor, and; (3) the data are requested from faculty rather than students. Although the situation appears dire, our analyses suggest that it is far from hopeless: recent initiatives by the scientific community -- including policy changes by journals and funding agencies -- are improving the state of affairs

Energy drink use, problem drinking and drinking motives in a diverse sample of Alaskan college students

Background. Recent research has identified the use of caffeinated energy drinks as a common, potentially risky behaviour among college students that is linked to alcohol misuse and consequences. Research also suggests that energy drink consumption is related to other risky behaviours such as tobacco use, marijuana use and risky sexual activity. Objective. This research sought to examine the associations between frequency of energy drink consumption and problematic alcohol use, alcohol-related consequences, symptoms of alcohol dependence and drinking motives in an ethnically diverse sample of college students in Alaska. We also sought to examine whether ethnic group moderated these associations in the present sample of White, Alaska Native/American Indian and other ethnic minority college students. Design. A paper-and-pencil self-report questionnaire was completed by a sample of 298 college students. Analysis of covariance (ANCOVA) was used to examine the effects of energy drink use, ethnic group and energy drink by ethnic group interactions on alcohol outcomes after controlling for variance attributed to gender, age and frequency of binge drinking. Results. Greater energy drink consumption was significantly associated with greater hazardous drinking, alcohol consequences, alcohol dependence symptoms, drinking for enhancement motives and drinking to cope. There were no main effects of ethnic group, and there were no significant energy drink by ethnic group interactions. Conclusion. These findings replicate those of other studies examining the associations between energy drink use and alcohol problems, but contrary to previous research we did not find ethnic minority status to be protective. It is possible that energy drink consumption may serve as a marker for other health risk behaviours among students of various ethnic groups

Automatically extracting functionally equivalent proteins from SwissProt

In summary, FOSTA provides an automated analysis of annotations in UniProtKB/Swiss-Prot to enable groups of proteins already annotated as functionally equivalent, to be extracted. Our results demonstrate that the vast majority of UniProtKB/Swiss-Prot functional annotations are of high quality, and that FOSTA can interpret annotations successfully. Where FOSTA is not successful, we are able to highlight inconsistencies in UniProtKB/Swiss-Prot annotation. Most of these would have presented equal difficulties for manual interpretation of annotations. We discuss limitations and possible future extensions to FOSTA, and recommend changes to the UniProtKB/Swiss-Prot format, which would facilitate text-mining of UniProtKB/Swiss-Prot