Who continues to stock oral artemisinin monotherapy? Results of a provider survey in Myanmar.

BackgroundArtemisinin-based combination therapy (ACT) is a key strategy for global malaria elimination efforts. However, the development of artemisinin-resistant malaria parasites threatens progress and continued usage of oral artemisinin monotherapies (AMT) predisposes the selection of drug resistant strains. This is particularly a problem along the Myanmar/Thailand border. The artemisinin monotherapy replacement programme (AMTR) was established in 2012 to remove oral AMT from stocks in Myanmar, specifically by replacing oral AMT with quality-assured ACT and conducting behavioural change communication activities to the outlets dispensing anti-malarial medications. This study attempts to quantify the characteristics of outlet providers who continue to stock oral AMT despite these concerted efforts.MethodsA cross-sectional survey of all types of private sector outlets that were stocking anti-malarial drugs in 13 townships of Eastern Myanmar was implemented from July to August 2014. A total of 573 outlets were included. Bivariate and multivariable logistic regressions were conducted to assess outlet and provider-level characteristics associated with stocking oral AMT.ResultsIn total, 2939 outlets in Eastern Myanmar were screened for presence of any anti-malarial drugs in August 2014. The study found that 573 (19.5 %) had some kind of oral anti-malarial drug in stock at the time of survey and among them, 96 (16.8 %) stocked oral AMT. In bivariate analyses, compared to health care facilities, itinerant drug vendors, retailers and health workers were less likely to stock oral AMT (33.3 vs 12.9, 10.0, 8.1 %, OR = 0.30, 0.22, 0.18, respectively). Providers who cut blister pack or sell partial courses (40.6 vs 11.7 %, OR 5.18, CI 3.18-8.44) and those who based their stock decision on consumer demand (32.8 vs 12.1 %, OR 3.54, CI 2.21-5.63) were more likely to stock oAMT. Multivariate logistic regressions produced similar significant associations.ConclusionPrivate healthcare facilities and drug shops and providers who prioritize consumers' demand instead of recommended practices were more likely to stock oral AMT. Malaria elimination strategies should include targeted interventions to effectively reach those outlets

Asymmetric ephaptic inhibition between compartmentalized olfactory receptor neurons.

In the Drosophila antenna, different subtypes of olfactory receptor neurons (ORNs) housed in the same sensory hair (sensillum) can inhibit each other non-synaptically. However, the mechanisms underlying this underexplored form of lateral inhibition remain unclear. Here we use recordings from pairs of sensilla impaled by the same tungsten electrode to demonstrate that direct electrical ("ephaptic") interactions mediate lateral inhibition between ORNs. Intriguingly, within individual sensilla, we find that ephaptic lateral inhibition is asymmetric such that one ORN exerts greater influence onto its neighbor. Serial block-face scanning electron microscopy of genetically identified ORNs and circuit modeling indicate that asymmetric lateral inhibition reflects a surprisingly simple mechanism: the physically larger ORN in a pair corresponds to the dominant neuron in ephaptic interactions. Thus, morphometric differences between compartmentalized ORNs account for highly specialized inhibitory interactions that govern information processing at the earliest stages of olfactory coding

Cellular plasticity, caspases and autophagy; that which does not kill us, well, makes us different.

The ability to regenerate is a fundamental requirement for tissue homeostasis. Regeneration draws on three sources of cells. First and best-studied are dedicated stem/progenitor cells. Second, existing cells may proliferate to compensate for the lost cells of the same type. Third, a different cell type may change fate to compensate for the lost cells. This review focuses on regeneration of the third type and will discuss the contributions by post-transcriptional mechanisms including the emerging evidence for cell-autonomous and non-lethal roles of cell death pathways

Ionizing radiation induces stem cell-like properties in a caspase-dependent manner in Drosophila.

Cancer treatments including ionizing radiation (IR) can induce cancer stem cell-like properties in non-stem cancer cells, an outcome that can interfere with therapeutic success. Yet, we understand little about what consequences of IR induces stem cell like properties and why some cancer cells show this response but not others. In previous studies, we identified a pool of epithelial cells in Drosophila larval wing discs that display IR-induced stem cell-like properties. These cells are resistant to killing by IR and, after radiation damage, change fate and translocate to regenerate parts of the disc that suffered more cell death. Here, we report the identification of two new pools of cells with IR-induced regenerative capability. We addressed how IR exposure results in the induction of stem cell-like behavior, and found a requirement for IR-induced caspase activity and for Zfh2, a transcription factor and an effector in the JAK/STAT pathway. Unexpectedly, the requirement for caspase activity was cell-autonomous within cell populations that display regenerative behavior. We propose a model in which the requirement for caspase activity and Zfh2 can be explained by apoptotic and non-apoptotic functions of caspases in the induction of stem cell-like behavior

Psychosocial risk factors in the development of fibromyalgia; and Compassion-Focused Therapy for chronic pain: mediators of improvement

Background: Chronic pain is a worldwide problem that can cause a great level of disability in a person’s life. The aetiology of conditions such as fibromyalgia is still under debate, and there are many biological, psychological and social hypotheses for its development. Past research in this area has explored the predictive impact of abuse and post-traumatic stress, but these are just some of the factors implicated in a wider picture. Psychological approaches to chronic pain have focused on Cognitive Behavioural Therapy and Acceptance and Commitment Therapy, two approaches that result in similar outcomes. Currently, very little research exists on Compassion-Focused Therapy (CFT) for chronic pain, even though the literature suggests conceptual overlaps between CFT and existing therapies. Objective: This thesis aims to reconcile existing information on the psychosocial risk factors that lead to the development of fibromyalgia (Chapter 1) and evaluate the suitability of an 11-week Compassion-Focused Therapy group intervention for adults with chronic pain (Chapter 2). Furthermore, this research also seeks to explore self-compassion, psychological flexibility and psychological inflexibility as potential mediators of improvement in outcome. Limited research and clinical resources can be better used by focusing on how therapies work, instead of if they work against similar treatments that have already proven efficacious. Methods: The evidence base for psychosocial risk factors in the development of fibromyalgia is systematically reviewed in Chapter 1. Electronic databases were searched for various descriptions of fibromyalgia, risk factors and observational study designs. Populations that included physical comorbidities were excluded. In Chapter 2, 122 participants attended the Pain Management Programme at the NHS Lothian Chronic Pain Service. Outcome measures were collected at three timepoints (pre, mid and post-group). One-way ANOVAs were used to evaluate the efficacy of the intervention, along with multiple regressions to perform mediation analysis. Results: 10 studies from a search of 889 potentially relevant studies met the inclusion criteria for systematic review. Most of these studies were deemed to be of good quality. Commonalities across studies included appropriate selection of control and comparison groups, valid random sampling techniques and adequate length to follow-up in the case of cohort studies. Studies, however, varied across their methods in ascertaining fibromyalgia and researchers relied on their own reports to establish outcomes. In Chapter 2, statistically significant improvements were demonstrated in measures of pain interference, anxiety, depression, psychological flexibility, psychological inflexibility, self-compassion and mental wellbeing by the end of the PMP. The largest improvements were found to occur in the second half of the PMP. Self-compassion was shown to mediate improvements in pain interference, whereas psychological flexibility and psychological inflexibility was shown to mediate improvements in depression and mental wellbeing. Neither predictor variable mediated improvements in anxiety. Discussion: Prospective cohort studies represent the best evidence for determining risk factors. Depression, anxiety, childhood adversity, work stress and low education were found to be risk factors for developing fibromyalgia. Based on these results, it is recommended that more conservative estimates of effect size be used. This research also provides evidence for the use of CFT as a group intervention for chronic pain. It can be concluded that pain interventions targeting psychological flexibility and psychological inflexibility are likely to be further improved by emphasising selfcompassion. CFT and ACT already share similar values, despite their differing theoretical backgrounds. Patients will be able to benefit from a combined approach since self-compassion, psychological flexibility and psychological inflexibility were shown to mediate improvement in different outcomes

Понятие и основные признаки административных налоговых правонарушений

Hadoop distributed file system (HDFS) wasoriginally designed for large files. HDFS stores eachsmall file as one separate block although the size ofseveral small files is lesser than the size of block size.Therefore, a large number of blocks are created withmassive small files. When the large number of smallfiles is accessed, NameNode often becomes thebottleneck. The problem of storing and accessinglarge number of small files is named as small fileproblem. In order to solve this issue in HDFS, anapproach of merging small files on HDFS isproposed. In this paper, small files are merged into alarger file based on the agglomerative hierarchicalclustering mechanism to reduce NameNode memoryconsumption. This approach will provide small filesfor cloud storage