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

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

Sophisticated lessons from simple organisms: appreciating the value of curiosity-driven research

Long before scientists learned to grow miniature organs from human cells in a dish, biological research was performed using organisms that were accessible: garden peas, sea urchins collected at low tide, newt eggs, and flies circling rotten fruit. These organisms help us to understand the world around us, attracting and inspiring each new generation of scientists with the promise of mystery and discovery. Subsequent studies repeatedly showed that fundamental biological mechanisms discovered in such simple organisms are conserved in more complex organisms, including humans. Yet, biologists are increasingly being tasked with problem solving rather than being allowed to follow the path of discovery. Here, we provide examples of important lessons learned fromresearch using selected non-vertebrate organisms. We argue that, for the purpose of understanding human disease, simple organisms cannot and should not be replaced solely by human-cell-based culture systems. Rather, these organisms serve as powerful discovery tools for new knowledge that may subsequently be tested for conservation in human-cell-based culture systems. In this way, curiosity-driven biological research in simple organisms has and will continue to pay huge dividends in both the short and long run for improving the human condition

Exploring the experience of travelling with and taking care for a guide dog: an interpretative phenomenological analysis

The mobility support that guide dogs provide to the visually impaired person is one of the most established forms of assistive dog partnership. The UK has the highest number of guide dog owners per capita globally. While there exists a small body of literature on guide dog partnerships, very few studies have specifically addressed owners in the UK or examined partnerships as experienced by first-time owners. Little attention is paid to the professionals who work with guide dog-owner teams. This thesis explores the guide dog–person partnership as it is perceived by guide dog professionals and first-time owners in the UK. Two empirical studies are presented; data collection and analysis are guided by Interpretative Phenomenological Analysis. Study 1 examines the perspectives of five mobility specialists and dog trainers employed by Guide Dogs UK. Study 2 concerns 11 London-based first-time owners and their guide dog experience within and outside the contexts of joint mobility. The two studies foreground the ambivalence and fluidity that characterise the participants’ perceptions of guide dog-person partnerships. The professionals’ and owners’ accounts depict the guide dogs taking up different and conflicting characters; they shift between being trustworthy guides and forces of dangerous unpredictability, between working animals and subjects of tender loving care. The person’s role in the partnership can also take different forms, such as user, carer, ‘manager,’ and ‘client.’ The first-time owners’ interviews shed further light on the guide dogs’ impact on the existential level. The partnership helps re-establish the security and openness of the self’s embodied relation with the physical world and re-embrace the possibility of a more home-like being within the sense of uncanny existence aggravated by sight loss. The owners’ connections with their guide dogs also shape the social terrain through which their senses of self arise, in both welcome and unwelcome ways

Determinants of active aging and quality of life among older adults : systematic review

Peer reviewedPublisher PD

Determinants of active aging and quality of life among older adults: systematic review

IntroductionPopulation demography across the globe shows an increasing trend in the aging population due to better healthcare, improved nutrition, advanced health-related technology, and decreased fertility rate. Despite these advancements, there remains a knowledge gap in understanding the association between active aging determinants and quality of life (QoL) among older adults, particularly within diverse cultural contexts, which has not been adequately explored in previous research. Therefore, understanding the association between active aging determinants and QoL can help policymakers plan early interventions or programs to assist future older adults in both aging actively and optimizing their quality of life (QoL), as these two factors have a bidirectional relationship.ObjectiveThis study aimed to review evidence regarding the association between active aging and quality of life (QoL) among older adults and to determine the most widely used study designs and measurement instruments in studies conducted between 2000 and 2020.MethodsRelevant studies were identified by a systematic search of four electronic databases and cross-reference lists. Original studies examining the association between active aging and QoL in individuals aged 60 years or older were considered. The quality of the included studies and the direction and consistency of the association between active aging and QoL were assessed.ResultsA total of 26 studies met the inclusion criteria and were included in this systematic review. Most studies reported a positive association between active aging and QoL among older adults. Active aging had a consistent association with various QoL domains including physical environment, health and social services, social environment, economic, personal, and behavioral determinants.ConclusionActive aging had a positive and consistent association with several QoL domains among older adults, backing the notion that the better the active aging determinants, the better the QoL among older adults. Considering the broader literature, it is necessary to facilitate and encourage the active participation of older adults in physical, social, and economic activities for the maintenance and/or improvement of QoL. Identifying other possible determinants and enhancing the methods to improve those determinants may help improve the QoL among older adults

The Dementia Health Literacy Intervention For Informal Caregivers: A Systematic Review Protocol

This review will systematically examine the effectiveness of educational interventions on dementia health literacy (DHL) among informal caregivers (ICs) in 42 Asia Pacific countries/territories. Methods: A systematic literature search will be performed in nine databases. No date nor language restriction will be applied. The quality of studies will be assessed using existing appraisal tools (i.e. Joanna Briggs Institute’s Checklists) and an inductive narrative synthesis technique will be used to analyse the extracted data. Randomized Controlled Trial (RCT) and non-RCT interventions will be full-reviewed but only RCT studies will be pooled in a meta-analysis. Heterogeneity, publication bias, and sensitivity will also be assessed. Results: The results will be reported following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement. The standardized procedure and reporting will ensure the review’s quality and could be used by the stakeholders in the region for planning DHL-related programs and significantly contribute to dementia caregiving and caregiver literature and programs. Conclusion: This protocol of the planned systematic review and meta-analysis of the effectiveness of educational interventions on DHL for ICs in the Asia Pacific countries/territories will set the foundation for its further progress.   Keywords: Aging, Alzheimer’s, Caregiving, Gerontology, Global Sout