Constructive role of dissipation for driven coupled bosonic modes

We describe four cases of childhood B-cell progenitor acute lymphoblastic leukaemia (BCP-ALL) and one of T-cell (T-ALL) with unexpected numbers of interphase signals for ETV6 with an ETV6-RUNX1 fusion probe. Three fusion negative cases each had a telomeric part of 12p terminating within intron 2 of ETV6, attached to sequences from 5q, 7p and 7q, respectively. Two fusion positive cases, with partial insertions of ETV6 into chromosome 21, also had a breakpoint in intron 2. Fluorescence in situ hybridisation ( FISH), array comparative genomic hybridization (aCGH) and Molecular Copy-Number Counting (MCC) results were concordant for the T-cell case. Sequences downstream of TLX3 on chromosome 5 were deleted, leaving the intact gene closely apposed to the first two exons of ETV6 and its upstream promoter. qRT-PCR showed a significant upregulation of TLX3. In this study we provide the first incontrovertible evidence that the upstream promoter of ETV6 attached to the first two exons of the gene was responsible for the ectopic expression of a proto-oncogene that became abnormally close as the result of deletion and translocation. We have also shown breakpoints in intron 2 of ETV6 in two cases of insertion with ETV6-RUNX1 fusion

Cellular and Cytokine Responses in the Granulomas of Asymptomatic Cattle naturally infected with Mycobacterium bovis in Ethiopia

Cells (CD3+ T cell and CD68+ macrophages), cytokines (IFN-γ+ and TNF-α+) and effector molecule (iNOS+) responses were evaluated in the lymph nodes and tissue of cattle naturally infected with Detailed post mortem and immunohistochemical examinations of lesions were performed on 16 cows positive for single intradermal cervical comparative tuberculin (SICCT) test which were identified from dairy farms located around the Addis Ababa City. The severity of the gross lesion was significantly higher (p=0.003) in culture positive (n=12) cows than in culture negative (n=4). Immunohistochemical techniques showed that in culture positive cows, the mean immunolabeling fraction of CD3+ T cells decreased as the stage of granuloma increased from stage I to stage IV (p<0.001). In contrast, the immunolabelling fraction of CD68+ macrophages, IFN-γ+, TNF-α+ and iNOS+ increased from stage I to stage IV (p< 0.001). In culture negative cows, early stages showed a significantly higher fraction of CD68+ macrophages (p=0.03) and iNOS+ (p=0.007) when compared to culture positive cows. Similarly, at advanced granuloma stages, culture negative cows demonstrated significantly higher mean proportions of CD3+ T cells (p< 0.001) compared to culture positive cows. Thus, this study demonstrates that following natural infection of cows with , as the stage of granuloma increases from stage I to stage IV, the immunolabelling fraction of CD3+ cells decreases while the immunolabeling fraction of CD68+ macrophages, IFN-γ+, TNF-α+ and iNOS+ increases. [Abstract copyright: Copyright © 2020 Tulu et al.

Serum anti-Müllerian hormone concentrations before and after treatment of an ovarian granulosa cell tumour in a cat

Case summary A 15-year-old female cat was presented for investigation of progressive behavioural changes, polyuria, polydipsia and periuria. An ovarian granulosa cell tumour was identified and the cat underwent therapeutic ovariohysterectomy (OHE). The cat’s clinical signs resolved, but 6 months later it was diagnosed as having an anaplastic astrocytoma and was euthanased. Serum anti-Müllerian hormone (AMH) concentration prior to OHE was increased vs a control group of entire and neutered female cats. Following OHE, serum AMH concentration decreased to <1% of the original value. Relevance and novel information Serum AMH measurement may represent a novel diagnostic and monitoring tool for functional ovarian neoplasms in cats

Can Action Research Strengthen District Health Management and Improve Health Workforce Performance? A Research Protocol.

The single biggest barrier for countries in sub-Saharan Africa (SSA) to scale up the necessary health services for addressing the three health-related Millennium Development Goals and achieving Universal Health Coverage is the lack of an adequate and well-performing health workforce. This deficit needs to be addressed both by training more new health personnel and by improving the performance of the existing and future health workforce. However, efforts have mostly been focused on training new staff and less on improving the performance of the existing health workforce. The purpose of this paper is to disseminate the protocol for the PERFORM project and reflect on the key challenges encountered during the development of this methodology and how they are being overcome. The overall aim of the PERFORM project is to identify ways of strengthening district management in order to address health workforce inadequacies by improving health workforce performance in SSA. The study will take place in three districts each in Ghana, Tanzania and Uganda using an action research approach. With the support of the country research teams, the district health management teams (DHMTs) will lead on planning, implementation, observation, reflection and redefinition of the activities in the study. Taking into account the national and local human resource (HR) and health systems (HS) policies and practices already in place, 'bundles' of HR/HS strategies that are feasible within the context and affordable within the districts' budget will be developed by the DHMTs to strengthen priority areas of health workforce performance. A comparative analysis of the findings from the three districts in each country will add new knowledge on the effects of these HR/HS bundles on DHMT management and workforce performance and the impact of an action research approach on improving the effectiveness of the DHMTs in implementing these interventions. Different challenges were faced during the development of the methodology. These include the changing context in the study districts, competing with other projects and duties for the time of district managers, complexity of the study design, maintaining the anonymity and confidentiality of study participants as well as how to record the processes during the study. We also discuss how these challenges are being addressed. The dissemination of this research protocol is intended to generate interest in the PERFORM project and also stimulate discussion on the use of action research in complex studies such as this on strengthening district health management to improve health workforce performance

Tuberculosis incidence correlates with sunshine : an ecological 28-year time series study

Birmingham is the largest UK city after London, and central Birmingham has an annual tuberculosis incidence of 80 per 100,000. We examined seasonality and sunlight as drivers of tuberculosis incidence. Hours of sunshine are seasonal, sunshine exposure is necessary for the production of vitamin D by the body and vitamin D plays a role in the host response to tuberculosis. Methods: We performed an ecological study that examined tuberculosis incidence in Birmingham from Dec 1981 to Nov 2009, using publicly-available data from statutory tuberculosis notifications, and related this to the seasons and hours of sunshine (UK Meteorological Office data) using unmeasured component models. Results: There were 9,739 tuberculosis cases over the study period. There was strong evidence for seasonality, with notifications being 24.1% higher in summer than winter (p<0.001). Winter dips in sunshine correlated with peaks in tuberculosis incidence six months later (4.7% increase in incidence for each 100 hours decrease in sunshine, p<0.001). Discussion and Conclusion: A potential mechanism for these associations includes decreased vitamin D levels with consequent impaired host defence arising from reduced sunshine exposure in winter. This is the longest time series of any published study and our use of statutory notifications means this data is essentially complete. We cannot, however, exclude the possibility that another factor closely correlated with the seasons, other than sunshine, is responsible. Furthermore, exposure to sunlight depends not only on total hours of sunshine but also on multiple individual factors. Our results should therefore be considered hypothesis-generating. Confirmation of a potential causal relationship between winter vitamin D deficiency and summer peaks in tuberculosis incidence would require a randomized-controlled trial of the effect of vitamin D supplementation on future tuberculosis incidence

Proceedings of the Rank Forum on Vitamin D

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations . 75 nmol/l). Any discussion of ‘optimal’ concentration of serum 25(OH)D needs to define ‘optimal’ with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations

What adaptation to research is needed following crises: a comparative, qualitative study of the health workforce in Sierra Leone and Nepal

Background: Health workers are critical to the performance of health systems; yet, evidence about their coping strategies and support needs during and post crisis is lacking. There is very limited discussion about how research teams should respond when unexpected crises occur during on-going research. This paper critically presents the approaches and findings of two health systems research projects that explored and evaluated health worker performance and were adapted during crises, and provides lessons learnt on re-orientating research when the unexpected occurs. Methods: Health systems research was adapted post crisis to assess health workers’ experiences and coping strategies. Qualitative in-depth interviews were conducted with 14 health workers in a heavily affected earthquake district in Nepal and 25 frontline health workers in four districts in Ebola-affected Sierra Leone. All data were transcribed and analysed using the framework approach, which included developing coding frameworks for each study, applying the frameworks, developing charts and describing the themes. A second layer of analysis included analysis across the two contexts, whereas a third layer involved the research teams reflecting on the approaches used to adapt the research during these crises and what was learned as individuals and research teams. Results: In Sierra Leone, health workers were heavily stigmatised by the epidemic, leading to a breakdown of trust. Coping strategies included finding renewed purpose in continuing to serve their community, peer and family support (in some cases), and religion. In Nepal, individual determination, a sense of responsibility to the community and professional duty compelled staff to stay or return to their workplace. The research teams had trusting relationships with policy-makers and practitioners, which brought credibility and legitimacy to the change of research direction as well as the relationships to maximise the opportunity for findings to inform practice. Conclusions: In both contexts, health workers demonstrated considerable resilience in continuing to provide services despite limited support. Embedded researchers and institutions are arguably best placed to navigate emerging ethical and social justice challenges and are strategically positioned to support the co-production of knowledge and ensure research findings have impact

Genetic diversity and population structure of Angiostrongylus vasorum parasites within and between local urban foxes (Vulpes Vulpes)

Angiostrongylus vasorum is a nematode parasite of the pulmonary arteries and heart that infects domestic and wild canids. Dogs (Canis familiaris) and red foxes (Vulpes vulpes) are the most commonly affected definitive hosts. Recent studies suggest that angiostrongylosis is an emerging disease, and that red foxes may play an important role in the epidemiology of the parasite. Genetic analyses of parasites collected from dogs and foxes throughout Europe have shown that the same parasite haplotypes are commonly shared between different host species. However, the extent of genetic diversity within local A. vasorum populations and individual hosts is unknown. The objective of the present study was to assess the occurrence of genetic diversity among A. vasorum (a) recovered from different foxes within the Greater London area (a localised population, single worm per fox dataset); and (b) hosted within single foxes (multiple worms per fox dataset). During 2016, A. vasorum worms were collected from foxes culled for other purposes in London. DNA was extracted from each parasite and a partial fragment of the mitochondrial cytochrome oxidase subunit 1 (mtCOI) gene was amplified and sequenced. Sequences from the single worm dataset were compared with those published elsewhere. Combined, 19 haplotypes were described of which 15 were identified from foxes found in London, indicating that considerable genetic diversity can be detected within a local geographic area. Analysis of the multiple worm dataset identified 22 haplotypes defining worms recovered from just six foxes, emphasising the relevance of wild canines as reservoirs of genetic diversity. This is the first study to explore the genetic complexity of individual fox-hosted A. vasorum population

Reassessment intervals for transition from low to high fracture risk among adults older than 50 years

Importance Fracture risk scores are used to identify individuals at high risk of major osteoporotic fracture or hip fracture for antiosteoporosis treatment. For those not meeting treatment thresholds at baseline, the optimal interval for reassessing fracture risk is uncertain. Objective To examine reassessment intervals for transition from low to high fracture risk under guidelines-defined treatment thresholds. Design, Setting, and Participants This retrospective cohort study included persons aged 50 years or older with fracture risk below treatment thresholds at baseline who had fracture risk reassessed at least 1 year later. Data were obtained from a population-based bone mineral density registry (baseline assessment during 1996-2015; reassessment to 2016) in the Province of Manitoba, Canada. Primary analysis was performed from May to June 2019. Analysis for the revision was performed in October 2019. Main Outcomes and Measures The primary outcome was time to transition from low (below the treatment threshold) to high fracture risk (treatment-qualifying risk score using osteoporosis clinical practice guidelines strategies for Canada, the United States, and the United Kingdom). Results The study population consisted of 10 564 individuals (94.1% women; mean [SD] age at baseline, 63.2 [8.2] years). At the time of reassessment (a mean [SD] interval of 5.2 [2.9] years between initial and subsequent fracture risk assessment), 690 (6.6%) had reached the fixed major osteoporotic fracture treatment threshold of 20%, 1546 (16.2%) had reached the fixed hip treatment threshold of 3%, and 932 (9.4%) had reached the age-dependent major osteoporotic fracture treatment threshold. Among those below 25% of the treatment threshold at baseline for each guideline, few (0%-3.0%) reached guidelines-defined high fracture risk at follow-up. In contrast, among those at the upper end of the scale for each guideline (75%-99% of the treatment threshold at baseline), 30.6% to 74.4% reached guidelines-defined high fracture risk. An increased number of clinical risk factors was associated with increased likelihood of reaching guidelines-defined high fracture risk (range for 3 guidelines, 17.1%-28.2%) compared with unchanged or decreased clinical risk factors (range for 3 guidelines, 3.3%-12.8%) (P < .001). Estimated time for 10% of the population to reach treatment-qualifying high fracture risk ranged from fewer than 3 years to more than 15 years. Conclusions and Relevance The findings suggest that baseline fracture risk (as a fraction of the treatment threshold) and change in clinical risk factors can identify individuals with low and high probability of guidelines-defined high fracture risk during follow-up, thereby potentially helping to inform the reassessment interval