Developing a Complex Understanding of Physical Activity in Cardiometabolic Disease from Low-to-Middle-Income Countries—A Qualitative Systematic Review with Meta-Synthesis

Physical activity behaviour is complex, particularly in low-resource settings, while existing behavioural models of physical activity behaviour are often linear and deterministic. The objective of this review was to (i) synthesise the wide scope of factors that affect physical activity and thereby (ii) underpin the complexity of physical activity in low-resource settings through a qualitative meta-synthesis of studies conducted among patients with cardiometabolic disease living in low-to-middle income countries (LMIC). A total of 41 studies were included from 1200 unique citations (up to 15 March 2021). Using a hybrid form of content analysis, unique factors (n = 208) that inform physical activity were identified, and, through qualitative meta-synthesis, these codes were aggregated into categories (n = 61) and synthesised findings (n = 26). An additional five findings were added through deliberation within the review team. Collectively, the 31 synthesised findings highlight the complexity of physical activity behaviour, and the connectedness between person, social context, healthcare system, and built and natural environment. Existing behavioural and ecological models are inadequate in fully understanding physical activity participation in patients with cardiometabolic disease living in LMIC. Future research, building on complexity science and systems thinking, is needed to identify key mechanisms of action applicable to the local context

Of Bits and Bugs — On the Use of Bioinformatics and a Bacterial Crystal Structure to Solve a Eukaryotic Repeat-Protein Structure

Pur-α is a nucleic acid-binding protein involved in cell cycle control, transcription, and neuronal function. Initially no prediction of the three-dimensional structure of Pur-α was possible. However, recently we solved the X-ray structure of Pur-α from the fruitfly Drosophila melanogaster and showed that it contains a so-called PUR domain. Here we explain how we exploited bioinformatics tools in combination with X-ray structure determination of a bacterial homolog to obtain diffracting crystals and the high-resolution structure of Drosophila Pur-α. First, we used sensitive methods for remote-homology detection to find three repetitive regions in Pur-α. We realized that our lack of understanding how these repeats interact to form a globular domain was a major problem for crystallization and structure determination. With our information on the repeat motifs we then identified a distant bacterial homolog that contains only one repeat. We determined the bacterial crystal structure and found that two of the repeats interact to form a globular domain. Based on this bacterial structure, we calculated a computational model of the eukaryotic protein. The model allowed us to design a crystallizable fragment and to determine the structure of Drosophila Pur-α. Key for success was the fact that single repeats of the bacterial protein self-assembled into a globular domain, instructing us on the number and boundaries of repeats to be included for crystallization trials with the eukaryotic protein. This study demonstrates that the simpler structural domain arrangement of a distant prokaryotic protein can guide the design of eukaryotic crystallization constructs. Since many eukaryotic proteins contain multiple repeats or repeating domains, this approach might be instructive for structural studies of a range of proteins

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

A participatory action research approach to strengthening health managers’ capacity at district level in Eastern Uganda

BACKGROUND: Many approaches to improving health managers’ capacity in poor countries, particularly those pursued by external agencies, employ non-participatory approaches and often seek to circumvent (rather than strengthen) weak public management structures. This limits opportunities for strengthening local health managers’ capacity, improving resource utilisation and enhancing service delivery. This study explored the contribution of a participatory action research approach to strengthening health managers’ capacity in Eastern Uganda. METHODS: This was a qualitative study that used open-ended key informant interviews, combined with review of meeting minutes and observations to collect data. Both inductive and deductive thematic analysis was undertaken. The Competing Values Framework of organisational management functions guided the deductive process of analysis and the interpretation of the findings. The framework builds on four earlier models of management and regards them as complementary rather than conflicting, and identifies four managers’ capacities (collaborate, create, compete and control) by categorising them along two axes, one contrasting flexibility versus control and the other internal versus external organisational focus. RESULTS: The findings indicate that the participatory action research approach enhanced health managers’ capacity to collaborate with others, be creative, attain goals and review progress. The enablers included expanded interaction spaces, encouragement of flexibility, empowerment of local managers, and the promotion of reflection and accountability. Tension and conflict across different management functions was apparent; for example, while there was a need to collaborate, maintaining control over processes was also needed. These tensions meant that managers needed to learn to simultaneously draw upon and use different capacities as reflected by the Competing Values Framework in order to maximise their effectiveness. CONCLUSIONS: Improved health manager capacity is essential if sustained improvements in health outcomes in lowincome countries are to be attained. The expansion of interaction spaces, encouragement of flexibility, empowerment of local managers, and the promotion of reflection and accountability were the key means by which participatory action research strengthened health managers’ capacity. The participatory approach to implementation therefore created opportunities to strengthen health managers’ capacity

Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) in the early stages of Alzheimer’s disease

Alzheimer’s disease (AD) is one of the most common causes of dementia in the world. Patients with AD frequently complain of vision disturbances that do not manifest as changes in routine ophthalmological examination findings. The main causes of these disturbances are neuropathological changes in the visual cortex, although abnormalities in the retina and optic nerve cannot be excluded. Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) tests are commonly used in ophthalmology to estimate bioelectrical function of the retina and optic nerve. The aim of this study was to determine whether retinal and optic nerve function, measured by PERG and PVEP tests, is changed in individuals in the early stages of AD with normal routine ophthalmological examination results. Standard PERG and PVEP tests were performed in 30 eyes of 30 patients with the early stages of AD. The results were compared to 30 eyes of 30 normal healthy controls. PERG and PVEP tests were recorded in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Additionally, neural conduction was measured using retinocortical time (RCT)—the difference between P100-wave latency in PVEP and P50-wave implicit time in PERG. In PERG test, PVEP test, and RCT, statistically significant changes were detected. In PERG examination, increased implicit time of P50-wave (P < 0.03) and amplitudes reductions in P50- and N95-waves (P < 0.0001) were observed. In PVEP examination, increased latency of P100-wave (P < 0.0001) was found. A significant increase in RCT (P < 0.0001) was observed. The most prevalent features were amplitude reduction in N95-wave and increased latency of P100-wave which were seen in 56.7% (17/30) of the AD eyes. In patients with the early stages of AD and normal routine ophthalmological examination results, dysfunction of the retinal ganglion cells as well as of the optic nerve is present, as detected by PERG and PVEP tests. These dysfunctions, at least partially, explain the cause of visual disturbances observed in patients with the early stages of AD