Unique type of isolated cardiac valvular amyloidosis

BACKGROUND: Amyloid deposition in heart is a common occurrence in systemic amyloidosis. But localised valvular amyloid deposits are very uncommon. It was only in 1922 that the cases of valvular amyloidosis were reported. Then in 1980, Goffin et al reported another type of valvular amyloidosis, which he called the dystrophic valvular amyloidosis. We report a case of aortic valve amyloidosis which is different from the yet described valvular amyloidosis. CASE PRESENTATION: A 72 years old gentleman underwent urgent aortic valve replacement. Intraoperatively, a lesion was found attached to the inferior surface of his bicuspid aortic valve. Histopathology examination of the valve revealed that the lesion contained amyloid deposits, identified as AL amyloidosis. The serum amyloid A protein (SAP) scan was normal and showed no evidence of systemic amyloidosis. The ECG and echocardiogram were not consistent with cardiac amyloidosis. CONCLUSION: Two major types of cardiac amyloidosis have been described in literature: primary-myelomatous type (occurs with systemic amyolidosis), and senile type(s). Recently, a localised cardiac dystrophic valvular amyloidosis has been described. In all previously reported cases, there was a strong association of localised valvular amyloidosis with calcific deposits. Ours is a unique case which differs from the previously reported cases of localised valvular amyloidosis. In this case, the lesion was not associated with any scar tissue. Also there was no calcific deposit found. This may well be a yet unknown type of isolated valvular amyloidosis

Examiner training: A study of examiners making sense of norm-referenced feedback

PURPOSE: Examiner training has an inconsistent impact on subsequent performance. To understand this variation, we explored how examiners think about changing the way they assess. METHOD: We provided comparative data to 17 experienced examiners about their assessments, captured their sense-making processes using a modified think-aloud protocol, and identified patterns by inductive thematic analysis. RESULTS: We observed five sense-making processes: (1) testing personal relevance (2) interpretation (3) attribution (4) considering the need for change, and (5) considering the nature of change. Three observed meta-themes describe the manner of examiners' thinking: Guarded curiosity - where examiners expressed curiosity over how their judgments compared with others', but they also expressed guardedness about the relevance of the comparisons; Dysfunctional assimilation - where examiners' interpretation and attribution exhibited cognitive anchoring, personalization, and affective bias; Moderated conservatism - where examiners expressed openness to change, but also loyalty to their judgment-framing values and aphorisms. CONCLUSIONS: Our examiners engaged in complex processes as they considered changing their assessments. The 'stabilising' mechanisms some used resembled learners assimilating educational feedback. If these are typical examiner responses, they may well explain the variable impact of examiner training, and have significant implications for the pursuit of meaningful and defensible judgment-based assessment

Building partnerships towards strengthening Makerere University College of Health Sciences: a stakeholder and sustainability analysis

<p>Abstract</p> <p>Background</p> <p>Partnerships and networking are important for an institution of higher learning like Makerere University College of Health Sciences (MakCHS) to be competitive and sustainable.</p> <p>Methods</p> <p>A stakeholder and sustainability analysis of 25 key informant interviews was conducted among past, current and potential stakeholders of MakCHS to obtain their perspectives and contributions to sustainability of the College in its role to improve health outcomes.</p> <p>Results</p> <p>The College has multiple internal and external stakeholders. Stakeholders from Uganda wanted the College to use its enormous academic capacity to fulfil its vision, take initiative, and be innovative in conducting more research and training relevant to the country’s health needs. Many stakeholders felt that the initiative for collaboration currently came more from the stakeholders than the College. External stakeholders felt that MakCHS was insufficiently marketing itself and not directly engaging the private sector or Parliament. Stakeholders also identified the opportunity for MakCHS to embrace information technology in research, learning and training, and many also wanted MakCHS to start leadership and management training programmes in health systems. The need for MakCHS to be more vigorous in training to enhance professionalism and ethical conduct was also identified.</p> <p>Discussion</p> <p>As a constituent of a public university, MakCHS has relied on public funding, which has been inadequate to fulfill its mission. Broader networking, marketing to mobilize resources, and providing strong leadership and management support to inspire confidence among its current and potential stakeholders will be essential to MakCHS’ further growth. MakCHS’ relevance is hinged on generating research knowledge for solving the country’s contemporary health problems and starting relevant programs and embracing technologies. It should share new knowledge widely through publications and other forms of dissemination. Whether institutional leadership is best in the hands of academicians or professional managers is a debatable matter.</p> <p>Conclusions</p> <p>This study points towards the need for MakCHS and other African public universities to build a broad network of partnerships to strengthen their operations, relevance, and sustainability. Conducting stakeholder and sustainability analyses are instructive toward this end, and have provided information and perspectives on how to make long-range informed choices for success.</p

Knowledge co-production for decision-making in human-natural systems under uncertainty

Decision-making under uncertainty is important for managing human-natural systems in a changing world. A major source of uncertainty is linked to the multi-actor settings of decisions with poorly understood values, complex relationships, and conflicting management approaches. Despite general agreement across disciplines on co-producing knowledge for viable and inclusive outcomes in a multi-actor context, there is still limited conceptual clarity and no systematic understanding on what co-production means in decision-making under uncertainty and how it can be approached. Here, we use content analysis and clustering to systematically analyse 50 decision-making cases with multiple time and spatial scales across 26 countries and in 9 different sectors in the last decade to serve two aims. The first is to synthesise the key recurring strategies that underpin high quality decision co-production across many cases of diverse features. The second is to identify important deficits and opportunities to leverage existing strategies towards flourishing co-production in support of decision-making. We find that four general strategies emerge centred around: promoting innovation for robust and equitable decisions; broadening the span of co-production across interacting systems; fostering social learning and inclusive participation; and improving pathways to impact. Additionally, five key areas that should be addressed to improve decision co-production are identified in relation to: participation diversity; collaborative action; power relationships; governance inclusivity; and transformative change. Characterising the emergent strategies and their key areas for improvement can help guide future works towards more pluralistic and integrated science and practice

Human peritoneal mesothelial cells display phagocytic and antigen-presenting functions to contribute to intraperitoneal immunity

Mesothelial cells lining the peritoneal cavity are strategically positioned to respond to and counter intraperitoneal infections, cancer cells, and other challenges. We have investigated human peritoneal mesothelial cells (HPMCs) for phagocytic activity, expression of surface MHC Class II and accessory molecules involved in antigen presentation, and the ability to present recall antigens to T cells. Phagocytosis of dextran, latex beads and Escherichia coli was observed by flow cytometry, and internalization was visualised using confocal and electron microscopy. Flow cytometry and/or cellular ELISA showed constitutive expression of ICAM-I, LFA-3, and B7-1, but not B7-2 or MHC II. Interferon-gamma induced MHC II and ICAM-1 expression in a dose- and time-dependent manner. Importantly, HPMCs induced autologous CD3+ T lymphocyte proliferation (3H-incorporation) after pulse with recall antigen. HPMCs equipped with phagocytic and antigen-presenting machinery are anticipated to have an integral role in intraperitoneal immune surveillance

Worry about crime in Europe: A model-based small area estimation from the European Social Survey

© The Author(s) 2019. Worry about crime is known to be higher in some European regions than others. However, cross-national surveys, which are the main source of information to map worry about crime across Europe, are designed to be representative of large areas (countries), and regions often suffer from small and unrepresentative sample sizes. This research produces reliable model-based small area estimates of worry about crime at regional level from European Social Survey data, in order to map the phenomenon and examine its macro-level predictors. Model-based small area estimation techniques borrow strength across areas to produce reliable estimates of parameters of interest. Estimates of worry about crime are higher in most South and East European regions, in contrast to Northern and Central Europe

Neutropenia in Barth syndrome:characteristics, risks, and management

PURPOSE OF REVIEW: Barth syndrome (BTHS) is an X-linked disease characterized by defective remodeling of phospholipid side chains in mitochondrial membranes. Major features include neutropenia, dilated cardiomyopathy, motor delay and proximal myopathy, feeding problems, and constitutional growth delay. We conducted this review of neutropenia in BTHS to aid in the diagnosis of this disease, and to improve understanding of both the consequences of neutropenia and the benefits of treatment with granulocyte colony-stimulating factor (G-CSF). RECENT FINDINGS: In 88 patients with BTHS, neutropenia, that is, at least one count below 1.5 × 10/l, was detected in 74 (84%) and 44% had severe chronic neutropenia, with multiple counts below 0.5 × 10/l. The pattern of neutropenia varied between intermittent and unpredictable, chronic and severe, or cyclical with mathematically regular oscillations. Monocytosis, that is, monocytes more than 1.0 × 10/l, was observed at least once in 64 of 85 (75%) patients. G-CSF was administered to 39 of 88 patients (44%). Weekly average G-CSF doses ranged from 0.12 to 10.92 μg/kg/day (mean 1.16 μg/kg/day, median 1.16 μg/kg/day). Antibiotic prophylaxis was additionally employed in 21 of 26 neutropenic patients. Pretreatment bone marrow evaluations predominantly showed reduced myeloid maturation which normalized on G-CSF therapy in seven of 13 examined. Consistent clinical improvement, with reduced signs and symptoms of infections, was observed in response to prophylactic G-CSF ± prophylactic antibiotics. However, despite G-CSF and antibiotics, one adult patient died with multiple infections related to indwelling medical devices and gastrostomy site infection after 15.5 years on G-CSF and a pediatric patient required gastrostomy removal for recurrent abdominal wall cellulitis. SUMMARY: BTHS should be considered in any men with neutropenia accompanied by any of the characteristic features of this syndrome. Prophylaxis with G-CSF ± antibiotics prevents serious bacterial infections in the more severe neutropenic patients although infections remain a threat even in patients who are very compliant with therapy, especially in those with indwelling devices

Human marginal zone B cell development from early T2 progenitors.

B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2, and T3 stages to become naive B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgMhi and IgMlo developmental trajectories. IgMhi T2 cells have higher expression of α4β7 integrin and lower expression of IL-4 receptor (IL4R) compared with the IgMlo branch and are selectively recruited into gut-associated lymphoid tissue. IgMhi T2 cells also share transcriptomic features with marginal zone B cells (MZBs). Lineage progression from T1 cells to MZBs via an IgMhi trajectory is identified by pseudotime analysis of scRNA-sequencing data. Reduced frequency of IgMhi gut-homing T2 cells is observed in severe SLE and is associated with reduction of MZBs and their putative IgMhi precursors. The collapse of the gut-associated MZB maturational axis in severe SLE affirms its existence in health

A population of luminous accreting black holes with hidden mergers

Major galaxy mergers are thought to play an important part in fuelling the growth of supermassive black holes. However, observational support for this hypothesis is mixed, with some studies showing a correlation between merging galaxies and luminous quasars and others showing no such association. Recent observations have shown that a black hole is likely to become heavily obscured behind merger-driven gas and dust, even in the early stages of the merger, when the galaxies are well separated (5 to 40 kiloparsecs). Merger simulations further suggest that such obscuration and black-hole accretion peaks in the final merger stage, when the two galactic nuclei are closely separated (less than 3 kiloparsecs). Resolving this final stage requires a combination of high-spatial-resolution infrared imaging and high-sensitivity hard-X-ray observations to detect highly obscured sources. However, large numbers of obscured luminous accreting supermassive black holes have been recently detected nearby (distances below 250 megaparsecs) in X-ray observations. Here we report high-resolution infrared observations of hard-X-ray-selected black holes and the discovery of obscured nuclear mergers, the parent populations of supermassive-black-hole mergers. We find that obscured luminous black holes (bolometric luminosity higher than 2x10^44 ergs per second) show a significant (P<0.001) excess of late-stage nuclear mergers (17.6 per cent) compared to a sample of inactive galaxies with matching stellar masses and star formation rates (1.1 per cent), in agreement with theoretical predictions. Using hydrodynamic simulations, we confirm that the excess of nuclear mergers is indeed strongest for gas-rich major-merger hosts of obscured luminous black holes in this final stage.Comment: To appear in the 8 November 2018 issue of Nature. This is the authors' version of the wor