Diagnosis of myocardial infarction at autopsy: AECVP reappraisal in the light of the current clinical classification.

Ischemic heart disease is one of the leading causes of morbidity and death worldwide. Consequently, myocardial infarctions are often encountered in clinical and forensic autopsies, and diagnosis can be challenging, especially in the absence of an acute coronary occlusion. Precise histopathological identification and timing of myocardial infarction in humans often remains uncertain while it can be of crucial importance, especially in a forensic setting when third person involvement or medical responsibilities are in question. A proper post-mortem diagnosis requires not only up-to-date knowledge of the ischemic coronary and myocardial pathology, but also a correct interpretation of such findings in relation to the clinical scenario of the deceased. For these reasons, it is important for pathologists to be familiar with the different clinically defined types of myocardial infarction and to discriminate myocardial infarction from other forms of myocardial injury. This article reviews present knowledge and post-mortem diagnostic methods, including post-mortem imaging, to reveal the different types of myocardial injury and the clinical-pathological correlations with currently defined types of myocardial infarction

The FIELDS Instrument Suite for Solar Probe Plus: Measuring the Coronal Plasma and Magnetic Field, Plasma Waves and Turbulence, and Radio Signatures of Solar Transients.

NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products

Present Limits to Heat-Adaptability in Corals and Population-Level Responses to Climate Extremes

Climate change scenarios suggest an increase in tropical ocean temperature by 1–3°C by 2099, potentially killing many coral reefs. But Arabian/Persian Gulf corals already exist in this future thermal environment predicted for most tropical reefs and survived severe bleaching in 2010, one of the hottest years on record. Exposure to 33–35°C was on average twice as long as in non-bleaching years. Gulf corals bleached after exposure to temperatures above 34°C for a total of 8 weeks of which 3 weeks were above 35°C. This is more heat than any other corals can survive, providing an insight into the present limits of holobiont adaptation. We show that average temperatures as well as heat-waves in the Gulf have been increasing, that coral population levels will fluctuate strongly, and reef-building capability will be compromised. This, in combination with ocean acidification and significant local threats posed by rampant coastal development puts even these most heat-adapted corals at risk. WWF considers the Gulf ecoregion as “critically endangered”. We argue here that Gulf corals should be considered for assisted migration to the tropical Indo-Pacific. This would have the double benefit of avoiding local extinction of the world's most heat-adapted holobionts while at the same time introducing their genetic information to populations naïve to such extremes, potentially assisting their survival. Thus, the heat-adaptation acquired by Gulf corals over 6 k, could benefit tropical Indo-Pacific corals who have <100 y until they will experience a similarly harsh climate. Population models suggest that the heat-adapted corals could become dominant on tropical reefs within ∼20 years

Coping with Commitment: Projected Thermal Stress on Coral Reefs under Different Future Scenarios

BACKGROUND: Periods of anomalously warm ocean temperatures can lead to mass coral bleaching. Past studies have concluded that anthropogenic climate change may rapidly increase the frequency of these thermal stress events, leading to declines in coral cover, shifts in the composition of corals and other reef-dwelling organisms, and stress on the human populations who depend on coral reef ecosystems for food, income and shoreline protection. The ability of greenhouse gas mitigation to alter the near-term forecast for coral reefs is limited by the time lag between greenhouse gas emissions and the physical climate response. METHODOLOGY/PRINCIPAL FINDINGS: This study uses observed sea surface temperatures and the results of global climate model forced with five different future emissions scenarios to evaluate the "committed warming" for coral reefs worldwide. The results show that the physical warming commitment from current accumulation of greenhouse gases in the atmosphere could cause over half of the world's coral reefs to experience harmfully frequent (p> or =0.2 year(-1)) thermal stress by 2080. An additional "societal" warming commitment, caused by the time required to shift from a business-as-usual emissions trajectory to a 550 ppm CO(2) stabilization trajectory, may cause over 80% of the world's coral reefs to experience harmfully frequent events by 2030. Thermal adaptation of 1.5 degrees C would delay the thermal stress forecast by 50-80 years. CONCLUSIONS/SIGNIFICANCE: The results suggest that adaptation -- via biological mechanisms, coral community shifts and/or management interventions -- could provide time to change the trajectory of greenhouse gas emissions and possibly avoid the recurrence of harmfully frequent events at the majority (97%) of the world's coral reefs this century. Without any thermal adaptation, atmospheric CO(2) concentrations may need to be stabilized below current levels to avoid the degradation of coral reef ecosystems from frequent thermal stress events

Enhancing students’ motivation to learn software engineering programming techniques: a collaborative and social interaction approach

To motivate students to study advanced programming techniques, including the use of architectural styles such as the model–view–controller pattern, we have con-ducted action research upon a project based-learning approach. In addition to collabo-ration, the approach includes students’ searching and analysis of scientific documents and their involvement in communities of practice outside academia. In this paper, we report the findings of second action research cycle, which took place throughout the fourth semester of a six-semester program. As with the previous cycle during the pre-vious academic year, students did not satisfactorily achieve expected learning out-comes. More groups completed the assigned activities, but results continue to reflect poor engagement in the communities of practice and very low performance in other learning tasks. From the collected data we have identified new approaches and recom-mendations for subsequent research.Fundação para a Ciência e Tecnologia (FCT), Portugal, for Ph.D. Grants SFRH/BD/91309/2012 and SFRH/BD/87815/201

Projected Changes to Growth and Mortality of Hawaiian Corals over the Next 100 Years

BACKGROUND: Recent reviews suggest that the warming and acidification of ocean surface waters predicated by most accepted climate projections will lead to mass mortality and declining calcification rates of reef-building corals. This study investigates the use of modeling techniques to quantitatively examine rates of coral cover change due to these effects. METHODOLOGY/PRINCIPAL FINDINGS: Broad-scale probabilities of change in shallow-water scleractinian coral cover in the Hawaiian Archipelago for years 2000-2099 A.D. were calculated assuming a single middle-of-the-road greenhouse gas emissions scenario. These projections were based on ensemble calculations of a growth and mortality model that used sea surface temperature (SST), atmospheric carbon dioxide (CO(2)), observed coral growth (calcification) rates, and observed mortality linked to mass coral bleaching episodes as inputs. SST and CO(2) predictions were derived from the World Climate Research Programme (WCRP) multi-model dataset, statistically downscaled with historical data. CONCLUSIONS/SIGNIFICANCE: The model calculations illustrate a practical approach to systematic evaluation of climate change effects on corals, and also show the effect of uncertainties in current climate predictions and in coral adaptation capabilities on estimated changes in coral cover. Despite these large uncertainties, this analysis quantitatively illustrates that a large decline in coral cover is highly likely in the 21(st) Century, but that there are significant spatial and temporal variances in outcomes, even under a single climate change scenario

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

Alpha-melanocyte stimulating hormone (alpha-MSH) is known to have pleiotrophic functions including pigmentary, anti-inflammatory, antipyretic and immunoregulatory roles in the mammalian body. It is also reported to influence melanoma invasion with levels of alpha-, beta- and gamma-MSH correlated clinically with malignant melanoma development, but other studies suggest alpha-MSH acts to retard invasion. In the present study, we investigated the action of alpha-MSH on three human melanoma cell lines (HBL, A375-SM and C8161) differing in metastatic potential. alpha-melanocyte-simulating hormone reduced invasion through fibronectin and also through a human reconstructed skin composite model for the HBL line, and inhibited proinflammatory cytokine-stimulated activation of the NF-kappaB transcription factor. However, A375-SM and C8161 cells did not respond to alpha-MSH. Immunofluorescent microscopy and Western blotting identified melanocortin-1 receptor (MC-1R) expression for all three lines and MC-2R on HBL and A375-SM lines. Receptor binding identified a similar affinity for alpha-MSH for all three lines with the highest number of binding sites on HBL cells. Only the HBL melanoma line demonstrated a detectable cyclic adenosine monophosphate (cAMP) response to alpha-MSH, although all three lines responded to acute alpha-MSH addition (+(-)-N(6)-(2-phenylisopropyl)-adenosine (PIA)) with an elevation in intracellular calcium. The nonresponsive lines displayed MC-1R polymorphisms (C8161, Arg (wt) 151/Cys 151; A375-SM, homozygous Cys 151), whereas the HBL line was wild type. Stable transfection of the C8161 line with wild-type MC-1R produced cells whose invasion was significantly inhibited by alpha-MSH. From this data, we conclude that alpha-MSH can reduce melanoma cell invasion and protect cells against proinflammatory cytokine attack in cells with the wild-type receptor (HBL).Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Effect of Pneumococcal Conjugate Vaccination on Serotype-Specific Carriage and Invasive Disease in England: A Cross-Sectional Study

A cross sectional study by Stefan Flasche and coworkers document the serotype replacement of Streptococcus pneumoniae that has occurred in England since the introduction of PCV7 vaccination

Pneumococcal serotype trends, surveillance and risk factors in UK adult pneumonia, 2013-18.

BACKGROUND: Changes over the last 5 years (2013-18) in the serotypes implicated in adult pneumococcal pneumonia and the patient groups associated with vaccine-type disease are largely unknown. METHODS: We conducted a population-based prospective cohort study of adults admitted to two large university hospitals with community-acquired pneumonia (CAP) between September 2013 and August 2018. Pneumococcal serotypes were identified using a novel 24-valent urinary monoclonal antibody assay and from blood cultures. Trends in incidence rates were compared against national invasive pneumococcal disease (IPD) data. Persons at risk of vaccine-type pneumonia (pneumococcal conjugate vaccine (PCV)13 and pneumococcal polysaccharide vaccine (PPV)23) were determined from multivariate analyses. FINDINGS: Of 2934 adults hospitalised with CAP, 1075 (36.6%) had pneumococcal pneumonia. The annual incidence of pneumococcal pneumonia increased from 32.2 to 48.2 per 100 000 population (2013-18), predominantly due to increases in PCV13non7-serotype and non-vaccine type (NVT)-serotype pneumonia (annual incidence rate ratio 1.12, 95% CI 1.04 to 1.21 and 1.19, 95% CI 1.10 to 1.28, respectively). Incidence trends were broadly similar to IPD data. PCV13non7 (56.9% serotype 3) and PPV23non13 (44.1% serotype 8) serotypes were identified in 349 (32.5%) and 431 (40.1%) patients with pneumococcal pneumonia, respectively. PCV13-serotype pneumonia (dominated by serotype 3) was more likely in patients in the UK pneumococcal vaccination clinical risk group (adjusted OR (aOR) 1.73, 95% CI 1.31 to 2.28) while PPV23-serotype pneumonia was more likely in patients outside the clinical risk group (aOR 1.54, 95% CI 1.13 to 2.10). INTERPRETATION: The incidence of pneumococcal CAP is increasing, predominantly due to NVT serotypes and serotype 3. PPV23-serotype pneumonia is more likely in adults outside currently identified clinical risk groups