Identifying Patients at High Risk of a Cardiovascular Event in the Near Future Current Status and Future Directions: Report of a National Heart, Lung, and Blood Institute Working Group

The National Heart, Lung, and Blood Institute convened a working group to provide basic and clinical research recommendations to the National Heart, Lung, and Blood Institute on the development of an integrated approach for identifying those individuals who are at high risk for a cardiovascular event such as acute coronary syndromes (ACS) or sudden cardiac death in the “near term.” The working group members defined near-term as occurring within 1 year of the time of assessment. The participants reviewed current clinical cardiology practices for risk assessment and state-of-the-science techniques in several areas, including biomarkers, proteomics, genetics, psychosocial factors, imaging, coagulation, and vascular and myocardial susceptibility. This report presents highlights of these reviews and a summary of suggested research directions

UK pneumonectomy outcome study (UKPOS): a prospective observational study of pneumonectomy outcome

<p>Abstract</p> <p>Background</p> <p>In order to assess the short term risks of pneumonectomy for lung cancer in contemporary practice a one year prospective observational study of pneumonectomy outcome was made. Current UK practice for pneumonectomy was observed to note patient and treatment factors associated with major complications.</p> <p>Methods</p> <p>A multicentre, prospective, observational cohort study was performed. All 35 UK thoracic surgical centres were invited to submit data to the study. All adult patients undergoing pneumonectomy for lung cancer between 1 January and 31 December 2005 were included. Patients undergoing pleuropneumonectomy, extended pneumonectomy, completion pneumonectomy following previous lobectomy and pneumonectomy for benign disease, were excluded from the study.</p> <p>The main outcome measure was suffering a major complication. Major complications were defined as: death within 30 days of surgery; treated cardiac arrhythmia or hypotension; unplanned intensive care admission; further surgery or inotrope usage.</p> <p>Results</p> <p>312 pneumonectomies from 28 participating centres were entered. The major complication incidence was: 30-day mortality 5.4%; treated cardiac arrhythmia 19.9%; unplanned intensive care unit admission 9.3%; further surgery 4.8%; inotrope usage 3.5%. Age, American Society of Anesthesiologists physical status ≥ P3, pre-operative diffusing capacity for carbon monoxide (DLCO) and epidural analgesia were collectively the strongest risk factors for major complications. Major complications prolonged median hospital stay by 2 days.</p> <p>Conclusion</p> <p>The 30 day mortality rate was less than 8%, in agreement with the British Thoracic Society guidelines. Pneumonectomy was associated with a high rate of major complications. Age, ASA physical status, DLCO and epidural analgesia appeared collectively most associated with major complications.</p

Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis.

BACKGROUND: Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barrett's oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barrett's oesophagus and oesophageal adenocarcinoma. METHODS: We did a meta-analysis of all genome-wide association studies of Barrett's oesophagus and oesophageal adenocarcinoma available in PubMed up to Feb 29, 2016; all patients were of European ancestry and disease was confirmed histopathologically. All participants were from four separate studies within Europe, North America, and Australia and were genotyped on high-density single nucleotide polymorphism (SNP) arrays. Meta-analysis was done with a fixed-effects inverse variance-weighting approach and with a standard genome-wide significance threshold (p<5 × 10-8). We also did an association analysis after reweighting of loci with an approach that investigates annotation enrichment among genome-wide significant loci. Furthermore, the entire dataset was analysed with bioinformatics approaches-including functional annotation databases and gene-based and pathway-based methods-to identify pathophysiologically relevant cellular mechanisms. FINDINGS: Our sample comprised 6167 patients with Barrett's oesophagus and 4112 individuals with oesophageal adenocarcinoma, in addition to 17 159 representative controls from four genome-wide association studies in Europe, North America, and Australia. We identified eight new risk loci associated with either Barrett's oesophagus or oesophageal adenocarcinoma, within or near the genes CFTR (rs17451754; p=4·8 × 10-10), MSRA (rs17749155; p=5·2 × 10-10), LINC00208 and BLK (rs10108511; p=2·1 × 10-9), KHDRBS2 (rs62423175; p=3·0 × 10-9), TPPP and CEP72 (rs9918259; p=3·2 × 10-9), TMOD1 (rs7852462; p=1·5 × 10-8), SATB2 (rs139606545; p=2·0 × 10-8), and HTR3C and ABCC5 (rs9823696; p=1·6 × 10-8). The locus identified near HTR3C and ABCC5 (rs9823696) was associated specifically with oesophageal adenocarcinoma (p=1·6 × 10-8) and was independent of Barrett's oesophagus development (p=0·45). A ninth novel risk locus was identified within the gene LPA (rs12207195; posterior probability 0·925) after reweighting with significantly enriched annotations. The strongest disease pathways identified (p<10-6) belonged to muscle cell differentiation and to mesenchyme development and differentiation. INTERPRETATION: Our meta-analysis of genome-wide association studies doubled the number of known risk loci for Barrett's oesophagus and oesophageal adenocarcinoma and revealed new insights into causes of these diseases. Furthermore, the specific association between oesophageal adenocarcinoma and the locus near HTR3C and ABCC5 might constitute a novel genetic marker for prediction of the transition from Barrett's oesophagus to oesophageal adenocarcinoma. Fine-mapping and functional studies of new risk loci could lead to identification of key molecules in the development of Barrett's oesophagus and oesophageal adenocarcinoma, which might encourage development of advanced prevention and intervention strategies. FUNDING: US National Cancer Institute, US National Institutes of Health, National Health and Medical Research Council of Australia, Swedish Cancer Society, Medical Research Council UK, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Else Kröner Fresenius Stiftung, Wellcome Trust, Cancer Research UK, AstraZeneca UK, University Hospitals of Leicester, University of Oxford, Australian Research Council

Late Holocene linkages between decade–century scale climate variability and productivity at Lake Tanganyika, Africa

Microlaminated sediment cores from the Kalya slope region of Lake Tanganyika provide a near-annually resolved paleoclimate record between ~~2,840 and 1,420 cal. yr B.P. demonstrating strong linkages between climate variability and lacustrine productivity. Laminae couplets comprise dark, terrigenous-dominated half couplets, interpreted as low density underflows deposited from riverine sources during the rainy season, alternating with light, planktonic diatomaceous ooze, with little terrigenous component, interpreted as windy/dry season deposits. Laminated portions of the studied cores consist of conspicuous dark and light colored bundles of laminae couplets. Light and dark bundles alternate at decadal time scales. Within dark bundles, both light and dark half couplets are significantly thinner than within light bundles, implying slower sediment accumulation rates during both seasons over those intervals. Time series analyses of laminae thickness patterns demonstrate significant periodicities at interannual¿centennial time scales. Longer time scale periodicities (multidecadal to centennial scale) of light and dark half couplet thicknesses are coherent and in some cases are similar to solar cycle periods on these time scales. Although laminae thickness cycles do not strongly covary with the actual ¿14C record for this same time period, two large ¿14C anomalies are associated with substantial decreases in both light and dark laminae thickness. In contrast to the multidecadal¿ centennial time scale, significant annual to decadal periodicities, which are broadly consistent with ENSO/PDO forcing and their impact on East African climate, are not coherent between light and dark half couplets. The coherency of light¿dark couplets at decadal¿centennial time scales, but not at shorter time scales, is consistent with a model of a long-term relationship between precipitation (recorded in wet season dark laminae thickness) and productivity (light laminae thickness), which is not manifest at shorter time scales. We hypothesize that this coupling results from long-term recharging of internal nutrient loading during wet periods (higher erosion of soil P) and reduced loading during drought intervals. The relationship is not expressed on short time scales during which the dominant control on productivity is wind-driven, dry season upwelling, which is uncorrelated with wet-season precipitation. Our record greatly extends the temporal record of this quasi-periodic behavior throughout the late Holocene and provides the first evidence linking decade- to century-scale episodes of enhanced productivity to enhanced precipitation levels and nutrient recharge in a productive tropical lake

Table_1_Network analysis and relationship of symptom factors to functional outcomes and quality of life following mild traumatic brain injury: a TRACK-TBI study.docx

IntroductionMild traumatic brain injury (mTBI) is a heterogenous injury which can be difficult to characterize and manage. Using cross-sectional network analysis (NA) to conceptualize mTBI symptoms offers an innovative solution to identify how mTBI symptoms relate to each other. The centrality hypothesis of network theory posits that certain symptoms in a network are more relevant (central) or have above average influence over the rest of the network. However, no studies have used NA to characterize the interrelationships between symptoms in a cohort of patients who presented with mTBI to a U.S. Level 1 trauma center emergency department and how subacute central symptoms relate to long-term outcomes.MethodsPatients with mTBI (Glasgow Coma Scale = 13–15) evaluated across 18 U.S. Level 1 trauma centers from 2013 to 2019 completed the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) at 2 weeks (W2) post-injury (n = 1,593) and at 3 months (M3), 6 months (M6), and 12 months (M12) post-injury. Network maps were developed from RPQ subscale scores at each timepoint. RPQ scores at W2 were associated with M6 and M12 functional and quality of life outcomes.ResultsNetwork structure did not differ across timepoints, indicating no difference in symptoms/factors influence on the overall symptom network across time. The cognitive factor had the highest expected influence at W2 (1.761), M3 (1.245), and M6 (1.349). Fatigue had the highest expected influence at M12 (1.275). The emotional factor was the only other node with expected influence >1 at any timepoint, indicating disproportionate influence of emotional symptoms on overall symptom burden (M3 = 1.011; M6 = 1.076).DiscussionSeveral symptom factors at 2-weeks post-injury were more strongly associated with incomplete recovery and/or poorer injury-related quality of life at 6 and 12 months post-injury than previously validated demographic and clinical covariates. The network analysis suggests that emotional, cognitive, and fatigue symptoms may be useful treatment targets in this population due to high centrality and activating potential of the overall symptom network.</p

Mimicry in coral reef fishes: ecological and behavioural responses of a mimic to its model

Mimicry is a widely documented phenomenon in coral reef fishes, but the underlying relationships between mimics and models are poorly understood. Juveniles of the surgeonfish Acanthurus pyroferus mimic the coloration of different pygmy angelfish Centropyge spp. at different locations throughout the geographic range of the surgeonfish, while adopting a common species-specific coloration as adults. This study examines the ecological and behavioural relationships between A. pyroferus and one of its models, Centropyge vroliki, in Papua New Guinea. Surgeonfish underwent a transition from the juvenile (mimetic) coloration to the adult (non-mimetic) coloration when they reached the maximum size of the angelfish. As typical of mimic-model relationships, mimic surgeonfish were always less abundant than their model. Spatial variation in the abundance of mimics was correlated with models, while the abundance of adults was not. We show that juvenile surgeonfish gain a foraging advantage by mimicking the angelfish. Mimic surgeonfish were always found within 1-2 m of a similar-sized individual of C. vroliki with which they spent c. 10% of their time in close association. When in association with angelfish, juvenile surgeonfish exhibited an increase of c. 10% in the amount of time spent feeding compared to when they were alone. This foraging benefit seems to be explained by reduced aggression by the territorial damselfish Plectroglyphidon lacrymatus, which dominates the reef crest habitat. While adult A. pyroferus and all other surgeonfish were aggressively displaced from damselfish territories, mimic surgeonfish and their models were attacked less frequently and were not always displaced. Stomach contents analysis showed that the diet of C. vroliki differed substantially from P. lacrymatus, while that of A. pyroferus was more similar to the damselfish. We hypothesize that mimics deceive damselfish as to their diet in order to gain access to food supplies in defended areas