ABSTRACT The Kepler Space Telescope is currently searching for planets transiting stars along the ecliptic plane as part of its extended K2 mission. We processed the publicly released data from the ...first year of K2 observations (Campaigns 0, 1, 2, and 3) and searched for periodic eclipse signals consistent with planetary transits. Out of the 59,174 targets that we searched, we detect 234 planetary candidates around 208 stars. These candidates range in size from gas giants to smaller than the Earth, and range in orbital periods from hours to over a month. We conducted initial reconnaissance spectroscopy of 68 of the brighter candidate host stars, and present high-resolution optical spectra for these stars. We make all of our data products, including light curves, spectra, and vetting diagnostics available to users online.
The Kepler Space Telescope is currently searching for planets transiting stars along the ecliptic plane as part of its extended K2 mission. We processed the publicly released data from the first year ...of K2 observations (Campaigns 0, 1, 2, and 3) and searched for periodic eclipse signals consistent with planetary transits. Out of 59,174 targets we searched, we detect 234 planetary candidates around 208 stars. These candidates range in size from gas giants to smaller than the Earth, and range in orbital periods from hours to over a month. We conducted initial reconnaissance spectroscopy of 68 of the brighter candidate host stars, and present high resolution optical spectra for these stars. We make all of our data products, including light curves, spectra, and vetting diagnostics available to users online.
Background: Evidence is limited on ethnic differences in associations between kidney function markers and mortality or cardiovascular disease (CVD). Methods: Baseline cross-sectional analysis and ...longitudinal follow-up study of a UK population-based cohort of 1,116 Europeans and 1,104 South Asians of predominantly Indian descent, age 52 ± 7 years at baseline (1988–1991). Kidney function was estimated using Cystatin C and creatinine-based chronic kidney disease (CKD) Epidemiology Collaboration estimated glomerular filtration rate (eGFR) equations, and urinary albumin-creatinine ratio (ACR). Mortality was captured at 27 years, and incident CVD at 22 years, from death certification, medical records and participant report. Longitudinal associations between eGFR/ACR and mortality/incident CVD were examined using Cox models. Results: eGFR cys was lower and ACR higher in South Asians than Europeans. eGFR cys and eGFR creat were more strongly associated with outcomes in Europeans than South Asians. Conversely, associations between ACR and outcomes were greater in South Asians than Europeans, for example, for CVD mortality: HRs (95% CI) adjusted for CVD risk factors and ACR/eGFR cys as appropriate, p for ethnicity interaction: eGFR cys : Europeans: 0.76 (0.62–0.92), South Asians: 0.92 (0.78–1.07), p = 0.05, eGFR creat : Europeans 0.81 (0.67–0.99), South Asians 1.18 (0.97–1.41), p = 0.002, ACR: Europeans: 1.24 (1.08–1.42), South Asians: 1.39 (1.25–1.57), p= 0.23. Addition of all CKD measures to a standard CVD risk factor model modestly improved prediction capability in Europeans; in South Asians only ACR contributed to improvement. Conclusions: Strong associations between ACR and outcomes in South Asians of predominantly Indian origin, and null associations for eGFR cys and eGFR creat , suggest that ACR may have greater utility in CVD risk prediction in South Asians. Further work is needed to validate these findings.
The minimal information for studies of extracellular vesicles (EVs, MISEV) is a field‐consensus rigour initiative of the International Society for Extracellular Vesicles (ISEV). The last update to ...MISEV, MISEV2018, was informed by input from more than 400 scientists and made recommendations in the six broad topics of EV nomenclature, sample collection and pre‐processing, EV separation and concentration, characterization, functional studies, and reporting requirements/exceptions. To gather opinions on MISEV and ideas for new updates, the ISEV Board of Directors canvassed previous MISEV authors and society members. Here, we share conclusions that are relevant to the ongoing evolution of the MISEV initiative and other ISEV rigour and standardization efforts.
Little is known about the neural substrates of suicide risk in mood disorders. Improving the identification of biomarkers of suicide risk, as indicated by a history of suicide-related behavior (SB), ...could lead to more targeted treatments to reduce risk.
Participants were 18 young adults with a mood disorder with a history of SB (as indicated by endorsing a past suicide attempt), 60 with a mood disorder with a history of suicidal ideation (SI) but not SB, 52 with a mood disorder with no history of SI or SB (MD), and 82 healthy comparison participants (HC). Resting-state functional connectivity within and between intrinsic neural networks, including cognitive control network (CCN), salience and emotion network (SEN), and default mode network (DMN), was compared between groups.
Several fronto-parietal regions (k > 57, p < 0.005) were identified in which individuals with SB demonstrated distinct patterns of connectivity within (in the CCN) and across networks (CCN-SEN and CCN-DMN). Connectivity with some of these same regions also distinguished the SB group when participants were re-scanned after 1-4 months. Extracted data defined SB group membership with good accuracy, sensitivity, and specificity (79-88%).
These results suggest that individuals with a history of SB in the context of mood disorders may show reliably distinct patterns of intrinsic network connectivity, even when compared to those with mood disorders without SB. Resting-state fMRI is a promising tool for identifying subtypes of patients with mood disorders who may be at risk for suicidal behavior.
Background
Operating room (OR) practice during the COVID‐19 pandemic is driven by basic principles, shared experience and nascent literature. This study aimed to identify the knowledge needs of the ...global OR workforce, and characterize supportive evidence to establish consensus.
Methods
A rapid, modified Delphi exercise was performed, open to all stakeholders, informed via an online international collaborative evaluation.
Results
The consensus exercise was completed by 339 individuals from 41 countries (64·3 per cent UK). Consensus was reached on 71 of 100 statements, predominantly standardization of OR pathways, OR staffing and preoperative screening or diagnosis. The highest levels of consensus were observed in statements relating to appropriate personal protective equipment (PPE) and risk distribution (96–99 per cent), clear consent processes (96 per cent), multidisciplinary decision‐making and working (97 per cent). Statements yielding equivocal responses predominantly related to technical and procedure choices, including: decontamination (40–68 per cent), laminar flow systems (13–61 per cent), PPE reuse (58 per cent), risk stratification of patients (21–48 per cent), open versus laparoscopic surgery (63 per cent), preferential cholecystostomy in biliary disease (48 per cent), and definition of aerosol‐generating procedures (19 per cent).
Conclusion
High levels of consensus existed for many statements within each domain, supporting much of the initial guidance issued by professional bodies. However, there were several contentious areas, which represent urgent targets for investigation to delineate safe COVID‐19‐related OR practice.
Antecedentes
La práctica en el quirófano (operating room, OR) durante la pandemia por la COVID‐ 19 se basa en principios básicos, experiencias compartidas y literatura reciente. Este estudio tuvo como objetivo identificar las necesidades de conocimiento global del personal de quirófano y caracterizar la evidencia existente para establecer un consenso.
Métodos
Se realizó un estudio basado en una metodología Delphi modificada y rápida, abierta a todos los interesados y a través de una evaluación colaborativa internacional online.
Resultados
El procedimiento de consenso fue completado por 339 personas de 41 países (64% Reino Unido). Se llegó a un consenso en 71/100 ítems, predominantemente en relación a la estandarización de los circuitos en OR, la dotación de personal y el cribaje preoperatorio o el diagnóstico. Los niveles más altos de consenso se observaron en los ítems relacionadas con el equipo personal y de protección (personal protective equipment, PPE) apropiado y la distribución de riesgos (96‐99%), claridad en los procesos de consentimiento (96%), toma de decisiones multidisciplinarias y trabajo (97%). Los ítems que generaron respuestas equívocas estaban relacionadas principalmente con opciones técnicas y de procedimiento, incluyendo: descontaminación (40‐68%), sistemas de flujo laminar (13‐61%), reutilización de PPE (58%), estratificación de los pacientes por riesgo (21‐48%), cirugía abierta versus laparoscópica (63%), colecistostomía preferente en patología biliar (48%) y definición de procedimientos generadores de aerosol (19%).
Conclusión
Existieron altos niveles de consenso para muchos ítems dentro de cada ámbito, apoyando gran parte de la orientación inicial emitida por los organismos profesionales. Sin embargo, surgieron varias áreas polémicas, que representan objetivos urgentes para la investigación para poder definir la práctica segura en OR relacionada con la COVID‐19.
This study has revealed global expert consensus on operating room practice during the COVID‐19 pandemic. Across 41 countries, 339 worldwide experts demonstrated consensus regarding 71 of 100 statements, supporting much of the initial guidance issued by a number of professional organizations. Non‐consensus items represent research targets.
Precaution and prevention
Aims/hypothesis
Diabetic cardiomyopathy (DCM) is a serious and under-recognised complication of diabetes. The first sign is diastolic dysfunction, which progresses to heart failure. The ...pathophysiology of DCM is incompletely understood but microcirculatory changes are important. Endothelial glycocalyx (eGlx) plays multiple vital roles in the microcirculation, including in the regulation of vascular permeability, and is compromised in diabetes but has not previously been studied in the coronary microcirculation in diabetes. We hypothesised that eGlx damage in the coronary microcirculation contributes to increased microvascular permeability and hence to cardiac dysfunction.
Methods
We investigated eGlx damage and cardiomyopathy in mouse models of type 1 (streptozotocin-induced) and type 2 (
db
/
db
) diabetes. Cardiac dysfunction was determined by echocardiography. We obtained eGlx depth and coverage by transmission electron microscopy (TEM) on mouse hearts perfusion-fixed with glutaraldehyde and Alcian Blue. Perivascular oedema was assessed from TEM images by measuring the perivascular space area. Lectin-based fluorescence was developed to study eGlx in paraformaldehyde-fixed mouse and human tissues. The eGlx of human conditionally immortalised coronary microvascular endothelial cells (CMVECs) in culture was removed with eGlx-degrading enzymes before measurement of protein passage across the cell monolayer. The mechanism of eGlx damage in the diabetic heart was investigated by quantitative reverse transcription-PCR array and matrix metalloproteinase (MMP) activity assay. To directly demonstrate that eGlx damage disturbs cardiac function, isolated rat hearts were treated with enzymes in a Langendorff preparation. Angiopoietin 1 (Ang1) is known to restore eGlx and so was used to investigate whether eGlx restoration reverses diastolic dysfunction in mice with type 1 diabetes.
Results
In a mouse model of type 1 diabetes, diastolic dysfunction (confirmed by echocardiography) was associated with loss of eGlx from CMVECs and the development of perivascular oedema, suggesting increased microvascular permeability. We confirmed in vitro that eGlx removal increases CMVEC monolayer permeability. We identified increased MMP activity as a potential mechanism of eGlx damage and we observed loss of syndecan 4 consistent with MMP activity. In a mouse model of type 2 diabetes we found a similar loss of eGlx preceding the development of diastolic dysfunction. We used isolated rat hearts to demonstrate that eGlx damage (induced by enzymes) is sufficient to disturb cardiac function. Ang1 restored eGlx and this was associated with reduced perivascular oedema and amelioration of the diastolic dysfunction seen in mice with type 1 diabetes.
Conclusions/interpretation
The association of CMVEC glycocalyx damage with diastolic dysfunction in two diabetes models suggests that it may play a pathophysiological role and the enzyme studies confirm that eGlx damage is sufficient to impair cardiac function. Ang1 rapidly restores the CMVEC glycocalyx and improves diastolic function. Our work identifies CMVEC glycocalyx damage as a potential contributor to the development of DCM and therefore as a therapeutic target.
Graphical abstract
Objective
To assess changes in presentations to EDs during the COVID‐19 pandemic lockdown in the Southern Region of New Zealand.
Methods
We conducted a retrospective audit of patients attending EDs ...in the Southern District Health Board (SDHB), from 1 March to 13 May 2020. We made comparisons with attendances during the same period in 2019. The 2020 study period included ‘pre‐lockdown’ (1 March–25 March), ‘level 4 (strict) lockdown’ (26 March–27 April) and ‘level 3 (eased) lockdown’ (28 April–13 May).
Results
Patient volumes reduced in all SDHB EDs during levels 4 and 3, mostly representing a loss of low acuity patients (Australasian Triage Scale 3, 4 and 5), although high‐acuity presentations also declined. Average patient age increased by 5 years; however, the proportions of sexes and ethnicities did not change. Presentations of cerebrovascular accidents and appendicitis did not change significantly. Trauma, mental health, acute coronary syndrome and infectious respiratory presentations decreased significantly during level 4, and infectious respiratory presentations decreased further in level 3.
Conclusions
Within the SDHB, patient volumes reduced during levels 4 and 3 of our lockdown, with reduced low‐acuity presentations. High‐acuity patient numbers also declined. Trauma, mental health, alcohol‐related, infectious respiratory and acute coronary syndrome presentations declined while cerebrovascular accident and appendicitis numbers showed little to no change.
We assessed changes in presentations to EDs during the COVID‐19 pandemic lockdown in the Southern Region of New Zealand. Patient volumes reduced during levels 4 and 3 of our lockdown, with reduced low‐acuity presentations. High‐acuity patient numbers also declined. Trauma, mental health, alcohol‐related, infectious respiratory and acute coronary syndrome presentations declined while cerebrovascular accident and appendicitis showed little‐to‐no change.
Genomic tests are being developed for use in cancer screening. As most screening is offered in primary care settings, primary care provider and patient perceptions of such tests are likely to affect ...uptake. We conducted a scoping review to synthesize information on factors likely to affect patient and provider use of biospecimen collection and analysis for cancer screening, methods referred to as liquid biopsy or multi-cancer early detection (MCED) testing when used to detect multiple cancers. We ultimately identified 7 articles for review and analyzed them for major themes. None reported on primary care provider perspectives. Six articles focused on patient perceptions about testing for a single cancer (colorectal), and 1 reported on patient views related to testing for multiple cancers. Factors favoring this type of testing included its non-invasiveness, and the perceived safety, convenience, and effectiveness of testing. There is a dearth of information in the literature on primary care provider perceptions about liquid biopsy and MCED testing. The limited information on patient perceptions suggests that they are receptive to such tests. Research on primary care provider and patient test-related knowledge, attitudes, and behavior is needed to guide future implementation in primary care settings.
Background Blood pressure and tissue perfusion are controlled in part by the level of intrinsic (myogenic) arterial tone. However, many of the molecular determinants of this response are unknown. We ...previously found that mice with targeted disruption of the gene encoding the angiotensin II type 1a receptor (AT1AR) (Agtr1a), the major murine angiotensin II type 1 receptor (AT1R) isoform, showed reduced myogenic tone; however, uncontrolled genetic events (in this case, gene ablation) can lead to phenotypes that are difficult or impossible to interpret. Methods and Results We tested the mechanosensitive function of AT1R using tamoxifen‐inducible smooth muscle‐specific AT1aR knockout (smooth muscle‐Agtr1a−/−) mice and studied downstream signaling cascades mediated by Gq/11 and/or β‐arrestins. FR900359, Sar1Ile4Ile8‐angiotensin II (SII), TRV120027 and TRV120055 were used as selective Gq/11 inhibitor and biased agonists to activate noncanonical β‐arrestin and canonical Gq/11 signaling of the AT1R, respectively. Myogenic and Ang II‐induced constrictions were diminished in the perfused renal vasculature, mesenteric and cerebral arteries of smooth muscle‐Agtr1a−/− mice. Similar effects were observed in arteries of global mutant Agtr1a−/− but not Agtr1b−/− mice. FR900359 decreased myogenic tone and angiotensin II‐induced constrictions whereas selective biased targeting of AT1R‐β‐arrestin signaling pathways had no effects. Conclusions This study demonstrates that myogenic arterial constriction requires Gq/11‐dependent signaling pathways of mechanoactivated AT1R but not G protein‐independent, noncanonical pathways in smooth muscle cells.
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