ABSTRACT
We present observations of ASASSN-19dj, a nearby tidal disruption event (TDE) discovered in the post-starburst galaxy KUG 0810+227 by the All-Sky Automated Survey for Supernovae (ASAS-SN) at ...a distance of d ≃ 98 Mpc. We observed ASASSN-19dj from −21 to 392 d relative to peak ultraviolet (UV)/optical emission using high-cadence, multiwavelength spectroscopy and photometry. From the ASAS-SN g-band data, we determine that the TDE began to brighten on 2019 February 6.8 and for the first 16 d the rise was consistent with a flux ∝t2 power law. ASASSN-19dj peaked in the UV/optical on 2019 March 6.5 (MJD = 58548.5) at a bolometric luminosity of L = (6.2 ± 0.2) × 1044 erg s−1. Initially remaining roughly constant in X-rays and slowly fading in the UV/optical, the X-ray flux increased by over an order of magnitude ∼225 d after peak, resulting from the expansion of the X-ray emitting region. The late-time X-ray emission is well fitted by a blackbody with an effective radius of ∼1 × 1012 cm and a temperature of ∼6 × 105 K. The X-ray hardness ratio becomes softer after brightening and then returns to a harder state as the X-rays fade. Analysis of Catalina Real-Time Transient Survey images reveals a nuclear outburst roughly 14.5 yr earlier with a smooth decline and a luminosity of LV ≥ 1.4 × 1043 erg s−1, although the nature of the flare is unknown. ASASSN-19dj occurred in the most extreme post-starburst galaxy yet to host a TDE, with Lick HδA = 7.67 ± 0.17 Å.
Background
Surgeons' non‐technical skills are an important part of surgical performance and surgical education. The most widely adopted assessment tool is the Non‐Technical Skills for Surgeons ...(NOTSS) behaviour rating system. Psychometric analysis of this tool to date has focused on inter‐rater reliability and feasibility rather than validation.
Methods
NOTSS assessments were collected from two groups of consultant/attending surgeons in the UK and USA, who rated behaviours of the lead surgeon during a video‐based simulated crisis scenario after either online or classroom instruction. The process of validation consisted of assessing construct validity, scale reliability and concurrent criterion validity, and undertaking a sensitivity analysis. Central to this was confirmatory factor analysis to evaluate the structure of the NOTSS taxonomy.
Results
Some 255 consultant surgeons participated in the study. The four‐category NOTSS model was found to have robust construct validity evidence, and a superior fit compared with alternative models. Logistic regression and sensitivity analysis revealed that, after adjusting for technical skills, for every 1‐point increase in NOTSS score of the lead surgeon, the odds of having a higher versus lower patient safety score was 2·29 times. The same pattern of results was obtained for a broad mix of surgical specialties (UK) as well as a single discipline (cardiothoracic, USA).
Conclusion
The NOTSS tool can be applied in research and education settings to measure non‐technical skills in a valid and efficient manner.
Useful for research and education
Introduction
Cell biological and genetic evidence implicate failures in degrading aggregating proteins, such as tau and TDP‐43, through the autophagy or lysosomal pathways in the pathogenesis of ...frontotemporal lobar degeneration (FTLD).
Methods
We investigated changes in the degradative pathways in 60 patients with different pathological or genetic forms of FTLD employing immunohistochemistry for marker proteins such as lysosomal‐associated membrane proteins 1 (LAMP‐1) and 2 (LAMP‐2), cathepsin D (CTSD) and microtubule‐associated protein 1 light chain 3 alpha (LC3A). Immunostained sections were qualitatively and semi‐quantitatively assessed for the appearance, distribution and intensity of staining in neurones of the dentate gyrus (DG) and CA4 region of the hippocampus, and the temporal cortex (Tcx).
Results
Lower levels of neuronal LAMP‐1 immunostaining were present in the DG and Tcx in FTLD‐tau compared to FTLD‐TDP. There was less LAMP‐1 immunostaining in FTLD‐tau with MAPT mutations, and FTLD‐tau with Pick bodies, compared to FTLD‐TDP types A and B, and less LAMP‐1 immunostaining in FTLD‐TDP type C than in FTLD‐TDP types A and B. There was greater LAMP‐1 immunostaining in GRN mutation which may reflect the underlying type A histology rather than mutation. There were no differences in neuronal LAMP‐2, CTSD, EEA‐1 or LC3A immunostaining between any of the five FTLD histological or four genetic groups, nor between FTLD‐TDP and FTLD‐tau.
Conclusions
The underlying pathological mechanism in FTLD‐tau may lie with a relative deficiency of lysosomes, or defective vesicular transport, whereas the failure to clear TDP‐43 aggregates may lie with lysosomal dysfunction rather than a lack of available lysosomes or degradative enzymes.
The 2019 novel coronavirus disease (COVID-19) has created unprecedented medical challenges. There remains a need for validated risk prediction models to assess short-term mortality risk among ...hospitalized patients with COVID-19. The objective of this study was to develop and validate a 7-day and 14-day mortality risk prediction model for patients hospitalized with COVID-19.
We performed a multicenter retrospective cohort study with a separate multicenter cohort for external validation using two hospitals in New York, NY, and 9 hospitals in Massachusetts, respectively. A total of 664 patients in NY and 265 patients with COVID-19 in Massachusetts, hospitalized from March to April 2020.
We developed a risk model consisting of patient age, hypoxia severity, mean arterial pressure and presence of kidney dysfunction at hospital presentation. Multivariable regression model was based on risk factors selected from univariable and Chi-squared automatic interaction detection analyses. Validation was by receiver operating characteristic curve (discrimination) and Hosmer-Lemeshow goodness of fit (GOF) test (calibration). In internal cross-validation, prediction of 7-day mortality had an AUC of 0.86 (95%CI 0.74-0.98; GOF p = 0.744); while 14-day had an AUC of 0.83 (95%CI 0.69-0.97; GOF p = 0.588). External validation was achieved using 265 patients from an outside cohort and confirmed 7- and 14-day mortality prediction performance with an AUC of 0.85 (95%CI 0.78-0.92; GOF p = 0.340) and 0.83 (95%CI 0.76-0.89; GOF p = 0.471) respectively, along with excellent calibration. Retrospective data collection, short follow-up time, and development in COVID-19 epicenter may limit model generalizability.
The COVID-AID risk tool is a well-calibrated model that demonstrates accuracy in the prediction of both 7-day and 14-day mortality risk among patients hospitalized with COVID-19. This prediction score could assist with resource utilization, patient and caregiver education, and provide a risk stratification instrument for future research trials.
Aims/hypothesis
The aim was to investigate the relationship between severe hypoglycaemia and cognitive impairment in older patients with diabetes.
Methods
A sample of 302 diabetic patients aged ...≥70 years was assessed for dementia or cognitive impairment without dementia in 2001–2002 and a subsample of non-demented patients (
n
= 205) was followed to assess cognitive decline. A history of severe hypoglycaemia was determined from self-reports, physician assessments and records of health service use for hypoglycaemia (HSH). Prospective HSH was determined up to 2006. Data analysis, including multiple logistic and Cox regression models, was used to determine whether: (1) there were cross-sectional associations between hypoglycaemia and cognitive status, (2) historical hypoglycaemia predicted cognitive decline, and (3) baseline cognitive status predicted subsequent HSH.
Results
There were significant cross-sectional associations between both cognitive impairment and dementia and hypoglycaemia. Independent risk factors for future HSH included dementia (hazard ratio 3.00, 95% CI 1.06–8.48) and inability to self-manage medications (hazard ratio 4.17, 95% CI 1.43–12.13). However, there were no significant associations between historical hypoglycaemia, incident HSH and cognitive decline.
Conclusions/interpretation
Dementia is an important risk factor for hypoglycaemia requiring health service utilisation. We found no evidence that hypoglycaemia contributes to cognitive impairment in older patients with diabetes.
Aim
Recurrence after surgery for Crohn’s disease is common. Anastomotic configuration may influence recurrence and the mesentery may be key. Recently the Kono‐S anastomosis and radical mesenteric ...excision have been proposed as methods of reducing recurrence. We analysed the literature pertaining to these novel techniques.
Method
We searched MEDLINE, Embase and the Cochrane Library for, and selected, studies evaluating Kono‐S anastomosis and/or radical mesenteric excision in Crohn’s disease. We assessed methodological quality and risk of bias using the Cochrane risk of bias tool for randomized controlled trials and the Joanna Briggs Institute tool for nonrandomized trials. A narrative synthesis was used to summarize the findings.
Results
Nine studies (896 patients) were identified. Apart from one randomized controlled trial with a low risk of bias the overall level of evidence was poor (Grade IV). The Kono‐S anastomosis was associated with a lower incidence of endoscopic and surgical recurrence (0%–3.4% vs 15%–24.4% respectively). Complications, particularly anastomotic leak rate, were also lower (1.8% vs 9.3% respectively). Evidence from a single poor quality study suggested that mesenteric excision may reduce surgical recurrence rates compared with mesentery preservation.
Conclusion
The existing literature suggests that the Kono‐S anastomosis is safe and may reduce endoscopic and surgical recurrence, but level of evidence is mainly poor. One element of the Kono‐S technique, preservation of the mesentery, may be detrimental to recurrence. Further, higher quality, studies are required to investigate these techniques. Such studies should consider the impact of the degree of mesenteric resection in addition to the anastomosis on disease recurrence.
ASASSN-14ae: a tidal disruption event at 200 Mpc Holoien, T. W.-S; Prieto, J. L; Bersier, D ...
Monthly notices of the Royal Astronomical Society,
12/2014, Letnik:
445, Številka:
3
Journal Article
Recenzirano
ASASSN-14ae is a candidate tidal disruption event (TDE) found at the centre of SDSS J110840.11+340552.2 (d ≃ 200 Mpc) by the All-Sky Automated Survey for Supernovae (ASAS-SN). We present ground-based ...and Swift follow-up photometric and spectroscopic observations of the source, finding that the transient had a peak luminosity of L ≃ 8 × 1043 erg s−1 and a total integrated energy of E ≃ 1.7 × 1050 erg radiated over the ∼5 months of observations presented. The blackbody temperature of the transient remains roughly constant at T ∼ 20 000 K while the luminosity declines by nearly 1.5 orders of magnitude during this time, a drop that is most consistent with an exponential, L ∝ e-t/t
0
with t
0 ≃ 39 d. The source has broad Balmer lines in emission at all epochs as well as a broad He ii feature emerging in later epochs. We compare the colour and spectral evolution to both supernovae and normal AGN to show that ASASSN-14ae does not resemble either type of object and conclude that a TDE is the most likely explanation for our observations. At z = 0.0436, ASASSN-14ae is the lowest-redshift TDE candidate discovered at optical/UV wavelengths to date, and we estimate that ASAS-SN may discover 0.1–3 of these events every year in the future.
Gas- and aerosol-phase measurements of oxidants, biogenic volatile organic compounds (BVOCs) and organic nitrates made during the Southern Oxidant and Aerosol Study (SOAS campaign, Summer 2013) in ...central Alabama show that a nitrate radical (NO3) reaction with monoterpenes leads to significant secondary aerosol formation. Cumulative losses of NO3 to terpenes are correlated with increase in gas- and aerosol-organic nitrate concentrations made during the campaign. Correlation of NO3 radical consumption to organic nitrate aerosol formation as measured by aerosol mass spectrometry and thermal dissociation laser-induced fluorescence suggests a molar yield of aerosol-phase monoterpene nitrates of 23-44 %. Compounds observed via chemical ionization mass spectrometry (CIMS) are correlated to predicted nitrate loss to BVOCs and show C10H17NO5, likely a hydroperoxy nitrate, is a major nitrate-oxidized terpene product being incorporated into aerosols. The comparable isoprene product C5H9NO5 was observed to contribute less than 1 % of the total organic nitrate in the aerosol phase and correlations show that it is principally a gas-phase product from nitrate oxidation of isoprene. Organic nitrates comprise between 30 and 45 % of the NOy budget during SOAS. Inorganic nitrates were also monitored and showed that during incidents of increased coarse-mode mineral dust, HNO3 uptake produced nitrate aerosol mass loading at a rate comparable to that of organic nitrate produced via NO3 + BVOCs.
Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which ...changes provide adaptive benefits. There is widespread recognition of the importance of these evolutionary and ecological processes in cancer, but to date, no system has been proposed for drawing clinically relevant distinctions between how different tumours are evolving. On the basis of a consensus conference of experts in the fields of cancer evolution and cancer ecology, we propose a framework for classifying tumours that is based on four relevant components. These are the diversity of neoplastic cells (intratumoural heterogeneity) and changes over time in that diversity, which make up an evolutionary index (Evo-index), as well as the hazards to neoplastic cell survival and the resources available to neoplastic cells, which make up an ecological index (Eco-index). We review evidence demonstrating the importance of each of these factors and describe multiple methods that can be used to measure them. Development of this classification system holds promise for enabling clinicians to personalize optimal interventions based on the evolvability of the patient's tumour. The Evo- and Eco-indices provide a common lexicon for communicating about how neoplasms change in response to interventions, with potential implications for clinical trials, personalized medicine and basic cancer research.
When human fibroblasts take up plasma low density lipoprotein (LDL), its cholesterol is liberated in lysosomes and eventually reaches the endoplasmic reticulum (ER) where it inhibits cholesterol ...synthesis by blocking activation of SREBPs. This feedback protects against cholesterol overaccumulation in the plasma membrane (PM). But how does ER know whether PM is saturated with cholesterol? In this study, we define three pools of PM cholesterol: (1) a pool accessible to bind 125I-PFO*, a mutant form of bacterial Perfringolysin O, which binds cholesterol in membranes; (2) a sphingomyelin(SM)-sequestered pool that binds 125I-PFO* only after SM is destroyed by sphingomyelinase; and (3) a residual pool that does not bind 125I-PFO* even after sphingomyelinase treatment. When LDL-derived cholesterol leaves lysosomes, it expands PM's PFO-accessible pool and, after a short lag, it also increases the ER's PFO-accessible regulatory pool. This regulatory mechanism allows cells to ensure optimal cholesterol levels in PM while avoiding cholesterol overaccumulation.
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