Improved care of acute exacerbation of chronic obstructive pulmonary disease in two academic emergency departments

Background: Although several chronic obstructive pulmonary disease (COPD) practice guidelines have been published, there is sparse data on the actual emergency department (ED) management of acute exacerbation of COPD (AECOPD). Aims: Our objectives were to examine concordance of ED care of AECOPD in older patients with guideline recommendations and to evaluate whether concordance has improved over time in two academic EDs. Methods: Data were obtained from two cohort studies on AECOPD performed in two academic EDs during two different time periods, 2000 and 2005–2006. Both studies included ED patients, aged 55 and older, who presented with AECOPD, and cases were confirmed by emergency physicians. Data on ED management and disposition were obtained from chart review for both cohorts. Results: The analysis included 272 patients: 72 in the 2000 database and 200 in the 2005–2006 database. The mean age of the patients was 72 years; 50% were women and 80% white. In 2005–2006, overall concordance with guideline recommendations was high (for chest radiography, pulse oximetry, bronchodilators, all ≥ 90%), except for arterial blood gas testing (7% among the admitted) and discharge medication with systemic corticosteroids (42%). Compared to the 2000 data, the use of systemic corticosteroids in the ED improved from 53 to 77% [absolute improvement: 24%, 95% confidence interval (CI): 11–37%], and the use of antibiotics among the patients with respiratory infection symptoms improved from 56 to 78% (absolute improvement: 22%, 95% CI: 6–38%). Conclusions: Overall concordance with guideline-recommended care for AECOPD was high in two academic EDs, and some emergency treatments have improved over time

Comparing a new risk prediction model with prostate cancer risk calculator apps in a Taiwanese population

PURPOSE: To develop a novel Taiwanese prostate cancer (PCa) risk model for predicting PCa, comparing its predictive performance with that of two well-established PCa risk calculator apps. METHODS: 1545 men undergoing prostate biopsies in a Taiwanese tertiary medical center between 2012 and 2019 were identified retrospectively. A five-fold cross-validated logistic regression risk model was created to calculate the probabilities of PCa and high-grade PCa (Gleason score ≧ 7), to compare those of the Rotterdam and Coral apps. Discrimination was analyzed using the area under the receiver operator characteristic curve (AUC). Calibration was graphically evaluated with the goodness-of-fit test. Decision-curve analysis was performed for clinical utility. At different risk thresholds to biopsy, the proportion of biopsies saved versus low- and high-grade PCa missed were presented. RESULTS: Overall, 278/1309 (21.2%) patients were diagnosed with PCa, and 181 out of 278 (65.1%) patients had high-grade PCa. Both our model and the Rotterdam app demonstrated better discriminative ability than the Coral app for detection of PCa (AUC: 0.795 vs 0.792 vs 0.697, DeLong's method: P < 0.001) and high-grade PCa (AUC: 0.869 vs 0.873 vs 0.767, P < 0.001). Using a ≥ 10% risk threshold for high-grade PCa to biopsy, our model could save 67.2% of total biopsies; among these saved biopsies, only 3.4% high-grade PCa would be missed. CONCLUSION: Our new logistic regression model, similar to the Rotterdam app, outperformed the Coral app in the prediction of PCa and high-grade PCa. Additionally, our model could save unnecessary biopsies and avoid missing clinically significant PCa in the Taiwanese population

Modeling of Polymer Clay Nanocomposite for a Multiscale Approach

The mechanical property enhancement of polymer reinforced with nano-thin clay platelets (of high aspect ratio) is associated with a high polymer-filler interfacial area per unit volume. The ideal case of fully separated (exfoliated) platelets is generally difficult to achieve in practice: a typical nanocomposite also contains multilayer stacks of intercalated platelets. Here we use numerical modelling to investigate how the platelet properties affect the overall mechanical properties. The configuration of platelets is modelled using a statistical interpretation of the Representative Volume Element (RVE) approach, in which an ensemble of "sample" heterogeneous material is generated (with periodic boundary conditions). A simple Monte Carlo algorithm is used to place non-intersecting platelets in the RVE according to a specified set of statistical distributions. The effective stiffness of the platelet-matrix system is determined by measuring the stress (using standard Finite Element analysis) produced as a result of applying a small deformation to the boundaries, and averaging over the entire statistical ensemble. In this work we determine the way in which the platelet properties (curvature, filling fraction, stiffness, aspect ratio) and the number of layers in the stack affect the overall stiffness enhancement of the nanocomposite. Thus, we bridge the gap between behaviour on the macroscopic scale with that on the scale of the nano-reinforcement, forming part of a multi-scale modelling framework.Comment: 39 pages, 19 figure

Population genomics of domestic and wild yeasts

The natural genetics of an organism is determined by the distribution of sequences of its genome. Here we present one- to four-fold, with some deeper, coverage of the genome sequences of over seventy isolates of the domesticated baker&#x27;s yeast, _Saccharomyces cerevisiae_, and its closest relative, the wild _S. paradoxus_, which has never been associated with human activity. These were collected from numerous geographic locations and sources (including wild, clinical, baking, wine, laboratory and food spoilage). These sequences provide an unprecedented view of the population structure, natural (and artificial) selection and genome evolution in these species. Variation in gene content, SNPs, indels, copy numbers and transposable elements provide insights into the evolution of different lineages. Phenotypic variation broadly correlates with global genome-wide phylogenetic relationships however there is no correlation with source. _S. paradoxus_ populations are well delineated along geographic boundaries while the variation among worldwide _S. cerevisiae_ isolates show less differentiation and is comparable to a single _S. paradoxus_ population. Rather than one or two domestication events leading to the extant baker&#x27;s yeasts, the population structure of _S. cerevisiae_ shows a few well defined geographically isolated lineages and many different mosaics of these lineages, supporting the notion that human influence provided the opportunity for outbreeding and production of new combinations of pre-existing variation

Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination

In meiotic DNA recombination, the Hop2-Mnd1 complex promotes Dmc1-mediated single-stranded DNA (ssDNA) invasion into homologous chromosomes to form a synaptic complex by a yet-unclear mechanism. Here, the crystal structure of Hop2-Mnd1 reveals that it forms a curved rod-like structure consisting of three leucine zippers and two kinked junctions. One end of the rod is linked to two juxtaposed winged-helix domains, and the other end is capped by extra ?-helices to form a helical bundle-like structure. Deletion analysis shows that the helical bundle-like structure is sufficient for interacting with the Dmc1-ssDNA nucleofilament, and molecular modeling suggests that the curved rod could be accommodated into the helical groove of the nucleofilament. Remarkably, the winged-helix domains are juxtaposed at fixed relative orientation, and their binding to DNA is likely to perturb the base pairing according to molecular simulations. These findings allow us to propose a model explaining how Hop2-Mnd1 juxtaposes Dmc1-bound ssDNA with distorted recipient double-stranded DNA and thus facilitates strand invasion

Effect of Surface and Bulk Properties of Mesoporous Carbons on the Electrochemical Behavior of GOx-Nanocomposites

Biofuel cell (BFC) electrodes are typically manufactured by combining enzymes that act as catalysts with conductive carbon nanomaterials in a form of enzyme-nanocomposite. However, a little attention has been paid to effects of the carbon nanomaterials' structural properties on the electrochemical performances of the enzyme-nanocomposites. This work aims at studying the effects of surface and bulk properties of carbon nanomaterials with different degrees of graphitization on the electrochemical performances of glucose oxidase (GOx)-nanocomposites produced by immobilizing GOx within a network of carbon nanopaticles. Two types of carbon nanomaterials were used: graphitized mesoporous carbon (GMC) and purified mesoporous carbon (PMC). Graphitization index, surface functional groups, hydrophobic properties, and rate of aggregation were measured for as-received and acid-treated GMC and PMC samples by using Raman spectrometry, X-ray photoelectron spectroscopy (XPS), contact angle measurement, and dynamic light scattering (DLS), respectively. In addition to these physical property characterizations, the enzyme loading and electrochemical performances of the GOx-nanocomposites were studied via elemental analysis and cyclic voltammetry tests, respectively. We also fabricated BFCs using our GOx-nanocomposite materials as the enzyme anodes, and tested their performances by obtaining current-voltage (IV) plots. Our findings suggest that the electrochemical performance of GOx-nanocomposite material is determined by the combined effects of graphitization index, electrical conductivity and surface chemistry of carbon nanomaterials

Sustained effectiveness and cost-effectiveness of Counselling for Alcohol Problems, a brief psychological treatment for harmful drinking in men, delivered by lay counsellors in primary care: 12-month followup of a randomised controlled trial

Background Counselling for Alcohol Problems (CAP), a brief intervention delivered by lay counsellors, enhanced remission and abstinence over 3 months among primary care male attendees with harmful drinking in a setting in India. We evaluate the sustainability of the effects after treatment termination, the cost-effectiveness of CAP over 12 months, and the effects of the hypothesized mediator of ‘readiness to change’ on clinical outcomes. Methods and Findings Male primary care attenders aged 18-65 screening with harmful drinking on the Alcohol Use Disorders Identification Test (AUDIT) were randomized to either CAP plus Enhanced Usual Care (EUC) (n=188) or EUC alone (n=189), of whom 89% completed assessments at 3 months and 84% at 12 months. Primary outcomes were remission and daily standard ethanol consumed in the past 14 days; and the proposed mediating variable was readiness to change at 3 months. CAP participants maintained the gains they showed at the end of treatment through the 12-month follow-up, with the proportion with remission (AUDIT<8: 54.3% vs 31.9%; aPR 1.71 [95% CI 1.32-2.22]; p<0.001) and abstinence in the past 14 days (45.1% vs 26.4%; aOR 1.92 [95% CI 1.19-3.10]; p=0.008) being significantly higher in the EUC plus CAP group than in the EUC alone group. They also fared better on secondary outcomes including recovery (AUDIT<8 at 3 and 12 months: 27.4% vs 15.1%; aPR 1.90 [95% CI 1.21-3.0]; p=0.006); and percent of days abstinent (mean% [SD] 71.0 [38.2] vs 55. 0 [39.8]; AMD 16.1 [95% CI 7.1-25.0]; p=0.001). The intervention effect for remission was higher at 12 months compared to that at 3 months (aPR 1·50 [95% CI 1·09–2·07]. There was no evidence of an intervention effect on Patient Health Questionnaire-9 score, suicidal behaviour, percentage days of heavy drinking, Short Inventory of Problems score, WHO Disability Assessment Schedule II score, days unable to work, and perpetration of intimate partner violence. Economic analyses indicated that CAP was dominant over EUC alone, with lower costs and better outcomes; uncertainty analysis showed a 99% chance of CAP being cost-effective per remission achieved from a health system perspective, using a willingness to pay threshold equivalent to one month’s wages for an unskilled manual worker in Goa. Readiness to change levels at 3 months mediated the effects of CAP on mean daily drinking at 12 months (Indirect effect -6.014, 95% CI -13.99- to -0.046). Serious adverse events were infrequent and prevalence was similar by arm. The methodological limitations of this trial are the susceptibility of self-reported drinking to social desirability bias, the modest participation rates of eligible patients, and examination of mediation effects of only one mediator and in only half of our sample. Conclusions CAP’s superiority over EUC at the end of treatment was largely stable over time and mediated by readiness to change. CAP provides better outcomes at lower costs from a societal perspective

A Novel Application of Amniotic Membrane in Patients with Bullous Keratopathy

To evaluate the efficacy of amniotic membrane in the management of painful bullous keratopathy secondary to the intractable glaucoma and in preventing exposure of drainage devices, we inserted Ahmed valve with amniotic membrane patch graft over the implant itself, and debrided corneal epithelium with amniotic membrane graft over the exposed stroma as a single operation. During the follow-up periods, we monitored vision, intraocular pressure (IOP), presence of ocular pain, and postoperative complications associated with the implants. The mean follow up period was 8.4±3.2 months. IOP was well controlled after the intervention. The preoperative mean IOP was measured as 43.9±9.0 mmHg and lowered to 16.1±1.8 mmHg at the last visit and no complications associated with the implants were noted. Even though the improvement in vision was not prominent, the ocular surface stabilized rapidly and ocular pain associated with bullous keratopathy disappeared soon after surgery. Conclusively the use of amniotic membrane in conjunction with Ahmed valve implantation is an effective way to relieve ocular pain and lessen the chances of complications associated with the implant in patients with intractable glaucoma and bullous keratopathy