Temporal-spatial analysis of severe acute respiratory syndrome among hospital inpatients

Background. We report the temporal-spatial spread of severe acute respiratory syndrome (SARS) among inpatients in a hospital ward during a major nosocomial outbreak and discuss possible mechanisms for the outbreak. Methods. All inpatients who had stayed in the same ward as the initial index case patient for any duration before isolation were recruited into a cohort and followed up to document the occurrence of SARS. The normalized concentration of virus-laden aerosols at different locations of the ward was estimated by use of computational fluid dynamics modeling. The attack rates in the various subgroups stratified by bed location were calculated. Multivariate Cox proportional hazards regression was used to document important risk factors. Results. The overall attack rate of SARS was 41% (30 of 74 subjects). It was 65%, 52%, and 18% in the same bay, adjacent bay, and distant bays, respectively (P = .001). Computation fluid dynamics modeling indicated that the normalized concentration of virus-laden aerosols was highest in the same bay and lowest in the distant bays. Cox regression indicated that staying in the ward on 6 or 10 March entailed higher risk, as well as staying in the same or adjacent bays. The epidemic curve showed 2 peaks, and stratified analyses by bed location suggested >1 generation of spread. Conclusions. The temporal-spatial spread of SARS in the ward was consistent with airborne transmission, as modeled by use of computational fluid dynamics. Infected health care workers likely acted as secondary sources in the latter phase of the outbreak. © 2005 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Development and validation of molecular markers for characterization of Boehmeria nivea var. nivea and Boehmeria nivea var. tenacissima

<p>Abstract</p> <p>Background</p> <p>The root of <it>Boehmeria </it>spp (ramie) is a hepatoprotective Chinese herbal medicine. Medicinal properties vary between <it>Boehmeria nivea </it>var. <it>nivea </it>and <it>Boehmeria nivea </it>var. <it>tenacissima</it>, which are local species found in Taiwan. As commercial preparations may use either species, there is a need for a rapid and simple assay to identify variants for quality control.</p> <p>Methods</p> <p>Four methods were developed and tested for their applicability in differentiating the two species. These methods were random amplified polymorphic DNA (RAPD); sequence characterized amplified regions (SCAR); single nucleotide polymorphisms (SNP) and cleaved amplified polymorphic sequences (CAPS).</p> <p>Results</p> <p>Three RAPD markers were developed that produced unique bands in <it>B. nivea </it>var. <it>tenacissima </it>and <it>B. nivea </it>var. <it>nivea</it>. Based on sequenced RAPD bands, one SCAR marker was developed that produced a single DNA band in <it>B. nivea </it>var. <it>nivea</it>. Two SNP markers differentiated between <it>B. nivea </it>var. <it>nivea </it>and <it>B. nivea </it>var. <it>tenacissima </it>based on single nucleotide substitutions. A pair of CAPS oligonucleotides was developed by amplifying a 0.55-kb DNA fragment that exhibited species-specific digestion patterns with restriction enzymes <it>Alf </it>III and <it>Nde </it>I. Consistent results were obtained with all the four markers on all tested <it>Boehmeria </it>lines.</p> <p>Conclusion</p> <p>The present study demonstrates the use of the RAPD, SCAR, SNP and CAPS markers for rapid identification of two closely related <it>Boehmeria </it>species.</p

A simple statistical speech recognition of mandarin monosyllables

Abstract Each mandarin syllable is represented by a sequence of vectors of linear predict coding cepstra (LPCC). Since all syllables have a simple phonetic structure, in our speech recognition, we partition the sequence of LPCC vectors of all syllables into equal segments and average the LPCC vectors in each segment. The mean vector of LPCC is used as the feature of a syllable. Our simple feature does not need any time consuming and complicated nonlinear contraction and expansion as adopted by the dynamic time-warping. We propose several probability distributions for the feature values. A simplified Bayes decision rule is used for classification of mandarin syllables. For the speaker-independent mandarin digits, the recognition rate is 98.6% if a normal distribution is used for feature values and the rate is 98.1% if an exponential distribution is used for the absolute values of the features. The feature proposed in this paper to represent a syllable is the simplest one, much easier to be extracted than any other known features. The computation for feature extraction and classification is much faster and more accurate than using the HMM method or any other known techniques

Controlled Decoding from Language Models

We propose controlled decoding (CD), a novel off-policy reinforcement learning method to control the autoregressive generation from language models towards high reward outcomes. CD solves an off-policy reinforcement learning problem through a value function for the reward, which we call a prefix scorer. The prefix scorer is used at inference time to steer the generation towards higher reward outcomes. We show that the prefix scorer may be trained on (possibly) off-policy data to predict the expected reward when decoding is continued from a partially decoded response. We empirically demonstrate that CD is effective as a control mechanism on Reddit conversations corpus. We also show that the modularity of the design of CD makes it possible to control for multiple rewards, effectively solving a multi-objective reinforcement learning problem with no additional complexity. Finally, we show that CD can be applied in a novel blockwise fashion at inference-time, again without the need for any training-time changes, essentially bridging the gap between the popular best-of-$K$ strategy and token-level reinforcement learning. This makes CD a promising approach for alignment of language models

How students cope with part-time study

This study provides a qualitative test and illustration of a model of how students cope with the demands of part-time study. The model shows that students who are successful in finding the time to complete the requirements of part-time courses do so by adopting three mechanisms; sacrifice, support and the negotiation of arrangements. All three mechanisms operate in four domains, namely work, family, social lives and the self. The mechanisms and domains were related together in a three by four matrix. Data to verify and illuminate the model were gathered by the researchers through an on-line forum discussion on the topic of coping with part-time study. The researchers themselves were studying part-time in a course called Adult Education and Professional Development. Analysis of the data showed that the work domain was very important but little adaptation was possible. The family was seen as the most important domain and all three mechanisms were used. Time was commonly found for part-time study by sacrificing social lives. The self-domain was interpreted as important in establishing motivation and self-determination

Cluster of SARS among Medical Students Exposed to Single Patient, Hong Kong

We studied transmission patterns of severe acute respiratory syndrome (SARS) among medical students exposed exclusively to the first SARS patient in the Prince of Wales Hospital in Hong Kong, before his illness was recognized. We conducted a retrospective cohort study of 66 medical students who visited the index patient’s ward, including 16 students with SARS and 50 healthy students. The risk of contracting SARS was sevenfold greater among students who definitely visited the index case’s cubicle than in those who did not (10/27 [41%] versus 1/20 [5%], relative risk [RR] 7.4; 95% confidence interval [CI] 1.0 to 53.3). Illness rates increased directly with proximity of exposure to the index case. However, four of eight students who were in the same cubicle, but were not within 1 m of the index case-patient, contracted SARS. Proximity to the index case-patient was associated with transmission, which is consistent with droplet spread. Transmission through fomites or small aerosols cannot be ruled out

Development of Interstitial Lung Disease Among Patients With Atrial Fibrillation Receiving Oral Anticoagulants in Taiwan.

ImportanceThere are emerging concerns from case reports and pharmacovigilance analyses of a possible risk of interstitial lung disease (ILD) associated with the use of factor Xa (FXa) inhibitors.ObjectiveTo evaluate the risk of incident ILD associated with the use of oral anticoagulants (OACs) in patients with nonvalvular atrial fibrillation (NVAF).Design, setting, and participantsThis nationwide retrospective cohort study used data from the Taiwan National Health Insurance Research Database. Patients with NVAF without preexisting lung disease who received OACs from June 1, 2012, to December 31, 2017, were included. Propensity score stabilized weighting (PSSW) was used to balance covariates across the medication groups (FXa inhibitors, dabigatran, and warfarin, with warfarin as the reference). Patients were followed up from the drug index date until the onset of ILD, death, or end of the study (December 31, 2019), whichever occurred first. Data were analyzed from September 11, 2021, to August 3, 2022.ExposuresPatients with NVAF were treated with FXa inhibitors, dabigatran, or warfarin.Main outcomes and measuresNew-onset idiopathic ILD.ResultsAmong the 106 044 patients (mean [SD] age, 73.4 [11.9] years; 59 995 men [56.6%]) included in the study, 64 555 (60.9%) received FXa inhibitors (apixban [n = 15 386], edoxaban [n = 12 413], and rivaroxaban [n = 36 756]), 22 501 (21.2%) received dabigatran, and 18 988 (17.9%) received warfarin at baseline. The FXa inhibitors were associated with a higher risk of incident ILD (0.29 vs 0.17 per 100 patient-years; hazard ratio, 1.54 [95% CI, 1.22-1.94]; P Conclusions and relevanceResults of this study suggest that FXa inhibitors were associated with lung injury among patients with NVAF who were treated with OACs. Physicians should be vigilant in monitoring for any potential adverse lung outcomes associated with the use of these drugs

Whole-Genome Cartography of Estrogen Receptor α Binding Sites

Using a chromatin immunoprecipitation-paired end diTag cloning and sequencing strategy, we mapped estrogen receptor α (ERα) binding sites in MCF-7 breast cancer cells. We identified 1,234 high confidence binding clusters of which 94% are projected to be bona fide ERα binding regions. Only 5% of the mapped estrogen receptor binding sites are located within 5 kb upstream of the transcriptional start sites of adjacent genes, regions containing the proximal promoters, whereas vast majority of the sites are mapped to intronic or distal locations (>5 kb from 5′ and 3′ ends of adjacent transcript), suggesting transcriptional regulatory mechanisms over significant physical distances. Of all the identified sites, 71% harbored putative full estrogen response elements (EREs), 25% bore ERE half sites, and only 4% had no recognizable ERE sequences. Genes in the vicinity of ERα binding sites were enriched for regulation by estradiol in MCF-7 cells, and their expression profiles in patient samples segregate ERα-positive from ERα-negative breast tumors. The expression dynamics of the genes adjacent to ERα binding sites suggest a direct induction of gene expression through binding to ERE-like sequences, whereas transcriptional repression by ERα appears to be through indirect mechanisms. Our analysis also indicates a number of candidate transcription factor binding sites adjacent to occupied EREs at frequencies much greater than by chance, including the previously reported FOXA1 sites, and demonstrate the potential involvement of one such putative adjacent factor, Sp1, in the global regulation of ERα target genes. Unexpectedly, we found that only 22%–24% of the bona fide human ERα binding sites were overlapping conserved regions in whole genome vertebrate alignments, which suggest limited conservation of functional binding sites. Taken together, this genome-scale analysis suggests complex but definable rules governing ERα binding and gene regulation

The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: a nationwide cohort study.

BackgroundAlthough a few meta-analyses were conducted to compare the risk of incident atrial fibrillation (AF) between sodium-glucose cotransporter-2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and other anti-hyperglycemic agents using indirect or direct comparison, the above analyses showed conflicting results with each other. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i, GLP-1RA, and dipeptidyl peptidase-4 inhibitor (DPP4i) among a large longitudinal cohort of diabetic patients.MethodsIn this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, a total of 344,893, 44,370, and 393,100 consecutive patients with type 2 diabetes without preexisting AF receiving GLP-1RA, SGLT2i, and DPP4i, respectively, were enrolled from May 1, 2016, to December 31, 2019. We used 1:1 propensity score matching (PSM) to balance covariates across paired study groups. Patients were followed from the drug index date until the occurrence of AF, death, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first.ResultsAfter PSM, there were 245,442, 43,682, and 39,190 paired cohorts of SGLT2i-DPP4i, SGLT2i-GLP-1RA, and GLP-1RA-DPP4i, respectively. SGLT2i treatment was associated with lower risk of new-onset AF in participants with type 2 diabetes compared with either DPP4i [hazard ratio (HR):0.90; 95% confidential interval (CI) 0.84-0.96; P = 0.0028] or GLP-1RA [HR 0.74; 95% CI 0.63-0.88; P = 0.0007] treatment after PSM. There was no difference in the risk of incident AF between GLP-1RA and DPP4i users [HR 1.01; 95% CI 0.86-1.19; P = 0.8980]. The above findings persisted among several important subgroups. Dapagliflozin was specifically associated with a lower risk of new-onset AF compared with DPP4i (P interaction = 0.02).ConclusionsCompared with DPP4i, SGLT2i but not GLP-1RA was associated with a lower risk of incident AF in patients with type 2 diabetes

In-Vitro Activity of Polymyxin B, Rifampicin, Tigecycline Alone and in Combination against Carbapenem-Resistant Acinetobacter baumannii in Singapore

OBJECTIVE: Carbapenem-resistant Acinetobacter baumannii (CR-AB) is an emerging cause of nosocomial infections worldwide. Combination therapy may be the only viable option until new antibiotics become available. The objective of this study is to identify potential antimicrobial combinations against CR-AB isolated from our local hospitals. METHODS: AB isolates from all public hospitals in Singapore were systematically collected between 2006 and 2007. MICs were determined according to CLSI guidelines. All CR-AB isolates were genotyped using a PCR-based method. Clonal relationship was elucidated. Time-kill studies (TKS) were conducted with polymyxin B, rifampicin and tigecycline alone and in combination using clinically relevant (achievable) unbound concentrations. RESULTS: 31 CR AB isolates were identified. They are multidrug-resistant, but are susceptible to polymyxin B. From clonal typing, 8 clonal groups were identified and 11 isolates exhibited clonal diversity. In single TKS, polymyxin B, rifampicin and tigecycline alone did not exhibit bactericidal activity at 24 hours. In combination TKS, polymyxin plus rifampicin, polymyxin B plus tigecycline and tigecycline plus rifampicin exhibited bactericidal killing in 13/31, 9/31 and 7/31 isolates respectively at 24 hours. Within a clonal group, there may be no consensus with the types of antibiotics combinations that could still kill effectively. CONCLUSION: Monotherapy with polymyxin B may not be adequate against polymyxin B susceptible AB isolates. These findings demonstrate that in-vitro synergy of antibiotic combinations in CR AB may be strain dependant. It may guide us in choosing a pre-emptive therapy for CR AB infections and warrants further investigations