Background
Frailty is associated with numerous post‐operative adverse outcomes in older adults. Current pre‐operative frailty screening tools require additional data collection or objective ...assessments, adding expense and limiting large‐scale implementation.
Objective
To evaluate the association of an automated measure of frailty integrated within the Electronic Health Record (EHR) with post‐operative outcomes for nonemergency surgeries.
Design
Retrospective cohort study.
Setting
Academic Medical Center.
Participants
Patients 65 years or older that underwent nonemergency surgery with an inpatient stay 24 hours or more between October 8th, 2017 and June 1st, 2019.
Exposures
Frailty as measured by a 54‐item electronic frailty index (eFI).
Outcomes and Measurements
Inpatient length of stay, requirements for post‐acute care, 30‐day readmission, and 6‐month all‐cause mortality.
Results
Of 4,831 unique patients (2,281 females (47.3%); mean (SD) age, 73.2 (5.9) years), 4,143 (85.7%) had sufficient EHR data to calculate the eFI, with 15.1% categorized as frail (eFI > 0.21) and 50.9% pre‐frail (0.10 < eFI ≤ 0.21). For all outcomes, there was a generally a gradation of risk with higher eFI scores. For example, adjusting for age, sex, race/ethnicity, and American Society of Anesthesiologists class, and accounting for variability by service line, patients identified as frail based on the eFI, compared to fit patients, had greater needs for post‐acute care (odds ratio (OR) = 1.68; 95% confidence interval (CI) = 1.36–2.08), higher rates of 30‐day readmission (hazard ratio (HR) = 2.46; 95%CI = 1.72–3.52) and higher all‐cause mortality (HR = 2.86; 95%CI = 1.84–4.44) over 6 months' follow‐up.
Conclusions
The eFI, an automated digital marker for frailty integrated within the EHR, can facilitate pre‐operative frailty screening at scale.
The exotic winter annual grass Bromus tectorum L. (downy brome or cheatgrass) infests millions of hectares of western rangelands. Weed-suppressive bacteria (ACK55 and D7 strains of Pseudomonas ...fluorescens Migula 1895) have been shown to reduce B. tectorum populations in eastern Washington. Unfortunately, outside of Washington, little is known about the efficacy of these or other weed-suppressive bacteria. We used Petri-plate and plant-soil bioassays to test effects of ACK55 and D7 on B. tectorum from Montana and Wyoming. We also tested effects of ACK55 on B. tectorum at six field sites in Montana and one in Wyoming. P. fluorescens reduced B. tectorum germination and root and shoot lengths in Petri-plates but had no effect on plants during growth chamber plant-soil bioassays or field experiments. Bromus arvensis L. (field brome or Japanese brome), a species similar to B. tectorum, was prevalent at two of our sites, and ACK55 was ineffective against B. arvensis as well. Our findings contribute to a growing body of evidence that the ACK55 and D7 strains of P. fluorescens are not reliable tools for controlling B. tectorum in the Northern Great Plains, Central Rocky Mountains, and elsewhere.
To further elucidate the cataract phenotype, and identify the gene and mutation for autosomal dominant cataract (ADC) in an American family of European descent (ADC2) by sequencing the major ...intrinsic protein gene (
MIP), a candidate based on linkage to chromosome 12q13.
Observational case series and laboratory experimental study.
We examined two at-risk individuals in ADC2. We PCR-amplified and sequenced all four exons and all intron-exon boundaries of the
MIP gene from genomic and cloned DNA in affected members to confirm one variant as the putative mutation.
We found a novel single deletion of nucleotide (nt) 3223 (within codon 235) in exon four, causing a frameshift that alters 41 of 45 subsequent amino acids and creates a premature stop codon.
We identified a novel single base pair deletion in the
MIP gene and conclude that it is a pathogenic sequence alteration.
The re-use of previously validated designs is critical to the evolution of synthetic biology from a research discipline to an engineering practice. Here we describe the Synthetic Biology Open ...Language (SBOL), a proposed data standard for exchanging designs within the synthetic biology community. SBOL represents synthetic biology designs in a community-driven, formalized format for exchange between software tools, research groups and commercial service providers. The SBOL Developers Group has implemented SBOL as an XML/RDF serialization and provides software libraries and specification documentation to help developers implement SBOL in their own software. We describe early successes, including a demonstration of the utility of SBOL for information exchange between several different software tools and repositories from both academic and industrial partners. As a community-driven standard, SBOL will be updated as synthetic biology evolves to provide specific capabilities for different aspects of the synthetic biology workflow.
Steroidogenic acute regulatory protein (StAR) appears to mediate the rapid increase in pregnenolone synthesis stimulated by tropic hormones. cDNAs encoding StAR were isolated from a human adrenal ...cortex library. Human StAR, coexpressed in COS-1 cells with cytochrome P450scc and adrenodoxin, increased pregnenolone synthesis > 4-fold. A major StAR transcript of 1.6 kb and less abundant transcripts of 4.4 and 7.5 kb were detected in ovary and testis. Kidney had a lower amount of the 1.6-kb message. StAR mRNA was not detected in other tissues including placenta. Treatment of granulosa cells with 8-bromo-adenosine 3',5'-cyclic monophosphate for 24 hr increased StAR mRNA 3-fold or more. The structural gene encoding StAR was mapped using somatic cell hybrid mapping panels to chromosome 8p. Fluorescence in situ hybridization placed the StAR locus in the region 8p11.2. A StAR pseudogene was mapped to chromosome 13. We conclude that StAR expression is restricted to tissues that carry out mitochondrial sterol oxidations subject to acute regulation by cAMP and that StAR mRNA levels are regulated by cAMP.
Recently, point mutations in superoxide dismutase 1 (SOD1) have been shown to lead to a subset of autosomal dominantly inherited familial amyotrophic lateral sclerosis (ALS). These findings have led ...to the hypothesis that defects in oxygen radical metabolism may be involved in the pathogenesis of ALS. Therefore, we decided to analyze other enzymes involved in oxygen radical metabolism for possible involvement in other forms of ALS. We report here analysis of two genes encoding the molybdenum hydroxylases aldehyde oxidase (AO) and xanthine dehydrogenase/oxidase (XDH) for involvement in ALS. Of particular interest, one gene identified as encoding aldehyde oxidase is shown to map to 2q33, a region recently shown to contain a gene responsible for a familial form of ALS with autosomal recessive inheritance (FALS-AR). The AO gene appears to be located within 280,000 bp of simple sequence repeat marker D2S116, which shows no recombination with the FALS-AR locus. The AO gene is highly expressed in glial cells of human spinal cord. In addition, we mapped a gene for XDH to 2p22, a region previously shown to contain a highly homologous but different form of XDH. Neither of these XDH genes appears to be highly expressed in human spinal cord. This evidence suggests that AO may be a candidate gene for FALS-AR.
Background. Microbiologic cultures, the current gold standard diagnostic method for invasive Candida infections, have low specificity and take up to 2–5 days to grow. We present the results of the ...first extensive multicenter clinical trial of a new nanodiagnostic approach, T2 magnetic resonance (T2MR), for diagnosis of candidemia. Methods. Blood specimens were collected from 1801 hospitalized patients who had a blood culture ordered for routine standard of care; 250 of them were manually supplemented with concentrations from <1 to 100 colony-forming units (CFUs)/mL for 5 different Candida species. Results. T2MR demonstrated an overall specificity per assay of 99.4% (95% confidence interval CI, 99.1%–99.6%) with a mean time to negative result of 4.2 ± 0.9 hours. Subanalysis yielded a specificity of 98.9% (95% CI, 98.3%–99.4%) for Candida albicans/Candida tropicalis, 99.3% (95% CI, 98.7%–99.6%) for Candida parapsilosis, and 99.9% (95% CI, 99.7%–100.0%) for Candida krusei/Candida glabrata. The overall sensitivity was found to be 91.1% (95% CI, 86.9%–94.2%) with a mean time of 4.4 ± 1.0 hours for detection and species identification. The subgroup analysis showed a sensitivity of 92.3% (95% CI, 85.4%–96.6%) for C. albicans/C. tropicalis, 94.2% (95% CI, 84.1%–98.8%) for C. parapsilosis, and 88.1% (95% CI, 80.2%–93.7%) for C. krusei/C. glabrata. The limit of detection was 1 CFU/mL for C. tropicalis and C. krusei, 2 CFU/mL for C. albicans and C. glabrata, and 3 CFU/mL for C. parapsilosis. The negative predictive value was estimated to range from 99.5% to 99.0% in a study population with 5% and 10% prevalence of candidemia, respectively. Conclusions. T2MR is the first fully automated technology that directly analyzes whole blood specimens to identify species without the need for prior isolation of Candida species, and represents a breakthrough shift into a new era of molecular diagnostics. Clinical Trials Registration. NCT01752166.
To map the gene for autosomal dominant cataracts (ADC) in an American white family of European descent.
Ophthalmic examinations and linkage analyses using a variety of polymorphisms were performed; ...two-point lod scores calculated.
Affected individuals (14 studied) exhibited variable expressivity of embryonal nuclear opacities based on morphology, location within the lens, and density. This ADC locus to 12q13 was mapped on the basis of statistically significantly positive lod scores and no recombinations (theta(m) = theta(f) = 0) with markers D12S368, D12S270, D12S96, D12S359, D12S1586, D12S312, D12S1632, D12S90, and D12S83; assuming full penetrance, a maximum lod score of 4.73 was calculated between the disease locus and D12S90.
The disease in this family represents the first ADC locus on chromosome 12; major intrinsic protein of lens fiber (MIP) is a candidate gene.
A genomic clone for the human heat shock protein (HSP) 70 gene located on chromosome 14 was isolated and sequenced. The gene, designated HSPA2, has a single open reading frame of 1917 bp that encodes ...a 639-amino acid protein with a predicted molecular weight of 70,030 Da. Analysis of the sequence indicates that HSPA2 is the human homologue of the murine Hsp70-2 gene with 91.7% identity in the nucleotide coding sequence and 98.2% in the corresponding amino acid sequence. HSPA2 has less amino acid homology to other members of the human HSP70 gene family, 83.3% to the heat-inducible HSP70-1 gene and 86.1% with the human heat shock cognate gene HSC70. HSPA2 is constitutively expressed in most tissues, with very high levels in testis and skeletal muscle. Significant but lower levels are also expressed in ovary, small intestine, colon, brain, placenta, and kidney. A yeast artificial chromosome (YAC) clone containing HSPA2 (YAC741H4) that also contained the polymorphic marker D14S63 was identified. This 670-kb YAC was mapped to 14q24.1 by fluorescence in situ hybridization (FISH). Subsequent two-color FISH and genetic mapping placed HSPA2/D14S63 proximal to the markers D14S57 and D14S77.
The outlook for people with cystic fibrosis (CF) has improved considerably as a result of conventional therapies including aerosolized agents for airway clearance. These will continue to play a ...significant role in maintaining well‐being and improving survival, even as newer agents emerge that correct the underlying CF defect. In this review, we explore the evidence supporting the use of dornase alfa, hypertonic saline, and mannitol in improving mucus clearance in patients with CF from different age groups with differing disease severity. We also discuss the clinical use of these agents in the context of available international guidelines as well as practical considerations in the clinic, highlighting the importance of a multidisciplinary approach and shared decision‐making. Unanswered questions regarding the optimal use of these agents are highlighted.
PDF
