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Author(s): Safavi, Kyan C; Deng, Hao; Driscoll, William; Nikolov, Milcho; Tolia, Kalpan; Wiener-Kronish, Jeanine P | Abstract: BackgroundThe traditional paradigm of hospital surgical ward care consists of episodic bedside visits by providers with periodic perusals of the patient's electronic health record (EHR). Vital signs and laboratory results are directly pushed to the EHR but not to providers themselves. Results that require intervention may not be recognized for hours. Remote surveillance programs continuously monitor electronic data and provide automatic alerts that can be routed to multidisciplinary providers. Such programs have not been explored in surgical general care wards.MethodsWe performed a quality improvement observational study of otolaryngology and ophthalmology patients on a general care ward from October 2017 to March 2019 during nighttime hours (17:00-07:00). The study was initiated due to the loss of on-site anesthesiology resources that historically helped respond to acute physiologic deterioration events. We implemented a remote surveillance software program to continuously monitor patients for severe vital signs and laboratory abnormalities and automatically alert the ward team and a remote critical care anesthesiology team. The primary end point was the true positive rate, defined as the proportion of alerts that were associated with a downstream action that changed the care of the patient. This was determined using systematic chart review. The secondary end point, as a measure of alarm fatigue, was the average number of alerts per clinician shift.ResultsThe software monitored 3926 hospital visits and analyzed 1,560,999 vitals signs and 16,635 laboratories. It generated 151 alerts, averaging 2.6 alerts per week. Of these, 143 (94.7%) were numerically accurate and 8 (5.3%) were inaccurate. Hypoxemia with oxygen saturation l88% was the most common etiology (92, 63%) followed by tachycardia g130 beats per minute (19, 13.3%). Among the accurate alerts, 133 (88.1%) were true positives with an associated clinical action. Actions included a change in management 113 (67.7%), new diagnostic test 26 (15.6%), change in discharge planning 20 (12.0%), and change in level of care to the intensive care unit (ICU) 8 (4.8%). As a measure of alarm fatigue, there were 0.4 alerts per clinician shift.ConclusionsIn a surgical general care ward, a remote surveillance software program that continually and automatically monitors physiologic data streams from the EHR and alerts multidisciplinary providers for severe derangements provided highly actionable alarms at a rate that is unlikely to cause alarm fatigue. Such programs are feasible and could be used to change the paradigm of monitoring.

A long-standing challenge in human microbiome research is achieving the taxonomic and functional resolution needed to generate testable hypotheses about the gut microbiota’s impact on health and disease. With a growing number of live microbial interventions in clinical development, this challenge is renewed by a need to understand the pharmacokinetics and pharmacodynamics of therapeutic candidates. While short-read sequencing of the bacterial 16S rRNA gene has been the standard for microbiota profiling, recent improvements in the fidelity of long-read sequencing underscores the need for a re-evaluation of the value of distinct microbiome-sequencing approaches. We leveraged samples from participants enrolled in a phase 1b clinical trial of a novel live biotherapeutic product to perform a comparative analysis of short-read and long-read amplicon and metagenomic sequencing approaches to assess their utility for generating clinical microbiome data. Across all methods, overall community taxonomic profiles were comparable and relationships between samples were conserved. Comparison of ubiquitous short-read 16S rRNA amplicon profiling to long-read profiling of the 16S-ITS-23S rRNA amplicon showed that only the latter provided strain-level community resolution and insight into novel taxa. All methods identified an active ingredient strain in treated study participants, though detection confidence was higher for long-read methods. Read coverage from both metagenomic methods provided evidence of active-ingredient strain replication in some treated participants. Compared to short-read metagenomics, approximately twice the proportion of long reads were assigned functional annotations. Finally, compositionally similar bacterial metagenome-assembled genomes (MAGs) were recovered from short-read and long-read metagenomic methods, although a greater number and more complete MAGs were recovered from long reads. Despite higher costs, both amplicon and metagenomic long-read approaches yielded added microbiome data value in the form of higher confidence taxonomic and functional resolution and improved recovery of microbial genomes compared to traditional short-read methodologies.

A longstanding challenge in human microbiome research is achieving the taxonomic and functional resolution needed to generate testable hypotheses about the gut microbiome’s impact on health and disease. More recently, this challenge has extended to a need for in-depth understanding of the pharmacokinetics and pharmacodynamics of clinical microbiome-based interventions. Whole genome metagenomic sequencing provides high taxonomic resolution and information on metagenome functional capacity, but the required deep sequencing is costly. For this reason, short-read sequencing of the bacterial 16S ribosomal RNA (rRNA) gene is the standard for microbiota profiling, despite its poor taxonomic resolution. The recent falling costs and improved fidelity of long-read sequencing warrant an evaluation of this approach for clinical microbiome analysis. We used samples from participants enrolled in a Phase 1b clinical trial of a novel live biotherapeutic product to perform a comparative analysis of short-read and long-read amplicon and metagenomic sequencing approaches to assess their value for generating informative and actionable clinical microbiome data. Comparison of ubiquitous short-read 16S rRNA amplicon profiling to long-read profiling of the 16S-ITS-23S rRNA amplicon showed that only the latter provided strain-level community resolution and insight into novel taxa. Across all methods, overall community taxonomic profiles were comparable and relationships between samples were conserved, highlighting the accuracy of modern microbiome analysis pipelines. All methods identified an active ingredient strain in treated study participants, though detection confidence was higher for long-read methods. Read coverage from both metagenomic methods provided evidence of active ingredient strain replication in some treated participants. Compared to short-read metagenomics, approximately twice the proportion of long reads were assigned functional annotations (63% vs. 34%). Finally, similar bacterial metagenome-assembled genomes (MAGs) were recovered across short-read and long-read metagenomic methods, although MAGs recovered from long reads were more complete. Overall, despite higher costs, long-read microbiome characterization provides added scientific value for clinical microbiome research in the form of higher taxonomic and functional resolution and improved recovery of microbial genomes compared to traditional short-read methodologies.Data SummaryAll supporting data, code and protocols have been provided within the article or as supplementary data files. Two supplementary figures and four supplementary tables are available with the online version of this article. Sequencing data are accessible in the National Center for Biotechnology Information (NCBI) database under BioProject accession number PRJNA754443. The R code and additional data files used for analysis and figure generation are accessible in a GitHub repository (https://github.com/jeanette-gehrig/Gehrig_et_al_sequencing_comparison).Impact StatementAccurate sequencing and analysis are essential for informative microbiome profiling, which is critical for the development of novel microbiome-targeted therapeutics. Recent improvements in long-read sequencing technology provide a promising, but more costly, alternative to ubiquitous short-read sequencing. To our knowledge, a direct comparison of the informational value of short-read and HiFi long-read sequencing approaches has not been reported for clinical microbiome samples. Using samples from participants in a Phase 1b trial of a live biotherapeutic product, we compare microbiome profiles generated from short-read and long-read sequencing for both amplicon-based 16S ribosomal RNA profiling and metagenomic sequencing. Though overall taxonomic profiles were similar across methods, only long-read amplicon sequencing provided strain-level resolution, and long-read metagenomic sequencing resulted in a significantly greater proportion of functionally annotated genes. Detection of a live biotherapeutic active ingredient strain in treated participants was achieved with all methods, and both metagenomic methods provided evidence of active replication of this strain in some participants. Similar taxonomies were recovered through metagenomic assemblies of short and long reads, although assemblies were more complete with long reads. Overall, we show the utility of long-read microbiome sequencing in direct comparison to commonly used short-read methods for clinically relevant microbiome profiling.

Identifying and tracking microbial strains as microbiomes evolve are major challenges in the field of microbiome research. We utilized a new sequencing kit that combines DNA extraction with PCR amplification of a large region of the rRNA operon and downstream bioinformatic data analysis. Longitudinal microbiome samples of coadmitted twins from two different neonatal intensive care units (NICUs) were analyzed using an ∼2,500-base amplicon that spans the 16S and 23S rRNA genes and mapped to a new, custom 16S-23S rRNA database. Amplicon sequence variants (ASVs) inferred using DADA2 provided sufficient resolution for the differentiation of rRNA variants from closely related but not previously sequenced Klebsiella, Escherichia coli, and Enterobacter strains, among the first bacteria colonizing the gut of these infants after admission to the NICU. Distinct ASV groups (fingerprints) were monitored between coadmitted twins over time, demonstrating the potential to track the source and spread of both commensals and pathogens. The high-resolution taxonomy obtained from long amplicon sequencing enables the tracking of strains temporally and spatially as microbiomes are established in infants in the hospital environment.IMPORTANCE Achieving strain-level resolution is a major obstacle for source tracking and temporal studies of microbiomes. In this study, we describe a novel deep-sequencing approach that provides species- and strain-level resolution of the neonatal microbiome. Using Klebsiella, E. coli, and Enterobacter as examples, we could monitor their temporal dynamics after antibiotic treatment and in pairs of twins. The strain-level resolution, combined with the greater sequencing depth and decreased cost per read of PacBio Sequel 2, enables this advantageous source- and strain-tracking analysis method to be implemented widely across more complex microbiomes.

Understanding and improving obstetrical quality and safety is an important goal of professional societies, and many interventions such as checklists, safety bundles, educational interventions, or other culture changes have been implemented to improve the quality of care provided to obstetrical patients. Although many factors contribute to delivery decisions, a reduced workload has addressed how provider issues such as fatigue or behaviors surrounding impending shift changes may influence the delivery mode and outcomes.The objective was to assess whether intrapartum obstetrical interventions and adverse outcomes differ based on the temporal proximity of the delivery to the attending's shift change.This was a secondary analysis from a multicenter obstetrical cohort in which all patients with cephalic, singleton gestations who attempted vaginal birth were eligible for inclusion. The primary exposure used to quantify the relationship between the proximity of the provider to their shift change and a delivery intervention was the ratio of time from the most recent attending shift change to vaginal delivery or decision for cesarean delivery to the total length of the shift. Ratios were used to represent the proportion of time completed in the shift by normalizing for varying shift lengths. A sensitivity analysis restricted to patients who were delivered by physicians working 12-hour shifts was performed. Outcomes chosen included cesarean delivery, episiotomy, third- or fourth-degree perineal laceration, 5-minute Apgar score of4, and neonatal intensive care unit admission. Chi-squared tests were used to evaluate outcomes based on the proportion of the attending's shift completed. Adjusted and unadjusted logistic models fitting a cubic spline (when indicated) were used to determine whether the frequency of outcomes throughout the shift occurred in a statistically significant, nonlinear pattern RESULTS: Of the 82,851 patients eligible for inclusion, 47,262 (57%) had ratio data available and constituted the analyzable sample. Deliveries were evenly distributed throughout shifts, with 50.6% taking place in the first half of shifts. There were no statistically significant differences in the frequency of cesarean delivery, episiotomy, third- or fourth-degree perineal lacerations, or 5-minute Apgar scores of4 based on the proportion of the shift completed. The findings were unchanged when evaluated with a cubic spline in unadjusted and adjusted logistic models. Sensitivity analyses performed on the 22.2% of patients who were delivered by a physician completing a 12-hour shift showed similar findings. There was a small increase in the frequency of neonatal intensive care unit admissions with a greater proportion of the shift completed (adjusted P=.009), but the findings did not persist in the sensitivity analysis.Clinically significant differences in obstetrical interventions and outcomes do not seem to exist based on the temporal proximity to the attending physician's shift change. Future work should attempt to directly study unit culture and provider fatigue to further investigate opportunities to improve obstetrical quality of care, and additional studies are needed to corroborate these findings in community settings.

To determine whether greater patient-reported symptom intensity and functional limitation influence expressed preferences for discretionary diagnostic and treatment interventions, we studied the association of patient factors and several Patient Reported Outcome Measure (PROM) scores with patient preferences for diagnostic and treatment interventions before and after the visit, a cross-sectional cohort study. One hundred and forty-three adult patients who completed several PROMs were asked their preferences for diagnostic and treatment interventions before and after a visit with an orthopedic surgeon. Patients with better physical function had fewer preferences for specific diagnostic interventions after the visit ( P = .02), but PROM scores had no association with preferences for treatment interventions before or after the visit. A greater percentage of patients expressed the preference for no diagnostic or treatment intervention after the visit with a physician than before (diagnostic intervention; 2.1% before vs 30% after the visit; P ≤ .001 and treatment intervention; 2.1% before vs 17% after the visit; P ≤ .001). This study suggests that physician expertise may be more reassuring to people with more adaptive mind sets.

Identifying and tracking microbial strains as microbiomes evolve is a major challenge in the field of microbiome research. Longitudinal microbiome samples of co-admitted twins from two different neonatal intensive care units (NICUs) were analyzed using a ∼2,500 base amplicon that spans the 16S and 23S rRNA genes, and mapped to a new 16S-23S rRNA database. Amplicon Sequence Variants inferred using DADA2 provided sufficient resolution for differentiation of rRNA variants from closely related, but not previously sequenced Klebsiella, E. coli, and Enterobacter, among the first bacteria colonizing the gut of these infants after admission to the NICU. Distinct ASV groups (fingerprints) were followed between co-admitted twins over time, demonstrating the potential to track the source and spread of both commensals and pathogens.The high-resolution taxonomy obtained from long amplicon sequencing enable tracking of strains temporally and spatially as microbiomes are established in infants in the hospital environment.

BACKGROUND Manual processes for verifying patient identification before blood transfusion and documenting this pretransfusion safety check are prone to errors, and compliance with manual systems is especially poor in urgent operating room settings. An automated, electronic barcode scanner system would be expected to improve pretransfusion verification and documentation. METHODS Audits were conducted of blood transfusion documentation under a manual paper system from January to October 2014. An electronic barcode scanning system was developed to streamline transfusion safety checking and automate documentation. This system was implemented in 58 operating rooms between October and December 2014, with follow-up compliance audits through December 2015. The association of barcode scanner implementation with transfusion documentation compliance was assessed using an interrupted time series analysis. Anesthesia providers were surveyed regarding their opinions on the electronic system. In mid-2016, the scanning system was modified to transfer from the Metavision medical record system to Epic OpTime. Follow-up analysis assessed performance of this system within Epic during 2017. RESULTS In an interrupted time series analysis, the proportion of units with compliant documentation was estimated to be 19.6% (95% confidence interval [CI], 10.7-25.6) the week before scanner implementation, and 74.4% (95% CI, 59.4-87.4) the week after implementation. There was a significant postintervention level change (odds ratio 10.80, 95% CI, 6.31-18.70; P < .001) and increase in slope (odds ratio 1.14 per 1-week increase, 95% CI, 1.11-1.17; P < .001). After implementation, providers chose to use the new electronic system for 98% of transfusions. Across the 2 years analyzed (15,997 transfusions), the electronic system detected 45 potential transfusion errors in 27 unique patients, and averted transfusion of 36 mismatched blood products into 20 unique patients. A total of 69%, 86%, and 88% of providers reported the electronic system improved patient safety, blood transfusion workflow, and transfusion documentation, respectively. When providers used the barcode scanner, no transfusion errors or reactions were reported. The scanner system was successfully transferred from Metavision to Epic without retraining staff or changing workflows. CONCLUSIONS A barcode-based system designed for easy integration to different commonly used anesthesia information management systems was implemented in a large urban academic hospital. The system allows a single user with the assistance of a software system to perform and document pretransfusion safety verification. The system improved transfusion documentation compliance, averted potential transfusion errors, and became the preferred method of blood transfusion safety checking.

BACKGROUND: Asian Americans (AAs) are more likely to use complementary and alternative medicine (CAM) compared to other race/ethnicities, yet previous studies have conflicting results. METHODS: The 2012 National Health Interview Survey data was analyzed to investigate AA’s (n=2,214) CAM use for treatment. AAs were divided into four subgroups: Chinese, Asian Indian, Filipino, and Other Asian. RESULTS: Only 9% of AAs reported using CAM for treatment, with 6% indicating CAM use specifically for chronic conditions. This could be a form of medical pluralism, a mixture of Eastern and Western health approaches. The “Other Asian” subgroup reported highest use of CAM for treatment. Significant predictors included age (≥65 years) and high educational attainment ((≥college degree). Sociodemographic factors were also significant predictors within Asian subgroups. CONCLUSION: Further investigation of this and other forms of medical pluralism among AAs are needed to explore potential cofounders and risks like underreporting, CAM schedules/dosages, cultural influences, and CAM’s impact on one’s health.

BACKGROUND: Adverse childhood experiences (ACEs) affect adult mental health and tend to contribute to greater symptoms of depression and more frequent suicide attempts. Given the relationship between symptoms of depression and patient-reported outcomes (PROs), adversity in childhood might be associated with PROs in patients seeking care for musculoskeletal problems, but it is not clear whether in fact there is such an association among patients seeking care in an outpatient, upper extremity orthopaedic practice. QUESTIONS/PURPOSES: (1) Are ACE scores independently associated with variation in physical limitations measured among patients seen by an orthopaedic surgeon? (2) Are ACE scores independently associated with variations in pain intensity? (3) What factors are associated with ACE scores when treated as a continuous variable or as a categorical variable? METHODS: We prospectively enrolled 143 adult patients visiting one of seven participating orthopaedic surgeons at three private and one academic orthopaedic surgery offices in a large urban area. We recorded their demographics and measured ACEs (using a validated 10-item binary questionnaire that measured physical, emotional, and sexual abuse in the first 18 years of life), magnitude of physical limitations, pain intensity, symptoms of depression, catastrophic thinking, and health anxiety. There were 143 patients with a mean age of 51 years, 62 (43%) of whom were men. In addition, 112 (78%) presented with a specific diagnosis and most (n = 79 [55%]) had upper extremity symptoms. We created one logistic and three linear regression models to test whether age, gender, race, marital status, having children, level of education, work status, insurance type, comorbidities, body mass index, smoking, site of symptoms, type of diagnosis, symptoms of depression, catastrophic thinking, and health anxiety were independently associated with (1) the magnitude of limitations; (2) pain intensity; (3) ACE scores on the continuum; and (4) ACE scores categorized (< 3 or ≥ 3). We calculated a priori that to detect a medium effect size with 90% statistical power and α set at 0.05, a sample of 136 patients was needed for a regression with five predictors if ACEs would account for ≥ 5% of the variability in physical function, and our complete model would account for 15% of the overall variability. To account for 5% incomplete responses, we enrolled 143 patients. RESULTS: We found no association between ACE scores and the magnitude of physical limitations measured by Patient-Reported Outcomes Measurement Information System Physical Function (p = 0.67; adjusted R(2) = 0.55). ACE scores were not independently associated with pain intensity (Pearson correlation [r] = 0.11; p = 0.18). Greater ACE scores were independently associated with diagnosed mental comorbidities both when analyzed on the continuum (regression coefficient [β] = 1.1; 95% confidence interval [CI], 0.32-1.9; standard error [SE] 0.41; p = 0.006) and categorized (odds ratio [OR], 3.3; 95% CI, 1.2-9.2; SE 1.7; p = 0.024), but not with greater levels of health anxiety (OR, 1.1; 95% CI, 0.90-1.3; SE 0.096; p = 0.44, C statistic = 0.71), symptoms of depression (ACE < 3 mean ± SD = 0.73 ± 1.4; ACE ≥ 3 = 1.0 ± 1.4; p = 0.29) or catastrophic thinking (ACE < 3 = 3.6 ± 3.5; ACE ≥ 3 = 4.9 ± 5.1; p = 0.88). CONCLUSIONS: ACEs may not contribute to greater pain intensity or magnitude of physical limitations unless they are accompanied by greater health anxiety or less effective coping strategies. Adverse events can contribute to anxiety and depression, but perhaps they sometimes lead to development of resilience and effective coping strategies. Future research might address whether ACEs affect symptoms and limitations in younger adult patients and patients with more severe musculoskeletal pathology such as major traumatic injuries. LEVEL OF EVIDENCE: Level II, prognostic study.

Kinetics and thermodynamics in supramolecular systems are intimately linked, yet both are independently important for application in sensing assays and stimuli-responsive switching/self-healing of materials. Host-guest interactions are of particular interest in many water-based materials, sensing and drug delivery applications. Herein we investigate the binding dynamics of a variety of electron-rich aromatic moieties forming hetero-ternary complexes with the macrocycle cucurbit[8]uril (CB[8]) and an auxiliary guest, dimethyl viologen, with high selectivity and equilibrium binding constants (Keq up to 1014M−2). Using stopped-flow spectrofluorimetry, association rate constants were observed to approach the diffusion limit, and were found to be insensitive to the structure of the guest. Conversely, the dissociation rate constants of the ternary complexes varied dramatically with the guest structure and were correlated with the thermodynamic binding selectivity. Hence differing molecular features were found to contribute to the associative and dissociative processes, mimicking naturally occurring reactions and giving rise to a decoupling of these kinetic parameters. Moreover, we demonstrate the ability to exploit the phenomena and selectively perturb the associative process with external stimuli (e.g.viscosity and pressure). Significantly, these complexes exhibit increased binding equilibria with increasing pressure, carrying important implications in the application of theCB[8] ternary complex for the formation of hydrogels, as these gels exhibit unprecedented pressure-insensitive rheological properties. A high degree of flexibility therefore exists in the design of host-guest systems with tunable kinetic and thermodynamic parameters for tailor-made applications across a broad range of fields.

When fingers or toes are injured, a digital block is commonly used to block the nerves to these digits, anesthetizing the digit to allow for more effective medical care.

The convergence of multiple recent developments in health care information technology and monitoring devices has made possible the creation of remote patient surveillance systems that increase the timeliness and quality of patient care. More convenient, less invasive monitoring devices, including patches, wearables, and biosensors, now allow for continuous physiological data to be gleaned from patients in a variety of care settings across the perioperative experience. These data can be bound into a single data repository, creating so-called data lakes. The high volume and diversity of data in these repositories must be processed into standard formats that can be queried in real time. These data can then be used by sophisticated prediction algorithms currently under development, enabling the early recognition of patterns of clinical deterioration otherwise undetectable to humans. Improved predictions can reduce alarm fatigue. In addition, data are now automatically queriable on a real-time basis such that they can be fed back to clinicians in a time frame that allows for meaningful intervention. These advancements are key components of successful remote surveillance systems. Anesthesiologists have the opportunity to be at the forefront of remote surveillance in the care they provide in the operating room, postanesthesia care unit, and intensive care unit, while also expanding their scope to include high-risk preoperative and postoperative patients on the general care wards. These systems hold the promise of enabling anesthesiologists to detect and intervene upon changes in the clinical status of the patient before adverse events have occurred. Importantly, however, significant barriers still exist to the effective deployment of these technologies and their study in impacting patient outcomes. Studies demonstrating the impact of remote surveillance on patient outcomes are limited. Critical to the impact of the technology are strategies of implementation, including who should receive and respond to alerts and how they should respond. Moreover, the lack of cost-effectiveness data and the uncertainty of whether clinical activities surrounding these technologies will be financially reimbursed remain significant challenges to future scale and sustainability. This narrative review will discuss the evolving technical components of remote surveillance systems, the clinical use cases relevant to the anesthesiologist's practice, the existing evidence for their impact on patients, the barriers that exist to their effective implementation and study, and important considerations regarding sustainability and cost-effectiveness.

BACKGROUND: It seems common for patients to conceive of care in physical terms, such as medications, injections, and procedures rather than advice and support. Clinicians often encounter patients who seem to prefer more testing or invasive treatments than expertise supports. We wanted to determine whether patients unconsciously associate suggestions for invasive treatments with better care. QUESTIONS/PURPOSES: (1) Do patients have (A) an implicit preference and (B) an expressed preference for a physical intervention (such as a pill, an injection, or surgery) over supportive care (such as reassurance and education)? (2) What factors are independently associated with both an implicit and an expressed preference for a physical intervention over supportive care? (3) Is there a relationship between a patient’s implicit preference toward or away from a physical intervention and his/her expressed preference on that subject? METHODS: In this study, we approached 129 new patients in a large urban area visiting one of 13 participating surgeons divided among six upper and lower extremity specialist offices. After excluding four patients based on our exclusion criteria, 125 patients (97%) completed a survey of demographics and their expressed preference about receiving either physical treatment or support. Treatment was defined as any surgery, procedure, injection, or medication; support was defined as reassurance, conversation, and education, but no physical treatment. Patients then completed the Implicit Association Test (IAT) to evaluate implicit preferences toward treatment or support. Although other IATs have been validated in numerous studies, the IAT used in this study was specifically made for this study. Scores (D scores) range from -2 to 2, where 0 indicates no implicit preference, positive scores indicate a preference toward receiving a physical treatment is good care, and negative scores indicate a preference toward receiving supportive care is good care. According to the original IAT, break points for a slight (± 0.15 to 0.35), moderate (± 0.35 to 0.65), and strong preference (± 0.65 to 2) were selected conservatively according to psychological conventions for effect size. Patients’ mean age was 50 ± 15 years (range, 18–79 years) and 56 (45%) were men. The patients had a broad spectrum of upper and lower extremity musculoskeletal conditions, ranging from trigger finger to patellofemoral syndrome. RESULTS: We found a slight implicit association of good care with support (D = -0.17 ± 0.62; range, -2 to 1.2) and an expressed preference for physical treatment (mean score = 0.63 ± 2.0; range, -3 to 3). Patients who received both physical and supportive treatment had greater implicit preference for good care, meaning supportive care, than patients receiving physical care alone (β = -0.42; 95% CI, -0.73 to -0.11; p = 0.008; semipartial R(2) = 0.04; adjusted R(2) full model = 0.13). Gender was independently associated with a greater expressed preference for physical treatment, with men expressing this preference more than women (β = 1.0; 95% CI, 0.31–1.7; p = 0.005; semipartial R(2) = 0.06; adjusted R(2) full model = 0.08); receiving supportive treatment was independently associated with more expressed preference for support (β = -0.98; 95% CI, -1.7 to -0.23; p = 0.011; semipartial R(2) = 0.05). An expressed preference for treatment was not associated with implicit preference (β = 0.01; 95% CI, -0.04 to 0.06; p = 0.721). CONCLUSIONS: Although surgeons may sometimes feel pressured toward physical treatments, based on our results and cutoff values, the average patient with upper or lower extremity symptoms has a slight implicit preference for supportive treatment and would likely be receptive. LEVEL OF EVIDENCE: Level II, prognostic study.

BACKGROUND: While there are well-accepted standards for the diagnosis of arrested active-phase labor, the definition of a "failed" induction of labor remains less certain. One approach to diagnosing a failed induction is based on the duration of the latent phase. However, a standard for the minimum duration that the latent phase of a labor induction should continue, absent acute maternal or fetal indications for cesarean delivery, remains lacking. OBJECTIVE: The objective of this study was to determine the frequency of adverse maternal and perinatal outcomes as a function of the duration of the latent phase among nulliparous women undergoing labor induction. METHODS: This study is based on data from an obstetric cohort of women delivering at 25 U.S. hospitals from 2008-2011. Nulliparous women who had a term singleton gestation in the cephalic presentation were eligible for this analysis if they underwent a labor induction. Consistent with prior studies, the latent phase was determined to begin once cervical ripening had ended, oxytocin was initiated and rupture of membranes (ROM) had occurred, and was determined to end once 5 cm dilation was achieved. The frequencies of cesarean delivery, as well as of adverse maternal (e.g., cesarean delivery, postpartum hemorrhage, chorioamnionitis) and perinatal outcomes (e.g., a composite frequency of either seizures, sepsis, bone or nerve injury, encephalopathy, or death), were compared as a function of the duration of the latent phase (analyzed with time both as a continuous measure and categorized in 3-hour increments). RESULTS: A total of 10,677 women were available for analysis. In the vast majority (96.4%) of women, the active phase had been reached by 15 hours. The longer the duration of a woman's latent phase, the greater her chance of ultimately undergoing a cesarean delivery (P

Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030. Funding: Bill & Melinda Gates Foundation. © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Restoration of glenoid bony integrity is critical to minimizing the risk of recurrence and re-creating normal kinematics in the setting of anterior glenohumeral instability. We present an arthroscopic suture anchor–based technique for treating large bony Bankart fractures in which the fragment is secured to the intact glenoid using mattress sutures placed through the bony fragment and augmented with soft-tissue repair proximal and distal to the bony lesion. This straightforward technique has led to excellent fragment reduction and good outcomes in our experience.

Fluorescent dyes that bind DNA have been demonstrated as a useful alternative to radionucleotides for the quantification of DNA and the in vitro measurement of the activity of DNA polymerases and nucleases. However, this approach is generally used in a semi-quantitative way to determine relative rates of reaction. In this report, we demonstrate a method for the simultaneous quantification of DNA in both its single-strand and double-strand forms using the dye PicoGreen. This approach is used in a steady-state assay of DNA polymerase Klenow fragment exo(−), where we determine kcat and Km values for the DNA polymerase that are in excellent agreement with literature values.

Mycobacterium tuberculosis (Mtb) causes the disease tuberculosis (TB). The virulent Mtb H37Rv strain encodes 20 cytochrome P450 (CYP) enzymes, many of which are implicated in Mtb survival and pathogenicity in the human host. Bioinformatics analysis revealed that CYP144A1 is retained exclusively within the Mycobacterium genus, particularly in species causing human and animal disease. Transcriptomic annotation revealed two possible CYP144A1 start codons, leading to expression of (i) a “full-length” 434 amino acid version (CYP144A1-FLV) and (ii) a “truncated” 404 amino acid version (CYP144A1-TRV). Computational analysis predicted that the extended N-terminal region of CYP144A1-FLV is largely unstructured. CYP144A1 FLV and TRV forms were purified in heme-bound states. Mass spectrometry confirmed production of intact, His6-tagged forms of CYP144A1-FLV and -TRV, with EPR demonstrating cysteine thiolate coordination of heme iron in both cases. Hydrodynamic analysis indicated that both CYP144A1 forms are monomeric. CYP144A1-TRV was crystallized and the first structure of a CYP144 family P450 protein determined. CYP144A1-TRV has an open structure primed for substrate binding, with a large active site cavity. Our data provide the first evidence that Mtb produces two different forms of CYP144A1 from alternative transcripts, with CYP144A1-TRV generated from a leaderless transcript lacking a 5′-untranslated region and Shine-Dalgarno ribosome binding site.

Extracting kinetic parameters from DNA polymerase-catalyzed processive polymerization data using traditional initial-rate analysis has proven to be problematic for multiple reasons. The first substrate, DNA template, is a heterogeneous polymer and binds tightly to DNA polymerase. Further, the affinity and speed of incorporation of the second substrate, deoxynucleoside triphosphate (dNTP), vary greatly depending on the nature of the templating base and surrounding sequence. Here, we present a mathematical model consisting of the DNA template-binding step and a Michaelis–Menten-type nucleotide incorporation step acting on a DNA template with a finite length. The model was numerically integrated and globally fitted to experimental reaction time courses. The time courses were determined by monitoring the processive synthesis of oligonucleotides of lengths between 50 and 120 nucleotides by DNA polymerase I (Klenow fragment exo–) using the fluorophore PicoGreen. For processive polymerization, we were able to estimate an enzyme–template association rate k1 of 7.4 μM–1 s–1, a disassociation rate k–1 of 0.07 s–1, and a Kd of 10 nM, and the steady-state parameters for correct dNTP incorporation give kcat values of 2.5–3.3 s–1 and Km values of 0.51–0.86 μM. From the analysis of time courses measured between 5 and 25 °C, an activation energy for kcat of 82 kJ mol–1 was calculated, and it was found that up to 73% of Klenow fragment becomes inactivated or involved in unproductive binding at lower temperatures. Finally, a solvent deuterium kinetic isotope effect (KIE) of 3.0–3.2 was observed under processive synthesis conditions, which suggests that either the intrinsic KIE is unusually high, at least 30–40, or previous findings, showing that the phosphoryl transfer step occurs rapidly and is flanked by two slow conformational changes, need to be re-evaluated. We suggest that the numerical integration of rate equations provides a high level of flexibility and generally produces superior results compared to those of initial-rate analysis in the study of DNA polymerase kinetics and, by extension, other complex enzyme systems.

We present results of very-high-energy gamma-ray observations (Eγ > 160 GeV) of two high-frequency-peaked BL Lac (HBL) objects, 1ES 1218 + 304 and H 1426 + 428, with the Solar Tower Atmospheric Cherenkov Effect Experiment (STACEE). Both sources are very-high-energy gamma-ray emitters above 100 GeV, detected using ground-based Cherenkov telescopes. STACEE observations of 1ES 1218 + 304 and H 1426 + 428 did not produce detections; we present 99% CL flux upper limits for both sources, assuming spectral indices measured mostly at higher energies.

Background: Chimeric antigen receptor (CAR) T-cell therapy is a rapidly emerging form of treatment for hematologic malignancies including lymphoma, multiple myeloma, and leukemia. Hospitalizations and readmissions after CAR T-cell therapy have not been systematically studied. A better understanding of hospital utilization patterns could inform design of clinical trials, advanced planning of hospitalizations, timing of discharge, and frequency and type of outpatient follow-up. Methods: We conducted a retrospective analysis of all patients admitted to the Massachusetts General Hospital for CAR T-cell therapy between 3/2016 and 3/2018. The primary outcome was hospital readmission within 30 days following discharge from CAR-T treatment visit. Secondary outcomes were ICU admission and inpatient mortality. Exploratory analyses were also conducted to determine whether patient age, length of initial hospitalization, laboratory measurements including ferritin and C-reactive protein (CRP), and tocilizumab exposure were associated with 30-day readmission. Summary statistics were reported by disease types, CAR-T products, and the primary and secondary outcomes using appropriate statistical functions. Comparison of laboratory values (ferritin and CRP) between the index admission (CAR T infusion) and first-readmission visits were analyzed using random intercept linear mixed effects models. Pairwise comparisons regarding mean difference of laboratory measurements during index admission and 30-day readmission/non-readmission were conducted and 95% confidence intervals reported. Bonferroni method was used for p-value adjustment (number of comparison groups = 4). This study was approved by the Partners Healthcare Institutional Review Board. Results: Forty-two patients were treated with CAR T-cells between 3/2016 and 3/2018. Thirty-six patients had non-Hodgkins lymphoma (NHL), 1 acute lymphoblastic leukemia, 1 chronic lymphocytic leukemia, and 4 multiple myeloma. Eight (19%) received the standard of care product, axicabtagene ciloleucel and all others were treated on a clinical trial with an investigational product. Median age at first treatment was 62.2 years old. Twenty-nine patients were male and 13 female. Fourteen patients (33.3%) experienced readmission within 30 days following discharge from CAR T infusion hospitalization. Twelve patients (29%) were readmitted within the first 14 days and 20 patients (47.6%) were readmitted to the hospital within 90 days of discharge (Figure 1). Patient age was not associated with 30-day readmission (P=0.642). Thirty-four (81%) patients received one CAR-T treatment and 8 (19%) received 2 treatments. Among those who received a second CAR-T treatment, 4 (50%) experienced 30-day readmission. Overall, 3 (7%) patients required transfer to the ICU (1 patient after both CAR T infusions) and two patients with NHL died during their first CAR T treatment admission. One patient died of progressive disease 44 days post-CAR T and the other died of disseminated candidemia 18 day post-CAR T. Our mixed effects model showed that median ferritin level was significantly elevated during the 30-day readmission visit as compared to initial CAR T infusion visit (1526.5 vs 1005.5 ug/L, difference in mean = 1088.5, 95% CI: 437.4 to 1739.6, adjusted P = 0.009). CAR T infusion visit ferritin levels did not differ among patients who were readmitted within 30 days and those who were not (1143.0 vs 1005.5 ug/L, P = 1.0). For readmissions which occurred after 30 days, we did not find a statistically significant increase in ferritin levels (P = 0.809). We did not find an association between initial length of hospitalization, CRP levels, and tocilizumab usage and early readmissions (all P-values > 0.05). Conclusions: CAR T-cell therapy is a promising evolving therapy for the treatment of relapsed, refractory hematologic malignancies. Further evaluation of pooled data may allow for early identification of patterns of deterioration which may limit premature hospital discharge, early readmission, and therapy-associated mortality. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

The Mycobacterium tuberculosis cytochrome P450 enzyme CYP142 is encoded in a large gene cluster involved in metabolism of host cholesterol. CYP142 was expressed and purified as a soluble, low spin P450 hemoprotein. CYP142 binds tightly to cholesterol and its oxidized derivative cholest-4-en-3-one, with extensive shift of the heme iron to the high spin state. High affinity for azole antibiotics was demonstrated, highlighting their therapeutic potential. CYP142 catalyzes either 27-hydroxylation of cholesterol/cholest-4-en-3-one or generates 5-cholestenoic acid/cholest-4-en-3-one-27-oic acid from these substrates by successive sterol oxidations, with the catalytic outcome dependent on the redox partner system used. The CYP142 crystal structure was solved to 1.6 Å, revealing a similar active site organization to the cholesterol-metabolizing M. tuberculosis CYP125, but having a near-identical organization of distal pocket residues to the branched fatty acid oxidizing M. tuberculosis CYP124. The cholesterol oxidizing activity of CYP142 provides an explanation for previous findings that ΔCYP125 strains of Mycobacterium bovis and M. bovis BCG cannot grow on cholesterol, because these strains have a defective CYP142 gene. CYP142 is revealed as a cholesterol 27-oxidase with likely roles in host response modulation and cholesterol metabolism.

We present a method to form an optical window in the mouse skull that spans millimeters and is stable for months without causing brain inflammation. This enabled us to repeatedly image blood flow in cortical capillaries of awake mice and determine long-range correlations in speed. We also repeatedly imaged dendritic spines, microglia and angioarchitecture, as well as used illumination to drive motor output via optogenetics and induce microstrokes via photosensitizers.

Background Studies of early-term birth after demonstrated fetal lung maturity show that respiratory and other outcomes are worse with early-term birth (370–386 weeks) even after demonstrated fetal lung maturity when compared with full-term birth (390–406 weeks). However, these studies included medically indicated births and are therefore potentially limited by confounding by the indication for delivery. Thus, the increase in adverse outcomes might be due to the indication for early-term birth rather than the early-term birth itself. Objective We examined the prevalence and risks of adverse neonatal outcomes associated with early-term birth after confirmed fetal lung maturity as compared with full-term birth in the absence of indications for early delivery. Study Design This is a secondary analysis of an observational study of births to 115,502 women in 25 hospitals in the United States from 2008 through 2011. Singleton nonanomalous births at 37–40 weeks with no identifiable indication for delivery were included; early-term births after positive fetal lung maturity testing were compared with full-term births. The primary outcome was a composite of death, ventilator for ≥2 days, continuous positive airway pressure, proven sepsis, pneumonia or meningitis, treated hypoglycemia, hyperbilirubinemia (phototherapy), and 5-minute Apgar Results In all, 48,137 births met inclusion criteria; the prevalence of fetal lung maturity testing in the absence of medical or obstetric indications for early delivery was 0.52% (n = 249). There were 180 (0.37%) early-term births after confirmed pulmonary maturity and 47,957 full-term births. Women in the former group were more likely to be non-Hispanic white, smoke, have received antenatal steroids, have induction, and have a cesarean. Risks of the composite (16.1% vs 5.4%; adjusted odds ratio, 3.2; 95% confidence interval, 2.1–4.8 from logistic regression) were more frequent with elective early-term birth. Propensity scores matching confirmed the increased primary composite in elective early-term births: adjusted odds ratios, 4.3 (95% confidence interval, 1.8–10.5) for 1:1 and 3.5 (95% confidence interval, 1.8–6.5) for 1:2 matching. Among components of the primary outcome, CPAP use and hyperbilirubinemia requiring phototherapy were significantly increased. Transient tachypnea of the newborn, neonatal intensive care unit admission, and prolonged neonatal intensive care unit stay (>2 days) were also increased with early-term birth. Conclusion Even with confirmed pulmonary maturity, early-term birth in the absence of medical or obstetric indications is associated with worse neonatal respiratory and hepatic outcomes compared with full-term birth, suggesting relative immaturity of these organ systems in early-term births.

Gamma-ray bursts (GRBs) are the most powerful explosions known in the universe. Sensitive measurements of the high-energy spectra of GRBs can place important constraints on the burst environments and radiation processes. Until recently, there were no observations during the first few minutes of GRB afterglows in the energy range between 30 GeV and ~1 TeV. With the launch of the Swift GRB Explorer in late 2004, GRB alerts and localizations within seconds of the bursts became available. The Solar Tower Atmospheric Cherenkov Effect Experiment (STACEE) was a ground-based, gamma-ray telescope with an energy threshold of ~150 GeV for sources at zenith. At the time of Swift's launch, STACEE was in a rare position to provide >150 GeV follow-up observations of GRBs as fast as three minutes after the burst alert. In addition, STACEE performed follow-up observations of several GRBs that were localized by the HETE-2 and INTEGRAL satellites. Between 2002 June and 2007 July, STACEE made follow-up observations of 23 GRBs. Upper limits are placed on the high-energy gamma-ray fluxes from 21 of these bursts.

The on-line identification of labeled cells and vessels is a rate-limiting step in scanning microscopy. We use supervised learning to formulate an algorithm that rapidly and automatically tags fluorescently labeled somata in full-field images of cortex and constructs an optimized scan path through these cells. A single classifier works across multiple subjects, regions of the cortex of similar depth, and different magnification and contrast levels without the need to retrain the algorithm. Retraining only has to be performed when the morphological properties of the cells change significantly. In conjunction with two-photon laser scanning microscopy and bulk-labeling of cells in layers 2/3 of rat parietal cortex with a calcium indicator, we can automatically identify ∼50 cells within 1 min and sample them at ∼100 Hz with a signal-to-noise ratio of ∼10.

Rapid laboratory methods provide optimal support for active surveillance efforts to screen for methicillin-resistant Staphylococcus aureus (MRSA). Most laboratories struggle to determine the optimal use of resources, considering options to balance cost, speed, and diagnostic accuracy. To assess the performance of common methods, the first comparison of MRSA Select agar (MS) and CHROMagar MRSA (CA), with and without broth enrichment followed by a 24-h subculture to MS, was performed. Results were compared to those of the Xpert MRSA assay. For direct culture methods, the agreement between MS and CA was 98.8%. At 18 h, direct MS identified 93% of all positive samples from direct culture and 84% of those identified by the Xpert MRSA. For Trypticase soy broth-enriched MS culture, incubated overnight and then subcultured for an additional 24 h, the agreement with Xpert MRSA was 96%. The agreement between direct MS and Xpert MRSA was 100% when semiquantitative culture revealed a bacterial density of 2+ or greater; however, discrepancies between culture and Xpert MRSA arose for MRSA bacterial densities of 1+ or less, indicating low density as a common cause of false-negative culture results. Since 1+ or less was established as the most common MRSA carrier state, broth enrichment or PCR may be critical for the identification of all MRSA carriers who may be reservoirs for transmission. In this active-surveillance convenience sample, the use of broth enrichment followed by subculture to MS offered a low-cost but sensitive method for MRSA screening, with performance similar to that of Xpert MRSA PCR.

The Solar Tower Atmospheric Cherenkov Effect Experiment (STACEE) is a ground-based telescope that uses the wave-front-sampling technique to detect very high energy (VHE) gamma rays. STACEE's sensitivity in the energy range near 100 GeV permits useful observations of pulsars with the potential to discriminate between various proposed mechanisms for pulsed gamma-ray emission. Based on the 11.3 hr of data taken during the 2005 and 2006 observing seasons, we derive an upper limit on the pulsed gamma-ray emission from PSR B1951+32 of

Suppression of the renin-angiotensin system has proven efficacy for mitigation and treatment of radiation nephropathy, and it has been hypothesized that this efficacy is due to suppression of radiation-induced chronic oxidative stress. It is known that radiation exposure leads to acute oxidative stress, but direct evidence for radiation-induced chronic renal oxidative stress is sparse. We looked for evidence of oxidative stress after total-body irradiation in a rat model, focusing on the period before there is physiologically significant renal damage. No statistically significant increase in urinary 8-isoprostane (a marker of lipid peroxidation) or carbonylated proteins (a marker of protein oxidation) was found over the first 42 days after irradiation, while a small but statistically significant increase in urinary 8-hydroxydeoxy-guanosine (a marker of DNA oxidation) was detected at 35-55 days. When we examined renal tissue from these animals, we found no significant increase in either DNA or protein oxidation products over the first 89 days after irradiation. Using five different standard methods for detecting oxidative stress in vivo, we found no definitive evidence for radiation-induced renal chronic oxidative stress. If chronic oxidative stress is part of the pathogenesis of radiation nephropathy, it does not leave widespread or easily detectable evidence behind.

Using the Solar Tower Atmospheric Cherenkov Effect Experiment (STACEE), we have observed the BL Lac objects 3C 66A and OJ 287. These are members of the class of low-frequency-peaked BL Lac objects (LBLs) and are two of the three LBLs predicted by Costamante and Ghisellini to be potential sources of very high energy (>100 GeV) gamma-ray emission. The third candidate, BL Lacertae, has recently been detected by the MAGIC collaboration. Our observations have not produced detections; we calculate a 99% CL upper limit of flux from 3C 66A of 0.15 Crab flux units and from OJ 287 our limit is 0.52 Crab. These limits assume a Crab-like energy spectrum with an effective energy threshold of 185 GeV., 24 pages, 15 figures, Accepted for publication in Astroparticle Physics

Studies of the accuracy and completeness of handwritten anesthesia records demonstrate deficiencies in documentation, suggesting that the quality of anesthesia records can be improved.We reviewed all electronic anesthesia records generated during a 1-month period at our institution to ascertain completion rates for six clinical documentation elements: allergies, IV access, electrocardiogram rhythm, ease of mask ventilation, laryngoscopic grade of view, and insertion depth of the endotracheal tube.Of 2838 records, 64% had the necessary free text remark in the allergy element. The free text required to complete endotracheal tube depth documentation appeared in 538 of 918 cases in which the patient was tracheally intubated (59%). Free text documentation of the electrocardiogram rhythm diagnosis appeared at least once in 86% of records. Documentation of mask ventilation characteristics was entered by touch screen from a pick list and was expected in 781 records but appeared in 664 records (85%). Laryngoscopic grade of view documentation was also selected by touch screen and expected in 883 records but present in 811 cases (92%). Any notation of IV access appeared in 84% of records.We found that electronic clinical anesthesia documentation was often incomplete. Dependence on free text remarks and the record keeping system's inability to automatically present entries in logical sequences consistent with workflow were associated with incomplete data entry. Our results suggest that the user interface for data entry, and the logic that an electronic system uses for preventing omissions and inconsistencies, merit further study and development in order to facilitate clinically useful documentation.

Objective We sought to evaluate whether the presence of condition-specific obstetric protocols within a hospital was associated with better maternal and neonatal outcomes. Study Design This was a cohort study of a random sample of deliveries performed at 25 hospitals over 3 years. Condition-specific protocols were collected from all hospitals and categorized independently by 2 authors. Data on maternal and neonatal outcomes, as well as data necessary for risk adjustment were collected. Risk-adjusted outcomes were compared according to whether the patient delivered in a hospital with condition-specific obstetric protocols at the time of delivery. Results Hemorrhage-specific protocols were not associated with a lower rate of postpartum hemorrhage or with fewer cases of estimated blood loss >1000 mL. Similarly, in the presence of a shoulder dystocia protocol, there were no differences in the frequency of shoulder dystocia or number of shoulder dystocia maneuvers used. Conversely, preeclampsia-specific protocols were associated with fewer intensive care unit admissions (odds ratio, 0.28; 95% confidence interval, 0.18–0.44) and fewer cases of severe maternal hypertension (odds ratio, 0.86; 95% confidence interval, 0.77–0.96). Conclusion The presence of condition-specific obstetric protocols was not consistently shown to be associated with improved risk-adjusted outcomes. Our study would suggest that the presence or absence of a protocol does not matter and regulations to require protocols are not fruitful.

A synchronous motor with a high-temperature superconducting field winding has been successfully constructed and tested. Designed to produce an output power of 1000 hp, this motor was operated successfully at this power rating and achieved an output power of 1600 hp during subsequent testing. This paper provides an overview of the design of the motor and discusses the results of a series of tests which were performed on the motor.

Genomic DNA was amplified about 5 billion-fold from single, flow-sorted bacterial cells by the multiple displacement amplification (MDA) reaction, using φ 29 DNA polymerase. A 662-bp segment of the 16S rRNA gene could be accurately sequenced from the amplified DNA. MDA methods enable new strategies for studying nonculturable microorganisms.

OBJECTIVE To determine whether exercise training in combination with metformin improves cardiovascular risk indices and insulin in comparison to metformin alone among HIV-infected patients. METHODS AND DESIGN We conducted a prospective, randomized, 3-month study of HIV patients on stable antiretroviral therapy with hyperinsulinemia and fat redistribution. Subjects received metformin alone or metformin and exercise training consisting of 1 h of aerobic and resistance training three times a week. Cardiovascular parameters, including blood pressure and endurance during sub-maximal stress testing, body composition, strength, insulin and other biochemical parameters were determined. RESULTS Thirty-seven patients were randomized and 25 subjects completed the study. Subjects receiving exercise training and metformin demonstrated significant decreases in median waist-to-hip ratio [-0.02 (-0.06, -0.01) (median (interquartile range) versus -0.01 (0.03, 0.02), P = 0.026], resting systolic [-12 (-20, -4) versus 0 (-11, 11), P = 0.012] and diastolic blood pressures [-10 (-14, -8) versus 0 (-7, 8), P = 0.001], increased thigh muscle cross-sectional area [3 (-3, 12) versus -7 (-11, 0), P = 0.015], and improved exercise time [3 (0, 4) versus 0 (-1, 1), P = 0.045] compared with subjects receiving metformin alone. Fasting insulin and insulin area under the curve decreased significantly more in the exercise and metformin group (P < 0.05). Lipids and resting lactate did not change significantly between treatment groups. CONCLUSIONS These data demonstrate that exercise training in combination with metformin significantly improves cardiovascular and biochemical parameters more than metformin alone in HIV-infected patients with fat redistribution and hyperinsulinemia. Combined treatment was safe, well tolerated and may be a useful strategy to decrease cardiovascular risk in this population.

A new diagnostic has been developed that is capable of obtaining simultaneous two-phase velocity measurements in a gasoline direct-injection fuel spray. This technique utilizes a two-laser (double-pulse) two-camera (double-frame) setup to simultaneously image the injected fuel and entrained air to determine the 2D velocity vector fields of both phases using cross-correlation particle image velocimetry (PIV). The air phase is visualized through fluorescence from seeding particles introduced into the static measurement volume while Mie scattering signals are collected from the fuel droplets. The combination of different laser wavelengths and a spectral signal shift for the air phase allows spectral separation of the signals. Independent timing of the laser pulses permits optimized adaptation of the velocity dynamic range for the two phases to account for the large difference in velocities between air and fuel droplets.

Fundamental to most genetic analysis is availability of genomic DNA of adequate quality and quantity. Because DNA yield from human samples is frequently limiting, much effort has been invested in developing methods for whole genome amplification (WGA) by random or degenerate oligonucleotide-primed PCR. However, existing WGA methods like degenerate oligonucleotide-primed PCR suffer from incomplete coverage and inadequate average DNA size. We describe a method, termed multiple displacement amplification (MDA), which provides a highly uniform representation across the genome. Amplification bias among eight chromosomal loci was less than 3-fold in contrast to 4–6 orders of magnitude for PCR-based WGA methods. Average product length was >10 kb. MDA is an isothermal, strand-displacing amplification yielding about 20–30 μg product from as few as 1–10 copies of human genomic DNA. Amplification can be carried out directly from biological samples including crude whole blood and tissue culture cells. MDA-amplified human DNA is useful for several common methods of genetic analysis, including genotyping of single nucleotide polymorphisms, chromosome painting, Southern blotting and restriction fragment length polymorphism analysis, subcloning, and DNA sequencing. MDA-based WGA is a simple and reliable method that could have significant implications for genetic studies, forensics, diagnostics, and long-term sample storage.

Estrogen signaling is mediated by ERα and -β. ERs are converted from an inactive form to a transcriptionally active state through conformational changes induced by ligand and estrogen-responsive element (ERE) sequences. We show here that ERα and ERβ bind to an ERE independently from ER ligands. We found that although the binding affinity of ERβ for an ERE is 2-fold lower than that of ERα, both ERs use the same nucleotides for DNA contacts. We show that both EREs and ligands are independent modulators of ER conformation. Specifically, the ERE primarily determines the receptor-DNA affinity, whereas the structure of the ER ligand dictates the affinity of ER for particular cofactors. We found that the ligand-dependent cofactor transcriptional intermediary factor-2, through a distinct surface, also interacts with ERα preferentially and independently of ligand. The extent of interaction, however, is dependent upon the ER-ERE affinity. In transfected cells, ERα is more transcriptionally active than ERβ. The ERE sequence, however, determines the potency of gene induction when either ER subtype binds to an agonist. Antagonists prevent ERs from inducing transcription independently from ERE sequences. Thus, ERE- and ligand-induced structural changes are independent determinants for the recruitment of cofactors and transcriptional responses. The ability of ERα to differentially recruit a cofactor could contribute to ER subtype-specific gene responses.

Background: Process improvement in healthcare delivery settings can be difficult, even when there is consensus among clinicians about a clinical practice or desired outcome. Airway management is a medical intervention fundamental to the delivery of anesthesia care. Like other medical interventions, a detailed description of the management methods should be documented. Despite this expectation, airway documentation is often insufficient. The authors hypothesized that formal adoption of process improvement methods could be used to increase the rate of “complete” airway management documentation. Methods: The authors defined a set of criteria as a local practice standard of “complete” airway management documentation. The authors then employed selected process improvement methodologies over 13 months in three iterative and escalating phases to increase the percentage of records with complete documentation. The criteria were applied retrospectively to determine the baseline frequency of complete records, and prospectively to measure the impact of process improvements efforts over the three phases of implementation. Results: Immediately before the initial intervention, a retrospective review of 23,011 general anesthesia cases over 6 months showed that 13.2% of patient records included complete documentation. At the conclusion of the 13-month improvement effort, documentation improved to a completion rate of 91.6% (P < 0.0001). During the subsequent 21 months, the completion rate was sustained at an average of 90.7% (SD, 0.9%) across 82,571 general anesthetic records. Conclusion: Systematic application of process improvement methodologies can improve airway documentation and may be similarly effective in improving other areas of anesthesia clinical practice.

Gd4O2S:Yb:Tm rare-earth upconversion phosphors have been utilised to monitor the redox behaviour of flavin mononucleotide and report on the turnover of a flavo-protein, (pentaerythritol tetranitrate reductase). The presence of two bands separated by over 300 nm in the UCP emission spectra allows ratiometric signalling of these processes with high sensitivity.

A combination of the temperature- and pressure-dependencies of the kinetic isotope effect on the proton coupled electron transfer during ascorbate oxidation by ferricyanide suggests that this reference reaction may exploit vibrationally assisted quantum tunnelling of the transferred proton. © 2014 the Owner Societies.

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), nucleocapsid protein (NC), genomic RNA, and the growing DNA strand all influence the copying of the HIV-1 RNA genome into DNA. A detailed understanding of these activities is required to understand the process of reverse transcription. HIV-1 viral DNA is initiated from a tRNA 3 Lys primer bound to the viral genome at the primer binding site. The U3 and R regions of the RNA genome are the first sequences to be copied. The TAR hairpin, a structure found within the R region of the viral genome, is the site of increased RT pausing, RNase H activity, and RT dissociation. Template RNA was digested approximately 17 bases behind the site where polymerase paused at the base of TAR. In most template RNAs, this was the only cleavage made by the RT responsible for initiating polymerization. If the RT that initiated DNA synthesis dissociated from the base of the TAR hairpin and an RT rebound at the end of the primer, there was competition between the polymerase and RNase H activities. After the complete heteroduplex was formed, there were additional RNase H cleavages that did not involve polymerization. Levels of NC that prevented TAR DNA self-priming did not protect genomic RNA from RNase H digestion. RNase H digestion of the 100-bp heteroduplex produced a 14-base RNA from the 5′ end of the RNA that remained annealed to the 3′ end of the minus-strand strong-stop DNA only if NC was present in the reaction.