A third indeterminacy of labour power: Worker health investment and the indeterminacy of labour health.

This article identifies the health of the worker as a third source of labour power indeterminacy to be added to the indeterminacy of labour effort and the indeterminacy of labour mobility. The paper clearly differentiates worker health from effort as a distinct source of labour power indeterminacy-something that cannot be guaranteed and that varies for an individual over time. It considers the relationship between worker health as a new source of indeterminacy and the two extant sources of labour power indeterminacy, focussing on the way in which health moderates the relationship between effort and output. The paper also considers the way in which worker health investment moderates the indeterminacy of labour effort and labour mobility, independently of its impact on the health of the worker. The paper documents the potential value of worker health investment to the organisation and also considers the boundary conditions for investment in worker health.

A Conduit for a Culturally Competent Consent: Medical Interpreters' Perspectives on Surgical Informed Consent Discussions.

OBJECTIVE: To understand medical interpreter's perspectives on surgical informed consent discussions and provide feedback for surgeons on improving these conversations. SUMMARY BACKGROUND DATA: Informed consent is a critical component of patient-centered surgical decision-making. For patients with limited English proficiency (LEP), this conversation may be less thorough, even with a medical interpreter, leaving patients with an inadequate understanding of their diagnosis or treatment options. METHODS: A semi-structured interview guide was developed with input from interpreters and a qualitative research expert. We purposively sampled medical interpreters representing multiple languages until thematic saturation was achieved. Participants discussed their experience with the surgical consent discussion and process. Interview transcripts were analyzed using emergent thematic analysis. RESULTS: Among 22 interpreters, there were ten languages represented and an average experience of 15 years (range 4-40 y). Four major themes were identified. First, interpreters consistently described their roles as patient advocates and cultural brokers. Second, interpreters reported unique patient attributes that influence the discussion, often based on patients' cultural values/expectations, anticipated decisional autonomy, and family support. Third, interpreters emphasized the importance of surgeons demonstrating compassion and patience, using simple terminology, conversing around the consent, providing context about the form/process, and initiating a pre-encounter discussion. Finally, interpreters suggested reducing legal terminology on consent forms and translation into other languages. CONCLUSIONS: Experienced interpreters highlighted multiple factors associated with effective and culturally tailored informed consent discussions. Surgeons should recognize interpreters' critical and complex roles, be cognizant of cultural variations among patients with LEP, and improve interpersonal and communication skills to facilitate effective understanding.

Surveillance is the first step to preventing injury among fast jet aircrew: results of a 2-year prospective cohort study.

OBJECTIVES: Injury surveillance is imperative for injury prevention but difficult in military populations. Our objective was to accurately describe the pattern of musculoskeletal complaints among Royal Australian Air Force (RAAF) fast jet aircrew (FJA) using the validated University of Canberra Fast Jet Aircrew Musculoskeletal Questionnaire (UC-FJAMQ) over a 2-year period, and determine injury burden on the workforce and operational capability. METHODS: 306 RAAF FJA were monitored over a 2-year period (4×5 month reporting periods). Musculoskeletal complaint episodes (MCEs) were captured weekly using the UC-FJAMQ. Time loss episodes (TLEs) were captured from the UC-FJAMQ and injury registers completed by embedded physiotherapists. Cumulative severity and operational impact scores from the UC-FJAMQ, and time loss duration, were used to describe severity and calculate burden. RESULTS: Mean weekly UC-FJAMQ response rate was 62%. 1012 MCEs were captured, with a mean weekly prevalence of 14.9% (95% CI 14.2-15.6), and incidence of 4.1 episodes per person-year (95% CI 3.9-4.4). A total of 145 TLEs were captured, with a mean 5-month prevalence of 12.4% (range 8.9-15.3%), and incidence of 0.37 episodes per person-year (95% CI 0.31-0.43). Spinal regions accounted for 81% of MCEs and contributed 76% and 85% of burden in relation to cumulative severity and operational impact, respectively. 57% of TLE burden came from spinal regions. CONCLUSIONS: Despite modest weekly UC-FJAMQ response rates, musculoskeletal complaints were shown to be widespread and negatively impact operational capability. Future injury prevention efforts among FJA should focus on spinal regions, particularly the neck.

Factors associated with neck pain in fighter aircrew: a systematic review and meta-analysis.

Neck pain is a common complaint among fighter aircrew, impacting workforce health and operational capability. This systematic review aimed to identify, evaluate and synthesise the current evidence for factors associated with the occurrence of neck pain among fighter aircrew. Six electronic databases were searched in June 2019 and updated in June 2020 utilising the maximum date ranges. Included studies were appraised for methodological quality, ranked according to level of evidence and relevant data extracted. Where methods were homogeneous and data availability allowed, meta-analyses were performed. A total of 20 studies (16 cross sectional, one case-control, one retrospective cohort and two prospective cohort) were eligible for inclusion. Of the 44 factors investigated, consistent evidence was reported for greater occurrence of neck pain among aircrew operating more advanced aircraft and those exposed to more desk/computer work, while another 12 factors reported consistent evidence for no association. Of the 20 factors where meta-analyses could be performed, greater occurrence of neck pain was indicated for aircrew: flying more advanced aircraft, undertaking warm-up stretching and not placing their head against the seat under greater +Gz. Despite many studies investigating factors associated with neck pain among fighter aircrew, methodological limitations limited the ability to identify those factors that are most important to future preventive programmes. High-quality prospective studies with consistent use of definitions are required before we can implement efficient and effective programmes to reduce the prevalence and impact of neck pain in fighter aircrew. PROSPERO registration number: CRD42019128952.Neck pain is a common complaint among fighter aircrew, impacting workforce health and operational capability. This systematic review aimed to identify, evaluate and synthesise the current evidence for factors associated with the occurrence of neck pain among fighter aircrew.

Emergency department management of older people living with frailty: a guide for emergency practitioners.

Emergency Departments (EDs) are increasingly seeing more seriously unwell older people living with frailty. In the context of limited resources and increasing demand it's the ED practitioner's challenge to unpick this constellation of physical, psychological, functional and social issues.To properly assess older people living with frailty at the ED it is crucial to use an holistic approach. This consists of triage with algorithms sensitive to the higher risk of older people living with frailty, a frailty assessment, and an assessment with the help of the principles of Comprehensive Geriatric Assessment. Multi-disciplinary care, a tailor-made treatment plan, based on what the person values most, will help the ED practitioner to deliver appropriate and valuable care during the ED stay, but also in transition from hospital to home.

Enhancing reaction-based de novo design using a multi-label reaction class recommender.

Reaction-based de novo design refers to the in-silico generation of novel chemical structures by combining reagents using structural transformations derived from known reactions. The driver for using reaction-based transformations is to increase the likelihood of the designed molecules being synthetically accessible. We have previously described a reaction-based de novo design method based on reaction vectors which are transformation rules that are encoded automatically from reaction databases. A limitation of reaction vectors is that they account for structural changes that occur at the core of a reaction only, and they do not consider the presence of competing functionalities that can compromise the reaction outcome. Here, we present the development of a Reaction Class Recommender to enhance the reaction vector framework. The recommender is intended to be used as a filter on the reaction vectors that are applied during de novo design to reduce the combinatorial explosion of in-silico molecules produced while limiting the generated structures to those which are most likely to be synthesisable. The recommender has been validated using an external data set extracted from the recent medicinal chemistry literature and in two simulated de novo design experiments. Results suggest that the use of the recommender drastically reduces the number of solutions explored by the algorithm while preserving the chance of finding relevant solutions and increasing the global synthetic accessibility of the designed molecules.

Transitional-turbulent spots and turbulent-turbulent spots in boundary layers.

Two observations drawn from a thoroughly validated direct numerical simulation of the canonical spatially developing, zero-pressure gradient, smooth, flat-plate boundary layer are presented here. The first is that, for bypass transition in the narrow sense defined herein, we found that the transitional-turbulent spot inception mechanism is analogous to the secondary instability of boundary-layer natural transition, namely a spanwise vortex filament becomes a [Formula: see text] vortex and then, a hairpin packet. Long streak meandering does occur but usually when a streak is infected by a nearby existing transitional-turbulent spot. Streak waviness and breakdown are, therefore, not the mechanisms for the inception of transitional-turbulent spots found here. Rather, they only facilitate the growth and spreading of existing transitional-turbulent spots. The second observation is the discovery, in the inner layer of the developed turbulent boundary layer, of what we call turbulent-turbulent spots. These turbulent-turbulent spots are dense concentrations of small-scale vortices with high swirling strength originating from hairpin packets. Although structurally quite similar to the transitional-turbulent spots, these turbulent-turbulent spots are generated locally in the fully turbulent environment, and they are persistent with a systematic variation of detection threshold level. They exert indentation, segmentation, and termination on the viscous sublayer streaks, and they coincide with local concentrations of high levels of Reynolds shear stress, enstrophy, and temperature fluctuations. The sublayer streaks seem to be passive and are often simply the rims of the indentation pockets arising from the turbulent-turbulent spots.

Outer retinal degeneration in two closely related Goeldi's monkeys (Callimico goeldii).

This case report comprises studies of four Goeldi's monkeys (Callimico goeldii) from the same enclosure. Globe samples from two related C goeldii (the female C goeldii and her male offspring) were available for a histopathological evaluation. Both cases presented histopathologically evident outer retinal degeneration with differences in severity. There was marked outer retinal atrophy characterized by loss of the outer and inner photoreceptor segments, and depletion of the outer retinal nuclear layer. Furthermore, we report a reduction in the thickness of the outer retinal plexiform, inner retinal nuclear layer, and inner retinal plexiform layer in these C goeldii monkeys. To the authors' knowledge, these findings have not yet been reported in wild- or captive-bred population of C goeldii.

Development and Application of a Data-Driven Reaction Classification Model: Comparison of an Electronic Lab Notebook and Medicinal Chemistry Literature.

Reaction classification has often been considered an important task for many different applications, and has traditionally been accomplished using hand-coded rule-based approaches. However, the availability of large collections of reactions enables data-driven approaches to be developed. We present the development and validation of a 336-class machine learning-based classification model integrated within a Conformal Prediction (CP) framework to associate reaction class predictions with confidence estimations. We also propose a data-driven approach for "dynamic" reaction fingerprinting to maximize the effectiveness of reaction encoding, as well as developing a novel reaction classification system that organizes labels into four hierarchical levels (SHREC: Sheffield Hierarchical REaction Classification). We show that the performance of the CP augmented model can be improved by defining confidence thresholds to detect predictions that are less likely to be false. For example, the external validation of the model reports 95% of predictions as correct by filtering out less than 15% of the uncertain classifications. The application of the model is demonstrated by classifying two reaction data sets: one extracted from an industrial ELN and the other from the medicinal chemistry literature. We show how confidence estimations and class compositions across different levels of information can be used to gain immediate insights on the nature of reaction collections and hidden relationships between reaction classes.

Human Oral Buccal Microbiomes Are Associated with Farmworker Status and Azinphos-Methyl Agricultural Pesticide Exposure.

In a longitudinal agricultural community cohort sampling of 65 adult farmworkers and 52 adult nonfarmworkers, we investigated agricultural pesticide exposure-associated changes in the oral buccal microbiota. We found a seasonally persistent association between the detected blood concentration of the insecticide azinphos-methyl and the taxonomic composition of the buccal swab oral microbiome. Blood and buccal samples were collected concurrently from individual subjects in two seasons, spring/summer 2005 and winter 2006. Mass spectrometry quantified blood concentrations of the organophosphate insecticide azinphos-methyl. Buccal oral microbiome samples were 16S rRNA gene DNA sequenced, assigned to the bacterial taxonomy, and analyzed after "centered-log-ratio" transformation to handle the compositional nature of the proportional abundances of bacteria per sample. Nonparametric analysis of the transformed microbiome data for individuals with and without azinphos-methyl blood detection showed significant perturbations in seven common bacterial taxa (>0.5% of sample mean read depth), including significant reductions in members of the common oral bacterial genus Streptococcus Diversity in centered-log-ratio composition between individuals' microbiomes was also investigated using principal-component analysis (PCA) to reveal two primary PCA clusters of microbiome types. The spring/summer "exposed" microbiome cluster with significantly less bacterial diversity was enriched for farmworkers and contained 27 of the 30 individuals who also had azinphos-methyl agricultural pesticide exposure detected in the blood. IMPORTANCE: In this study, we show in human subjects that organophosphate pesticide exposure is associated with large-scale significant alterations of the oral buccal microbiota composition, with extinctions of whole taxa suggested in some individuals. The persistence of this association from the spring/summer to the winter also suggests that long-lasting effects on the commensal microbiota have occurred. The important health-related outcomes of these agricultural community individuals' pesticide-associated microbiome perturbations are not understood at this time. Future investigations should index medical and dental records for common and chronic diseases that may be interactively caused by this association between pesticide exposure and microbiome alteration.

Assessing the Climate Trade-Offs of Gasoline Direct Injection Engines.

Compared to port fuel injection (PFI) engine exhaust, gasoline direct injection (GDI) engine exhaust has higher emissions of black carbon (BC), a climate-warming pollutant. However, the relative increase in BC emissions and climate trade-offs of replacing PFI vehicles with more fuel efficient GDI vehicles remain uncertain. In this study, BC emissions from GDI and PFI vehicles were compiled and BC emissions scenarios were developed to evaluate the climate impact of GDI vehicles using global warming potential (GWP) and global temperature potential (GTP) metrics. From a 20 year time horizon GWP analysis, average fuel economy improvements ranging from 0.14 to 14% with GDI vehicles are required to offset BC-induced warming. For all but the lowest BC scenario, installing a gasoline particulate filter with an 80% BC removal efficiency and <1% fuel penalty is climate beneficial. From the GTP-based analysis, it was also determined that GDI vehicles are climate beneficial within <1-20 years; longer time horizons were associated with higher BC scenarios. The GDI BC emissions spanned 2 orders of magnitude and varied by ambient temperature, engine operation, and fuel composition. More work is needed to understand BC formation mechanisms in GDI engines to ensure that the climate impacts of this engine technology are minimal.

Field Measurements of Gasoline Direct Injection Emission Factors: Spatial and Seasonal Variability.

Four field campaigns were conducted between February 2014 and January 2015 to measure emissions from light-duty gasoline direct injection (GDI) vehicles (2013 Ford Focus) in an urban near-road environment in Toronto, Canada. Measurements of CO2, CO, NOx, black carbon (BC), benzene, toluene, ethylbenzene-xylenes (BTEX), and size-resolved particle number (PN) were recorded 15 m from the roadway and converted to fuel-based emission factors (EFs). Other than for NOx and CO, the GDI engine had elevated emissions compared to the Toronto fleet, with BC EFs in the 73rd percentile, BTEX EFs in the 80-90th percentile, and PN EFs in the 75th percentile during wintertime measurements. Additionally, for three campaigns, a second platform for measuring PN and CO2 was placed 1.5-3 m from the roadway to quantify changes in PN with distance from point of emission. GDI vehicle PN EFs were found to increase by up to 240% with increasing distance from the roadway, predominantly due to an increasing fraction of sub-40 nm particles. PN and BC EFs from the same engine technology were also measured in the laboratory. BC EFs agreed within 20% between the laboratory and real-world measurements; however, laboratory PN EFs were an order of magnitude lower due to exhaust conditioning.

A web-based data visualization tool for the MIMIC-II database.

BACKGROUND: Although MIMIC-II, a public intensive care database, has been recognized as an invaluable resource for many medical researchers worldwide, becoming a proficient MIMIC-II researcher requires knowledge of SQL programming and an understanding of the MIMIC-II database schema. These are challenging requirements especially for health researchers and clinicians who may have limited computer proficiency. In order to overcome this challenge, our objective was to create an interactive, web-based MIMIC-II data visualization tool that first-time MIMIC-II users can easily use to explore the database. RESULTS: The tool offers two main features: Explore and Compare. The Explore feature enables the user to select a patient cohort within MIMIC-II and visualize the distributions of various administrative, demographic, and clinical variables within the selected cohort. The Compare feature enables the user to select two patient cohorts and visually compare them with respect to a variety of variables. The tool is also helpful to experienced MIMIC-II researchers who can use it to substantially accelerate the cumbersome and time-consuming steps of writing SQL queries and manually visualizing extracted data. CONCLUSIONS: Any interested researcher can use the MIMIC-II data visualization tool for free to quickly and conveniently conduct a preliminary investigation on MIMIC-II with a few mouse clicks. Researchers can also use the tool to learn the characteristics of the MIMIC-II patients. Since it is still impossible to conduct multivariable regression inside the tool, future work includes adding analytics capabilities. Also, the next version of the tool will aim to utilize MIMIC-III which contains more data.

Surgery duration predicts urinary retention after inguinal herniorrhaphy: a single institution review.

BACKGROUND: Inguinal hernia repair, laparoscopic or open, is one of the most frequently performed operations in general surgery. Postoperative urinary retention (POUR) can occur in 0.2-35 % of patients after inguinal hernia repair. The primary objective of this study was to determine the incidence of POUR after inguinal hernia repair. As a secondary goal, we sought to determine whether perioperative and patient factors predicted urinary retention. METHODS: This study is a retrospective review of patients who underwent inguinal hernia repair with synthetic mesh at the Medical College of Wisconsin from January 2007 to June 2012. Procedures were performed by four surgeons. Clinical information and perioperative outcomes were collected up to hospital discharge. Urinary retention was defined as need for urinary catheterization postoperatively. RESULTS: A total of 192 patients were included in the study (88 bilateral, 46 %) and (104 unilateral, 54 %). The majority of subjects (76 %) underwent laparoscopic repair. The overall POUR rate was 13 %, with 25 of 192 patients requiring a Foley catheter prior to discharge. POUR was significantly associated with bilateral hernia repairs (p = 0.04), BMI ≥ 35 kg/m(2) (p = 0.05) and longer operative times (p = 0.03). Based on odds ratio (OR) estimates, for every 10-min increase in operative time, an 11 % increase in the odds of urinary retention is expected (OR 1.11, CI 1.004-1.223; p = 0.04). For every 10-min increase in operative time, an 11 % increase in POUR is expected. CONCLUSIONS: Bilateral hernia repairs, BMI ≥ 35 kg/m(2), and operative time are significant predictors of POUR. These factors are important to determine potential risk to patients and interventions such as strict fluid administration, use of catheters, and potential premedication.

Improvement of spinal non-viral IL-10 gene delivery by D-mannose as a transgene adjuvant to control chronic neuropathic pain.

BACKGROUND: Peri-spinal subarachnoid (intrathecal; i.t.) injection of non-viral naked plasmid DNA encoding the anti-inflammatory cytokine, IL-10 (pDNA-IL-10) suppresses chronic neuropathic pain in animal models. However, two sequential i.t. pDNA injections are required within a discrete 5 to 72-hour period for prolonged efficacy. Previous reports identified phagocytic immune cells present in the peri-spinal milieu surrounding the i.t injection site that may play a role in transgene uptake resulting in subsequent IL-10 transgene expression. METHODS: In the present study, we aimed to examine whether factors known to induce pro-phagocytic anti-inflammatory properties of immune cells improve i.t. IL-10 transgene uptake using reduced naked pDNA-IL-10 doses previously determined ineffective. Both the synthetic glucocorticoid, dexamethasone, and the hexose sugar, D-mannose, were factors examined that could optimize i.t. pDNA-IL-10 uptake leading to enduring suppression of neuropathic pain as assessed by light touch sensitivity of the rat hindpaw (allodynia). RESULTS: Compared to dexamethasone, i.t. mannose pretreatment significantly and dose-dependently prolonged pDNA-IL-10 pain suppressive effects, reduced spinal IL-1ß and enhanced spinal and dorsal root ganglia IL-10 immunoreactivity. Macrophages exposed to D-mannose revealed reduced proinflammatory TNF-α, IL-1ß, and nitric oxide, and increased IL-10 protein release, while IL-4 revealed no improvement in transgene uptake. Separately, D-mannose dramatically increased pDNA-derived IL-10 protein release in culture supernatants. Lastly, a single i.t. co-injection of mannose with a 25-fold lower pDNA-IL-10 dose produced prolonged pain suppression in neuropathic rats. CONCLUSIONS: Peri-spinal treatment with D-mannose may optimize naked pDNA-IL-10 transgene uptake for suppression of allodynia, and is a novel approach to tune spinal immune cells toward pro-phagocytic phenotype for improved non-viral gene therapy.

Phase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumors.

PURPOSE: To define maximum tolerated dose (MTD), toxicities, and pharmacodynamics of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumor patients. DESIGN: This was a standard "3 + 3" dose-escalation trial. All subjects received bevacizumab 7.5 mg/kg on day 1 of each cycle. Doses for capecitabine, oxaliplatin and everolimus were modified per dose limiting toxicity (DLT). Baseline and on-treatment plasma biomarkers were analyzed. Archived tumor mRNA levels were evaluated for NRP1, NRP2 and VEGF-A isoforms. RESULTS: Twenty-nine patients were evaluable for toxicity and 30 for efficacy. Two DLTs were observed in cohort 1 and one DLT each was observed in cohort -1 and -1b. Grade ≥3 toxicities included neutropenia, hypertension, perforation/fistula/hemorrhage, hypertriglyceridemia, diarrhea, and thromboembolism. Twelve subjects experienced partial response (PR); 12 had stable disease as best response. Three of seven chemorefractory metastatic colorectal cancer (mCRC) subjects experienced PR; 8 of 15 chemonaive mCRC subjects experienced PR. Plasma TßRIII and IL-6 increased on treatment but without correlation to outcome. Increased VEGF165 levels significantly correlated with longer progression free survival. CONCLUSIONS: Everolimus with full dose capecitabine, oxaliplatin, and bevacizumab had unacceptable toxicity. MTD was: everolimus 5 mg daily; capecitabine 680 mg/m(2) BID days 1-14; oxaliplatin 100 mg/m(2) and bevacizumab 7.5 mg/kg, day 1. Activity was noted in mCRC.

Medically refractory gastroesophageal reflux disease in the obese: what is the best surgical approach?

BACKGROUND: Obesity is a recognized risk factor for gastroesophageal reflux disease (GERD). Traditional antireflux surgery (fundoplication) may not be appropriate in the morbidly obese, especially when other effective alternatives exist (bariatric surgery). METHODS: A 13-item survey was designed to elicit professional opinions regarding the treatment of medically refractory GERD in obese patients. Members of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) were randomly selected and emailed a link to an online survey. RESULTS: A total of 550 surgeons were contacted via email, and 92 (17 %) completed the survey. Of the respondents, 88 % perform laparoscopic antireflux surgery, 63 % perform bariatric surgery, and 59 % perform both. Overall, 77 % completed a minimally invasive surgery fellowship. In response to the question "Would you perform a laparoscopic fundoplication in a patient with medically refractory GERD and a BMI of 'X'?" surgeons were less likely to offer fundoplication at a higher body mass index (BMI). The majority of respondents felt that laparoscopic Roux-en-Y gastric bypass was the best option (91 %), followed by laparoscopic sleeve gastrectomy (6 %). Many had a morbidly obese patient with a primary surgical indication of GERD denied a bariatric procedure by their insurance company (57 %), and 35 % of those surgeons chose to do nothing rather than subject the patient to a fundoplication. Respondents uniformly felt that bariatric surgery should be recognized as a standard surgical option for treating GERD in the obese (96 %). CONCLUSION: When surgical treatment of GERD is indicated in an obese patient, bariatric surgery is the optimal approach, in the opinion of surgeons responding to our survey. Unfortunately, third-party payers often decline to provide benefits for a bariatric procedure for this indication. Additional data is necessary to confirm our belief that the opinions elicited through this survey are consistent with the standard of care as defined by the medical community.

A population-based analysis of emergent versus elective paraesophageal hernia repair using the Nationwide Inpatient Sample.

BACKGROUND: As the life expectancy in the United States continues to increase, more elderly, sometimes frail patients present with sub-acute surgical conditions such as a symptomatic paraesophageal hernia (PEH). While the outcomes of PEH repair have improved largely due to the proliferation of laparoscopic surgery, there is still a defined rate of morbidity and mortality. We sought to characterize the outcomes of both elective and emergent PEH repair using a large population-based data set. METHODS: The Nationwide Inpatient Sample was queried for primary ICD-9 codes associated with PEH repair (years 2006-2008). Outcomes were in-hospital mortality and the occurrence of a pre-identified complication. Multivariate analysis was performed to determine the risk factors for complications and mortality following both elective and emergent PEH repair. RESULTS: A total of 8,462 records in the data, representing 41,723 patients in the US undergoing PEH repair in the study interval, were identified. Of these procedures, 74.2% was elective and 42.4% was laparoscopic. The overall complication and mortality rates were 20.8 and 1.1%, respectively. Emergent repair was associated with a higher rate of morbidity (33.4 vs. 16.5%, p < 0.001) and mortality (3.2 vs. 0.37%, p < 0.001) than elective repair. Emergent repair patients were more likely to be male, were older, and more likely to be minority. Logistic modeling revealed that younger age, elective case status, and a laparoscopic approach were independently associated with a lower probability of complications and mortality. CONCLUSIONS: Patients undergoing emergent PEH repair in the United States tend to be older, more likely a racial minority, and less likely to undergo laparoscopic repair. Elective repair, younger age, and a laparoscopic approach are associated with improved outcomes. Considering all of the above, we recommend that patients consider elective repair with a surgeon experienced in the laparoscopic approach, especially when symptoms related to the hernia are present.

"The machine doesn't judge": Counternarratives on surveillance among people accessing a safer opioid supply via biometric machines.

People who use illegal drugs experience routine surveillance, including in healthcare and harm reduction settings. The MySafe Project - a safer supply pilot project that dispenses prescription opioids via a biometric vending machine - exists in the Canadian province of British Columbia. The machine scans a participant's palmprint and has a built-in camera that records every machine interaction. The aim of this paper is to understand participants' experiences of surveillance, privacy, and personal security when accessing this novel program. An integrative case study and grounded theory methodology was employed. Qualitative one-to-one interviews were conducted with 46 MySafe participants across three different program sites in Vancouver. We used a team-based approach to code interview transcripts and utilized directed and conventional content analyses for deductive and inductive analyses. While participants described negative experiences of surveillance in other public and harm reduction settings, they did not have concerns regarding cameras, collection of personal information, tracking, nor staff issues associated with MySafe. Similarly, while some participants had privacy concerns in other settings, very few privacy and confidentiality concerns were expressed regarding accessing the machine in front of others. Lastly, while some participants reported being targeted by others when accessing the machines, most participants described how cameras, staff, and machine locations helped ensure a sense of safety. Despite negative experiences of surveillance and privacy issues elsewhere, participants largely lacked concern regarding the MySafe program and machines. The machine-human interaction was characterized as different than some human-human interactions as the machine is completing tasks in a manner that is acceptable and comfortable to participants, leading to a social preference toward the machines in comparison to other surveilled means of accessing medications. These findings provide an opportunity to rethink how we conceptualize surveillance, medication access, and harm reduction programs targeting people who use drugs.

Synthetically accessible de novo design using reaction vectors: Application to PARP1 inhibitors.

De novo design has been a hotly pursued topic for many years. Most recent developments have involved the use of deep learning methods for generative molecular design. Despite increasing levels of algorithmic sophistication, the design of molecules that are synthetically accessible remains a major challenge. Reaction-based de novo design takes a conceptually simpler approach and aims to address synthesisability directly by mimicking synthetic chemistry and driving structural transformations by known reactions that are applied in a stepwise manner. However, the use of a small number of hand-coded transformations restricts the chemical space that can be accessed and there are few examples in the literature where molecules and their synthetic routes have been designed and executed successfully. Here we describe the application of reaction-based de novo design to the design of synthetically accessible and biologically active compounds as proof-of-concept of our reaction vector-based software. Reaction vectors are derived automatically from known reactions and allow access to a wide region of synthetically accessible chemical space. The design was aimed at producing molecules that are active against PARP1 and which have improved brain penetration properties compared to existing PARP1 inhibitors. We synthesised a selection of the designed molecules according to the provided synthetic routes and tested them experimentally. The results demonstrate that reaction vectors can be applied to the design of novel molecules of biological relevance that are also synthetically accessible.