Impact of genome build on RNA-seq interpretation and diagnostics.

Transcriptomics is a powerful tool for unraveling the molecular effects of genetic variants and disease diagnosis. Prior studies have demonstrated that choice of genome build impacts variant interpretation and diagnostic yield for genomic analyses. To identify the extent genome build also impacts transcriptomics analyses, we studied the effect of the hg19, hg38, and CHM13 genome builds on expression quantification and outlier detection in 386 rare disease and familial control samples from both the Undiagnosed Diseases Network and Genomics Research to Elucidate the Genetics of Rare Disease Consortium. Across six routinely collected biospecimens, 61% of quantified genes were not influenced by genome build. However, we identified 1,492 genes with build-dependent quantification, 3,377 genes with build-exclusive expression, and 9,077 genes with annotation-specific expression across six routinely collected biospecimens, including 566 clinically relevant and 512 known OMIM genes. Further, we demonstrate that between builds for a given gene, a larger difference in quantification is well correlated with a larger change in expression outlier calling. Combined, we provide a database of genes impacted by build choice and recommend that transcriptomics-guided analyses and diagnoses are cross referenced with these data for robustness.

Traumatic Abdominal Wall Hernia: Management Using a Standardized Approach.

Traumatic abdominal wall hernias are a rare complication of high energy blunt trauma. There exist several studies evaluating and outlining potential management options but still no generalized consensus on management. This series was meant to evaluate the diagnosis and management of traumatic abdominal wall hernias. A prospectively maintained database was used to identify patients with TAWH from 2021 to 2022. The primary outcome was operative management. Secondary outcomes included: time to diagnosis and post-operative outcomes. Of the 19 patients in this case series, 100% (n = 19/19) were secondary to blunt trauma with a mean ISS of 21. Exploratory laparotomy was performed in 17 cases. 14 cases had concomitant traumatic injuries to visceral structures. Complications were found in nearly half of the patients with 3 experiencing wound dehiscence. Future studies should be aimed at standardizing management approach taking into account nature of the mechanism and concomitant injuries.

Integration of transcriptomics and long-read genomics prioritizes structural variants in rare disease.

Rare structural variants (SVs) - insertions, deletions, and complex rearrangements - can cause Mendelian disease, yet they remain difficult to accurately detect and interpret. We sequenced and analyzed Oxford Nanopore long-read genomes of 68 individuals from the Undiagnosed Disease Network (UDN) with no previously identified diagnostic mutations from short-read sequencing. Using our optimized SV detection pipelines and 571 control long-read genomes, we detected 716 long-read rare (MAF < 0.01) SV alleles per genome on average, achieving a 2.4x increase from short-reads. To characterize the functional effects of rare SVs, we assessed their relationship with gene expression from blood or fibroblasts from the same individuals, and found that rare SVs overlapping enhancers were enriched (LOR = 0.46) near expression outliers. We also evaluated tandem repeat expansions (TREs) and found 14 rare TREs per genome; notably these TREs were also enriched near overexpression outliers. To prioritize candidate functional SVs, we developed Watershed-SV, a probabilistic model that integrates expression data with SV-specific genomic annotations, which significantly outperforms baseline models that don't incorporate expression data. Watershed-SV identified a median of eight high-confidence functional SVs per UDN genome. Notably, this included compound heterozygous deletions in FAM177A1 shared by two siblings, which were likely causal for a rare neurodevelopmental disorder. Our observations demonstrate the promise of integrating long-read sequencing with gene expression towards improving the prioritization of functional SVs and TREs in rare disease patients.

Nanopore sequencing of 1000 Genomes Project samples to build a comprehensive catalog of human genetic variation.

Less than half of individuals with a suspected Mendelian condition receive a precise molecular diagnosis after comprehensive clinical genetic testing. Improvements in data quality and costs have heightened interest in using long-read sequencing (LRS) to streamline clinical genomic testing, but the absence of control datasets for variant filtering and prioritization has made tertiary analysis of LRS data challenging. To address this, the 1000 Genomes Project ONT Sequencing Consortium aims to generate LRS data from at least 800 of the 1000 Genomes Project samples. Our goal is to use LRS to identify a broader spectrum of variation so we may improve our understanding of normal patterns of human variation. Here, we present data from analysis of the first 100 samples, representing all 5 superpopulations and 19 subpopulations. These samples, sequenced to an average depth of coverage of 37x and sequence read N50 of 54 kbp, have high concordance with previous studies for identifying single nucleotide and indel variants outside of homopolymer regions. Using multiple structural variant (SV) callers, we identify an average of 24,543 high-confidence SVs per genome, including shared and private SVs likely to disrupt gene function as well as pathogenic expansions within disease-associated repeats that were not detected using short reads. Evaluation of methylation signatures revealed expected patterns at known imprinted loci, samples with skewed X-inactivation patterns, and novel differentially methylated regions. All raw sequencing data, processed data, and summary statistics are publicly available, providing a valuable resource for the clinical genetics community to discover pathogenic SVs.

APOE loss-of-function variants: Compatible with longevity and associated with resistance to Alzheimer's disease pathology.

The ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Knockdown of ε4 may provide a therapeutic strategy for AD, but the effect of APOE loss of function (LoF) on AD pathogenesis is unknown. We searched for APOE LoF variants in a large cohort of controls and patients with AD and identified seven heterozygote carriers of APOE LoF variants. Five carriers were controls (aged 71-90 years), one carrier was affected by progressive supranuclear palsy, and one carrier was affected by AD with an unremarkable age at onset of 75 years. Two APOE ε3/ε4 controls carried a stop-gain affecting ε4: one was cognitively normal at 90 years and had no neuritic plaques at autopsy; the other was cognitively healthy at 79 years, and lumbar puncture at 76 years showed normal levels of amyloid. These results suggest that ε4 drives AD risk through the gain of abnormal function and support ε4 knockdown as a viable therapeutic option.

Impact of genome build on RNA-seq interpretation and diagnostics.

Transcriptomics is a powerful tool for unraveling the molecular effects of genetic variants and disease diagnosis. Prior studies have demonstrated that choice of genome build impacts variant interpretation and diagnostic yield for genomic analyses. To identify the extent genome build also impacts transcriptomics analyses, we studied the effect of the hg19, hg38, and CHM13 genome builds on expression quantification and outlier detection in 386 rare disease and familial control samples from both the Undiagnosed Diseases Network (UDN) and Genomics Research to Elucidate the Genetics of Rare Disease (GREGoR) Consortium. We identified 2,800 genes with build-dependent quantification across six routinely-collected biospecimens, including 1,391 protein-coding genes and 341 known rare disease genes. We further observed multiple genes that only have detectable expression in a subset of genome builds. Finally, we characterized how genome build impacts the detection of outlier transcriptomic events. Combined, we provide a database of genes impacted by build choice, and recommend that transcriptomics-guided analyses and diagnoses are cross-referenced with these data for robustness.

One-Pot Assembly of Drug-Eluting Silk Coatings with Applications for Nerve Regeneration.

Clinical use of polymeric scaffolds for tissue engineering often suffers from their inability to promote strong cellular interactions. Functionalization with biomolecules may improve outcomes; however, current functionalization approaches using covalent chemistry or physical adsorption can lead to loss of biomolecule bioactivity. Here, we demonstrate a novel bottom-up approach for enhancing the bioactivity of poly(l-lactic acid) electrospun scaffolds though interfacial coassembly of protein payloads with silk fibroin into nanothin coatings. In our approach, protein payloads are first added into an aqueous solution with Bombyx mori-derived silk fibroin. Phosphate anions are then added to trigger coassembly of the payload and silk fibroin, as well as noncovalent formation of a payload-silk fibroin coating at poly(l-lactic) acid fiber surfaces. Importantly, the coassembly process results in homogeneous distribution of protein payloads, with the loading quantity depending on payload concentration in solution and coating time. This coassembly process yields greater loading capacity than physical adsorption methods, and the payloads can be released over time in physiologically relevant conditions. We also demonstrate that the coating coassembly process can incorporate nerve growth factor and that coassembled coatings lead to significantly more neurite extension than loading via adsorption in a rat dorsal root ganglia explant culture model.

Dark matter axion search using a Josephson Traveling wave parametric amplifier.

We describe the first implementation of a Josephson Traveling Wave Parametric Amplifier (JTWPA) in an axion dark matter search. The operation of the JTWPA for a period of about two weeks achieved sensitivity to axion-like particle dark matter with axion-photon couplings above 10-13 Ge V-1 over a narrow range of axion masses centered around 19.84 µeV by tuning the resonant frequency of the cavity over the frequency range of 4796.7-4799.5 MHz. The JTWPA was operated in the insert of the axion dark matter experiment as part of an independent receiver chain that was attached to a 0.56-l cavity. The ability of the JTWPA to deliver high gain over a wide (3 GHz) bandwidth has engendered interest from those aiming to perform broadband axion searches, a longstanding goal in this field.

New avenue of diagnostic stewardship: procedural stewardship for recurrent urinary tract infections in female patients.

Introduction: Societal guidelines offer a weak recommendation to perform cystoscopy for female patients with recurrent urinary tract infections (rUTI) of advanced age and/or with high-risk features. These guidelines lack the support of robust data and are instead based on expert opinion. In this retrospective cohort study, we aim to determine the utility of cystoscopy in patients with and without high-risk features for rUTI. Materials and methods: We identified 476 women who underwent cystoscopy for the evaluation of rUTI at a single tertiary academic medical center from May 1, 2015 and March 15, 2021. Patients were excluded if they had a competing indication for cystoscopy. Risk factors, demographic information, cystoscopic findings, and patient outcomes were analyzed. Results: 192 (41.1%) were classified as having complicated UTI. We identified six patients (1.3%) with findings that prompted management to significantly impact patient outcomes. All six patients had high-risk features. 14 patients (3.0%) were found to have mucosal abnormalities prompting biopsy, three of which required general anesthesia. All 14 biopsies were ultimately benign. Conclusions: Our findings demonstrate a low diagnostic yield and increased risk exposure for women undergoing cystoscopy for the evaluation of complicated rUTI. Additionally, our observations support prior studies indicating that cystoscopy has limited utility in the evaluation of rUTI without high-risk features.

For plantar taping, direction of elasticity matters.

Plantar taping has been used in clinical settings as a short-term conservative treatment for plantar heel pain and related pathologies. The rise of at-home taping methods may offer patients more independence, but effectiveness has not been established. The purpose of this study was to evaluate the effects of plantar taping on foot mechanics during gait. We hypothesized that material compliance would drive mechanical effectiveness, with longitudinally inelastic tape reducing medial longitudinal arch (MLA) motion and anterior/posterior (A/P) plantar tissue spreading forces, and laterally inelastic tape reducing medial/lateral (M/L) tissue spreading. We also hypothesized that these effects would be influenced by foot structure. Fifteen healthy participants were tested in a randomized cross-over study design. Barefoot (BF) plus four taping methods were evaluated, including two inelastic tapes (Low-Dye, LD, and FasciaDerm, FD) along with longitudinally elastic kinesiology tape (KT) and a novel laterally elastic kinesiology tape (FAST, FS). Participants' arch height and flexibility were measured followed by instrumented gait analysis with a multi-segment foot model. Ankle eversion and MLA drop/rise were calculated from rearfoot and forefoot reference frames, while plantar tissue spreading was calculated from shear stresses. ANOVAs with Holm pairwise tests evaluated tape effects while correlations connected arch structure and taping effectiveness (α = 0.05). The three longitudinally inelastic tapes (LD, FD, FS) reduced MLA drop by 11-15% compared with KT and BF. In late stance, these tapes also inhibited MLA rise (LD by 29%, FD and FS by 10-15%). FS and FD reduced A/P spreading forces, while FD reduced M/L spreading forces compared with all other conditions. Arch height had a moderately strong correlation (r = -0.67) with the difference in MLA drop between BF and FS. At-home plantar taping can affect the mechanical function of the foot, but tape elasticity direction matters. Longitudinally elastic kinesiology tape has little effect on mechanics, while inelastic tapes control MLA drop but also restrict MLA rise in late stance. Lateral elasticity does not limit tissue spreading and may increase comfort without sacrificing MLA control. At-home taping has the potential to broaden conservative treatment of plantar heel pain, flat foot deformity, and related pathologies, but additional studies are needed to connect mechanics with symptom relief.

Descriptive cross-sectional survey of tobacco and cannabis restrictions on state and local film incentives in the USA.

BACKGROUND: Reducing tobacco depictions in media has significant health benefits because tobacco placements in films normalise tobacco use and are linked to youth initiation. Cannabis depictions may have similar effects. Placing restrictions on film incentives has been suggested; however, it remains an unexplored strategy for reducing tobacco depictions. We investigated whether states and localities that offer film incentives have established funding restrictions to deter tobacco or cannabis depictions. METHODS: We conducted a descriptive cross-sectional survey of official state and local government websites in the USA that listed film incentives. We coded policy level (ie, state, local), incentive type (ie, tax credit, rebate), incentive amounts, programme qualifiers and presence and characteristics of tobacco and cannabis restrictions. RESULTS: Quantifiable tax incentives at the state level offered over $1.6 billion to producers. Among 50 US states and Washington, DC, 39 provided film incentives: 4 restricted tobacco and 0 restricted cannabis. Among the 238 local film offices we identified, 24 offered incentives; 5 restricted tobacco and 1 restricted cannabis. All the incentive restrictions excluded tobacco or cannabis purchases from reimbursement; there were no penalties for tobacco or cannabis depictions. CONCLUSIONS: Film incentives are large financial commitments that may undermine public health since they allow depictions of tobacco and cannabis that contribute to initiation and use. Few states or localities limit film incentives related to tobacco or cannabis, and the existing restrictions are unlikely to deter depictions or product placement. Restrictions on incentives are an underused tool for deterring tobacco and cannabis depictions in film.

Search for a Dark-Matter-Induced Cosmic Axion Background with ADMX.

We report the first result of a direct search for a cosmic axion background (CaB)-a relativistic background of axions that is not dark matter-performed with the axion haloscope, the Axion Dark Matter eXperiment (ADMX). Conventional haloscope analyses search for a signal with a narrow bandwidth, as predicted for dark matter, whereas the CaB will be broad. We introduce a novel analysis strategy, which searches for a CaB induced daily modulation in the power measured by the haloscope. Using this, we repurpose data collected to search for dark matter to set a limit on the axion photon coupling of a CaB originating from dark matter cascade decay via a mediator in the 800-995 MHz frequency range. We find that the present sensitivity is limited by fluctuations in the cavity readout as the instrument scans across dark matter masses. Nevertheless, we suggest that these challenges can be surmounted using superconducting qubits as single photon counters, and allow ADMX to operate as a telescope searching for axions emerging from the decay of dark matter. The daily modulation analysis technique we introduce can be deployed for various broadband rf signals, such as other forms of a CaB or even high-frequency gravitational waves.

Electronic Health Record Recording of Patient Pain: Challenges and Discrepancies.

PURPOSE OF REVIEW: In the present review, various categories of pain, clinician-observed pain scales, and patient-reported pain scales are evaluated to better understand factors that impact patient pain perceptions. Additionally, the expansion of areas that require further research to determine the optimal way to evaluate pain scale data for treatment and management are discussed. RECENT FINDINGS: Electronic health record (EHR) data provides a starting point for evaluating whether patient predictors influence postoperative pain. There are several ways to assess pain and choosing the most effective form of pain treatment. Identifying individuals at high risk for severe postoperative pain enables more effective pain treatment. However, there are discrepancies in patient pain reporting dependent on instruments used to measure pain and their storage in the EHR. Additionally, whether administered by a physician or another healthcare practitioner, differences in patient pain perception occur. While each scale has distinct advantages and limitations, pain scale data is a valuable therapeutic tool for assisting clinicians in providing patients with optimal pain control. Accurate assessment of patient pain perceptions by data extraction from electronic health records provides a potential for pain alleviation improvement. Predicting high-risk postoperative pain syndromes is a difficult clinical challenge. Numerous studies have been conducted on factors that impact pain prediction. Postoperative pain is significantly predicted by the kind of operation, the existence of prior discomfort, patient anxiety, and age.

A Multi-Institutional Experience Utilizing Boari Flap in Robotic Urinary Reconstruction.

Objectives: There is presently scarce literature describing the outcomes of patients undergoing robotic ureteral reconstruction (RUR) using the Boari flap (BF) technique. Herein, we report our prospective, multi-institutional experience using BF in patients undergoing robotic urinary reconstruction. Patients and Methods: We reviewed our prospective, multicenter database for all patients undergoing RUR between September 2013 and September 2021 in which a BF was utilized. Preoperative, perioperative, and follow-up data were collected and analyzed. Major complications were defined as a Clavien-Dindo classification grade >2. Surgical failure was defined as recurrent symptoms, obstruction on imaging, or the need for additional surgical interventions. Results: We identified 50 patients who underwent RUR using a BF. Four (8%) underwent the Single Port approach. Twenty-four patients (48%) were active or former tobacco users. Thirty-four patients (68%) had previously undergone abdominal surgery, 17 (34%) had prior ureteral stricture interventions, and 9 (18%) had prior abdominopelvic radiation. The most common stricture etiology was malignancy (34.4%). The median follow-up was 15.0 months with a 90% (45/50) success rate. The five documented cases of failure occurred at a median of 1.8 months following the procedure. Conclusion: In the largest prospective, multi-institutional study of patients undergoing RUR with BF in the literature to date, we demonstrate a low rate of complications and a high rate of surgical success in three tertiary academic medical centers. All observed failures occurred within 2 months of surgical intervention.

Electrospun fiber-mediated delivery of neurotrophin-3 mRNA for neural tissue engineering applications.

Aligned electrospun fibers provide topographical cues and local therapeutic delivery to facilitate robust peripheral nerve regeneration. mRNA delivery enables transient expression of desired proteins that promote axonal regeneration. However, no prior work delivers mRNA from electrospun fibers for peripheral nerve regeneration applications. Here, we developed the first aligned electrospun fibers to deliver pseudouridine-modified (Ψ) neurotrophin-3 (NT-3) mRNA (ΨNT-3mRNA) to primary Schwann cells and assessed NT-3 secretion and bioactivity. We first electrospun aligned poly(L-lactic acid) (PLLA) fibers and coated them with the anionic substrates dextran sulfate sodium salt (DSS) or poly(3,4-dihydroxy-L-phenylalanine) (pDOPA). Cationic lipoplexes containing ΨNT-3mRNA complexed to JetMESSENGER® were then immobilized to the fibers, resulting in detectable ΨNT-3mRNA release for 28 days from all fiber groups investigated (PLLA+mRNA, 0.5DSS4h+mRNA, and 2pDOPA4h+mRNA). The 2pDOPA4h+mRNA group significantly increased Schwann cell secretion of NT-3 for 21 days compared to control PLLA fibers (p < 0.001-0.05) and, on average, increased Schwann cell secretion of NT-3 by ≥ 2-fold compared to bolus mRNA delivery from the 1µgBolus+mRNA and 3µgBolus+mRNA groups. The 2pDOPA4h+mRNA fibers supported Schwann cell secretion of NT-3 at levels that significantly increased dorsal root ganglia (DRG) neurite extension by 44% (p < 0.0001) and neurite area by 64% (p < 0.001) compared to control PLLA fibers. The data show that the 2pDOPA4h+mRNA fibers enhance the ability of Schwann cells to promote neurite growth from DRG, demonstrating this platform's potential capability to improve peripheral nerve regeneration. STATEMENT OF SIGNIFICANCE: Aligned electrospun fibers enhance axonal regeneration by providing structural support and guidance cues, but further therapeutic stimulation is necessary to improve functional outcomes. mRNA delivery enables the transient expression of therapeutic proteins, yet achieving local, sustained delivery remains challenging. Previous work shows that genetic material delivery from electrospun fibers improves regeneration; however, mRNA delivery has not been explored. Here, we examine mRNA delivery from aligned electrospun fibers to enhance neurite outgrowth. We show that immobilization of NT-3mRNA/JetMESSENGER® lipoplexes to aligned electrospun fibers functionalized with pDOPA enables local, sustained NT-3mRNA delivery to Schwann cells, increasing Schwann cell secretion of NT-3 and enhancing DRG neurite outgrowth. This study displays the potential benefits of electrospun fiber-mediated mRNA delivery platforms for neural tissue engineering.

Manual wheelchair use leads to a series of failed shoulder replacements: A case report and literature review.

Manual wheelchair users place high stress on their shoulders. We describe a 69-year-old male who developed end-stage shoulder osteoarthritis from chronic manual wheelchair (MW) use. Three prosthetic total shoulder replacements failed, reflecting his refusal to transition to an electric wheelchair. MW use must be avoided in some of these patients.

Helical remodeling augments 5-lipoxygenase activity in the synthesis of proinflammatory mediators.

The synthesis of proinflammatory leukotrienes implicated in asthma, allergic rhinitis, and atherosclerosis is initiated by the enzyme 5-lipoxygenase (5-LOX). The crystal structure of human Stable-5-LOX revealed a conformation where the catalytic iron was inaccessible to bulk solvent as two aromatic residues on a conserved helix-α2 (Hα2) plugged the substrate access portal. Whether 5-LOX can also adopt a more open conformation has not been resolved. Here, we present a new conformation of 5-LOX where Hα2 adopts an elongated conformation equivalent to that described in other animal lipoxygenase structures. Our observation of the sigmoidal kinetic behavior of 5-LOX, which is indicative of positive cooperativity, is consistent with a substrate-induced conformational change that shifts the ensemble of enzyme populations to favor the catalytically competent state. Strategic point mutations along Hα2 designed to unlock the closed conformation and elongate Hα2 resulted in improved kinetic parameters, altered limited proteolysis data, and a drastic reduction in the length of the lag phase yielding the most active Stable-5-LOX to date. Structural predictions by AlphaFold2 of these variants statistically favor an elongated Hα2 and reinforce a model in which improved kinetic parameters correlate with a more readily adopted open conformation. Taken together, these data provide valuable insights into the synthesis of leukotrienes.

Virucidal N95 Respirator Face Masks via Ultrathin Surface-Grafted Quaternary Ammonium Polymer Coatings.

N95 respirator face masks serve as effective physical barriers against airborne virus transmission, especially in a hospital setting. However, conventional filtration materials, such as nonwoven polypropylene fibers, have no inherent virucidal activity, and thus, the risk of surface contamination increases with wear time. The ability of face masks to protect against infection can be likely improved by incorporating components that deactivate viruses on contact. We present a facile method for covalently attaching antiviral quaternary ammonium polymers to the fiber surfaces of nonwoven polypropylene fabrics that are commonly used as filtration materials in N95 respirators via ultraviolet (UV)-initiated grafting of biocidal agents. Here, C12-quaternized benzophenone is simultaneously polymerized and grafted onto melt-blown or spunbond polypropylene fabric using 254 nm UV light. This grafting method generated ultrathin polymer coatings which imparted a permanent cationic charge without grossly changing fiber morphology or air resistance across the filter. For melt-blown polypropylene, which comprises the active filtration layer of N95 respirator masks, filtration efficiency was negatively impacted from 72.5 to 51.3% for uncoated and coated single-ply samples, respectively. Similarly, directly applying the antiviral polymer to full N95 masks decreased the filtration efficiency from 90.4 to 79.8%. This effect was due to the exposure of melt-blown polypropylene to organic solvents used in the coating process. However, N95-level filtration efficiency could be achieved by wearing coated spunbond polypropylene over an N95 mask or by fabricating N95 masks with coated spunbond as the exterior layer. Coated materials demonstrated broad-spectrum antimicrobial activity against several lipid-enveloped viruses, as well as Staphylococcus aureus and Escherichia coli bacteria. For example, a 4.3-log reduction in infectious MHV-A59 virus and a 3.3-log reduction in infectious SuHV-1 virus after contact with coated filters were observed, although the level of viral deactivation varied significantly depending on the virus strain and protocol for assaying infectivity.

Head Impact Kinematics and Brain Deformation in Paired Opposing Youth Football Players.

Head impact exposure is often quantified using peak resultant kinematics. While kinematics describes the inertial response of the brain to impact, they do not fully capture the dynamic brain response. Strain, a measure of the tissue-level response of the brain, may be a better predictor of injury. In this study, kinematic and strain metrics were compared to contact characteristics in youth football. Players on 2 opposing teams were instrumented with head impact sensors to record impact kinematics. Video was collected to identify contact scenarios involving opposing instrumented players (ie, paired contact scenarios) and code contact characteristics (eg, player role, impact location). A previously validated, high-resolution brain finite element model, the atlas-based brain model, was used to simulate head impacts and calculate strain metrics. Fifty-two paired contact scenarios (n = 105 impacts) were evaluated. Lighter players tended to have greater biomechanical metrics compared to heavier players. Impacts to the top of the helmet were associated with lower strain metrics. Overall, strain was better correlated with rotational kinematics, suggesting these metrics may be better predictors of the tissue-level brain response than linear kinematics. Understanding the effect of contact characteristics on brain strain will inform future efforts to improve sport safety.

Securing Smokefree Laws Covering Casinos and Bars in Louisiana via Messaging, Continuous Campaigning and Health Coalitions.

In this paper, we examine efforts by health organizations seeking comprehensive smokefree ordinances over Louisiana casinos and bars between 2010 and 2020 to determine best practices for increasing coverage. Bars and casinos remain less protected from secondhand smoke compared to other workplaces in the United States. Casino behavior is compared to the Policy Dystopia Model (PDM), a tobacco industry strategy framework. We performed a historical case study using snowball searches for news on the Access World News Database and the internet. We performed web searches using the names of key actors, organizations, and locations and interviewed nine participants. Starting in 2010, the Louisiana Campaign for Tobacco-Free Living ran ordinance campaigns supplemented by an ongoing statewide smokefree media initiative. Utilizing consistent strategies, including promoting performers as cultural emblems deserving protection, health organizations coalesced in New Orleans during 2014 and Baton Rouge in 2016 and 2017 to pursue ordinances. The coalitions secured ordinances in Louisiana's population and tourism centers despite business resistance. Organizations obtained 30 smokefree laws across Louisiana by 2021. Casinos used PDM strategies to resist ordinances, indicating the framework may predict strategies by non-tobacco entities resisting tobacco control. Louisiana shows that ongoing local campaigns, social justice themes and cultural messaging with coalitions in cities can secure smokefree laws covering casinos and bars and that local ordinance campaigns are a viable method for advancing smokefree protections over those venues in states where the state legislatures are resistant to action.