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In acute myeloid leukemia (AML), leukemogenesis depends on cell-intrinsic genetic aberrations and thus, studies on AML require investigations in an in vivo setting as provided by patient derived xenografts (PDX) models. Here we report that, next to leukemic cell characteristics, recipient sex highly influences the outgrowth of AML cells in PDX models, with females being much better repopulated than males in primary as well as secondary transplantation assays. Testosterone may be the more important player since, strikingly, better engraftment was seen in castrated versus control male recipients, while ovariectomy did not significantly impair engraftment in females. Shorter time-to-engraftment and mouse survival were observed with adverse molecular risk, and respectively with high FLT3-ITD ratio mutated AML cells. Adverse risk AML furthermore showed higher percentages of phenotypic leukemic stem cells (LSCs), suggesting impaired differentiation capacity in these AML subtypes. Overall, we achieved successful repopulation with 14/23 (61%) favorable, 18/30 (60%) intermediate and 4/8 (50%) adverse risk AML cases in female recipient PDX models. Our data identify recipient sex as an important experimental confounder in leukemia PDX models, and the contribution of the sex hormones to leukemogenesis as an intriguing, underexplored research area.

Background: Long-read 16S rRNA gene amplicon sequencing has a high potential for characterizing food-associated microbiomes. The advantage results from sequencing the full-length (1,500 bp) gene, enabling taxonomic resolution at species level. Here we present a benchmarking study using mock communities representative of milking machine biofilms and raw meat, revealing challenges relevant to food-associated habitats. These were varying species abundances, reliable intra-genus differentiation of species, and detection of novel species with < 98.7% sequence identity to type strains. By using mock communities at different levels of preparation - as mixed whole cells, mixed extracted DNA, and mixed PCR products - we systematically investigated the influence of DNA extraction using two different kits, PCR amplification of 16S rRNA genes, sequencing, and bioinformatics analysis including reference database and gene copy number normalization on bacterial composition and alpha diversity., Results: We demonstrated that PacBio ccs-reads allowed for correct taxonomic assignment of all species present within the mock communities using a custom Refseq database. However, choice of percent identity values for taxonomic assignment had a strong influence on identification and processing of reads from novel species. PCR amplification of 16S rRNA genes produced the strongest bias on the observed community composition, while sequencing alone reproduced the preset composition well. The PCR bias can in part be attributed to differences in mol% G + C content of 16S rRNA genes resulting in preferred amplification of low mol% G + C-containing taxa., Conclusions: This study underlines the importance of benchmarking studies with mock communities representing the habitat of interest to evaluate the methodology prior to analyzing real samples of unknown composition. It demonstrates the advantage of long-read sequencing over short-read sequencing, as species level identification enables in-depth characterization of the habitat. One benefit is improved risk assessment by enabling differentiation between pathogenic and apathogenic species of the same genus., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Understanding the reciprocal interaction between root development and coadapted beneficial microbes in response to elevated CO 2 (eCO 2 ) will facilitate the identification of nutrient-efficient cultivars for sustainable agriculture. Here, systematic morphological, anatomical, chemical and gene expression assays performed under low-nitrogen conditions revealed that eCO 2 drove the development of the endodermal barrier with respect to L-/S-shaped lateral roots (LRs) in rice. Next, we applied metabolome and endodermal-cell-specific RNA sequencing and showed that rice adapts to eCO 2 by spatially recruiting diazotrophs via flavonoid secretion in L-shaped LRs. Using the rice Casparian strip mutant Oscasp1-1, we confirmed that reduced lignin deposition selectively recruits the diazotrophic family of Oxalobacteraceae to confer tolerance to low nitrogen availability., (© 2024 The Author(s). Plant, Cell & Environment published by John Wiley & Sons Ltd.)

Objectives: For nerve injuries, not amendable to tensionless epineural coaptation of the nerve, autografts are the preferred treatment. Although absorbable sutures are not recommended for nerve repair, there is no evidence that non-absorbable sutures are superior to absorbable sutures. This study aims to assess the effectiveness of non-absorbable monofilament nylon sutures, absorbable monofilament vicryl sutures, and fibrin glue when used for nerve grafting., Methods: Lewis rats ( N  = 32) were subjected to a sciatic nerve transection and randomly assigned to a group: graft with Nylon, graft with Vicryl, graft with Fibrin Glue, or no graft. Motor function, sensory function, and thermal pain were assessed during a 12-week recovery period, and immunohistochemistry was used to assess macrophage response., Results: At 12 weeks, the Vicryl and Nylon groups had significantly larger ankle angles at to lift off, which is a measure of motor function, compared to injured controls ( p  < 0.05). Grafted rats displayed no difference in thermal response but hypersensitivity to mechanical stimuli compared to the uninjured hindlimb. The Nylon, Vicryl, and Fibrin Glue groups all had significantly less atrophy of the gastrocnemius muscle compared to injured controls ( p  < 0.0001). In the Fibrin Glue group, 3/9 grafts did not incorporate. The Nylon group had significantly less ( p  = 0.0004) axon growth surrounding the suture holes compared to the Vicryl group. There were no differences in the axon counts, motor neurons, or sensory neurons between all grafted rats., Conclusions: These results demonstrate that vicryl sutures work just as well as nylon for nerve recovery after injury and grafting.

In behavioral-variant frontotemporal degeneration (bvFTD) and amyotrophic lateral sclerosis (ALS), secondary motor or cognitive-behavioral symptoms, respectively, are associated with shorter survival. However, factors influencing secondary symptom development remain largely unexplored. We performed a retrospective evaluation of the entire disease course of individuals with ALS (n=172) and bvFTD (n=69). Only individuals who had neuropathological confirmation of TDP-43 proteinopathy at autopsy or a C9orf72 hexanucleotide repeat expansion were included for analysis. We examined the odds and hazard of secondary symptom development and assessed whether each was modified by the presence of a C9orf72 expansion or initial clinical syndrome. Binary logistic regression and Cox proportional hazard analyses revealed increased odds (OR=4.25 [95% CI 1.97-9.14], p<0.001) and an increased hazard (HR= 4.77 [95% CI 2.33-9.79], p<0.001) for developing secondary symptoms in those with a C9orf72 expansion compared to those without. Initial clinical syndrome (bvFTD or ALS), age at symptom onset, and sex were not associated with development of secondary symptoms. These data highlight the need for clinician vigilance to detect the onset of secondary motor and cognitive-behavioral symptoms in patients carrying a C9orf72 expansion, regardless of initial clinical syndrome. C9orf72 clinical care can be enhanced through coordination between cognitive and neuromuscular clinics.

Akin to the traditional quasi-classical trajectory method for investigating the dynamics on a single adiabatic potential energy surface for an elementary chemical reaction, we carry out the dynamics on a 2-state ab initio potential energy surface including nonadiabatic coupling terms as friction terms for D + + H 2 collisions. It is shown that the resulting dynamics correctly accounts for nonreactive charge transfer, reactive non-charge transfer and reactive charge transfer processes. In addition, it leads to the formation of triatomic DH 2 + species as well.

Objective: Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous neurodegenerative condition featuring variable degrees of motor and cognitive impairment. We assessed the impact of specific, empirically derived occupational skills and requirements on cognitive and motor functioning in ALS., Methods: Individuals with ALS (n = 150) were recruited from the University of Pennsylvania's Comprehensive ALS Clinic. The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) measured cognition, and the Penn Upper Motor Neuron (PUMNS) and ALS Functional Rating Scales (ALSFRS-R) measured motor symptoms. We derived 17 factors representing distinct occupational skills and requirements from the Occupational Information Network (O*NET), which were related to cognitive and motor scores using multiple linear regression., Results: Occupational roles involving greater reasoning ability (β = 2.12, p  < .05), social ability (β = 1.73, p  < .05), analytic skills, (β = 3.12, p  < .01) and humanities knowledge (β = 1.83, p <.01) were associated with better performance on the ECAS, while jobs involving more exposure to environmental hazards (β=-2.57, p  < .01) and technical skills (β=-2.16, p <.01) were associated with lower ECAS scores. Jobs requiring more precision skills (β = 1.91, p  < .05) were associated with greater motor dysfunction on the PUMNS., Conclusions: Occupational histories involving more cognitively complex skills and activities were related to preserved cognitive functioning in ALS consistent with the cognitive reserve hypothesis, while jobs with greater exposure to environmental hazards and technical demands were linked to poorer cognitive functioning. Jobs involving more repetitive movements were associated with worse motor functioning, possibly due to overuse. Occupational history provides insight into protective and risk factors for variable degrees of cognitive and motor dysfunction in ALS.

Background: Beneficial associations between plants and soil microorganisms are critical for crop fitness and resilience. However, it remains obscure how microorganisms are assembled across different root compartments and to what extent such recruited microbiomes determine crop performance. Here, we surveyed the root transcriptome and the root and rhizosphere microbiome via RNA sequencing and full-length (V1-V9) 16S rRNA gene sequencing from genetically distinct monogenic root mutants of maize (Zea mays L.) under different nutrient-limiting conditions., Results: Overall transcriptome and microbiome display a clear assembly pattern across the compartments, i.e., from the soil through the rhizosphere to the root tissues. Co-variation analysis identified that genotype dominated the effect on the microbial community and gene expression over the nutrient stress conditions. Integrated transcriptomic and microbial analyses demonstrated that mutations affecting lateral root development had the largest effect on host gene expression and microbiome assembly, as compared to mutations affecting other root types. Cooccurrence and trans-kingdom network association analysis demonstrated that the keystone bacterial taxon Massilia (Oxalobacteraceae) is associated with root functional genes involved in flowering time and overall plant biomass. We further observed that the developmental stage drives the differentiation of the rhizosphere microbial assembly, especially the associations of the keystone bacteria Massilia with functional genes in reproduction. Taking advantage of microbial inoculation experiments using a maize early flowering mutant, we confirmed that Massilia-driven maize growth promotion indeed depends on flowering time., Conclusion: We conclude that specific microbiota supporting lateral root formation could enhance crop performance by mediating functional gene expression underlying plant flowering time in maize. Video Abstract., (© 2024. The Author(s).)

Introduction/aims: The aim of this study was to examine clinical utilization and discontinuation rates of sodium phenylbutyrate-taurursodiol (PB-TURSO) in a single Amyotrophic Lateral Sclerosis (ALS) center. PB-TURSO was approved by the United States Food and Drug Administration (FDA) in September 2022. Prior experience has been limited to clinical trials or expanded access protocols. In this manuscript, we discuss insurance approval rates, patient uptake, and discontinuation of PB-TURSO in a large academic center., Methods: Records of patients seen for clinical visits between January 2022 and May 2023 were reviewed. Demographic and clinical characteristics of our clinic population and those initiating PB-TURSO were obtained from our clinical database., Results: A total of 228 patients were seen during the observation period and 122 requested PB-TURSO prescriptions. 77% (94) were approved by insurance. 66% (65) of those who were approved or received free drug chose to start medication. 51% (34) of those who initiated PB-TURSO continued to take it through the end of the observation period. Four patients discontinued due to death during the observation period. Of the 29 patients who survived and discontinued, the main reasons for discontinuation were GI symptoms (17, 58.6%) and taste (8, 29.6%)., Discussion: PB-TURSO was approved by insurance for most patients. The discontinuation rate was high and was driven largely by GI side effects and taste. Future considerations would include deeper examination of demographic trends, patient costs, side effects, and potential benefits in clinical practice., (© 2024 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Objective: To evaluate automated digital speech measures, derived from spontaneous speech (picture descriptions), in assessing bulbar motor impairments in patients with ALS-FTD spectrum disorders (ALS-FTSD)., Methods: Automated vowel algorithms were employed to extract two vowel acoustic measures: vowel space area (VSA), and mean second formant slope (F2 slope). Vowel measures were compared between ALS with and without clinical bulbar symptoms (ALS + bulbar (n = 49, ALSFRS-r bulbar subscore: x¯ = 9.8 (SD = 1.7)) vs. ALS-nonbulbar (n = 23), behavioral variant frontotemporal dementia (bvFTD, n = 25) without a motor syndrome, and healthy controls (HC, n = 32). Correlations with bulbar motor clinical scales, perceived listener effort, and MRI cortical thickness of the orobuccal primary motor cortex (oral PMC) were examined. We compared vowel measures to speaking rate, a conventional metric for assessing bulbar dysfunction., Results: ALS + bulbar had significantly reduced VSA and F2 slope than ALS-nonbulbar (|d|=0.94 and |d|=1.04, respectively), bvFTD (|d|=0.89 and |d|=1.47), and HC (|d|=0.73 and |d|=0.99). These reductions correlated with worse bulbar clinical scores (VSA: R = 0.33, p  = 0.043; F2 slope: R = 0.38, p  = 0.011), greater listener effort (VSA: R=-0.43, p  = 0.041; F2 slope: p  > 0.05), and cortical thinning in oral PMC (F2 slope: β = 0.0026, p  = 0.017). Vowel measures demonstrated greater sensitivity and specificity for bulbar impairment than speaking rate, while showing independence from cognitive and respiratory impairments., Conclusion: Automatic vowel measures are easily derived from a brief spontaneous speech sample, are sensitive to mild-moderate stage of bulbar disease in ALS-FTSD, and may present better sensitivity to bulbar impairment compared to traditional assessments such as speaking rate.

Beneficial interactions with microorganisms are pivotal for crop performance and resilience. However, it remains unclear how heritable the microbiome is with respect to the host plant genotype and to what extent host genetic mechanisms can modulate plant-microbiota interactions in the face of environmental stresses. Here we surveyed 3,168 root and rhizosphere microbiome samples from 129 accessions of locally adapted Zea, sourced from diverse habitats and grown under control and different stress conditions. We quantified stress treatment and host genotype effects on the microbiome. Plant genotype and source environment were predictive of microbiome abundance. Genome-wide association analysis identified host genetic variants linked to both rhizosphere microbiome abundance and source environment. We identified transposon insertions in a candidate gene linked to both the abundance of a keystone bacterium Massilia in our controlled experiments and total soil nitrogen in the source environment. Isolation and controlled inoculation of Massilia alone can contribute to root development, whole-plant biomass production and adaptation to low nitrogen availability. We conclude that locally adapted maize varieties exert patterns of genetic control on their root and rhizosphere microbiomes that follow variation in their home environments, consistent with a role in tolerance to prevailing stress., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objectives: Genetic testing is now the standard of care for many neurologic conditions. Health care disparities are unfortunately widespread in the US health care system, but disparities in the utilization of genetic testing for neurologic conditions have not been studied. We tested the hypothesis that access to and results of genetic testing vary according to race, ethnicity, sex, socioeconomic status, and insurance status for adults with neurologic conditions., Methods: We analyzed retrospective data from patients who underwent genetic evaluation and testing through our institution's neurogenetics program. We tested for differences between demographic groups in 3 steps of a genetic evaluation pathway: (1) attending a neurogenetic evaluation, (2) completing genetic testing, and (3) receiving a diagnostic result. We compared patients on this genetic evaluation pathway with the population of all neurology outpatients at our institution, using univariate and multivariable logistic regression analyses., Results: Between 2015 and 2022, a total of 128,440 patients were seen in our outpatient neurology clinics and 2,540 patients underwent genetic evaluation. Black patients were less than half as likely as White patients to be evaluated (odds ratio [OR] 0.49, p < 0.001), and this disparity was similar after controlling for other demographic factors in multivariable analysis. Patients from the least wealthy quartile of zip codes were also less likely to be evaluated (OR 0.67, p < 0.001). Among patients who underwent evaluation, there were no disparities in the likelihood of completing genetic testing, nor in the likelihood of a diagnostic result after adjusting for age. Analyses restricted to specific indications for genetic testing supported these findings., Discussion: We observed unequal utilization of our clinical neurogenetics program for patients from marginalized and minoritized demographic groups, especially Black patients. Among patients who do undergo evaluation, all groups benefit similarly from genetic testing when it is indicated. Understanding and removing barriers to accessing genetic testing will be essential to health care equity and optimal care for all patients with neurologic disorders.

The role of genetic testing in neurologic clinical practice has increased dramatically in recent years, driven by research on genetic causes of neurologic disease and increased availability of genetic sequencing technology. Genetic testing is now indicated for adults with a wide range of common neurologic conditions. The potential clinical impacts of a genetic diagnosis are also rapidly expanding, with a growing list of gene-specific treatments and clinical trials, in addition to important implications for prognosis, surveillance, family planning, and diagnostic closure. The goals of this review are to provide practical guidance for clinicians about the role of genetics in their practice and to provide the neuroscience research community with a broad survey of current progress in this field. We aim to answer three questions for the neurologist in practice: Which of my patients need genetic testing? What testing should I order? And how will genetic testing help my patient? We focus on common neurologic disorders and presentations to the neurology clinic. For each condition, we review the most current guidelines and evidence regarding indications for genetic testing, expected diagnostic yield, and recommended testing approach. We also focus on clinical impacts of genetic diagnoses, highlighting a number of gene-specific therapies recently approved for clinical use, and a rapidly expanding landscape of gene-specific clinical trials, many using novel nucleotide-based therapeutic modalities like antisense oligonucleotides and gene transfer. We anticipate that more widespread use of genetic testing will help advance therapeutic development and improve the care, and outcomes, of patients with neurologic conditions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: TDP-43 proteinopathies represent a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The ALS-FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes, highlighting its heterogeneity. This study was aimed to use disease progression modeling to identify novel data-driven spatial and temporal subtypes of brain atrophy and its progression in the ALS-FTD spectrum., Methods: We used a data-driven procedure to identify 13 anatomic clusters of brain volume for 57 behavioral variant FTD (bvFTD; with either autopsy-confirmed TDP-43 or TDP-43 proteinopathy-associated genetic variants), 103 ALS, and 47 ALS-FTD patients with likely TDP-43. A Subtype and Stage Inference (SuStaIn) model was trained to identify subtypes of individuals along the ALS-FTD spectrum with distinct brain atrophy patterns, and we related subtypes and stages to clinical, genetic, and neuropathological features of disease., Results: SuStaIn identified three novel subtypes: two disease subtypes with predominant brain atrophy in either prefrontal/somatomotor regions or limbic-related regions, and a normal-appearing group without obvious brain atrophy. The limbic-predominant subtype tended to present with more impaired cognition, higher frequencies of pathogenic variants in TBK1 and TARDBP genes, and a higher proportion of TDP-43 types B, E and C. In contrast, the prefrontal/somatomotor-predominant subtype had higher frequencies of pathogenic variants in C9orf72 and GRN genes and higher proportion of TDP-43 type A. The normal-appearing brain group showed higher frequency of ALS relative to ALS-FTD and bvFTD patients, higher cognitive capacity, higher proportion of lower motor neuron onset, milder motor symptoms, and lower frequencies of genetic pathogenic variants. The overall SuStaIn stages also correlated with evidence for clinical progression including longer disease duration, higher King's stage, and cognitive decline. Additionally, SuStaIn stages differed across clinical phenotypes, genotypes and types of TDP-43 pathology., Conclusions: Our findings suggest distinct neurodegenerative subtypes of disease along the ALS-FTD spectrum that can be identified in vivo, each with distinct brain atrophy, clinical, genetic and pathological patterns., (© 2023. The Author(s).)

Prior to 2021, the neuromuscular medicine fellowship application process suffered from non-standardized timelines and substantial variability. To rectify this, the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) established a standardized application timeline and an online application portal in 2020-2021, followed by the introduction of a partial match process. In 2021-2022, AANEM launched a traditional, binding, two-way match system for fellowship positions allocation based on the Gale-Shapley stable matching algorithm. Surveys assessing perceptions of fairness in the application portal and match process were dispatched to applicants and program directors following the 2021 and 2022 recruitment cycles. In the 2020-21 cycle, 90% of program directors and 95% of applicants affirmed the standardized timeline benefited applicants. However, 57% of applicants deemed the process as unfair. All programs and most applicants (58%) favored a transition to a two-way match. The implementation of the two-way match in 2021-22 attracted participation from 97% of programs, with 80% of applicants and 95% of programs viewing the process as fair to applicants. A significant majority of both applicants (86%) and programs (94%) supported maintaining the standardized timeline and two-way match. We advocate for the universal adoption of the AANEM Match for neuromuscular fellowship recruitment and a standardized fellowship application timeline across all neurologic specialties to promote transparency, fairness, and equity for applicants., Competing Interests: The authors report no disclosures relevant to the manuscript. Go to Neurology.org/NE for full disclosures., (© 2023 American Academy of Neurology.)

Background: TDP-43 proteinopathies represents a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The ALS-FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes, highlighting its heterogeneity. This study aimed to use disease progression modeling to identify novel data-driven spatial and temporal subtypes of brain atrophy and its progression in the ALS-FTD spectrum., Methods: We used a data-driven procedure to identify 13 anatomic clusters of brain volumes for 57 behavioral variant FTD (bvFTD; with either autopsy-confirmed TDP-43 or TDP-43 proteinopathy-associated genetic variants), 103 ALS, and 47 ALS-FTD patients with likely TDP-43. A Subtype and Stage Inference (SuStaIn) model was trained to identify subtypes of individuals along the ALS-FTD spectrum with distinct brain atrophy patterns, and we related subtypes and stages to clinical, genetic, and neuropathological features of disease., Results: SuStaIn identified three novel subtypes: two disease subtypes with predominant brain atrophy either in prefrontal/somatomotor regions or limbic-related regions, and a normal-appearing group without obvious brain atrophy. The Limbic-predominant subtype tended to present with more impaired cognition, higher frequencies of pathogenic variants in TBK1 and TARDBP genes, and a higher proportion of TDP-43 type B, E and C. In contrast, the Prefrontal/Somatomotor-predominant subtype had higher frequencies of pathogenic variants in C9orf72 and GRN genes and higher proportion of TDP-43 type A. The normal-appearing brain group showed higher frequency of ALS relative to ALS-FTD and bvFTD patients, higher cognitive capacity, higher proportion of lower motor neuron onset, milder motor symptoms, and lower frequencies of genetic pathogenic variants. Overall SuStaIn stages also correlated with evidence for clinical progression including longer disease duration, higher King's stage, and cognitive decline. Additionally, SuStaIn stages differed across clinical phenotypes, genotypes and types of TDP-43 pathology., Conclusions: Our findings suggest distinct neurodegenerative subtypes of disease along the ALS-FTD spectrum that can be identified in vivo , each with distinct brain atrophy, clinical, genetic and pathological patterns., Competing Interests: Competing interests All authors report that they have no competing interests to disclose.

We have carried out fully close-coupled three dimensional quantum mechanical wave packet dynamical calculations for the reaction He+H2+→HeH++H on the ground electronic adiabatic potential energy surface and on the lowest two electronic states of newly constructed ab initio calculated diabatic potential energy surfaces for the system [Naskar et al., J. Phys. Chem. A 127, 3832 (2023)]. With the reactant diatom (H2+) in its roto-vibrational ground state (v = 0, j = 0), the calculations have been carried out in hyperspherical coordinates to obtain the reaction attributes. Convergence profiles of the reaction probability with respect to the total angular momentum quantum number at different collision energies are presented for the title reaction. State-to-state as well as initial state selected integral reaction cross sections are calculated from the fully converged reaction probabilities over a range of collision energies. The integral cross section values computed using the two-state diabatic potential energy surfaces are significantly lower than those obtained using the ground electronic state adiabatic potential energy surface and are in much better agreement with the available experimental results than the latter for total energy greater than 1.1 eV. Therefore, it becomes clear that it is important to include the nonadiabatic coupling terms for a quantitative prediction of the dynamical observables., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous neurodegenerative condition featuring variable degrees of motor decline and cognitive impairment. We test the hypothesis that cognitive reserve (CR), defined by occupational histories involving more complex cognitive demands, may protect against cognitive decline, while motor reserve (MR), defined by working jobs requiring complex motor skills, may protect against motor dysfunction., Methods: Individuals with ALS (n=150) were recruited from the University of Pennsylvania's Comprehensive ALS Clinic. Cognitive performance was evaluated using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), and motor functioning was measured using Penn Upper Motor Neuron (PUMNS) scale and ALS Functional Rating Scales (ALSFRS-R). The Occupational Information Network (O*NET) Database was used to derive 17 factors representing distinct worker characteristics, occupational requirements, and worker requirements, which were related to ECAS, PUMNS, and ALSFRS-R scores using multiple linear regression., Results: A history of working jobs involving greater reasoning ability (β=2.12, p<.05), social ability (β=1.73, p<.05), analytic skills, (β=3.12, p<.01) and humanities knowledge (β=1.83, p<.01) was associated with better performance on the ECAS, while jobs involving more exposure to environmental hazards (β=-2.57, p<.01) and technical skills (β=-2.16, p<.01) were associated with lower ECAS Total Scores. Jobs involving greater precision skills (β=1.91, p<.05) were associated with greater disease severity on the PUMNS. Findings for the ALSFRS-R did not survive correction for multiple comparisons., Discussion: Jobs requiring greater reasoning abilities, social skills, and humanities knowledge were related to preserved cognitive functioning consistent with CR, while jobs with greater exposure to environmental hazards and technical demands were linked to poorer cognitive functioning. We did not find evidence of MR as no protective effects of occupational skills and requirements were found for motor symptoms, and jobs involving greater precision skills and reasoning abilities were associated with worse motor functioning. Occupational history provides insight into protective and risk factors for variable degrees of cognitive and motor dysfunction in ALS.

First-principles based beyond Born-Oppenheimer theory has been employed to construct multistate global Potential-Energy Surfaces (PESs) for the HeH 2 + system by explicitly incorporating the Nonadiabatic Coupling Terms (NACTs). Adiabatic PESs and NACTs for the lowest four electronic states (1 2 A', 2 2 A', 3 2 A' and 4 2 A') are evaluated as functions of hyperangles for a grid of fixed values of the hyperradius in hyperspherical coordinates. Conical intersection between different states are validated by integrating the NACTs along appropriately chosen contours. Subsequently, adiabatic-to-diabatic (ADT) transformation angles are determined by solving the ADT equations to construct the diabatic potential matrix for the HeH 2 + system which are smooth, single-valued, continuous, and symmetric and are suitable for performing accurate scattering calculations for the titled system.

Robust and cost-effective membrane-based separations are essential to solving many global crises, such as the lack of clean water. Even though the current polymer-based membranes are widely used for separations, their performance and precision can be enhanced by using a biomimetic membrane architecture that consists of highly permeable and selective channels embedded in a universal membrane matrix. Researchers have shown that artificial water and ion channels, such as carbon nanotube porins (CNTPs), embedded in lipid membranes can deliver strong separation performance. However, their applications are limited by the relative fragility and low stability of the lipid matrix. In this work, we demonstrate that CNTPs can co-assemble into two dimension (2D) peptoid membrane nanosheets, opening up a way to produce highly programmable synthetic membranes with superior crystallinity and robustness. A combination of molecular dynamics (MD) simulations, Raman spectroscopy, X-ray diffraction (XRD), and atomic force microscopy (AFM) measurements to verify the co-assembly of CNTP and peptoids are used and show that it does not disrupt peptoid monomer packing within the membrane. These results provide a new option for designing affordable artificial membranes and highly robust nanoporous solids., (© 2023 Wiley-VCH GmbH.)

Background and Objectives: Patients with ALS-FTD spectrum disorders (ALS-FTSD) have mixed motor and cognitive impairments and require valid and quantitative assessment tools to support diagnosis and tracking of bulbar motor disease. This study aimed to validate a novel automated digital speech tool that analyzes vowel acoustics from natural, connected speech as a marker for impaired articulation due to bulbar motor disease in ALS-FTSD., Methods: We used an automatic algorithm called Forced Alignment Vowel Extraction (FAVE) to detect spoken vowels and extract vowel acoustics from 1 minute audio-recorded picture descriptions. Using automated acoustic analysis scripts, we derived two articulatory-acoustic measures: vowel space area (VSA, in Bark 2 ) which represents tongue range-of-motion (size), and average second formant slope of vowel trajectories (F2 slope) which represents tongue movement speed. We compared vowel measures between ALS with and without clinically-evident bulbar motor disease (ALS+bulbar vs. ALS-bulbar), behavioral variant frontotemporal dementia (bvFTD) without a motor syndrome, and healthy controls (HC). We correlated impaired vowel measures with bulbar disease severity, estimated by clinical bulbar scores and perceived listener effort, and with MRI cortical thickness of the orobuccal part of the primary motor cortex innervating the tongue (oralPMC). We also tested correlations with respiratory capacity and cognitive impairment., Results: Participants were 45 ALS+bulbar (30 males, mean age=61±11), 22 ALS-nonbulbar (11 males, age=62±10), 22 bvFTD (13 males, age=63±7), and 34 HC (14 males, age=69±8). ALS+bulbar had smaller VSA and shallower average F2 slopes than ALS-bulbar (VSA: | d |=0.86, p =0.0088; F2 slope: | d |=0.98, p =0.0054), bvFTD (VSA: | d |=0.67, p =0.043; F2 slope: | d |=1.4, p <0.001), and HC (VSA: | d |=0.73, p =0.024; F2 slope: | d |=1.0, p <0.001). Vowel measures declined with worsening bulbar clinical scores (VSA: R=0.33, p =0.033; F2 slope: R=0.25, p =0.048), and smaller VSA was associated with greater listener effort (R=-0.43, p =0.041). Shallower F2 slopes were related to cortical thinning in oralPMC (R=0.50, p =0.03). Neither vowel measure was associated with respiratory nor cognitive test scores., Conclusions: Vowel measures extracted with automatic processing from natural speech are sensitive to bulbar motor disease in ALS-FTD and are robust to cognitive impairment.

Root gravitropism includes gravity perception in the root cap, signal transduction between root cap and elongation zone, and curvature response in the elongation zone. The barley (Hordeum vulgare) mutant enhanced gravitropism 2 (egt2) displays a hypergravitropic root phenotype. We compared the transcriptomic reprogramming of the root cap, the meristem, and the elongation zone of wild-type (WT) and egt2 seminal roots upon gravistimulation in a time-course experiment and identified direct interaction partners of EGT2 by yeast-two-hybrid screening and bimolecular fluorescence complementation validation. We demonstrated that the elongation zone is subjected to most transcriptomic changes after gravistimulation. Here, 33% of graviregulated genes are also transcriptionally controlled by EGT2, suggesting a central role of this gene in controlling the molecular networks associated with gravitropic bending. Gene co-expression analyses suggested a role of EGT2 in cell wall and reactive oxygen species-related processes, in which direct interaction partners of EGT2 regulated by EGT2 and gravity might be involved. Taken together, this study demonstrated the central role of EGT2 and its interaction partners in the networks controlling root zone-specific transcriptomic reprogramming of barley roots upon gravistimulation. These findings can contribute to the development of novel root idiotypes leading to improved crop performance., (© 2023 The Authors. New Phytologist © 2023 New Phytologist Foundation.)

In this commentary, Sonne-Hansen and colleagues argue that research leaders and organizations should encourage more "theory-guessing" by budding young scientists, rather than incentivizing safe mainstream research., (© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

In maize (Zea mays L.), lateral roots are formed in the differentiation zone of all root types in a multi-step process. The maize mutant lateral rootless 1 (lrt1) is defective in lateral root formation in primary and seminal roots but not in shoot-borne roots. We cloned the lrt1 gene by mapping in combination with BSA-seq and subsequent validation via CRISPR/Cas9. The lrt1 gene encodes a 209 kDa homolog of the DDB1-CUL4-ASSOCIATED FACTOR (DCAF) subunit of the CUL4-based E3 ubiquitin ligase (CRL4) complex localized in the nucleus. DDB1-CUL4-ASSOCIATED FACTOR proteins are encoded by an evolutionary old gene family already present in nonseed plants. They are adaptors that bind substrate proteins and promote their ubiquitylation, thus typically marking them for subsequent degradation in the 26S proteasome. Gene expression studies demonstrated that lrt1 transcripts are expressed preferentially in the meristematic zone of all root types of maize. Downregulation of the rum1 gene in lrt1 mutants suggests that lrt1 acts upstream of the lateral root regulator rum1. Our results demonstrate that DCAF proteins play a key role in root-type-specific lateral root formation in maize. Together with its role in nitrogen acquisition in nitrogen-poor soil, lrt1 could be a promising target for maize improvement., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Sustaining creativity is difficult. We identify the conditions that determine repeat production of novelty among first-time producers, and the psychological mechanism transmitting their effects. Our theoretical model highlights that the novelty of a first production can lower the probability of creating a second production, particularly when the first production is bestowed with an award or recognition. This effect occurs primarily because individuals who win an award for a prior novel production experience a greater threat to their creative identity when anticipating having to produce follow-up novel work. We test our theoretical model in three studies: an archival study of first-time cookbook authors in the United Kingdom and two experiments. Our results provide some support for our theoretical model-award-winning producers of novel cookbooks (or ideas for them) are less likely to follow-up their initial production with a second one, largely because of the potential erosion to a person's creative identity that doing so may cause. Our findings highlight the intricacies of sustaining creativity over time and offer insights into why some producers abandon their creative efforts. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Electroconvulsive therapy (ECT) appears to be the most effective treatment for severe depression. However, its mechanisms of action are incompletely understood. Evidence suggests ECT enhances neuroplasticity and neurogenesis. While studies on ECT-induced neuroplasticity focused on brain-derived neurotrophic factor (BDNF), other factors of the BDNF/TrkB signaling cascade remain underinvestigated. We assessed longitudinal changes in depression scores, serum BDNF protein levels, and mRNA expression of BDNF/TrkB related genes (BDNF, AKT1, ERK1, CREB), NR3C1 and IGF1 in peripheral blood in 19 treatment-resistant depressed patients undergoing ECT. We also analysed DNA methylation patterns at various timepoints to explore possible epigenetic regulation of mRNA expression. Using multilevel regression, we found a negative association between depression scores and blood-based mRNA expression of BDNF/TrkB related genes and NR3C1. Expression of BDNF, ERK1 and NR3C1 increased significantly over time (BDNF: β = 0.0295, p = 0.003; ERK1: β = 0.0170, p = 0.034; NR3C1: β = 0.0035, p = 0.050). For these three genes changes in mRNA expression were highly correlated (R = 0.59 - 0.88) with changes in DNA methylation for multiple CpG sites in the respective genes. Also, serum BDNF protein levels increased across the study period (β = 0.11, p = 0.001). Our findings show that the antidepressant effects of ECT are associated with changes in expression of BDNF and its signaling molecules and that these molecular markers can be detected in peripheral blood. Alterations in DNA methylation could be a key mechanism whereby ECT influences gene expression., Competing Interests: Conflict of interest BR is supported by the European Community's Seventh Framework Programme under Grant agreement no. HEALTH-F2-2009-241909 (Project EU-GEI) and via VENI and VIDI Awards from the Netherlands Organization for Scientific Research (NWO, grant numbers 916.11.086 and 917.18.336). LRI received CME-related financing or served as speaker for Adamed, Angelini, Janssen-Cilag, Otsuka-Lundbeck, Pfizer and Servier. The other authors declare no competing interests and have nothing to disclose., (Copyright © 2022. Published by Elsevier B.V.)

For many years, Neuromuscular Medicine programs lacked a standardized means of handling fellowship applications and offering positions. Programs interviewed applicants and made offers as early as the first half of Post Graduate Year 3 (PGY3), a suboptimal timeline for applicants who may have had little prior exposure to neuromuscular or electrodiagnostic medicine. In 2021, the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) developed the Neuromuscular Fellowship Portal to standardize a later timeline and establish a process for fellowship applications and offers. In its first year, the Neuromuscular Fellowship Portal used a unique one-way match, in which the portal released serial offers to applicants based on rank order lists submitted by programs. Fifty-two Neuromuscular Medicine programs and seven electromyography (EMG)-focused Clinical Neurophysiology programs participated. Sixty-eight positions were filled, a similar number to previous years. A survey of fellowship directors and applicants following this process showed overwhelming support for the standardized timeline and application portal, but all program directors and most applicants favored moving to a traditional match. To maintain the existing application timeline and minimize costs for all parties, the AANEM Neuromuscular Fellowship Portal will host a two-way match, based on existing commercial match algorithms, in 2022. A match will afford a fair and efficient process for all involved. Both Neuromuscular Medicine and EMG-focused Clinical Neurophysiology programs will be encouraged to participate. The process undertaken by the AANEM can stand as an example for other neurologic subspecialties who are interested in standardizing their application timeline., (© 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Learning adaptive behaviour to control aversion is a major brain function. Detecting the absence of control is also important, although chronic uncontrollable aversion can impact maladaptively on stimulus processing in general. The mouse basomedial amygdala (BMA) contributes to aversion processing with high BMA activity associated with active behavioural responding. The overall aim of the present study was to investigate the associations between aversion (un)controllability, BMA activity and behaviour. Fibre photometry of GCaMP6-expressing BMA neuron populations was applied in freely behaving adult male mice during exposure to mild electrical shocks, and effects of specific or general (un)controllability were investigated. In a discrete learned helplessness (LH) effect paradigm, mice underwent discrete sessions of pre-exposure to either escapable shock (ES) or inescapable shock (IES) followed by an escape test. IES mice acquired fewer escape attempts than ES mice, and this co-occurred with higher aversion-related BMA activity in the IES group. After 30 days, ES and IES mice were allocated equally to either chronic social stress (CSS)-exposure to continuous uncontrollable social aversion-or control handling (CON), and on days 5 and 15 underwent an IES session. CSS mice made fewer escape attempts than CON mice, and this was now associated with lower aversion-related BMA activity in the CSS group. These findings suggest that mouse BMA activity is higher when discrete aversion is uncontrollable but becomes lower following chronic uncontrollable aversion exposure. Therefore, BMA activity could be a neural marker of adaptive and maladaptive states consequent to specific and general uncontrollability, respectively., (© 2020 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

(1) Influenza viruses constantly change and evade prior immune responses, forcing seasonal re-vaccinations with updated vaccines. Current FDA-approved vaccine manufacturing technologies are too slow and/or expensive to quickly adapt to mid-season changes in the virus or to the emergence of pandemic strains. Therefore, cost-effective vaccine technologies that can quickly adapt to newly emerged strains are desirable. (2) The filamentous fungal host Thermothelomyces heterothallica C1 (C1, formerly Myceliophthora thermophila ) offers a highly efficient and cost-effective alternative to reliably produce immunogens of vaccine quality at large scale. (3) We showed the utility of the C1 system expressing hemagglutinin (HA) and a HA fusion protein from different H1N1 influenza A virus strains. Mice vaccinated with the C1-derived HA proteins elicited anti-HA immune responses similar, or stronger than mice vaccinated with HA products derived from prototypical expression systems. A challenge study demonstrated that vaccinated mice were protected against the aggressive homologous viral challenge. (4) The C1 expression system is proposed as part of a set of protein expression systems for plug-and-play vaccine manufacturing platforms. Upon the emergence of pathogens of concern these platforms could serve as a quick solution for producing enough vaccines for immunizing the world population in a much shorter time and more affordably than is possible with current platforms.

Background: The use of personal protective equipment (PPE) by emergency medical services (EMS) providers requires specific attention, as it takes place in out-of-hospital unsecured settings. The aim of this study was to evaluate which PPE gown was less contaminating during doffing procedures in an EMS setting. Six well-trained healthcare worker (HCW) subjects tested 4 different gowns: (1) surgical gowns (SG), (2) full body coveralls (FBC), (3) self-made alternative PPEs (SMP), and (4) non-surgical isolation gowns (NSIG). An invisible tracer was sprayed on the gown after donning each subject. After doffing, each HCW was photographed under UV lights to show areas of fluorescent "contamination" on their clothes. The number, size, and intensity level of contaminated areas were noted, as well as observational deviation from the procedure and doffing time. In addition, the subjects were asked to take a questionnaire about their perception of the level of comfort, ease of doffing, and overall safety for each gown., Results: Despite a well-trained team of HCW subjects, contamination while doffing was observed with every type of PPE gown, and with each HCW subject. All body areas were contaminated at least once, except the face. Contamination was more frequent while doffing FBCs. On the other hand, the removal of SG was found to be the least contaminating. The mean doffing time was significantly shorter with SG 1:29 and longer with FBC 2:26 (p=0.005)., Conclusion: Results of this study converge towards the selection of surgical gowns over other types of PPE gowns, which met both contamination criteria as well as staff appreciation in this context. Specific attention should be paid to the legs and abdomino-pelvic areas. Additional protection such as protective trousers or aprons could be added., (© 2021. The Author(s).)

Background: During the COVID-19 pandemic, as the number of available Intensive Care beds in France did not meet the needs, it appeared necessary to transfer a large number of patients from the most affected areas to the less ones. Mass transportation resources were deemed necessary. To achieve that goal, the concept of a Collective Critical Care Ambulance (CCCA) was proposed in the form of a long-distance bus re-designed and equipped to accommodate up to six intensive care patients and allow Advanced Life Support (ALS) techniques to be performed while en route., Methods: The expected benefit of the CCCA, when compared to ALS ambulances accommodating a single patient, was to reduce the resources requirements, in particular by a lower personnel headcount for several patients being transferred to the same destination. A foreseen prospect, comparing to other collective transportation vectors such as airplanes, was the door-to-door capability, minimalizing patients' handovers for safety concerns and time efficiency. With the project of a short-distance transfer of several Intensive Care Unit (ICU) patients together, the opportunity came to test the CCCA under real-life conditions and evaluate safely its technical feasibility and impact in time and resources saving, before it could be proposed for longer distances., Results: Four COVID-19 patients were transported over 37 km. All patients were intubated and under controlled ventilation. One of them was under Norepinephrine support. Mean loading time was 1 min 39 s. Transportation time was 29 min. At destination, the mean unloading time was 1 min 15 s. No serious adverse effect, in particular regarding hemodynamic instability or ventilation disorder, has been observed. No harmful incident has occurred., Conclusions: It was a very instructive test. Collective medical evacuation by bus for critically ill patients under controlled ventilation is suitable and easy to implement. Design, ALS equipment, power autonomy, safety and resources saving, open the way for carrying up to 6 ICU-patients over a long distance. The CCCA could bring a real added-value in an epidemic context and could also be helpful in many other events generating multiple victims such as an armed conflict, a terrorist attack or a natural disaster.

Background: Hypoglycemia usually includes various neurological symptoms, which are the consequence of neuroglycopenia. When it is severe, it is associated with altered mental status, even coma., Case Presentation: We report the case of a patient with severe hypoglycemia, completely asymptomatic, due to the increase of lactate production in response to tissue hypoperfusion following a hemorrhagic shock. This illustrates that lactate can substitute glucose as an energy substrate for the brain. It is also a reminder that this metabolite, despite its bad reputation maintained by its role as a marker of severity in critical care patients, has a fundamental role in our metabolism., Conclusions: Following the example of the "happy hypoxemia" recently reported in the literature describing asymptomatic hypoxemia in COVID-19 patients, we describe a case of "happy hypoglycemia."

Beneficial interactions between plant roots and rhizosphere microorganisms are pivotal for plant fitness. Nevertheless, the molecular mechanisms controlling the feedback between root architecture and microbial community structure remain elusive in maize. Here, we demonstrate that transcriptomic gradients along the longitudinal root axis associate with specific shifts in rhizosphere microbial diversity. Moreover, we have established that root-derived flavones predominantly promote the enrichment of bacteria of the taxa Oxalobacteraceae in the rhizosphere, which in turn promote maize growth and nitrogen acquisition. Genetic experiments demonstrate that LRT1-mediated lateral root development coordinates the interactions of the root system with flavone-dependent Oxalobacteraceae under nitrogen deprivation. In summary, these experiments reveal the genetic basis of the reciprocal interactions between root architecture and the composition and diversity of specific microbial taxa in the rhizosphere resulting in improved plant performance. These findings may open new avenues towards the breeding of high-yielding and nutrient-efficient crops by exploiting their interaction with beneficial soil microorganisms.

Objective: High bacterial load contributes to chronicity of wounds and is diagnosed based on assessment of clinical signs and symptoms (CSS) of infection, but these characteristics are poor predictors of bacterial burden. Point-of-care fluorescence imaging (FL) MolecuLight i:X can improve identification of wounds with high bacterial burden (>10 4 colony-forming unit [CFU]/g). FL detects bacteria, whether planktonic or in biofilm, but does not distinguish between the two. In this study, diagnostic accuracy of FL was compared to CSS during routine wound assessment. Postassessment, clinicians were surveyed to assess impact of FL on treatment plan. Approach: A prospective multicenter controlled study was conducted by 20 study clinicians from 14 outpatient advanced wound care centers across the United States. Wounds underwent assessment for CSS followed by FL. Biopsies were collected to confirm total bacterial load. Three hundred fifty patients completed the study (138 diabetic foot ulcers, 106 venous leg ulcers, 60 surgical sites, 22 pressure ulcers, and 24 others). Results: Around 287/350 wounds (82%) had bacterial loads >10 4 CFU/g, and CSS missed detection of 85% of these wounds. FL significantly increased detection of bacteria (>10 4 CFU/g) by fourfold, and this was consistent across wound types ( p  < 0.001). Specificity of CSS+FL remained comparably high to CSS ( p  = 1.0). FL information modified treatment plans (69% of wounds), influenced wound bed preparation (85%), and improved overall patient care (90%) as reported by study clinicians. Innovation: This novel noncontact, handheld FL device provides immediate, objective information on presence, location, and load of bacteria at point of care. Conclusion: Use of FL facilitates adherence to clinical guidelines recommending prompt detection and removal of bacterial burden to reduce wound infection and facilitate healing.

Cerebral amyloid angiopathy (CAA) is a condition characterised by accumulation of amyloid beta protein (Aβ) in the wall of cerebral blood vessels which increases the risk of intracranial haemorrhage and contributes to cognitive impairment. We describe the case of a man around the age of 70 with 'probable' CAA according to the modified Boston criteria and severe depression whose depression was treated successfully with electroconvulsive therapy (ECT). To the best of our knowledge, there are no earlier published reports of ECT in a patient with CAA. We briefly discuss possible safety measures for these patients, the impact of ECT on cognition in CAA and a possible influence of ECT on Aβ clearance., Competing Interests: Competing interests: AAP reports an institutional grant from Siemens Healthcare, outside the submitted work., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The dynamics of the H + H 2 + reaction has been analyzed from the electronically first excited state of diabatic potential energy surfaces constructed by employing the Beyond Born-Oppenheimer theory [ J. Chem. Phys . 2014 , 141 , 204306]. We have employed the coupled 3D time-dependent wavepacket formalism in hyperspherical coordinates for multisurface reactive scattering problems. To be specific, the charge transfer processes have been investigated extensively by calculating state-to-state as well as total reaction probabilities and integral cross sections, when the reaction process is initiated from the first excited electronic state (2 1 A'). We have depicted the convergence profiles of reaction probabilities for the competing charge transfer processes, namely, reactive charge transfer (RCT) and nonreactive charge transfer (NRCT) processes for different total energies with respect to total angular momentum, J . Total and state-to-state integral cross sections are calculated as a function of total energy for the initial rovibrational state, namely, v = 0, j = 0 level of H 2 + ( 2 Σ g + ) molecule and are compared with previous theoretical calculations. Finally, we have calculated temperature-dependent rate constants using our presently evaluated cross sections and compared their average with the experimentally measured one.

In this work, we introduce polarimetric balanced detection as a new attenuated total reflection (ATR) infrared (IR) sensing scheme, leveraging unequal effective thicknesses achieved with laser light of different polarizations. We combined a monolithic widely tunable Vernier quantum cascade laser (QCL-XT) and a multibounce ATR IR spectroscopy setup for analysis of liquids in a process analytical setting. Polarimetric balanced detection enables simultaneous recording of background and sample spectra, significantly reducing long-term drifts. The root-mean-square noise could be improved by a factor of 10 in a long-term experiment, compared to conventional absorbance measurements obtained via the single-ended optical channel. The sensing performance of the device was further evaluated by on-site measurements of ethanol in water, leading to an improved limit of detection (LOD) achieved with polarimetric balanced detection. Sequential injection analysis was employed for automated injection of samples into a custom-built ATR flow cell mounted above a zinc sulfide multibounce ATR element. The QCL-XT posed to be suitable for mid-IR-based sensing in liquids due to its wide tunability. Polarimetric balanced detection proved to enhance the robustness and long-term stability of the sensing device, along with improving the LOD by a factor of 5. This demonstrates the potential for new polarimetric QCL-based ATR mid-IR sensing schemes for in-field measurements or process monitoring usually prone to a multitude of interferences.

Diffuse reflecting (white) and highly absorbing (black) fused silica based materials are presented, which combine volume modified substrates and surfaces equipped with anti-reflective moth-eye-structures. For diffuse reflection, micrometer sized cavities are created in bulk fused silica during a sol-gel process. In contrast, carbon black particles are added to get the highly absorbing material. The moth-eye-structures are prepared by block copolymer micelle nanolithography (BCML), followed by a reactive-ion-etching (RIE) step. The moth-eye-structures drastically reduce the specular reflectance on both diffuse reflecting and highly absorbing samples across a wide spectral range from 250 nm to 2500 nm and for varying incidence angles. The adjustment of the height of the moth-eye-structures allows us to select the spectral position of the specular reflectance minimum, which measures less than 0.1%. Diffuse Lambertian-like scattering and absorbance appear nearly uniform across the selected spectral range, showing a slight decrease with increasing wavelength.

Background: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of individual experts. Evidence from mechanistic data and prior studies suggests that exposure to long working hours may cause stroke. In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from stroke that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates., Objectives: We aimed to systematically review and meta-analyse estimates of the effect of exposure to long working hours (three categories: 41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on stroke (three outcomes: prevalence, incidence, and mortality)., Data Sources: A protocol was developed and published, applying the Navigation Guide to systematic reviews as an organizing framework where feasible. We searched electronic databases for potentially relevant records from published and unpublished studies, including Ovid MEDLINE, PubMed, EMBASE, Scopus, Web of Science, CISDOC, PsycINFO, and WHO ICTRP. We also searched grey literature databases, Internet search engines, and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts., Study Eligibility and Criteria: We included working-age (≥15 years) individuals in the formal and informal economy in any WHO and/or ILO Member State but excluded children (aged < 15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the effect of exposure to long working hours (41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on stroke (prevalence, incidence or mortality)., Study Appraisal and Synthesis Methods: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first review stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. Missing data were requested from principal study authors. We combined relative risks using random-effects meta-analysis. Two or more review authors assessed the risk of bias, quality of evidence and strength of evidence, using the Navigation Guide and GRADE tools and approaches adapted to this project., Results: Twenty-two studies (20 cohort studies, 2 case-control studies) met the inclusion criteria, comprising a total of 839,680 participants (364,616 females) in eight countries from three WHO regions (Americas, Europe, and Western Pacific). The exposure was measured using self-reports in all studies, and the outcome was assessed with administrative health records (13 studies), self-reported physician diagnosis (7 studies), direct diagnosis by a physician (1 study) or during a medical interview (1 study). The outcome was defined as an incident non-fatal stroke event in nine studies (7 cohort studies, 2 case-control studies), incident fatal stroke event in one cohort study and incident non-fatal or fatal ("mixed") event in 12 studies (all cohort studies). Cohort studies were judged to have a relatively low risk of bias; therefore, we prioritized evidence from these studies, but synthesised evidence from case-control studies as supporting evidence. For the bodies of evidence for both outcomes with any eligible studies (i.e. stroke incidence and mortality), we did not have serious concerns for risk of bias (at least for the cohort studies). Eligible studies were found on the effects of long working hours on stroke incidence and mortality, but not prevalence. Compared with working 35-40 h/week, we were uncertain about the effect on incidence of stroke due to working 41-48 h/week (relative risk (RR) 1.04, 95% confidence interval (CI) 0.94-1.14, 18 studies, 277,202 participants, I 2 0%, low quality of evidence). There may have been an increased risk for acquiring stroke when working 49-54 h/week compared with 35-40 h/week (RR 1.13, 95% CI 1.00-1.28, 17 studies, 275,181participants, I 2 0%, p 0.04, moderate quality of evidence). Compared with working 35-40 h/week, working ≥55 h/week may have led to a moderate, clinically meaningful increase in the risk of acquiring stroke, when followed up between one year and 20 years (RR 1.35, 95% CI 1.13 to 1.61, 7 studies, 162,644 participants, I 2 3%, moderate quality of evidence). Compared with working 35-40 h/week, we were very uncertain about the effect on dying (mortality) of stroke due to working 41-48 h/week (RR 1.01, 95% CI 0.91-1.12, 12 studies, 265,937 participants, I 2 0%, low quality of evidence), 49-54 h/week (RR 1.13, 95% CI 0.99-1.29, 11 studies, 256,129 participants, I 2 0%, low quality of evidence) and 55 h/week (RR 1.08, 95% CI 0.89-1.31, 10 studies, 664,647 participants, I 2 20%, low quality of evidence). Subgroup analyses found no evidence for differences by WHO region, age, sex, socioeconomic status and type of stroke. Sensitivity analyses found no differences by outcome definition (exclusively non-fatal or fatal versus "mixed") except for the comparison working ≥55 h/week versus 35-40 h/week for stroke incidence (p for subgroup differences: 0.05), risk of bias ("high"/"probably high" ratings in any domain versus "low"/"probably low" in all domains), effect estimate measures (risk versus hazard versus odds ratios) and comparator (exact versus approximate definition)., Conclusions: We judged the existing bodies of evidence for human evidence as "inadequate evidence for harmfulness" for all exposure categories for stroke prevalence and mortality and for exposure to 41-48 h/week for stroke incidence. Evidence on exposure to 48-54 h/week and ≥55 h/week was judged as "limited evidence for harmfulness" and "sufficient evidence for harmfulness" for stroke incidence, respectively. Producing estimates for the burden of stroke attributable to exposures to working 48-54 and ≥55 h/week appears evidence-based, and the pooled effect estimates presented in this systematic review could be used as input data for the WHO/ILO Joint Estimates. PROTOCOL IDENTIFIER: https://doi.org/10.1016/j.envint.2018.06.016., Prospero Registration Number: CRD42017060124., (Copyright © 2020 , , , , , , , , , , , , , , , , , , , , , , , , , , , World Health Organization and International Labour Organization. Published by Elsevier Ltd.. All rights reserved.)

Background Long-working hours (LWH) are a probable risk factor for ischemic heart diseases (IHD); however, no previous study has considered duration of exposure to LWH when addressing this topic. We aimed to determine the association between cumulative exposure to LWH and IHD while accounting for relevant confounders. Methods and Results In this retrospective study, we included all baseline participants from the French population-based cohort CONSTANCES. Part-time employees and those who reported a cardiac event in the 5 years before LWH exposure were excluded. From self-administered questionnaires and clinical examinations, we obtained participants' age, sex, body mass index, occupational status, smoking habits, high blood pressure, diabetes mellitus, familial history of cardiovascular disease, dyslipidemia, exposure to LWH, and its duration. We defined LWH as working for >10 hours daily for at least 50 days per year. The main outcome was reported history of IHD, ie, myocardial infarction or angina pectoris, during a clinical examination. Of 137 854 included participants, 69 774 were men. There were 1875 cases (1.36%) of IHD, and exposure to LWH was reported by 42 462 subjects (30.8%) among whom 14 474 (10.50%) reported exposure for at least 10 years. Overall, exposure to LWH for ≥10 years was associated with an increased risk of IHD, adjusted odds ratio (aOR) 1.24 (1.08-1.43), P =0.0021. In stratified analyses, this effect was not observed in women, but was significant amongst men, aOR 1.28 (1.11-1.48), P =0.0008. Conclusions This large population-based study supports an association between cumulative exposure to LWH and IHD in men. Future research should consider relevant strategies for reducing LWH exposure and duration.

Background and Purpose- Long working hours (LWHs) are a potential risk factor for stroke. The aim of this study was to investigate this association in a large general population cohort. Methods- We used the French population-based cohort, CONSTANCES (Cohorte des Consultants des Centres d'Examens de Santé), to retrieve information on age, sex, smoking, and working hours from the baseline, self-administered questionnaire. Other cardiovascular risk factors and previous occurrence of stroke were taken from a parallel medical interview. We defined LWH as working time >10 hours daily for at least 50 days per year. Participants with primarily part-time jobs were excluded as were those with stroke before LWH exposure. We used logistic models to estimate the association between LWH and stroke, stratified by age, sex, and occupation. In additional modeling, we excluded subjects whose stroke occurred within 5 years of the first reported work exposure. Results- Among the 143 592 participants in the analyses, there were 1224 (0.9%) strokes, 42 542 (29.6%) reported LWH, and 14 481 (10.1%) reported LWH for 10 years or more. LWH was associated with an increased risk of stroke: adjusted odds ratio of 1.29 (95% CI, 1.11-1.49). Being exposed to LWH for 10 years or more was more strongly associated with stroke, adjusted odds ratio of 1.45 (95% CI, 1.21-1.74). The association showed no differences between men and women but was stronger in white-collar workers under 50 years of age. Conclusions- This large analysis reveals a significant association between stroke and exposure to LWH for 10 years or more. The findings are relevant for individual and global prevention.

Introduction: Early recovery of mobilization after a fracture of the hip is associated with improved long-term ability to walk, lower complication rates, and mortality. In this context, early mobilization and full weight bearing are favorable. The aim of this study was (1) to analyze the influence of time between operation and first mobilization on in-hospital outcome and (2) the influence of early mobilization, full weight bearing, and ASA on pain, mobility of the hip, and ability to walk during the in-hospital phase of recovery., Methods: This is a retrospective in-hospital study of 219 patients aged 70 years or older who were treated with surgery after a hip fracture. Data were collected by a review of medical records. The outcomes were mortality, complications, length of stay, and the Merle d'Aubigné score which evaluates pain, mobility of the hip, and ability to walk. Factors were sought in bivariate and multivariate analyses., Results: A shorter time between operation and first mobilization was significantly associated with lower in-hospital mortality and complications. Early mobilization (within 24 h after the operation) and full weight bearing had no influence on pain, mobility of the hip, and ability to walk as well as length of stay in our cohort. Fracture type and treatment influenced mobility of the hip, while age as well as physical health status affected the ability to walk., Discussion: Patients with femoral neck fractures, respectively after total hip arthroplasty, had less pain and showed better mobility of the hip and ability to walk during hospitalization than patients with trochanteric fractures; these results were irrespective of early vs. late mobilization and full vs. partial weight bearing. Foremost, a shorter time between operation and first mobilization is associated with lower complication and mortality rates., (© The Authors, published by EDP Sciences, 2019.)

In this paper, we present WaterSpy, a project developing an innovative, compact, cost-effective photonic device for pervasive water quality sensing, operating in the mid-IR spectral range. The approach combines the use of advanced Quantum Cascade Lasers (QCLs) employing the Vernier effect, used as light source, with novel, fibre-coupled, fast and sensitive Higher Operation Temperature (HOT) photodetectors, used as sensors. These will be complemented by optimised laser driving and detector electronics, laser modulation and signal conditioning technologies. The paper presents the WaterSpy concept, the requirements elicited, the preliminary architecture design of the device, the use cases in which it will be validated, while highlighting the innovative technologies that contribute to the advancement of the current state of the art., Competing Interests: The authors declare no conflict of interest.

Objective: The aims of this study were to quantitatively assess two new scan modes on a photon-counting detector computed tomography system, each designed to maximize spatial resolution, and to qualitatively demonstrate potential clinical impact using patient data., Materials and Methods: This Health Insurance Portability Act-compliant study was approved by our institutional review board. Two high-spatial-resolution scan modes (Sharp and UHR) were evaluated using phantoms to quantify spatial resolution and image noise, and results were compared with the standard mode (Macro). Patients were scanned using a conventional energy-integrating detector scanner and the photon-counting detector scanner using the same radiation dose. In first patient images, anatomic details were qualitatively evaluated to demonstrate potential clinical impact., Results: Sharp and UHR modes had a 69% and 87% improvement in in-plane spatial resolution, respectively, compared with Macro mode (10% modulation-translation-function values of 16.05, 17.69, and 9.48 lp/cm, respectively). The cutoff spatial frequency of the UHR mode (32.4 lp/cm) corresponded to a limiting spatial resolution of 150 μm. The full-width-at-half-maximum values of the section sensitivity profiles were 0.41, 0.44, and 0.67 mm for the thinnest image thickness for each mode (0.25, 0.25, and 0.5 mm, respectively). At the same in-plane spatial resolution, Sharp and UHR images had up to 15% lower noise than Macro images. Patient images acquired in Sharp mode demonstrated better delineation of fine anatomic structures compared with Macro mode images., Conclusions: Phantom studies demonstrated superior resolution and noise properties for the Sharp and UHR modes relative to the standard Macro mode and patient images demonstrated the potential benefit of these scan modes for clinical practice.

Background: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing a joint methodology for estimating the national and global work-related burden of disease and injury (WHO/ILO joint methodology), with contributions from a large network of experts. In this paper, we present the protocol for two systematic reviews of parameters for estimating the number of deaths and disability-adjusted life years from stroke attributable to exposure to long working hours, to inform the development of the WHO/ILO joint methodology., Objectives: We aim to systematically review studies on occupational exposure to long working hours (called Systematic Review 1 in the protocol) and systematically review and meta-analyse estimates of the effect of long working hours on stroke (called Systematic Review 2), applying the Navigation Guide systematic review methodology as an organizing framework, conducting both systematic reviews in tandem and in a harmonized way., Data Sources: Separately for Systematic Reviews 1 and 2, we will search electronic academic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science, CISDOC and PsychINFO. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand-search reference list of previous systematic reviews and included study records; and consult additional experts., Study Eligibility and Criteria: We will include working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State, but exclude children (<15 years) and unpaid domestic workers. For Systematic Review 1, we will include quantitative prevalence studies of relevant levels of occupational exposure to long working hours (i.e. 35-40, 41-48, 49-54 and ≥55 h/week) stratified by country, sex, age and industrial sector or occupation, in the years 2005-2018. For Systematic Review 2, we will include randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the relative effect of a relevant level of long working hours on the incidence of or mortality due to stroke, compared with the theoretical minimum risk exposure level (i.e. 35-40 h/week)., Study Appraisal and Synthesis Methods: At least two review authors will independently screen titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. At least two review authors will assess risk of bias and the quality of evidence, using the most suited tools currently available. For Systematic Review 2, if feasible, we will combine relative risks using meta-analysis. We will report results using the guidelines for accurate and transparent health estimates reporting (GATHER) for Systematic Review 1 and the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) for Systematic Review 2. PROSPERO registration number: CRD42017060124., (Copyright © 2018 Elsevier Ltd. All rights reserved.)