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A previous gas-phase study has uncovered formal catalytic cycles for the dehydrogenation of model liquid organic hydrogen carriers (LOHCs) pyrrolidine, N -methylpyrrolidine, and piperidine by the coordinatively unsaturated half-sandwich cyclopentadienyl iron cation, [CpFe] + . That work is extended here to the well-known condensed-phase [CpFe(CO) 2 ] + cation, which was generated via electrospray ionization for gas-phase reactions with model LOHCs in a linear ion trap mass spectrometer, in which the helium bath gas was seeded with 0.1% carbon monoxide. The initial ion-molecule reaction (IMR) was exothermic enough to expel one CO molecule from the complex to form [CpFe(CO)L] + (L = pyrrolidine, N -methylpyrrolidine, or piperidine). Collision-induced dissociation (CID) of these cations revealed two fragmentation pathways: (i) removal of another CO molecule leading to the species [CpFeL] + that was studied previously; (ii) dehydrogenation of the ligand L (except for L= N -methylpyrrolidine). Two new formal catalytic cycles (for dehydrogenation of pyrrolidine and piperidine) were found that operate via a combination of IMR and CID experiments and which rely on the presence of CO for re-ligation of iron complexes. Density functional theory calculations were performed to compute the structures of all species observed as well as the reaction energetics.

Neurological disorders pose a challenge for targeted therapy due to restricted access of therapeutic agents to the central nervous system (CNS). Current methods are limited by procedure-related risks, invasiveness, and insufficient CNS biodistribution. A novel percutaneous transvenous technology, currently in clinical trials for communicating hydrocephalus, offers a minimally invasive approach by providing endovascular access to the cerebrospinal fluid-filled cerebellopontine angle (CPA) cistern. We hypothesized that drug delivery to the CPA cistern could yield widespread CNS distribution. Using an ovine model, we compared the biodistribution of scAAV9-CB-GFP following CPA cistern infusion with previously reported cisterna magna (CM) administration. Targeting both the CPA cistern and CM in sheep, we employed a lumbar spine-inserted microcatheter under fluoroscopy. CPA delivery of AAV9 demonstrated biodistribution and transduction in the cerebral cortices, striatum, thalamus, midbrain, cerebellum, and spinal cord, with minor liver distribution comparable to CM. The favorable safety profile in humans with hydrocephalus suggests that percutaneous endovascular injection into the CPA could offer a clinically safer and minimally invasive delivery system for CNS gene and cell-based therapies., Competing Interests: Declaration of interests C.B.H. is a shareholder, consultant, investor, and co-founder of CereVasc, Inc. B.M.B. is a shareholder and employee of CereVasc, Inc. M.J.G. is a consultant on a fee-per-hour basis for Alembic LLC, Astrocyte Pharmaceuticals, BendIt Technologies, Cerenovus, Imperative Care, Jacob’s Institute, Medtronic Neurovascular, Mivi Neurosciences, phenox GMbH, Q’Apel, Route 92 Medical, Scientia, Simcerre, Stryker Neurovascular, Stryker Sustainability Solutions, Wallaby Medical; holds stock in Imperative Care, InNeuroCo, Galaxy Therapeutics, Kapto, Neurogami and Synchron and receives research support from the NIH, the United States-Israel Binational Science Foundation, Anaconda, ApicBio, Arsenal Medical, Axovant, Balt, Cerenovus, Ceretrieve, CereVasc LLC, Cook Medical, Galaxy Therapeutics, Gentuity, Gilbert Foundation, Imperative Care, InNeuroCo, Insera, Jacob’s Institute, Magneto, MicroBot, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Q’Apel, Philips Healthcare, Progressive Medical, Pulse Medical, Rapid Medical, Route 92 Medical, Scientia, Stryker Neurovascular, Syntheon, ThrombX Medical, Wallaby Medical, the Wyss Institute, and Xtract Medical. A.M.M. is a shareholder, consultant, investor, and co-founder of CereVasc, Inc., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: GM1-gangliosidosis (GM1) leads to extensive neurodegenerative changes and atrophy that precludes the use of automated MRI segmentation techniques for generating brain volumetrics. We developed a standardized segmentation protocol for brain MRIs of patients with type II GM1 and then assessed the inter- and intra-rater reliability of this methodology. The volumetric data may be used as a biomarker of disease burden and progression, and standardized methodology may support research into the natural history of the disease which is currently lacking in the literature., Approach: Twenty-five brain MRIs were included in this study from 22 type II GM1 patients of which 8 were late-infantile subtype and 14 were juvenile subtype. The following structures were segmented by two rating teams on a slice-by-slice basis: whole brain, ventricles, cerebellum, lentiform nucleus, thalamus, corpus callosum, and caudate nucleus. The inter- and intra-rater reliability of the segmentation method was assessed with an intraclass correlation coefficient as well as Sorensen-Dice and Jaccard coefficients., Results: Based on the Sorensen-Dice and Jaccard coefficients, the inter- and intra-rater reliability of the segmentation method was significantly better for the juvenile patients compared to late-infantile ( p < 0.01). In addition, the agreement between the two rater teams and within themselves can be considered good with all p -values < 0.05., Conclusions: The standardized segmentation approach described here has good inter- and intra-rater reliability and may provide greater accuracy and reproducibility for neuromorphological studies in this group of patients and help to further expand our understanding of the natural history of this disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zoppo, Kolstad, Johnston, D'Souza, Kühn, Vardar, Peker, Lindsay, Rentiya, King, Gray-Edwards, Vachha, Acosta, Tifft and Shazeeb.)

Rapid climate changes bear significant consequences on various aspects of our lives, notably by deteriorating living conditions in certain areas to such extent that inhabitants have no choice but flee. Despite recognition of this issue, the dynamics of the relationship between the environmental factors and the human mobility have yet to be thoroughly investigated. This study aims to explore the application of advanced remote sensing analytics for developing detailed climate indicators at a micro (district) level, and to examine the relationship between climate factors and internally displaced persons. After detailing our data sources and the analytics employed for indicator development, we discuss various types of events and their repercussions. Our findings corroborate that slow-onset and rapid-onset climate events differently impact society, and the responses hinge on the urgency precipitated by the detrimental aftermath of the extreme weather event and, most crucially, on people's capabilities. We also underscore the importance of data quality and availability for the socio-economic indicators to enhance future studies, given the intertwined associations between climate change, economic deprivation, and violent conflict., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Momeni et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Wheat (Triticum aestivum L.) is a major source of nutrients for populations across the globe, but the amino acid composition of wheat grain does not provide optimal nutrition. The nutritional value of wheat grain is limited by low concentrations of lysine (the most limiting essential amino acid) and high concentrations of free asparagine (precursor to the processing contaminant acrylamide). There are currently few available solutions for asparagine reduction and lysine biofortification through breeding. In this study, we investigated the genetic architecture controlling grain free amino acid composition and its relationship to other traits in a Robigus × Claire doubled haploid population. Multivariate analysis of amino acids and other traits showed that the two groups are largely independent of one another, with the largest effect on amino acids being from the environment. Linkage analysis of the population allowed identification of quantitative trait loci (QTL) controlling free amino acids and other traits, and this was compared against genomic prediction methods. Following identification of a QTL controlling free lysine content, wheat pangenome resources facilitated analysis of candidate genes in this region of the genome. These findings can be used to select appropriate strategies for lysine biofortification and free asparagine reduction in wheat breeding programs., (© 2023 The Authors. The Plant Genome published by Wiley Periodicals LLC on behalf of Crop Science Society of America.)

Purpose: Healthcare avoidance and delay (HAD) in the transgender population has been well documented, and research has explored a range of associated factors that help to identify those most at risk of HAD. This review addresses a gap in the research by synthesizing research exploring associations between HAD and demographic factors., Methods: A systematic search of literature published at any time up to December 2021 was conducted, using five databases (EBSCO, EMBASE, PubMed, Scopus, and Web of Science) and manually searching reference lists of included studies. After exclusion of duplicates, 608 unique records were subjected to double screening. Papers reporting statistical analyses of HAD in association with any sociodemographic variables were included in this review. Papers consisted of nineteen cross-sectional studies. Narrative synthesis was used to address findings., Results: Nineteen studies met inclusion criteria, exploring HAD in association with a wide range of demographic factors, including sex and gender, social transition factors, age, race and ethnicity, socioeconomic factors, veteran status, education, sexuality, relationship status, citizenship, place of residence, and state demographics. Findings identified intra-community demographic risk factors, with consistent evidence for increased HAD among transmasculine, and younger, participants. Lower income and higher educational attainment were also associated with increased HAD, while remaining areas had weak or little evidence for association with HAD., Conclusion: This review expands knowledge in this area by highlighting demographic factors associated with increased HAD in research literature, and exploring how these may be further investigated to address substantial gaps in the body of research., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Siobhan D. Thomas reports financial support was provided by Irish Research Council., (© 2023 The Authors. Published by Elsevier Inc. CC BY 4.0.)

Oligonucleotide therapeutics offer great promise in the treatment of previously untreatable neurodegenerative disorders; however, there are some challenges to overcome in pre-clinical studies. (1) They carry a well-established dose-related acute neurotoxicity at the time of administration. (2) Repeated administration into the cerebrospinal fluid may be required for long-term therapeutic effect. Modifying oligonucleotide formulation has been postulated to prevent acute toxicity, but a sensitive and quantitative way to track seizure activity in pre-clinical studies is lacking. The use of intracerebroventricular (i.c.v.) catheters offers a solution for repeated dosing; however, fixation techniques in large animal models are not standardized and are not reliable. Here we describe a novel surgical technique in a sheep model for i.c.v. delivery of neurotherapeutics based on the fixation of the i.c.v. catheter with a 3D-printed anchorage system composed of plastic and ceramic parts, compatible with magnetic resonance imaging, computed tomography, and electroencephalography (EEG). Our technique allowed tracking electrical brain activity in awake animals via EEG and video recording during and for the 24-h period after administration of a novel oligonucleotide in sheep. Its anchoring efficiency was demonstrated for at least 2 months and will be tested for up to a year in ongoing studies., Competing Interests: There are no conflicts to disclose., (© 2023 The Authors.)

Background: Traditional health economic evaluations of antimicrobials currently underestimate their value to wider society. They can be supplemented by additional value elements including insurance value, which captures the value of an antimicrobial in preventing or mitigating impacts of adverse risk events. Despite being commonplace in other sectors, constituents of the impacts and approaches for estimating insurance value have not been investigated. Objectives: This study assessed the insurance value of a novel gram-negative antimicrobial from operational healthcare, wider population health, productivity, and informal care perspectives. Methods: A novel mixed-methods approach was used to model insurance value in the United Kingdom: (1) literature review and multidisciplinary expert workshops to identify risk events for 4 relevant scenarios: ward closures, unavoidable shortage of conventional antimicrobials, viral respiratory pandemics, and catastrophic antimicrobial resistance (AMR); (2) parameterizing mitigable costs and frequencies of risk events across perspectives and scenarios; (3) estimating insurance value through a Monte Carlo simulation model for extreme events and a dynamic disease transmission model. Results: The mean insurance value across all scenarios and perspectives over 10 years in the UK was £718 million, should AMR remain unchanged, where only £134 million related to operational healthcare costs. It would be 50%-70% higher if AMR steadily increased or if a more risk-averse view (1-in-10 year downside) of future events is taken. Discussion: The overall insurance value if AMR remains at current levels (a conservative projection), is over 5 times greater than insurance value from just the operational healthcare costs perspective, traditionally the sole perspective used in health budgeting. Insurance value was generally larger for nationwide or universal (catastrophic AMR, pandemic, and conventional antimicrobial shortages) rather than localized (ward closure) scenarios, across perspectives. Components of this insurance value match previously published estimates of operational costs and mortality impacts. Conclusions: Insurance value of novel antimicrobials can be systematically modeled and substantially augments their traditional health economic value in normal circumstances. These approaches are generalizable to similar health interventions and form a framework for health systems and governments to capture broader value in health technology assessments, improve healthcare access, and increase resilience by planning for adverse scenarios.

"Mutagenomics" is the combination of random mutagenesis, phenotypic screening, and whole-genome re-sequencing to uncover all tagged and untagged mutations linked with phenotypic changes in an organism. In this study, we performed a mutagenomics screen on the wheat pathogenic fungus Zymoseptoria tritici for altered morphogenetic switching and stress sensitivity phenotypes using Agrobacterium -mediated "random" T-DNA mutagenesis (ATMT). Biological screening identified four mutants which were strongly reduced in virulence on wheat. Whole genome re-sequencing defined the positions of the T-DNA insertion events and revealed several unlinked mutations potentially affecting gene functions. Remarkably, two independent reduced virulence mutant strains, with similarly altered stress sensitivities and aberrant hyphal growth phenotypes, were found to have a distinct loss of function mutations in the Zt SSK2 MAPKKK gene. One mutant strain had a direct T-DNA insertion affecting the predicted protein's N-terminus, while the other possessed an unlinked frameshift mutation towards the C-terminus. We used genetic complementation to restore both strains' wild-type (WT) function (virulence, morphogenesis, and stress response). We demonstrated that ZtSSK2 has a non-redundant function with ZtSTE11 in virulence through the biochemical activation of the stress-activated HOG1 MAPK pathway. Moreover, we present data suggesting that SSK2 has a unique role in activating this pathway in response to specific stresses. Finally, dual RNAseq-based transcriptome profiling of WT and SSK2 mutant strains revealed many HOG1-dependent transcriptional changes in the fungus during early infection and suggested that the host response does not discriminate between WT and mutant strains during this early phase. Together these data define new genes implicated in the virulence of the pathogen and emphasise the importance of a whole genome sequencing step in mutagenomic discovery pipelines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Blyth, Smith, King, Bayon, Ashfield, Walpole, Venter, Ray, Kanyuka and Rudd.)

Background: Telehealth use has had widespread expansion and adoption over the past two years. This study aims to evaluate access to telehealth essentials (TE) using a novel metric., Methods: This single institute study surveyed outpatient surgical patients to determine their access to TE. Generalized linear mixed models were used to determine the relationship of demographic and county-level variables on access to four TE., Results: 138 patients were surveyed. Sixty-six (47.8%) were from Appalachian Kentucky. In the survey cohort, 122 (88.4%) had smart phones, 109 (80.7%) had devices with video messaging capabilities, 106 (80.9%) had cellular reception, and 112 (82.4%) had access to WiFi. Increasing age and Medicare insurance were the most consistent predictors of lack of access to TE., Conclusion: Rural Appalachian Kentucky has access to TE. Telehealth has the potential to decrease the healthcare inequity in rural populations, but incompletely address this inequity for the aging population.

Competing Interests: The authors declare no conflict of interest.

Background: Studying genomic variation in rapidly evolving pathogens potentially enables identification of genes supporting their "core biology", being present, functional and expressed by all strains or "flexible biology", varying between strains. Genes supporting flexible biology may be considered to be "accessory", whilst the "core" gene set is likely to be important for common features of a pathogen species biology, including virulence on all host genotypes. The wheat-pathogenic fungus Zymoseptoria tritici represents one of the most rapidly evolving threats to global food security and was the focus of this study., Results: We constructed a pangenome of 18 European field isolates, with 12 also subjected to RNAseq transcription profiling during infection. Combining this data, we predicted a "core" gene set comprising 9807 sequences which were (1) present in all isolates, (2) lacking inactivating polymorphisms and (3) expressed by all isolates. A large accessory genome, consisting of 45% of the total genes, was also defined. We classified genetic and genomic polymorphism at both chromosomal and individual gene scales. Proteins required for essential functions including virulence had lower-than average sequence variability amongst core genes. Both core and accessory genomes encoded many small, secreted candidate effector proteins that likely interact with plant immunity. Viral vector-mediated transient in planta overexpression of 88 candidates failed to identify any which induced leaf necrosis characteristic of disease. However, functional complementation of a non-pathogenic deletion mutant lacking five core genes demonstrated that full virulence was restored by re-introduction of the single gene exhibiting least sequence polymorphism and highest expression., Conclusions: These data support the combined use of pangenomics and transcriptomics for defining genes which represent core, and potentially exploitable, weaknesses in rapidly evolving pathogens., (© 2023. The Author(s).)

The composition of proanthocyanidins in the testa (seed coat) of bread wheat was analyzed by thiolysis of PA oligomers from developing grain and found to consist of (+)-catechin monomers, with a small amount of (+)-gallocatechin. The average chain length of soluble PA stayed relatively constant between 10 and 20 days post-anthesis, whereas that of unextractable PA increased over the same period, suggesting that increases in chain length might account for the insolubility of PAs from mature wheat grain. We carried out RNA-Seq followed by differential expression analysis from dissected tissues of developing grain from red- and white-grained near-isogenic lines differing in the presence of an active R gene that encodes a MYB transcription factor involved in control of PA biosynthesis. In addition to genes already identified encoding chalcone synthase, chalcone isomerase, flavanone 3-hydroxylase, and dihydroxyflavonoid 4-reductase, we showed that wheat genes encoding phenylalanine ammonia lyase, flavonoid 3',5'-hydroxylase, leucoanthocyanidin reductase, and a glutathione S -transferase (the orthologue of maize Bronze-2 ) were more highly expressed in the red NIL. We also identified candidate orthologues of other catalytic and regulatory components of flavonoid biosynthesis in wheat., Competing Interests: The authors did not report any conflicts of interest., (© 2022 The Authors. Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

A data set of promoter and 5'UTR sequences of homoeo-alleles of 459 wheat genes that contribute to agriculturally important traits in 95 ancestral and commercial wheat cultivars is presented here. The high-stringency myBaits technology used made individual capture of homoeo-allele promoters possible, which is reported here for the first time. Promoters of most genes are remarkably conserved across the 83 hexaploid cultivars used with <7 haplotypes per promoter and 21% being identical to the reference Chinese Spring. InDels and many high-confidence SNPs are located within predicted plant transcription factor binding sites, potentially changing gene expression. Most haplotypes found in the Watkins landraces and a few haplotypes found in Triticum monococcum, germplasms hitherto not thought to have been used in modern wheat breeding, are already found in many commercial hexaploid wheats. The full data set which is useful for genomic and gene function studies and wheat breeding is available at https://rrescloud.rothamsted.ac.uk/index.php/s/DMCFDu5iAGTl50u/authenticate., (© 2021 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Purpose: This study aimed to investigate the effects of blood flow restriction (BFR) combined with electrical muscle stimulation (EMS) on skeletal muscle mass and strength during a period of limb disuse., Methods: Thirty healthy participants (22 ± 3 yr; 23 ± 3 kg·m-2) were randomly assigned to control (CON; n = 10), BFR alone (BFR; n = 10), or BFR combined with EMS (BFR + EMS; n = 10). All participants completed unloading of a single leg for 14 d, with no treatment (CON), or while treated with either BFR or BFR + EMS (twice daily, 5 d·wk-1). BFR treatment involved arterial three cycles of 5-min occlusion using suprasystolic pressure, each separated by 5 min of reperfusion. EMS (6 s on, 15 s off; 200 μs; 60 Hz; 15% maximal voluntary contraction [MVC]) was applied continuously throughout the three BFR cycles. Quadriceps muscle mass (whole-thigh lean mass via dual-energy x-ray absorptiometry and vastus lateralis [VL] muscle thickness via ultrasound) and strength (via knee extension MVC) were assessed before and after the 14-d unloading period., Results: After limb unloading, whole-thigh lean mass decreased in the control group (-4% ± 1%, P < 0.001) and BFR group (-3% ± 2%, P = 0.001), but not in the BFR + EMS group (-0.3% ± 3%, P = 0.8). VL muscle thickness decreased in the control group (-4% ± 4%, P = 0.005) and was trending toward a decrease in the BFR group (-8% ± 11%, P = 0.07) and increase in the BFR + EMS group (+5% ± 10%, P = 0.07). Knee extension MVC decreased over time (P < 0.005) in the control group (-18% ± 15%), BFR group (-10% ± 13%), and BFR + EMS group (-18% ± 15%), with no difference between groups (P > 0.5)., Conclusion: Unlike BFR performed in isolation, BFR + EMS represents an effective interventional strategy to attenuate the loss of muscle mass during limb disuse, but it does not demonstrate preservation of strength., (Copyright © 2020 by the American College of Sports Medicine.)

Background: Research into psychotherapy for binge-eating disorder (BED) has focused mainly on cognitive behavioural therapies, but efficacy, failure to abstain, and dropout rates continue to be problematic. The experience of negative emotions is among the most accurate predictors for the occurrence of binge eating episodes in BED, suggesting benefits to exploring psychological treatments with a more specific focus on the role of emotion. The present study aimed to explore the feasibility of individual emotion-focused therapy (EFT) as a treatment for BED by examining the outcomes of a pilot randomised wait-list controlled trial., Methods: Twenty-one participants were assessed using a variety of feasibility measures relating to recruitment, credibility and expectancy, therapy retention, objective binge episodes and days, and binge eating psychopathology outcomes. The treatment consisted of 12 weekly one-hour sessions of EFT for maladaptive emotions over 3 months. A mixed model approach was utilised with one between effect (group) using a one-way analysis of variance (ANOVA) to test the hypothesis that participants immediately receiving the EFT treatment would demonstrate a greater degree of improvement on outcomes relating to objective binge episodes and days, and binge eating psychopathology, compared to participants on the EFT wait-list; and one within effect (time) using a repeated-measures ANOVA to test the hypothesis that participation in the EFT intervention would result in significant improvements in outcome measures from pre to post-therapy and then maintained at follow-up., Results: Recruitment, credibility and expectancy, therapy retention outcomes indicated EFT is a feasible treatment for BED. Further, participants receiving EFT demonstrated a greater degree of improvement in objective binge episodes and days, and binge eating psychopathology compared to EFT wait-list control group participants. When participants in the EFT wait-list control group then received treatment and outcomes data were combined with participants who initially received the treatment, EFT demonstrated significant improvement in objective binge episodes and days, and binge eating psychopathology for the entire sample., Conclusions: These findings provide further preliminary evidence for the feasibility of individual EFT for BED and support more extensive randomised control trials to assess efficacy., Trial Registration: The study was retrospectively registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12620000563965 ) on 14 May 2020.

NPF genes encode membrane transporters involved in the transport of a large variety of substrates including nitrate and peptides. The NPF gene family has been described for many plants, but the whole NPF gene family for wheat has not been completely identified. The release of the wheat reference genome has enabled the identification of the entire wheat NPF gene family. A systematic analysis of the whole wheat NPF gene family was performed, including responses of specific gene expression to development and nitrogen supply. A total of 331 NPF genes (113 homoeologous groups) have been identified in wheat. The chromosomal location of the NPF genes is unevenly distributed, with predominant occurrence in the long arms of the chromosomes. The phylogenetic analysis indicated that wheat NPF genes are closely clustered with Arabidopsis, Brachypodium, and rice orthologues, and subdivided into eight subfamilies. The expression profiles of wheat NPF genes were examined using RNA-seq data, and a subset of 44 NPF genes (homoeologous groups) with contrasting expression responses to nitrogen and/or development in different tissues were identified. The systematic identification of gene composition, chromosomal locations, evolutionary relationships, and expression profiles contributes to a better understanding of the roles of the wheat NPF genes and lays the foundation for further functional analysis in wheat., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Background: Activity in the supplementary motor area (SMA) has been associated with tics in Tourette syndrome (TS). The aim of this study was to test a novel intervention-real-time functional magnetic resonance imaging neurofeedback from the SMA-for reduction of tics in adolescents with TS., Methods: Twenty-one adolescents with TS were enrolled in a double-blind, randomized, sham-controlled, crossover study involving two sessions of neurofeedback from their SMA. The primary outcome measure of tic severity was the Yale Global Tic Severity Scale administered by an independent evaluator before and after each arm. The secondary outcome was control over the SMA assessed in neuroimaging scans, in which subjects were cued to increase/decrease activity in SMA without receiving feedback., Results: All 21 subjects completed both arms of the study and all assessments. Participants had significantly greater reduction of tics on the Yale Global Tic Severity Scale after real neurofeedback as compared with the sham control (p < .05). Mean Yale Global Tic Severity Scale Total Tic score decreased from 25.2 ± 4.6 at baseline to 19.9 ± 5.7 at end point in the neurofeedback condition and from 24.8 ± 8.1 to 23.3 ± 8.5 in the sham control condition. The 3.8-point difference is clinically meaningful and corresponds to an effect size of 0.59. However, there were no differences in changes on the secondary measure of control over the SMA., Conclusions: This first randomized controlled trial of real-time functional magnetic resonance imaging neurofeedback in adolescents with TS suggests that this neurofeedback intervention may be helpful for improving tic symptoms. However, no effects were found in terms of change in control over the SMA, the hypothesized mechanism of action., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Fusarium graminearum is a global fungal pathogen of wheat and other small grains, causing Fusarium head blight (FHB) disease, also known as wheat scab. We report here the annotated genome of a deoxynivalenol/15-acetyl-deoxynivalenol-producing Brazilian strain called CML3066, isolated from FHB-symptomatic wheat spikes collected in 2009., (Copyright © 2020 Machado Wood et al.)

Due to DNA heterozygosity and repeat content, assembly of non-model plant genomes is challenging. Herein, we report a high-quality genome reference of one of the oldest known domesticated species, fig (Ficus carica L.), using Pacific Biosciences single-molecule, real-time sequencing. The fig genome is ~333 Mbp in size, of which 80% has been anchored to 13 chromosomes. Genome-wide analysis of N 6 -methyladenine and N 4 -methylcytosine revealed high methylation levels in both genes and transposable elements, and a prevalence of methylated over non-methylated genes. Furthermore, the characterization of N 6 -methyladenine sites led to the identification of ANHGA, a species-specific motif, which is prevalent for both genes and transposable elements. Finally, exploiting the contiguity of the 13 pseudomolecules, we identified 13 putative centromeric regions. The high-quality reference genome and the characterization of methylation profiles, provides an important resource for both fig breeding and for fundamental research into the relationship between epigenetic changes and phenotype, using fig as a model species., (© 2019 The Authors The Plant Journal © 2019 John Wiley & Sons Ltd.)

Irish Travellers constitute a pre-demographic-shift population living among a post-demographic-shift one. Their socio-medico profile identifies them as largely on fast life-history trajectories. In addition, they are strongly religious (typically using no contraception), highly sexually behaviorally dimorphic, with strong traditions of male-male competition (bare-knuckle fighting) and quasi-symbolic bride capture ("grabbing"). Their male-male competitions thus allow for the comparative testing of a number of interesting theories pertaining to the nature and function of types of violence in society. As a pilot study, we used expert raters (some naive to the hypotheses) to analyze a number of real-life bare-knuckle competitions in terms of the support said spectacles offered to theories of this sort of violence as reinforcing ideas of antisociality, hierarchical promotion, intersexual signaling, or maintenance of within-group equality. We found good evidence to support theories of within-group, prosocial hierarchical functions for these contests. Limitations and implications for future research, such as direct measurement of fitness, are discussed.

Background: Free asparagine is the precursor for acrylamide formation during cooking and processing of grains, tubers, beans and other crop products. In wheat grain, free asparagine, free glutamine and total free amino acids accumulate to high levels in response to sulphur deficiency. In this study, RNA-seq data were acquired for the embryo and endosperm of two genotypes of bread wheat, Spark and SR3, growing under conditions of sulphur sufficiency and deficiency, and sampled at 14 and 21 days post anthesis (dpa). The aim was to provide new knowledge and understanding of the genetic control of asparagine accumulation and breakdown in wheat grain., Results: There were clear differences in gene expression patterns between the genotypes. Sulphur responses were greater at 21 dpa than 14 dpa, and more evident in SR3 than Spark. TaASN2 was the most highly expressed asparagine synthetase gene in the grain, with expression in the embryo much higher than in the endosperm, and higher in Spark than SR3 during early development. There was a trend for genes encoding enzymes of nitrogen assimilation to be more highly expressed in Spark than SR3 when sulphur was supplied. TaASN2 expression in the embryo of SR3 increased in response to sulphur deficiency at 21 dpa, although this was not observed in Spark. This increase in TaASN2 expression was accompanied by an increase in glutamine synthetase gene expression and a decrease in asparaginase gene expression. Asparagine synthetase and asparaginase gene expression in the endosperm responded in the opposite way. Genes encoding regulatory protein kinases, SnRK1 and GCN2, both implicated in regulating asparagine synthetase gene expression, also responded to sulphur deficiency. Genes encoding bZIP transcription factors, including Opaque2/bZIP9, SPA/bZIP25 and BLZ1/OHP1/bZIP63, all of which contain SnRK1 target sites, were also expressed. Homeologues of many genes showed differential expression patterns and responses, including TaASN2., Conclusions: Data on the genetic control of free asparagine accumulation in wheat grain and its response to sulphur supply showed grain asparagine levels to be determined in the embryo, and identified genes encoding signalling and metabolic proteins involved in asparagine metabolism that respond to sulphur availability.

Background: Ablative lesions are current treatments for epilepsy and brain tumors. Interstitial magnetic resonance (MR) guided focused ultrasound (iMRgFUS) may be an alternate ablation technique which limits thermal tissue charring as compared to laser therapy (LITT) and can produce larger ablation patterns nearer the surface than transcranial MR guided focused ultrasound (tcMRgFUS)., Objective: To describe our experience with interstitial focused ultrasound (iFUS) ablations in swine, using MR-guided robotically assisted (MRgRA) delivery., Methods: In an initial 3 animals, we optimized the workflow of the robot in the MR suite and made modifications to the robotic arm to allow range of motion. Then, 6 farm pigs (4 acute, 2 survival) underwent 7 iMRgFUS ablations using MRgRA. We altered dosing to explore differences between thermal dosing in brain as compared to other tissues. Imaging was compared to gross examination., Results: Our work culminated in adjustments to the MRgRA, iMRgFUS probes, and dosing, culminating in 2 survival surgeries; swine had ablations with no neurological sequelae at 2 wk postprocedure. Immediately following iMRgFUS therapy, diffusion-weighted imaging, and T1 weighted MR were accurate reflections of the ablation volume. T2 and fluid-attenuated inversion-recovery (FLAIR) images were accurate reflections of ablation volume 1-wk postprocedure., Conclusion: We successfully performed MRgRA iFUS ablation in swine and found intraoperative and postoperative imaging to correlate with histological examination. These data are useful to validate our system and to guide imaging follow-up for thermal ablation lesions in brain tissue from our therapy, tcMRgFUS, and LITT., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Host-associated bacterial communities have received limited attention in polar habitats, but are likely to represent distinct nutrient-rich niches compared to the surrounding environment. Antarctic krill ( Euphausia superba ) are a super-abundant species with a circumpolar distribution, and the krill microbiome may make a substantial contribution to marine bacterial diversity in the Southern Ocean. We used high-throughput sequencing of the bacterial 16S ribosomal RNA gene to characterize bacterial diversity in seawater and krill tissue samples from four locations south of the Kerguelen Plateau, one of the most productive regions in the Indian Sector of the Southern Ocean. Krill-associated bacterial communities were distinct from those of the surrounding seawater, with different communities inhabiting the moults, digestive tract and faecal pellets, including several phyla not detected in the surrounding seawater. Digestive tissues from many individuals contained a potential gut symbiont (order: Mycoplasmoidales) shown to improve survival on a low quality diet in other crustaceans. Antarctic krill swarms thus influence Southern Ocean microbial communities not only through top-down grazing of eukaryotic cells and release of nutrients into the water column, but also by transporting distinct microbial assemblages horizontally via migration and vertically via sinking faecal pellets and moulted exuviae. Changes to Antarctic krill demographics or distribution through fishing pressure or climate-induced range shifts will also influence the composition and dispersal of Southern Ocean microbial communities.

Background: Hospital-related factors associated with mortality and morbidity after hip fracture surgery are not completely understood. The Veterans Health Administration (VHA) is the largest single-payer, networked healthcare system in the country serving a relatively homogenous patient population with facilities that vary in size and resource availability. These characteristics provide some degree of financial and patient-level controls to explore the association, if any, between surgical volume and facility resource availability and hospital performance regarding postoperative complications after hip fracture surgery., Questions/purposes: (1) Do VHA facilities with the highest complexity level designation (Level 1a) have a disproportionate number of better-than-expected performance outliers for major postoperative complications compared with lower-complexity level facilities? (2) Do VHA facilities with higher hip fracture surgical volume have a disproportionate number of better-than-expected performance outliers for major postoperative complications compared with lower-volume facilities?, Methods: We explored the Veterans Affairs Surgical Quality Improvement Project (VASQIP) database from October 2001 to September 2012 for records of hip fracture surgery performed. Data reliability of the VASQIP database has been previously validated. We excluded nine of the 98 VHA facilities for contributing fewer than 30 records. The remaining 89 VHA facilities provided 23,029 records. The VHA designates a complexity level to each facility based on multiple criteria. We labeled facilities with a complexity Level 1a (38 facilities)-the highest achievable VHA designated complexity level-as high complexity; we labeled all other complexity level designations as low complexity (51 facilities). Facility volume was divided into tertiles: high (> 277 hip fracture procedures during the sampling frame), medium (204 to 277 procedures), and low (< 204 procedures). The patient population treated by low-complexity facilities was older, had a higher prevalence of severe chronic obstructive pulmonary disease (26% versus 22%, p < 0.001), and had a higher percentage of patients having surgery within 2 days of hospital admission (83% versus 76%, p < 0.001). High-complexity facilities treated more patients with recent congestive heart failure exacerbation (4% versus 3%, p < 0.001). We defined major postoperative complications as having at least one of the following: death within 30 days of surgery, cardiac arrest requiring cardiopulmonary resuscitation, new q-wave myocardial infarction, deep vein thrombosis and/or pulmonary embolism, ventilator dependence for at least 48 hours after surgery, reintubation for respiratory or cardiac failure, acute renal failure requiring renal replacement therapy, progressive renal insufficiency with a rise in serum creatinine of at least 2 mg/dL from preoperative value, pneumonia, or surgical site infection. We used the observed-to-expected ratio (O/E ratio)-a risk-adjusted metric to classify facility performance-for major postoperative complications to assess the performance of VHA facilities. Outlier facilities with 95% confidence intervals (95% CI) for O/E ratio completely less than 1.0 were labeled "exceed expectation;" those that were completely greater than 1.0 were labeled "below expectation." We compared differences in the distribution of outlier facilities between high and low-complexity facilities, and between high-, medium-, and low-volume facilities using Fisher's exact test., Results: We observed no association between facility complexity level and the distribution of outlier facilities (high-complexity: 5% exceeded expectation, 5% below expectation; low-complexity: 8% exceeded expectation, 2% below expectation; p = 0.742). Compared with high-complexity facilities, the adjusted odds ratio for major postoperative complications for low-complexity facilities was 0.85 (95% CI, 0.67-1.09; p = 0.108).We observed no association between facility volume and the distribution of outlier facilities: 3% exceeded expectation and 3% below expectation for high-volume; 10% exceeded expectation and 3% below expectation for medium-volume; and 7% exceeded expectation and 3% below expectation for low-volume; p = 0.890). The adjusted odds ratios for major postoperative complications were 0.87 (95% CI, 0.73-1.05) for low- versus high-volume facilities and 0.89 (95% CI, 0.79-1.02] for medium- versus high-volume facilities (p = 0.155)., Conclusions: These results do not support restricting facilities from treating hip fracture patients based on historical surgical volume or facility resource availability. Identification of consistent performance outliers may help health care organizations with multiple facilities determine allocation of services and identify characteristics and processes that determine outlier status in the interest of continued quality improvement., Level of Evidence: Level III, therapeutic study.

Antarctic krill ( Euphausia superba ), a key species in the Southern Ocean, reduce their metabolism as an energy saving mechanism in response to the harsh environmental conditions during the Antarctic winter. Although the adaptive significance of this seasonal metabolic shift seems obvious, the driving factors are still unclear. In particular, it is debated whether the seasonal metabolic cycle is driven by changes in food availability, or if an endogenous timing system entrained by photoperiod might be involved. In this study, we used different long-term photoperiodic simulations to examine the influence of light regime and endogenous rhythmicity on the regulation of krill seasonal metabolic cycle. Krill showed a seasonal cycle of growth characterized by null-to-negative growth rates during autumn-winter and positive growth rates during spring-summer, which was manifested also in constant darkness, indicating strong endogenous regulation. Similar endogenous cycles were observed for the activity of the key-metabolic enzyme malate dehydrogenase (MDH) and for the expression levels of a selection of metabolic-related genes, with higher values in spring-summer and lower values in autumn-winter. On the other side, a seasonal cycle of oxygen consumption was observed only when krill were exposed to simulated seasonal changes in photoperiod, indicating that light-related cues might play a major role in the regulation of krill oxygen consumption. The influence of light-regime on oxygen consumption was minimal during winter, when light-phase duration was below 8 h, and it was maximal during summer, when light-phase duration was above 16 h. Significant upregulation of the krill clock genes clk , cry 2, and tim 1, as well as of the circadian-related opsins rh 1a and rrh , was observed after light-phase duration had started to decrease in early autumn, suggesting the presence of a signaling cascade linking specific seasonal changes in the Antarctic light regime with clock gene activity and the regulation of krill metabolic dormancy over the winter.

Objective: This study aimed to provide preliminary evidence of the usefulness of emotion-focused therapy (EFT) for binge-eating disorder (BED)., Methods: We used a single-subject design in which 12 weeks of individual EFT were applied nonconcurrently to six female adult participants with BED, following three weekly baseline sessions. Participants were assessed for binge-eating psychopathology and emotion regulation difficulties on a weekly basis during baseline and treatment. They were assessed on a 2-, 4-, and 8-week basis during posttreatment, and they were assessed for binge-eating episodes, eating disorder attitudes, alexithymia, and psychiatric comorbidity at pretreatment and posttreatment., Results: All cases experienced reliable recovery from binge-eating psychopathology and a significant decrease in binge-eating frequency. For all cases, there was reliable improvement or recovery on eating and shape concerns, and there was improvement on weight concern for the majority of cases. For all cases, reliable recovery or improvement occurred in overall emotion regulation. Most cases that were in the clinical range pretreatment recovered for anxiety, and reliable improvement in or recovery from depression occurred for all cases. There was reliable recovery or improvement in alexithymia for half of the cases; however, the other half experienced no change or deteriorated. There were no treatment dropouts., Conclusion: Individual EFT demonstrates potential as a psychological treatment for BED. The current study provides preliminary evidence to guide the development of a more extensive trial to test the efficacy of individual EFT for BED as well as to identify possible mechanisms of change., (© 2018 John Wiley & Sons, Ltd.)

The Multidimensional State Boredom Scale (MSBS) is a promising new self-report measure of state boredom. Two condensed versions of the scale have also been introduced. This study helped explore the psychometric qualities of these scales, using a large sample of Australian adults ( N = 1,716), as well as two smaller samples ( N = 199 and N = 422). Data analyses indicated strong convergent validity and very high internal consistency for the scales. Test-retest reliability over a 6- to 8-day period was moderately high. Confirmatory factor analyses of the MSBS authors' suggested factor structure indicated good fit for this model. However, some of the data analyses raise questions as to whether the scale includes meaningful subfactors. Overall, the MSBS (and Short Form) is recommended for researchers who wish to assess state boredom.

In the field of hernia surgery, there have been many advances in techniques that have provided the surgeon with a variety of options to repair the difficult abdominal wall hernia. Regardless of the technique, the ultimate goal was to provide a tension-free repair, which attempts to approximate the midline while returning abdominal wall musculature to its normal anatomic position, thus providing the patient with both a cosmetic and durable result with or without the use of a prosthetic reinforcement. Component separation techniques have been widely popularized as techniques to repair complex hernias and are frequently categorized based upon the anatomic location of the myofascial release. CSTs are generally categorized as either an anterior component separation or posterior component separation based upon the surgical approach to the abdominal wall musculature. This report objectively outlines the various techniques of component separation and specifically compares the outcomes among techniques to facilitate decision making in abdominal wall reconstruction.

Fusarium culmorum is a fungal pathogen causing economically important diseases on a variety of crops. Fungicides can be applied to control this species with triazoles being the most efficient molecules. F. culmorum strains resistant to these molecules have been reported, but the underlying resistance mechanisms remain unknown. In this study, a tebuconazole-adapted F. culmorum strain was developed with a level of fitness similar to its parental strain. The adapted strain showed cross-resistance to all demethylation inhibitors (DMIs), but not to other classes of fungicides tested. RNA-Seq analysis revealed high transcriptomic differences between the resistant strain and its parental strain after tebuconazole treatment. Among these changes, Fc ABC1 (FCUL&#95;06717), a pleiotropic drug resistance transporter, had a 30-fold higher expression level upon tebuconazole treatment in the adapted strains as compared to the wild-type strain. The implication of this transporter in triazole resistance was subsequently confirmed in field strains harboring distinct levels of sensitivity to triazoles. FcABC1 is present in other species/genera, including F. graminearum in which it is known to be necessary for azole resistance. No difference in FcABC1 sequences, including the surrounding regions, were found when comparing the resistant strain to the wild-type strain. Fusarium culmorum is therefore capable to adapt to triazole pressure by overexpressing a drug resistance transporter when submitted to triazoles and the same mechanism is anticipated to occur in other species.

Radiation is a well-known cause of the development of cataracts. For children with brain tumors, craniospinal irradiation (CSI) would be expected to result in a significant risk of cataract development. We reviewed the incidence of cataracts in children with brain tumors who received CSI at our institution. Of 45 children who received CSI and had ophthalmologic examinations, 13 developed cataracts. The median time to develop cataracts was 27.6 months. Seven children underwent surgery for cataract. Given this high incidence of cataracts, we suggest routine eye examinations for all children receiving CSI.

Background: The soil dwelling saprotrophic non-pathogenic fungus Fusarium venenatum, routinely used in the commercial fermentation industry, is phylogenetically closely related to the globally important cereal and non-cereal infecting pathogen F. graminearum. This study aimed to sequence, assemble and annotate the F. venenatum (strain A3/5) genome, and compare this genome with F. graminearum., Results: Using shotgun sequencing, a 38,660,329 bp F. venenatum genome was assembled into four chromosomes, and a 78,618 bp mitochondrial genome. In comparison to F. graminearum, the predicted gene count of 13,946 was slightly lower. The F. venenatum centromeres were found to be 25% smaller compared to F. graminearum. Chromosome length was 2.8% greater in F. venenatum, primarily due to an increased abundance of repetitive elements and transposons, but not transposon diversity. On chromosome 3 a major sequence rearrangement was found, but its overall gene content was relatively unchanged. Unlike homothallic F. graminearum, heterothallic F. venenatum possessed the MAT1-1 type locus, but lacked the MAT1-2 locus. The F. venenatum genome has the type A trichothecene mycotoxin TRI5 cluster, whereas F. graminearum has type B. From the F. venenatum gene set, 786 predicted proteins were species-specific versus NCBI. The annotated F. venenatum genome was predicted to possess more genes coding for hydrolytic enzymes and species-specific genes involved in the breakdown of polysaccharides than F. graminearum. Comparison of the two genomes reduced the previously defined F. graminearum-specific gene set from 741 to 692 genes. A comparison of the F. graminearum versus F. venenatum proteomes identified 15 putative secondary metabolite gene clusters (SMC), 109 secreted proteins and 38 candidate effectors not found in F. venenatum. Five of the 15 F. graminearum-specific SMCs that were either absent or highly divergent in the F. venenatum genome showed increased in planta expression. In addition, two predicted F. graminearum transcription factors previously shown to be required for fungal virulence on wheat plants were absent or exhibited high sequence divergence., Conclusions: This study identifies differences between the F. venenatum and F. graminearum genomes that may contribute to contrasting lifestyles, and highlights the repertoire of F. graminearum-specific candidate genes and SMCs potentially required for pathogenesis.

Microplastics (plastics <5 mm diameter) are at the forefront of current environmental pollution research, however, little is known about the degradation of microplastics through ingestion. Here, by exposing Antarctic krill (Euphausia superba) to microplastics under acute static renewal conditions, we present evidence of physical size alteration of microplastics ingested by a planktonic crustacean. Ingested microplastics (31.5 µm) are fragmented into pieces less than 1 µm in diameter. Previous feeding studies have shown spherical microplastics either; pass unaffected through an organism and are excreted, or are sufficiently small for translocation to occur. We identify a new pathway; microplastics are fragmented into sizes small enough to cross physical barriers, or are egested as a mixture of triturated particles. These findings suggest that current laboratory-based feeding studies may be oversimplifying interactions between zooplankton and microplastics but also introduces a new role of Antarctic krill, and potentially other species, in the biogeochemical cycling and fate of plastic.

Decades-long research efforts have shown that Heart Failure (HF) is the most expensive diagnosis for hospitalizations and the most frequent diagnosis for 30-day readmissions. If risk stratification for readmission of HF patients could be carried out at the time of discharge from the index hospitalization, corresponding appropriate post-discharge interventions could be arranged to avoid potential readmission. We, therefore, sought to explore and compare two newer machine learning methods of risk prediction using 56 predictors from electronic health records data of 1778 unique HF patients from 31 hospitals across the United States. We used two approaches boosted trees and spike-and-slab regression for analysis and found that boosted trees provided better predictive results (AUC: 0.719) as compared to spike-and-slab regression (AUC: 0.621) in our dataset.

Objective: To determine the association between cardiorespiratory fitness (CRF) and annual health care costs in Veterans., Patients and Methods: The sample included 9942 subjects (mean age, 59±11 years) undergoing a maximal exercise test for clinical reasons between January 2005 and December 2012. Cardiorespiratory fitness, expressed as a percentage of age-predicted peak metabolic equivalents (METs) achieved, was categorized in quartiles. Total and annualized health care costs, derived from the Veterans Administration Allocated Resource Center, were compared using multiple regression, controlling for demographic and clinical characteristics., Results: A gradient for reduced health care costs was observed as CRF increased, with subjects in the least-fit quartile having approximately $14,662 (P<.001) higher overall costs per patient per year compared with those in the fittest quartile, after controlling for potential confounding variables. Each 1-MET higher increment in fitness was associated with a $1592 annual reduction in health care costs (5.6% lower cost per MET), and each higher quartile of fitness was associated with a $4163 annual cost reduction per patient. The effect of CRF was more pronounced among subjects without cardiovascular disease (CVD), suggesting that the results were not driven by the possibility that less-fit individuals had greater CVD. Cost savings attributable to higher fitness were greatest in overweight and obese subjects, with lower savings observed among those individuals with a body mass index less than 25 kg/m 2 . In a model including historical, clinical, and exercise test responses, heart failure was the strongest predictor of health care costs, followed by CRF (P<.01)., Conclusion: Low CRF is associated with higher health care costs. Efforts to improve CRF may not only improve health but also result in lower health care costs., (Published by Elsevier Inc.)

Background: Few longitudinal studies have investigated the functional outcomes of individuals with recent-onset psychotic illness in low- and middle-income countries., Aims: To investigate short-term functional remission and its predictors in a central Vietnamese sample., Methods: A naturalistic 6-month prospective cohort study recruited 79 patients of public health facilities who had experienced a first episode of schizophrenia or related illness in the past 18 months. Individuals and their family members were interviewed using standardised assessments of community functioning, symptoms, treatment, demographics and various psychosocial variables. Rates of functional remission (i.e. no or minimal impairment) were calculated based on rigorous, culturally appropriate criteria. Generalised estimating equations were used to explore predictors of remission., Results: Rates of global functional remission were 28% at baseline and 53% at follow-up. In individual functional domains, remission was least common for occupational activities, intermediate for relationships and relatively common for daily living activities. Global functional remission was significantly associated with absence of negative and cognitive symptoms, average or better household economic status and unimpaired premorbid functioning., Conclusion: Remission rates appeared similar to those seen in many international intervention studies. However, individuals from poor households had markedly unfavourable outcomes, suggesting the need for community-based interventions targeting low-socioeconomic status (SES) groups.

Pathogenic fungi must extend filamentous hyphae across solid surfaces to cause diseases of plants. However, the full inventory of genes which support this is incomplete and many may be currently concealed due to their essentiality for the hyphal growth form. During a random T-DNA mutagenesis screen performed on the pleomorphic wheat (Triticum aestivum) pathogen Zymoseptoria tritici, we acquired a mutant unable to extend hyphae specifically when on solid surfaces. In contrast "yeast-like" growth, and all other growth forms, were unaffected. The inability to extend surface hyphae resulted in a complete loss of virulence on plants. The affected gene encoded a predicted type 2 glycosyltransferase (ZtGT2). Analysis of >800 genomes from taxonomically diverse fungi highlighted a generally widespread, but discontinuous, distribution of ZtGT2 orthologues, and a complete absence of any similar proteins in non-filamentous ascomycete yeasts. Deletion mutants of the ZtGT2 orthologue in the taxonomically un-related fungus Fusarium graminearum were also severely impaired in hyphal growth and non-pathogenic on wheat ears. ZtGT2 expression increased during filamentous growth and electron microscopy on deletion mutants (ΔZtGT2) suggested the protein functions to maintain the outermost surface of the fungal cell wall. Despite this, adhesion to leaf surfaces was unaffected in ΔZtGT2 mutants and global RNAseq-based gene expression profiling highlighted that surface-sensing and protein secretion was also largely unaffected. However, ΔZtGT2 mutants constitutively overexpressed several transmembrane and secreted proteins, including an important LysM-domain chitin-binding virulence effector, Zt3LysM. ZtGT2 likely functions in the synthesis of a currently unknown, potentially minor but widespread, extracellular or outer cell wall polysaccharide which plays a key role in facilitating many interactions between plants and fungi by enabling hyphal growth on solid matrices.

For select total knee arthroplasty (TKA) patients, we have established an alternative pathway to bypass the acute care surgical ward and directly admit patients from the post-anesthesia care unit to on-campus rehabilitation. We retrospectively examined whether this 'fast track' pathway decreased costs and improved patient outcomes. After reviewing records of consecutive primary unilateral TKA patients over a 15-month period, each patient admitted to rehabilitation was matched with a control admitted to the acute care ward. The primary outcome was estimated total hospitalization cost (length of stay in days multiplied by the average cost per day). Secondary outcomes were length of stay, in-hospital pain scores, opioid use, maximum ambulatory distance and 30-day readmission, morbidity, and mortality. Of the 262 TKA patients during the study period, 14 were admitted to rehabilitation and were matched to 14 patients admitted to acute care. Estimated total hospitalization cost [median (10th-90th percentiles)] was US$30,755 (US$23,066-38,444) for ward patients compared to US$17,620 (US$13,215-33,918) for rehabilitation patients (P = 0.006). This difference [mean (95% CI)] was US$10,143 (US$2174-18,112). There were no other differences. For facilities similar to ours, direct postoperative admission of select TKA patients to subacute rehabilitation may be less costly than acute care and may not negatively affect outcomes.

Pneumatosis intestinalis is a radiographic finding that represents a spectrum of conditions ranging from benign disease to abdominal sepsis and death. Along with portal venous gas, it is generally considered an ominous sign prompting emergency operative intervention. We report a rare case showing that nonoperative therapy can be considered in a seriously ill patient with esophageal, gastric and portal venous air.

This study investigated the relationship between two therapist attributes (reflective functioning and attachment style) and client outcome. Twenty-five therapists treated a total of 1001 clients. Therapists were assessed for reflective functioning and attachment style using the Adult Attachment Interview and the Experiences in Close Relationships Scale. Clinical outcome was measured using the Outcome Questionnaire (OQ-45). Data were analysed using hierarchical linear modelling. Results indicated that therapist reflective functioning predicted therapist effectiveness, whereas attachment style did not. However, there was evidence of an interaction between therapist attachment style and therapist reflective functioning. Secure attachment compensated somewhat for low reflective functioning and high reflective functioning compensated for insecure attachment. Possible implications for the selection of therapy training candidates and therapist training are discussed.

Amino acid transporters have roles in amino acid uptake from soil, long-distance transport, remobilization from vegetative tissues and accumulation in grain. Critically, the majority of wheat grain nitrogen is derived from amino acids remobilized from vegetative organs. However, no systematic analysis of wheat AAT genes has been reported to date. Here, 283 full length wheat AAT genes representing 100 distinct groups of homeologs were identified and curated by selectively consolidating IWGSC CSSv2 and TGACv1 Triticum aestivum genome assemblies and reassembling or mapping of IWGSC CSS chromosome sorted reads to fill any gaps. Gene expression profiling was performed using public RNA-seq data from root, leaf, stem, spike, grain and grain cells (transfer cell (TC), aleurone cell (AL), and starchy endosperm (SE)). AATs highly expressed in roots are good candidates for amino acid uptake from soil whilst AATs highly expressed in senescing leaves and stems may be involved in translocation to grain. AATs in TC (TaAAP2 and TaAAP19) and SE (TaAAP13) may play important roles in determining grain protein content and grain yield. The expression levels of AAT homeologs showed unequal contributions in response to abiotic stresses and development, which may aid wheat adaptation to a wide range of environments.

Objective: Bipolar disorder is associated with high risk for suicidal behavior that often develops in adolescence and young adulthood. Elucidation of involved neural systems is critical for prevention. This study of adolescents and young adults with bipolar disorder with and without a history of suicide attempts combines structural, diffusion tensor, and functional MR imaging methods to investigate implicated abnormalities in the morphology and structural and functional connectivity within frontolimbic systems., Method: The study had 26 participants with bipolar disorder who had a prior suicide attempt (the attempter group) and 42 participants with bipolar disorder without a suicide attempt (the nonattempter group). Regional gray matter volume, white matter integrity, and functional connectivity during processing of emotional stimuli were compared between groups, and differences were explored for relationships between imaging modalities and associations with suicide-related symptoms and behaviors., Results: Compared with the nonattempter group, the attempter group showed significant reductions in gray matter volume in the orbitofrontal cortex, hippocampus, and cerebellum; white matter integrity in the uncinate fasciculus, ventral frontal, and right cerebellum regions; and amygdala functional connectivity to the left ventral and right rostral prefrontal cortex. In exploratory analyses, among attempters, there was a significant negative correlation between right rostral prefrontal connectivity and suicidal ideation and between left ventral prefrontal connectivity and attempt lethality., Conclusions: Adolescent and young adult suicide attempters with bipolar disorder demonstrate less gray matter volume and decreased structural and functional connectivity in a ventral frontolimbic neural system subserving emotion regulation. Among attempters, reductions in amygdala-prefrontal functional connectivity may be associated with severity of suicidal ideation and attempt lethality.

Objective: Tourette's disorder (TD) and autism spectrum disorder (ASD) share clinical features and possibly an overlapping etiology. The aims of this study were to examine ASD symptom rates in participants with TD, and to characterize the relationships between ASD symptom patterns and TD, obsessive-compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD)., Method: Participants with TD (n = 535) and their family members (n =234) recruited for genetic studies reported TD, OCD, and ADHD symptoms and completed the Social Responsiveness Scale Second Edition (SRS), which was used to characterize ASD symptoms., Results: SRS scores in participants with TD were similar to those observed in other clinical samples but lower than in ASD samples (mean SRS total raw score = 51; SD = 32.4). More children with TD met cut-off criteria for ASD (22.8%) than adults with TD (8.7%). The elevated rate in children was primarily due to high scores on the SRS Repetitive and Restricted Behaviors (RRB) subscale. Total SRS scores were correlated with TD (r = 0.27), OCD (r = 0.37), and ADHD (r = 0.44) and were higher among individuals with OCD symptom-based phenotypes than for those with tics alone., Conclusion: Higher observed rates of ASD among children affected by TD may in part be due to difficulty in discriminating complex tics and OCD symptoms from ASD symptoms. Careful examination of ASD-specific symptom patterns (social communication vs. repetitive behaviors) is essential. Independent of ASD, the SRS may be a useful tool for identifying patients with TD with impairments in social communication that potentially place them at risk for bullying and other negative sequelae., (Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Phenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts., Method: Assessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals. Classes were characterized by comorbidity rates and proportion of parents included. Heritability and polygenic load associated with Tourette syndrome, OCD, and ADHD were estimated., Results: The authors identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia, and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high and statistically significant (disinhibition factor=0.35, SE=0.03; symmetry factor=0.39, SE=0.03; symmetry class=0.38, SE=0.10). Mothers of Tourette syndrome probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a Tourette syndrome genome-wide association study (GWAS) were significantly associated with symmetry, while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were significantly associated with disinhibition, while Tourette syndrome and ADHD risk scores were not., Conclusions: The analyses identified two heritable endophenotypes related to Tourette syndrome that cross traditional diagnostic boundaries. The symmetry phenotype correlated with Tourette syndrome polygenic load and was present in otherwise Tourette-unaffected mothers, suggesting that this phenotype may reflect additional Tourette syndrome (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses.

Fusarium graminearum floral infections are a major risk to the global supply of safe cereal grains. We report updates to the PH-1 reference genome and significant improvements to the annotation. Changes include introduction of legacy annotation identifiers, new gene models, secretome and effectorP predictions, and inclusion of extensive untranslated region (UTR) annotations., (Copyright © 2017 King et al.)