Early-life gut bacterial community structure predicts disease risk and athletic performance in horses bred for racing.

Gut bacterial communities have a profound influence on the health of humans and animals. Early-life gut microbial community structure influences the development of immunological competence and susceptibility to disease. For the Thoroughbred racehorse, the significance of early-life microbial colonisation events on subsequent health and athletic performance is unknown. Here we present data from a three-year cohort study of horses bred for racing designed to explore interactions between early-life gut bacterial community structure, health events in later life and athletic performance on the racetrack. Our data show that gut bacterial community structure in the first months of life predicts the risk of specific diseases and athletic performance up to three years old. Foals with lower faecal bacterial diversity at one month old had a significantly increased risk of respiratory disease in later life which was also associated with higher relative abundance of faecal Pseudomonadaceae. Surprisingly, athletic performance up to three years old, measured by three different metrics, was positively associated with higher faecal bacterial diversity at one month old and with the relative abundance of specific bacterial families. We also present data on the impact of antibiotic exposure of foals during the first month of life. This resulted in significantly lower faecal bacterial diversity at 28 days old, a significantly increased risk of respiratory disease in later life and a significant reduction in average prize money earnings, a proxy for athletic performance. Our study reveals associations between early-life bacterial community profiles and health events in later life and it provides evidence of the detrimental impact of antimicrobial treatment in the first month of life on health and performance outcomes in later life. For the first time, this study demonstrates a relationship between early-life gut bacterial communities and subsequent athletic performance that has implications for athletes of all species including humans.

Simulation of a scintillator-based fast ion loss detector for steady-state operation in Wendelstein 7-X (invited).

A quantitative theoretical framework has been created to model neutral beam injection and fast ion losses in the Wendelstein 7-X (W7-X) stellarator, including a novel method to develop synthetic diagnostics for fast ion loss detectors (FILDs) of many types, such as scintillating and Faraday Cup FILDs. This is the first time that this has been done in stellarator geometry with this level of fidelity, providing a way for fast ion losses to be predicted more precisely in future stellarator experiments and in W7-X. Simulations of the signal seen by a Faraday Cup FILD have been completed for multiple W7-X plasmas and show close agreement with the measured signals. This method is now applied to an actively water-cooled, scintillator-based FILD, which is currently in development to measure the fast ion loss distribution in W7-X in greater detail. The design makes use of a double slit to measure energy-and-pitch-angle-resolved losses of both co-going and counter-going fast ions. The diagnostic, which can be inserted to different radial positions, has been designed to withstand steady-state heat fluxes of up to 120 kW/m2 along with additional transient heat loads of 100 kW/m2 lasting for up to 20 s at a time. Simulations of W7-X standard magnetic configuration show up to 8 × 1013 (s-1 cm-2) ion fluxes onto the sensor from each neutral beam source and no signal from the counter-going slit. These simulations will help inform experimental proposals for future W7-X campaigns after installation of this diagnostic.

Outcomes of posterior sheath supplementation with Vicryl mesh in TAR-a single-center study.

INTRODUCTION: In the Transversus Abdominis Release (TAR) procedure, ideally, the posterior sheath is completely reapproximated to establish an interface isolating the polypropylene mesh from visceral contents. When primary closure of the posterior sheath is unachievable, Vicryl mesh is commonly used to supplement the posterior sheath closure and an uncoated polypropylene mesh is placed superficial to the Vicryl mesh. The long-term implications of utilizing Vicryl mesh as an antiadhesive barrier are poorly understood. In this study, we aimed to assess our outcomes when utilizing Vicryl mesh to supplement the posterior sheath defects when placed underneath polypropylene mesh in patients undergoing posterior component separation. METHODS: Adult patients who underwent VHR with concurrent TAR procedure with a permanent synthetic mesh and posterior sheath supplementation with Vicryl mesh in the Cleveland Clinic Center for Abdominal Core Health between January 2014 and December 2022 were queried retrospectively from a prospectively collected database in the Abdominal Core Health Quality Collaborative. We evaluated 30-day wound morbidity, perioperative complications, long-term mesh-related complications, and pragmatic hernia recurrence. RESULTS: 53 patients who underwent TAR procedure with posterior sheath supplementation using Vicryl mesh and had a minimum 12-month follow-up were identified. Of the 53 patients, 94.3% presented with recurrent hernias, 73.6% had a midline hernia, 7.5% had a flank hernia, and 18.9% had concurrent parastomal hernia. The mean hernia width was 24.9 cm (± 8.8 cm). No Vicryl mesh-related operative complications were identified in our study, with no instances of mesh erosion, fistulas, or interventions for small bowel obstruction. Skin necrosis requiring reoperations was observed in three patients (5.7%), leading to permanent mesh excision in two cases (3.8%) without intraabdominal visceral involvement. Throughout the 12-month follow-up, 23 incidences (43.4%) of surgical site occurrences (SSOs) and surgical site occurrences requiring procedural intervention (SSOPI) were documented. CONCLUSIONS: Our findings suggest that posterior sheath supplementation with Vicryl mesh is a feasible approach to achieve posterior sheath closure in challenging abdominal wall reconstruction cases. Given the absence of notable mesh-related complications and a similar hernia recurrence rate to cases without posterior sheath supplementation, Vicryl mesh can be used to safely achieve posterior sheath closure in complex reconstructions with insufficient native tissue.

Parastomal hernia repair, trying to optimize the impossible reconstruction.

PURPOSE: Parastomal hernias are a common and challenging problem with high rates of wound complications and hernia recurrence after repair. We present our approach to optimizing parastomal hernia repair through preoperative preparation, surgical approach, and postoperative management. METHODS: Patients are carefully evaluated and optimized prior to surgery. Our typical surgical approach involves a generous midline laparotomy and retrorectus dissection followed by a posterior component separation with transversus abdominis release. We typically utilize a Sugarbaker technique for retromuscular mesh placement but also use the retromuscular keyhole or cruciate technique if there is insufficient bowel length. RESULTS: Previously published results from our institution include wound complication rates of up to 16% after open retromuscular parastomal hernia repair. Stoma-specific complications, such as mesh erosion in the bowel, may be attributed to the mesh placement techniques. Hernia recurrence rates range from 11 to 30% up to 2 years postoperatively. CONCLUSION: We prefer an open retromuscular approach with a Sugarbaker mesh configuration to treat complex parastomal hernias. However, wound morbidity and repair failure rates remain high, and additional research is needed to optimize surgical outcomes.

Diversity and Evolution of Frog Visual Opsins: Spectral Tuning and Adaptation to Distinct Light Environments.

Visual systems adapt to different light environments through several avenues including optical changes to the eye and neurological changes in how light signals are processed and interpreted. Spectral sensitivity can evolve via changes to visual pigments housed in the retinal photoreceptors through gene duplication and loss, differential and coexpression, and sequence evolution. Frogs provide an excellent, yet understudied, system for visual evolution research due to their diversity of ecologies (including biphasic aquatic-terrestrial life cycles) that we hypothesize imposed different selective pressures leading to adaptive evolution of the visual system, notably the opsins that encode the protein component of the visual pigments responsible for the first step in visual perception. Here, we analyze the diversity and evolution of visual opsin genes from 93 new eye transcriptomes plus published data for a combined dataset spanning 122 frog species and 34 families. We find that most species express the four visual opsins previously identified in frogs but show evidence for gene loss in two lineages. Further, we present evidence of positive selection in three opsins and shifts in selective pressures associated with differences in habitat and life history, but not activity pattern. We identify substantial novel variation in the visual opsins and, using microspectrophotometry, find highly variable spectral sensitivities, expanding known ranges for all frog visual pigments. Mutations at spectral-tuning sites only partially account for this variation, suggesting that frogs have used tuning pathways that are unique among vertebrates. These results support the hypothesis of adaptive evolution in photoreceptor physiology across the frog tree of life in response to varying environmental and ecological factors and further our growing understanding of vertebrate visual evolution.

Can surgeons accurately identify mesh type when interpreting computed tomography scans after ventral hernia repair?

BACKGROUND: Recurrent ventral hernia repair can be challenging due to scarred tissue planes and the increasing complexity of disease related to multiple recurrences. Given the challenges of acquiring complete and accurate prior operative reports, surgeons often rely on computed tomography (CT) scans to obtain information and plan for re-operation. Still, the contribution of CT scans and the ability of surgeons to interpret them is controversial. Previously, we examined the ability of surgeons to determine prior operative techniques based on CT scans. Here, we assessed the accuracy of expert abdominal wall reconstruction (AWR) surgeons in identifying the type of prior mesh using CT imaging. METHODS: A total of 22 highly experienced AWR surgeons were asked to evaluate 21 CT scans of patients who had undergone open ventral hernia repair with bilateral transversus abdominis release utilizing mesh. The surgeons were required to identify the mesh type from a multiple-choice selection. Additionally, negative controls (patients without a history of prior laparotomy) and positive controls (patients with laparotomy but no ventral hernia repair) were incorporated. The accuracy of the surgeons and interrater reliability was calculated. RESULTS: The accuracy rate of the surgeons in correctly identifying the mesh type was 46%, with heavy-weight synthetic mesh (HWSM) being identified only 35.4% of the time, Strattice mesh and medium-weight synthetic mesh (MWSM) were identified at 46.3%, and 51.8%, respectively. The interrater reliability analysis found a moderate level of agreement 0.428 (95% CI 0.356-0.503), and the repeatability measure was poor-0.053 (95% CI 0-0.119); this indicates that surgeons cannot reliably replicate the identification process. CONCLUSIONS: Surgeons' ability to accurately identify the type of previous mesh using CT scans is poor. This study underscores the importance of documenting the type of mesh used in the operative report and the need for standardized operative notes to improve the accuracy and consistency of documentation.

Outcomes of complex abdominal wall reconstruction in patients with connective tissue disorders: a single center experience.

INTRODUCTION: Individuals diagnosed with connective tissue disorders (CTD) are known to be predisposed to incisional hernia formation. However, there is a scarcity of data on outcomes for these patients undergoing hernia repair. We sought to describe our outcomes in performing abdominal wall reconstructions in these complex patients. METHODS: Adult patients with CTD undergoing open, elective, posterior component separation with permanent synthetic mesh at our institution from January 2018 to October 2022 were queried from a prospectively collected database in the Abdominal Core Health Quality Collaborative. We evaluated 30-day wound morbidity, perioperative complications, long-term hernia recurrence, and patient-reported quality of life. RESULTS: Twelve patients were identified. Connective tissue disorders included Marfan's n = 7 (58.3%), Loeys-Dietz syndrome n = 2 (16.7%), Systemic Lupus Erythematosus n = 2 (16.7%), and Scleroderma n = 1 (8.3%). Prior incisions included three midline laparotomies and nine thoracoabdominal, mean hernia width measured 14 cm, and 9 were recurrent hernias. Surgical site occurrences (SSOs) were observed in 25% of cases, and 16.7% necessitated procedural intervention. All twelve patients were available for long-term follow-up, with a mean of 34 (12-62) months. There were no instances of reoperation or mesh excision related to the TAR procedure. One patient developed a recurrence after having his mesh violated for repair of a new visceral aneurysm. Mean HerQLes scores at 1 year were 70 and 89 at ≥ 2 years; Mean scaled PROMIS scores were 30.7 at 1 year and 36.3 at ≥ 2 years. CONCLUSION: Ventral hernia repair with TAR is feasible in patients with connective tissue disorder and can be a suitable alternative in patients with large complex hernias.

Individual distribution of muscle hypertrophy among hamstring muscle heads: Adding muscle volume where you need is not so simple.

PURPOSE: The aim of this study was to determine whether a 9-week resistance training program based on high load (HL) versus low load combined with blood flow restriction (LL-BFR) induced a similar (i) distribution of muscle hypertrophy among hamstring heads (semimembranosus, SM; semitendinosus, ST; and biceps femoris long head, BF) and (ii) magnitude of tendon hypertrophy of ST, using a parallel randomized controlled trial. METHODS: A total of 45 participants were randomly allocated to one of three groups: HL, LL-BFR, and control (CON). Both HL and LL-BFR performed a 9-week resistance training program composed of seated leg curl and stiff-leg deadlift exercises. Freehand 3D ultrasound was used to assess the changes in muscle and tendon volume. RESULTS: The increase in ST volume was greater in HL (26.5 ± 25.5%) compared to CON (p = 0.004). No difference was found between CON and LL-BFR for the ST muscle volume (p = 0.627). The change in SM muscle volume was greater for LL-BFR (21.6 ± 27.8%) compared to CON (p = 0.025). No difference was found between HL and CON for the SM muscle volume (p = 0.178).There was no change in BF muscle volume in LL-BFR (14.0 ± 16.5%; p = 0.436) compared to CON group. No difference was found between HL and CON for the BF muscle volume (p = 1.0). Regarding ST tendon volume, we did not report an effect of training regimens (p = 0.411). CONCLUSION: These results provide evidence that the HL program induced a selective hypertrophy of the ST while LL-BFR induced hypertrophy of SM. The magnitude of the selective hypertrophy observed within each group varied greatly between individuals. This finding suggests that it is very difficult to early determine the location of the hypertrophy among a muscle group.

Can the Reboot coaching programme support critical care nurses in coping with stressful clinical events? A mixed-methods evaluation assessing resilience, burnout, depression and turnover intentions.

BACKGROUND: Critical care nurses (CCNs) are routinely exposed to highly stressful situations, and at high-risk of suffering from work-related stress and developing burnout. Thus, supporting CCN wellbeing is crucial. One approach for delivering this support is by preparing CCNs for situations they may encounter, drawing on evidence-based techniques to strengthen psychological coping strategies. The current study tailored a Resilience-boosting psychological coaching programme [Reboot] to CCNs. Other healthcare staff receiving Reboot have reported improvements in confidence in coping with stressful clinical events and increased psychological resilience. The current study tailored Reboot for online, remote delivery to CCNs (as it had not previously been delivered to nurses, or in remote format), to (1) assess the feasibility of delivering Reboot remotely, and to (2) provide a preliminary assessment of whether Reboot could increase resilience, confidence in coping with adverse events and burnout. METHODS: A single-arm mixed-methods (questionnaires, interviews) before-after feasibility study design was used. Feasibility was measured via demand, recruitment, and retention (recruitment goal: 80 CCNs, retention goal: 70% of recruited CCNs). Potential efficacy was measured via questionnaires at five timepoints; measures included confidence in coping with adverse events (Confidence scale), Resilience (Brief Resilience Scale), depression (PHQ-9) and burnout (Oldenburg-Burnout-Inventory). Intention to leave (current role, nursing more generally) was measured post-intervention. Interviews were analysed using Reflexive Thematic Analysis. RESULTS: Results suggest that delivering Reboot remotely is feasible and acceptable. Seventy-seven nurses were recruited, 81% of whom completed the 8-week intervention. Thus, the retention rate was over 10% higher than the target. Regarding preliminary efficacy, follow-up measures showed significant increases in resilience, confidence in coping with adverse events and reductions in depression, burnout, and intention to leave. Qualitative analysis suggested that CCNs found the psychological techniques helpful and particularly valued practical exercises that could be translated into everyday practice. CONCLUSION: This study demonstrates the feasibility of remote delivery of Reboot and potential efficacy for CCNs. Results are limited due to the single-arm feasibility design; thus, a larger trial with a control group is needed.

Cannabis smoking and abdominal wall reconstruction outcomes: a propensity score-matched analysis.

PURPOSE: Despite increasing use of cannabis, literature on perioperative effects is lagging. We compared active cannabis-smokers versus non-smokers and postoperative wound morbidity and reoperations following open abdominal wall reconstruction (AWR). METHODS: Patients who underwent open, clean, AWR with transversus abdominis release and retromuscular synthetic mesh placement at our institution between January 2014 and May 2022 were identified using the Abdominal Core Health Quality Collaborative database. Active cannabis-smokers were 1:3 propensity matched to non-smokers based on demographics and comorbidities. Wound complications, 30 day morbidity, pain (PROMIS 3a-Pain Intensity), and hernia-specific quality of life (HerQles) were compared. RESULTS: Seventy-two cannabis-smokers were matched to 216 non-smokers. SSO (18% vs 17% p = 0.86), SSI (11.1% vs 9.3%, p = 0.65), SSOPI (12% vs 12%, p = 0.92), and all postoperative complications (46% vs 43%, p = 0.63) were similar between cannabis-smokers and non-smokers. Reoperations were more common in the cannabis-smoker group (8.3% vs 2.8%, p = 0.041), driven by major wound complications (6.9% vs 3.2%, p = 0.004). No mesh excisions occurred. HerQles scores were similar at baseline (22 [11, 41] vs 35 [14, 55], p = 0.06), and were worse for cannabis-smokers compared to non-smokers at 30 days (30 [12, 50] vs 38 [20, 67], p = 0.032), but not significantly different at 1 year postoperatively (72 [53, 90] vs 78 [57, 92], p = 0.39). Pain scores were worse for cannabis-smokers compared to non-smokers at 30 days postoperatively (52 [46, 58] vs 49 [44, 54], p = 0.01), but there were no differences at 6 months or 1 year postoperatively (p > 0.05 for all). CONCLUSION: Cannabis smokers will likely experience similar complication rates after clean, open AWR, but should be counseled that despite similar wound complication rates, the severity of their wound complications may be greater than non-smokers.

Analysis of retromuscular drain output and postoperative outcomes for heavyweight versus mediumweight polypropylene mesh following open ventral hernia repair.

PURPOSE: Heavyweight polypropylene (HWPP) mesh is thought to increase inflammatory response and delay tissue integration compared to mediumweight (MWPP). Reactive fluid volume (i.e., drain output) may be a reasonable surrogate for integration. We hypothesized that daily drain output is higher with HWPP compared to MWPP in open retromuscular ventral hernia repair (VHR). METHODS: This is a post-hoc analysis of a multicenter, randomized clinical trial conducted March 2017-April 2019 comparing MWPP and HWPP for VHR. Retromuscular drain output in milliliters was measured at 24-h intervals up to postoperative day seven. Univariate analyses compared differences in daily drain output and time to drain removal. Multivariable analyses compared total drain output and wound morbidity within 30 days and hernia recurrence at 1 year. RESULTS: 288 patients were included; 140 (48.6%) HWPP and 148 (51.4%) MWPP. Daily drain output for days 1-3 was higher for HWPP vs. MWPP (total volume: 837.8 mL vs. 656.5 mL) (p < 0.001), but similar on days 4-7 (p > 0.05). Median drain removal time was 5 days for both groups. Total drain output was not predictive of 30-day wound morbidity (p > 0.05) or hernia recurrence at 1 year (OR 1, p = 0.29). CONCLUSION: While HWPP mesh initially had higher drain outputs, it rapidly returned to levels similar to MWPP by postoperative day three and there was no difference in clinical outcomes. We believe that drains placed around HWPP mesh can be managed similarly to MWPP mesh.

Much more to explore with an oxidation state of nearly four: Pr valence instability in intermetallic m-Pr2Co3Ge5.

For some intermetallic compounds containing lanthanides, structural transitions can result in intermediate electronic states between trivalency and tetravalency; however, this is rarely observed for praseodymium compounds. The dominant trivalency of praseodymium limits potential discoveries of emergent quantum states in itinerant 4f1 systems accessible using Pr4+-based compounds. Here, we use in situ powder x-ray diffraction and in situ electron energy-loss spectroscopy (EELS) to identify an intermetallic example of a dominantly Pr4+ state in the polymorphic system Pr2Co3Ge5. The structure-valence transition from a nearly full Pr4+ electronic state to a typical Pr3+ state shows the potential of Pr-based intermetallic compounds to host valence-unstable states and provides an opportunity to discover previously unknown quantum phenomena. In addition, this work emphasizes the need for complementary techniques like EELS when evaluating the magnetic and electronic properties of Pr intermetallic systems to reveal details easily overlooked when relying on bulk magnetic measurements alone.

Uncovering the Network Modifier for Highly Disordered Amorphous Li-Garnet Glass-Ceramics.

Highly disordered amorphous Li7La3Zr2O12 (aLLZO) is a promising class of electrolyte separators and protective layers for hybrid or all-solid-state batteries due to its grain-boundary-free nature and wide electrochemical stability window. Unlike low-entropy ionic glasses such as LixPOyNz (LiPON), these medium-entropy non-Zachariasen aLLZO phases offer a higher number of stable structure arrangements over a wide range of tunable synthesis temperatures, providing the potential to tune the LBU-Li+ transport relation. It is revealed that lanthanum is the active "network modifier" for this new class of highly disordered Li+ conductors, whereas zirconium and lithium serve as "network formers". Specifically, within the solubility limit of La in aLLZO, increasing the La concentration can result in longer bond distances between the first nearest neighbors of Zr─O and La─O within the same local building unit (LBU) and the second nearest neighbors of Zr─La across two adjacent network-former and network-modifier LBUs, suggesting a more disordered medium- and long-range order structure in LLZO. These findings open new avenues for future designs of amorphous Li+ electrolytes and the selection of network-modifier dopants. Moreover, the wide yet relatively low synthesis temperatures of these glass-ceramics make them attractive candidates for low-cost and more sustainable hybrid- or all-solid-state batteries for energy storage.

Abdominal wall mass resections: single-center closure practices and outcomes following oncologic resections of abdominal wall fascia.

PURPOSE: Radical resections for abdominal wall tumors are rare, thus yielding limited data on reconstruction of defects. We describe surgical management and long-term outcomes following radical tumor resection. METHODS: This was a single-center retrospective review of patients between January 2010 and December 2022. Variables included operative characteristics, wound complications, hernia development, tumor recurrence, and reoperation. A multivariable analysis compared wound morbidity for suture and mesh repairs while adjusting for defect width, fascial closure, and CDC wound class. RESULTS: 120 patients were identified. Mean follow-up was 3.9 ± 3.4 years. Seventy-five (62.5%) of the masses were primary; most commonly desmoid (n = 25) and endometrioma (n = 27). Forty-five masses were metastases. Mean tumor width was 6.2 ± 3.4 cm; mean defect width was 8.1 ± 4.1 cm. Sixty-one patients (50.8%) had mesh placed, with variation in technique. Postoperative CT scans were available for 88 (73.3%) patients. Forty SSOs (33.3%), 11 SSIs (9.2%), and 18 (15%) SSOPIs occurred within 30 days. On multivariable analysis, increased defect width was associated with SSOPI (OR 1.17, p = 0.041) and CDC wound class II-III was associated with SSI (OR 8.38 and 49.1, p < 0.05) and SSOPI (OR 5.77 and 17.4, p < 0.05); mesh was not associated with these outcomes. Seven patients (5.8%) underwent 30-day reoperations and 35 (20.8%) required additional operations after 30 days. Thirteen percent developed abdominal wall (n = 8) or intra-abdominal tumor recurrence (n = 8) requiring reoperation. Twenty-seven (22.5%) patients developed hernias with a mean fascial defect width of 9.8 ± 7.2 cm. CONCLUSION: Abdominal wall mass resections are morbid, often contaminated cases with high postoperative complication rates. Risks and benefits of mesh implantation should be tailored on an individual basis.

PKR-like ER kinase (PERK) Haplotypes Are Associated with Depressive Symptoms in People with HIV.

Background: Depression is a debilitating and difficult-to-treat condition in people with HIV (PWH) despite viral suppression on antiretroviral therapy (ART). Depression is associated with activation of the PKR-like ER kinase (PERK) pathway, which regulates protein synthesis in response to metabolic stress. We evaluated common PERK haplotypes that influence PERK expression in relation to depressed mood in PWH. Methods: PWH from 6 research centers were enrolled in the study. Genotyping was conducted using targeted sequencing with TaqMan. The major PERK haplotypes A, B, and D were identified. Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II). Covariates including genetically-defined ancestry, demographics, HIV disease/treatment parameters and antidepressant treatments were assessed. Data were analyzed using multivariable regression models. Results: A total of 287 PWH with a mean (SD) age of 57.1±7.8 years were enrolled. Although the largest ethnic group was non-Hispanic white (n=129, 45.3%), African-American (n=124, 43.5%) and Hispanic (n=30, 10.5%) made up over half the sample. 20.3% were female and 96.5% were virally suppressed. Mean BDI-II was 9.6±9.5, and 28.9% scored above the cutoff for mild depression (BDI-II>13). PERK haplotype frequencies were AA57.8%, AB25.8%, AD 10.1%, and BB4.88%. PERK haplotypes were differentially represented according to genetic ancestry (p=6.84e-6). BDI-II scores were significantly higher in participants with the AB haplotype (F=4.45, p=0.0007).This finding was robust to consideration of potential confounds. Conclusion: PERK haplotypes were associated with depressed mood in PWH.Consequently, pharmacological targeting of PERK-related pathways might amelioratedepression in PWH.

Management and analysis of high-throughput sequence data for infectious animal diseases.

Advances in technology and decreasing costs have accelerated the use of high-throughput sequencing (HTS) for both diagnosis and characterisation of infectious animal diseases. High-throughput sequencing offers several advantages over previous techniques, including rapid turnaround times and the ability to resolve single nucleotide changes among samples, both of which are important for epidemiological investigations of outbreaks. However, due to the plethora of genetic data being routinely generated, the storage and analysis of these data are proving challenging in their own right. In this article, the authors provide insight into the aspects of data management and analysis that should be considered before adopting HTS for routine animal health diagnostics. These elements fall largely into three interrelated categories: data storage, data analysis and quality assurance. Each has numerous complexities and may need to be adapted as HTS evolves. Making appropriate strategic decisions about bioinformatic sequence analysis early on in project development will help to avert major issues in the long term.

Les avancées technologiques dans le domaine du séquençage à haut débit (SHD) et la diminution des coûts liés à cette technique en ont accéléré l'utilisation à des fins de diagnostic et de caractérisation des maladies animales infectieuses. Le séquençage à haut débit offre plusieurs avantages par rapport aux techniques antérieures, en particulier la rapidité de son exécution et une résolution de l'ordre d'un seul changement de nucléotide parmi plusieurs échantillons, ce qui présente un grand intérêt lors des enquêtes épidémiologiques sur les foyers. Néanmoins, la pléthore de données génétiques générées en routine par le SHD devient un véritable problème en termes de stockage et d'analyse de ces données. Les auteurs apportent un éclairage sur les aspects de la gestion et de l'analyse des données qu'il convient de prendre en compte avant d'adopter le SHD pour le diagnostic de routine en santé animale. Ces éléments relèvent de trois catégories étroitement reliées : le stockage de données, l'analyse de données et l'assurance qualité. Chacun de ces aspects présente de nombreuses complexités et nécessitera sans doute d'être adapté à mesure que le SHD évolue. Lorsqu'elles sont prises dès la phase initiale d'un projet, des décisions stratégiques appropriées en matière d'analyse bio-informatique de séquences peuvent contribuer à éviter des problèmes majeurs sur le long terme.

Los avances tecnológicos y la reducción de los costos han acelerado el uso de la secuenciación de alto rendimiento (SAR) con fines de diagnóstico y caracterización de enfermedades animales infecciosas. La secuenciación de alto rendimiento presenta varias ventajas en comparación con otras técnicas anteriores, en particular ciclos más rápidos y una resolución que permite detectar diferencias de un solo nucleótido entre las muestras, aspectos ambos de gran importancia para el estudio epidemiológico de brotes infecciosos. Sin embargo, debido al sinnúmero de datos genéticos que constantemente se generan, no es de extrañar que esté resultando problemático almacenar y analizar los datos obtenidos. Los autores arrojan luz sobre los aspectos de la gestión y el análisis de datos que conviene tener en cuenta antes de aplicar la SAR a las labores sistemáticas de diagnóstico en sanidad animal. Estos elementos corresponden a grandes líneas a tres categorías relacionadas entre sí: el almacenamiento de datos; el análisis de datos; y la garantía de calidad. Cada una de ellas presenta multitud de complicaciones y exige un proceso permanente de adaptación a medida que la técnica de secuenciación va evolucionando. El hecho de adoptar las buenas decisiones estratégicas sobre el análisis bioinformático de secuencias en los primeros momentos de la concepción de un proyecto ayudará a evitar importantes problemas a largo plazo.

Both Nuclear and Membrane Estrogen Receptor Alpha Impact the Expression of Estrogen Receptors and Plasticity Markers in the Mouse Hypothalamus and Hippocampus.

Estrogens via estrogen receptor alpha (ERα) genomic and nongenomic signaling can influence plasticity processes in numerous brain regions. Using mice that express nuclear only ERα (NOER) or membrane only ERα (MOER), this study examined the effect of receptor compartmentalization on the paraventricular nucleus of the hypothalamus (PVN) and the hippocampus. The absence of nuclear and membrane ERα expression impacted females but not males in these two brain areas. In the PVN, quantitative immunohistochemistry showed that the absence of nuclear ERα increased nuclear ERß. Moreover, in the hippocampus CA1, immuno-electron microscopy revealed that the absence of either nuclear or membrane ERα decreased extranuclear ERα and pTrkB in synapses. In contrast, in the dentate gyrus, the absence of nuclear ERα increased pTrkB in synapses, whereas the absence of membrane ERα decreased pTrkB in axons. However, the absence of membrane only ERα decreased the sprouting of mossy fibers in CA3 as reflected by changes in zinc transporter immunolabeling. Altogether these findings support the idea that both membrane and nuclear ERα contribute overlapping and unique actions of estrogen that are tissue- and cellular-specific.

Membrane Estrogen Receptor ß Is Sufficient to Mitigate Cardiac Cell Pathology.

Estrogen acting through estrogen receptor ß (ERß) has been shown to oppose the stimulation of cardiac myocytes and cardiac fibroblasts that results in cardiac hypertrophy and fibrosis. Previous work has implicated signal transduction from ERß as being important to the function of estrogen in this regard. Here we address whether membrane ERß is sufficient to oppose key mechanisms by which angiotensin II (AngII) stimulates cardiac cell pathology. To do this we first defined essential structural elements within ERß that are necessary for membrane or nuclear localization in cells. We previously determined that cysteine 418 is the site of palmitoylation of ERß that is required and sufficient for cell membrane localization in mice and is the same site in humans. Here we determined in Chinese hamster ovarian (CHO) cells, and mouse and rat myocytes and cardiac fibroblasts, the effect on multiple aspects of signal transduction by expressing wild-type (WT ) or a C418A-mutant ERß. To test the importance of the nuclear receptor, we determined a 4-amino acid deletion in the E domain of ERß that strongly blocked nuclear localization. Using these tools, we expressed WT and mutant ERß constructs into cardiomyocytes and cardiac fibroblasts from ERß-deleted mice. We determined the ability of estrogen to mitigate cell pathology stimulated by AngII and whether the membrane ERß is necessary and sufficient.

Evaluation of a new DIII-D Doppler backscattering system for higher wavenumber measurement and signal enhancement.

The high density fluctuation poloidal wavenumber, kθ (kθ > 8 cm-1, kθρs > 5, ρs is the ion gyro radius using the ion sound velocity), measurement capability of a new Doppler backscattering (DBS) system at the DIII-D tokamak has been experimentally evaluated. In DBS, wavenumber (k) matching becomes more important at higher wavenumbers, owing to the exponential dependence of the measured signal loss factor on wave vector mismatch. Wave vector matching allows for the Bragg scattering condition to be satisfied, which minimizes the signal loss at higher k's. In the previous DBS system, without toroidal wave vector matching, the measured DBS signal-to-noise ratio at higher kθ (>8 cm-1) is substantially reduced, making it difficult to measure higher kθ turbulence. The new DBS system has been optimized to access higher wavenumber, kθ ≤ 20 cm-1, density turbulence measurement. The optimization hardware addresses fluctuation wave vector matching using toroidal steering of the launch mirror to produce a backscattered signal with improved intensity. The probe's sensitivity to high-k density fluctuations has been increased by approximately an order of magnitude compared to the old system that has been in use at DIII-D. Note that typical measurement locations are above or below the tokamak midplane on the low field side with normalized radial ranges of 0.5-1.0. The new DBS probe system with the toroidal matching of fluctuation wave vectors is thought to be critical to understanding high-k turbulent transport in fusion-relevant research at DIII-D.

Strategic directions in the what and how of learning and teaching innovation-a fifty-year synopsis.

Student learning experiences at university are constantly evolving; new disciplinary discoveries, new knowledge, interdisciplinary synergies and new exigencies make learning a dynamic experience for students, teachers and researchers alike; and that is just the what of learning. Add to this, changes in the how of learning, new pedagogies and new technologies, new partners in the provision of learning, as well as new configurations of where learning takes place, such as on campus, at home, in the workplace and online; and it is not hard to make the case that learning experiences of students enrolled in a degree are relatively more complex today than they were even 20 years ago. Much of this change has been captured over the last five decades in the journal Higher Education. The ongoing challenge of these changes is the complexity that accompanies them. How do we improve the student experience of learning in a complex context? What should the outcomes of a higher education degree be? What learning processes are likely to lead better outcomes? How do you assess the quality of learning that may occur in small groups on campus or online, or in large groups in both places, or in laboratories or the workplace? What is the role of material objects in these experiences and do they contribute to outcomes? This manuscript will consider such questions and where the journal is pointing researchers towards new avenues that are developing in learning and teaching internationally.