A Systematic Review and Meta-Analysis of the Efficacy of Antimicrobial Chemoprophylaxis for Recurrent Acute Otitis Media in Children.

OBJECTIVES: Acute otitis media (AOM) is a common childhood infection. Recurrent AOM affects a subset of children, resulting in an adverse impact on quality of life, socioeconomic disadvantage, and risk of long-term sequelae. Antimicrobial chemoprophylaxis is used in some settings but is increasingly controversial due to an awareness of adverse long-term effects and contribution to global antibiotic resistance. DESIGN AND SETTING: A comprehensive literature search was undertaken using Medline (1946-October 2023) and Embase (1974-October 2023). The primary aim was to assess the efficacy of antimicrobial chemoprophylaxis on AOM episodes in children < 18 years of age. Bias and quality assessment was performed. Dichotomous data were analysed using risk ratio with 95% confidence intervals. Meta-analysis was carried out using random-effects models for pooled analysis, independent of heterogeneity. Heterogeneity was assessed using the I2 statistic. MAIN OUTCOME MEASURES: The effect of antimicrobial chemoprophylaxis in children with rAOM on the number of individual AOM episodes. SECONDARY OUTCOMES: assessment of antimicrobial agents and outcomes in children with risk factors. RESULTS: Assessment of qualitative data was performed on 20 studies (n = 2210). No controlled trials were identified post-multivalent pneumococcal conjugate vaccine (PCV) introduction, restricting current generalisability. Quantitative meta-analysis on nine pre-PCV studies (n = 1087) demonstrated antimicrobial chemoprophylaxis reduced any episode of AOM with a risk ratio 0.59 (95% CI 0.45-0.77). CONCLUSION: Families and clinicians must balance marginal short-medium term benefit (based on pre-PCV data), and the potential for adverse effects to that individual, and the societal risk of antimicrobial resistance with prolonged antibiotic use.

Effect of High-Volume Cluster Sets vs. Lower-Volume Traditional Sets on Accuracy of Estimated Repetitions to Failure.

ABSTRACT: Davies, TB, Li, J, and Hackett, DA. Effect of high-volume cluster sets vs. lower-volume traditional sets on accuracy of estimated repetitions to failure. J Strength Cond Res 37(6): 1191-1198, 2023-This study investigated the effects of resistance training using cluster (CLUS) vs. traditional (TRAD) set structures on the accuracy of estimated repetitions to failure (ERF). Nineteen healthy male resistance trainers (age 21.0 ± 4.4 years) were randomized into 1 of the 2 bench press training routines performed for 6 weeks. Cluster ( n = 10) performed 6 sets of 5 repetitions at 85% of 1 repetition maximum (1RM) with 30-second interrepetition rest and 3 minutes of interset rest. Traditional ( n = 9) performed 3 sets of 5 repetitions at 85% 1RM with 5 minutes of interset rest. Maximum repetitions at 85% 1RM was performed before and after intervention to assess error in ERF and mean concentric velocity (MCV). The ERF, rating of perceived exertion, and maintenance of MCV were assessed throughout the intervention. Rating of perceived exertion was lower for sets 1-3 in CLUS compared with TRAD from weeks 1 to 4 (effect size [ES] = 0.8-2.4, p ≤ 0.04). The ERF was greater for sets 1-3 in CLUS than in TRAD during all intervention weeks (ES = 1.0-5.1, p ≤ 0.04). Maintenance of MCV was greater in CLUS compared with TRAD for all sets at week 1 (ES = 0.76, p = 0.002) and sets 4-6 at week 6 (ES = 0.77, p = 0.006). After the intervention, error in ERF did not change, and no differences were found between the groups. Findings indicate that accuracy of ERF does not improve after resistance training using set structures that induce different transient fatigue-related effects when using high loads in experienced resistance trainers.

Self-Reported Training and Supplementation Practices Between Performance-Enhancing Drug-User Bodybuilders Compared with Natural Bodybuilders.

ABSTRACT: Li, J, Davies, TB, and Hackett, DA. Self-reported training and supplementation practices between performance-enhancing drug-user bodybuilders compared with natural bodybuilders. J Strength Cond Res 37(5): 1079-1088, 2023-This study aimed to examine whether the training and supplementation practices differ between performance-enhancing drug (PED)-using bodybuilders (BB) and natural BB. One hundred eighty-seven competitive male bodybuilders with a median age of 27.0 years completed an online survey. Of this sample, 40 respondents reported using PED (PED-user) and 147 respondents reported to be natural. Compared with natural BB, PED-user BB reported greater off-season body weight ( p < 0.001) and weight loss before a competition ( p < 0.001). In the off-season, PED-user BB performed a greater number of exercises per muscle group ( p < 0.001), number of repetition maximum (RM) per set ( p < 0.01), and less recovery between the sets ( p < 0.01). During the precompetition phase, the natural BB increased their number of RM; however, the PED-user BB still reported using a greater number of RM per set ( p = 0.02), exercises per muscle group ( p < 0.001), and less recovery time between the sets ( p < 0.01). Both the PED-user BB and natural BB reported greater aerobic exercise frequency ( p < 0.001) and session duration ( p < 0.001), although PED-user BB performed a greater number of aerobic exercise sessions ( p = 0.04) and at a higher intensity ( p < 0.01). Advanced training techniques, including negatives, partial repetitions, preexhaustion sets, and timed repetitions, were more popular among PED-user BB ( p < 0.05). Creatine monohydrate usage was more popular among natural BB ( p < 0.001), whereas branched-chain and essential amino acids were more popular among PED-user BB ( p ≤ 0.001). Findings suggest that PED-user BB perform more metabolically demanding resistance training sessions, more strenuous aerobic training during the precompetition phase, and may have different supplementation preferences compared with natural BB.

Effect of Set-Structure on Upper-Body Muscular Hypertrophy and Performance in Recreationally-Trained Male and Female.

ABSTRACT: Davies, TB, Halaki, M, Orr, R, Mitchell, L, Helms, ER, Clarke, J, and Hackett, DA. Effect of set structure on upper-body muscular hypertrophy and performance in recreationally trained men and women. J Strength Cond Res 36(8): 2176-2185, 2022-This study explored the effect of volume-equated traditional-set and cluster-set structures on muscular hypertrophy and performance after high-load resistance training manipulating the bench press exercise. Twenty-one recreationally trained subjects (12 men and 9 women) performed a 3-week familiarization phase and were then randomized into one of two 8-week upper-body and lower-body split programs occurring over 3 and then progressing to 4 sessions per week. Subjects performed 4 sets of 5 repetitions at 85% one repetition maximum (1RM) using a traditional-set structure (TRAD, n = 10), which involved 5 minutes of interset rest only, or a cluster-set structure, which included 30-second inter-repetition rest and 3 minutes of interset rest (CLUS, n = 11). A 1RM bench press, repetitions to failure at 70% 1RM, regional muscle thickness, and dual-energy x-ray absorptiometry were used to estimate changes in muscular strength, local muscular endurance, regional muscular hypertrophy, and body composition, respectively. Velocity loss was assessed using a linear position transducer at the intervention midpoint. TRAD demonstrated a significantly greater velocity loss magnitude (g = 1.50) and muscle thickness of the proximal pectoralis major (g = -0.34) compared with CLUS. There were no significant differences between groups for the remaining outcomes, although a small effect size favoring TRAD was observed for the middle region of the pectoralis major (g = -0.25). It seems that the greater velocity losses during sets observed in traditional-set compared with cluster-set structures may promote superior muscular hypertrophy within specific regions of the pectoralis major in recreationally trained subjects.

Ten Years of Population-Level Genomic Escherichia coli and Klebsiella pneumoniae Serotype Surveillance Informs Vaccine Development for Invasive Infections.

BACKGROUND: The incidence of bloodstream infections (BSIs) caused by Escherichia coli and Klebsiella pneumoniae is increasing, with substantial associated morbidity, mortality, and antimicrobial resistance. Unbiased serotyping studies to guide vaccine target selection are limited. METHODS: We conducted unselected, population-level genomic surveillance of bloodstream E. coli and Klebsiella pneumoniae isolates from 2008 to 2018 in Oxfordshire, United Kingdom. We supplemented this with an analysis of publicly available global sequencing data (n = 3678). RESULTS: We sequenced 3478 E. coli isolates (3278 passed quality control) and 556 K. pneumoniae isolates (535 [K-antigen] and 549 [O-antigen] passed quality control). The 4 most common E. coli O-antigens (O1/O2/O6/O25) were identified in 1499/3278 isolates; the incidence of these O-types increased over time (incidence rate ratio per year [IRRy] = 1.14, 95% confidence interval [CI]: 1.11-1.16). These O-types accounted for 616/1434 multidrug-resistant (MDR) and 173/256 extended-spectrum beta-lactamase (ESBL)-resistant isolates in Oxfordshire but only 19/90 carbapenem-resistant isolates across all studies. For Klebsiella pneumoniae, the most common O-antigens (O2v2/O1v1/O3b/O1v2) accounted for 410/549 isolates; the incidence of BSIs caused by these also increased annually (IRRy = 1.09; 95% CI: 1.05-1.12). These O-types accounted for 122/148 MDR and 106/123 ESBL isolates in Oxfordshire and 557/734 carbapenem-resistant isolates across all studies. Conversely we observed substantial capsular antigen diversity. Analysis of 3678 isolates from global studies demonstrated the generalizability of these findings. For E. coli, based on serotyping, the ExPEC4V and ExPEC10V vaccines under investigation would cover 46% and 72% of Oxfordshire isolates respectively, and 47% and 71% of MDR isolates. CONCLUSIONS: O-antigen targeted vaccines may be useful in reducing the morbidity, mortality, and antimicrobial resistance associated with E. coli and K. pneumoniae BSIs.

Induced pluripotent stem cells reprogrammed from primary dendritic cells provide an abundant source of immunostimulatory dendritic cells for use in immunotherapy.

Cell types differentiated from induced pluripotent stem cells (iPSCs) are frequently arrested in their development program, more closely resembling a fetal rather than an adult phenotype, potentially limiting their utility for downstream clinical applications. The fetal phenotype of iPSC-derived dendritic cells (ipDCs) is evidenced by their low expression of MHC class II and costimulatory molecules, impaired secretion of IL-12, and poor responsiveness to conventional maturation stimuli, undermining their use for applications such as immune-oncology. Given that iPSCs display an epigenetic memory of the cell type from which they were originally derived, we investigated the feasibility of reprogramming adult DCs to pluripotency to determine the impact on the phenotype and function of ipDCs differentiated from them. Using murine bone marrow-derived DCs (bmDCs) as proof of principle, we show here that immature DCs are tractable candidates for reprogramming using non-integrating Sendai virus for the delivery of Oct4, Sox2, Klf4, and c-Myc transcription factors. Reprogramming efficiency of DCs was lower than mouse embryonic fibroblasts (MEFs) and highly dependent on their maturation status. Although control iPSCs derived from conventional MEFs yielded DCs that displayed a predictable fetal phenotype and impaired immunostimulatory capacity in vitro and in vivo, DCs differentiated from DC-derived iPSCs exhibited a surface phenotype, immunostimulatory capacity, and responsiveness to maturation stimuli indistinguishable from the source DCs, a phenotype that was retained for 15 passages of the parent iPSCs. Our results suggest that the epigenetic memory of iPSCs may be productively exploited for the generation of potently immunogenic DCs for immunotherapeutic applications.

Effect of Set-Structure on Upper-Body Muscular Hypertrophy and Performance in Recreationally-Trained Male and Female.

ABSTRACT: Davies, TB, Halaki, M, Orr, R, Mitchell, L, Helms, ER, Clarke, J, and Hackett, DA. Effect of set structure on upper-body muscular hypertrophy and performance in recreationally trained men and women. J Strength Cond Res XX(X): 000-000, 2021-This study explored the effect of volume-equated traditional-set and cluster-set structures on muscular hypertrophy and performance after high-load resistance training manipulating the bench press exercise. Twenty-one recreationally trained subjects (12 men and 9 women) performed a 3-week familiarization phase and were then randomized into one of two 8-week upper-body and lower-body split programs occurring over 3 and then progressing to 4 sessions per week. Subjects performed 4 sets of 5 repetitions at 85% one repetition maximum (1RM) using a traditional-set structure (TRAD, n = 10), which involved 5 minutes of interset rest only, or a cluster-set structure, which included 30-second inter-repetition rest and 3 minutes of interset rest (CLUS, n = 11). A 1RM bench press, repetitions to failure at 70% 1RM, regional muscle thickness, and dual-energy x-ray absorptiometry were used to estimate changes in muscular strength, local muscular endurance, regional muscular hypertrophy, and body composition, respectively. Velocity loss was assessed using a linear position transducer at the intervention midpoint. TRAD demonstrated a significantly greater velocity loss magnitude (g = 1.50) and muscle thickness of the proximal pectoralis major (g = -0.34) compared with CLUS. There were no significant differences between groups for the remaining outcomes, although a small effect size favoring TRAD was observed for the middle region of the pectoralis major (g = -0.25). It seems that the greater velocity losses during sets observed in traditional-set compared with cluster-set structures may promote superior muscular hypertrophy within specific regions of the pectoralis major in recreationally trained subjects.

The impact of frailty on epistaxis admission, a retrospective cohort study.

OBJECTIVES: Epistaxis is frequently managed with intra-nasal packing devices, traditionally requiring patient admission. Current COVID-19 guidelines encourage ambulatory care where possible in this patient cohort. This paper aims to establish the impact of the Clinical Frailty Scale, anticoagulant/antiplatelet therapeutics and season variation on pre-pandemic admissions to help identify patients suitable for ambulatory epistaxis management. DESIGN: Retrospective cohort study SETTING: Scottish Regional Health Board PARTICIPANTS: Adult patients attending secondary care with epistaxis between March 2019 and March 2020. MAIN OUTCOME MEASURES: Likelihood of epistaxis hospital admission based on Clinical Frailty Scale. RESULTS: 299 epistaxis presentations were identified, of which 122 (40.8%) required admission. Clinical Frailty Scale of ≥4 had an increased likelihood of admission (OR 3.15 (95% CI:1.94-5.16), P < .05). In the majority of presentations (66.2%), patients were taking either an antiplatelet or anticoagulant. Of these presentations, the use of an anticoagulant (OR: 2.00 (95% CI: 1.20-3.33), P < .05 and dual antiplatelet (OR: 2.82 (95% CI: 1.02-7.86), P < .05) demonstrated increased likelihood of admission. CONCLUSIONS: We have shown that frailty increases the risk of admission in adult patients presenting with epistaxis. Clinical Frailty Scale (CFS) could be utilised in risk stratification to identify suitable patients for outpatient management. Patients with CFS ≤ 3 could be considered for outpatient management of their epistaxis. It is likely that patients with CFS ≥4 on anticoagulant or dual antiplatelet will require admission.

Investigation and management of papillary thyroid microcarcinoma - a Scottish regional case series and literature review.

BACKGROUND AND AIMS: Papillary thyroid microcarcinoma is defined as papillary thyroid cancer with a diameter of ≤1 cm. Despite its prevalence, there is wide variation in practice in the investigation and management of patients with papillary thyroid microcarcinoma throughout the UK and internationally. The primary aim of this paper is to describe the experience of investigation and management in a Scottish health board over the past 10 years. METHODS AND RESULTS: Retrospective analysis of thyroidectomy and hemithyroidectomy resection samples from March 2009 to March 2020. 532 specimens were reviewed and 20 patients with PTMC were identified. 12 patients had an incidental finding of PTMC. Median U score- 3, Median Thy score- 2.5 for dominant or radiologically suspicious nodules. 8 specimens demonstrated aggressive histopathological features. 1 patient with positive nodal disease in the neck and 0 patients with positive nodal disease in the thorax on CT Neck and Chest. CONCLUSION: Here we report the first UK Cohort describing the radiological investigation and management of papillary thyroid microcarcinoma. The results of our study are in accordance with a recent meta-analysis which found 4% nodal disease and 0.025% distant metastasis at time of presentation in patients with PTMC.

Reconciling the Potentially Irreconcilable? Genotypic and Phenotypic Amoxicillin-Clavulanate Resistance in Escherichia coli.

Resistance to amoxicillin-clavulanate, a widely used beta-lactam/beta-lactamase inhibitor combination antibiotic, is rising globally, and yet susceptibility testing remains challenging. To test whether whole-genome sequencing (WGS) could provide a more reliable assessment of susceptibility than traditional methods, we predicted resistance from WGS for 976 Escherichia coli bloodstream infection isolates from Oxfordshire, United Kingdom, comparing against phenotypes from the BD Phoenix (calibrated against EUCAST guidelines). A total of 339/976 (35%) isolates were amoxicillin-clavulanate resistant. Predictions based solely on beta-lactamase presence/absence performed poorly (sensitivity, 23% [78/339]) but improved when genetic features associated with penicillinase hyperproduction (e.g., promoter mutations and copy number estimates) were considered (sensitivity, 82% [277/339]; P < 0.0001). Most discrepancies occurred in isolates with MICs within ±1 doubling dilution of the breakpoint. We investigated two potential causes: the phenotypic reference and the binary resistant/susceptible classification. We performed reference standard, replicated phenotyping in a random stratified subsample of 261/976 (27%) isolates using agar dilution, following both EUCAST and CLSI guidelines, which use different clavulanate concentrations. As well as disagreeing with each other, neither agar dilution phenotype aligned perfectly with genetic features. A random-effects model investigating associations between genetic features and MICs showed that some genetic features had small, variable and additive effects, resulting in variable resistance classification. Using model fixed-effects to predict MICs for the non-agar dilution isolates, predicted MICs were in essential agreement (±1 doubling dilution) with observed (BD Phoenix) MICs for 691/715 (97%) isolates. This suggests amoxicillin-clavulanate resistance in E. coli is quantitative, rather than qualitative, explaining the poorly reproducible binary (resistant/susceptible) phenotypes and suboptimal concordance between different phenotypic methods and with WGS-based predictions.

Changes in Bench Press Velocity and Power After 8 Weeks of High-Load Cluster- or Traditional-Set Structures.

Davies, TB, Halaki, M, Orr, R, Helms, ER, and Hackett, DA. Changes in bench press velocity and power after 8 weeks of high-load cluster- or traditional-set structures. J Strength Cond Res 34(10): 2734-2742, 2020-This study investigated the effects of high-load cluster- vs. traditional-set structures using the bench press on velocity and power. Twenty-one resistance-trained individuals (male = 12, female = 9) performed a 3-week familiarization block followed by randomization into 1 of 2 upper- and lower-body split training routines performed for 8 weeks. The bench press was the only exercise manipulated with subjects using either cluster-set (CLUS, n = 11) or traditional-set (TRAD, n = 10) structures during training sessions. Subjects performed 4 sets of 5 repetitions at 85% 1 repetition maximum (1RM) with CLUS having a 30-second inter-repetition, and 3-minute interset rest while TRAD had a 5-minute interset rest. A load-velocity profile of relative loads derived from a 1RM test was used to assess velocity and power (absolute and relative to body mass) on the bench press. Significant improvements over time were found across various loads ranging from 45 to 75% 1RM for absolute and relative peak power (p = 0.006-0.041), and mean power (p = 0.001-0.032). Significant decreases over time were found at 55% 1RM and 65% 1RM for peak velocity (p = 0.027 and p = 0.012, respectively) and mean velocity (p = 0.047 and p = 0.022, respectively). There were no significant group or group by time interactions found for all outcomes. Within the context of high-load resistance training, set structure seems to be of less importance for changes in bench press velocity and power provided there is an intention to lift with maximal concentric velocity.

Validating a 14-Drug Microtiter Plate Containing Bedaquiline and Delamanid for Large-Scale Research Susceptibility Testing of Mycobacterium tuberculosis.

The UKMYC5 plate is a 96-well microtiter plate designed by the CRyPTIC Consortium (Comprehensive Resistance Prediction for Tuberculosis: an International Consortium) to enable the measurement of MICs of 14 different antituberculosis (anti-TB) compounds for >30,000 clinical Mycobacterium tuberculosis isolates. Unlike the MYCOTB plate, on which the UKMYC5 plate is based, the UKMYC5 plate includes two new (bedaquiline and delamanid) and two repurposed (clofazimine and linezolid) compounds. UKMYC5 plates were tested by seven laboratories on four continents by use of a panel of 19 external quality assessment (EQA) strains, including H37Rv. To assess the optimal combination of reading method and incubation time, MICs were measured from each plate by two readers, using three methods (mirrored box, microscope, and Vizion digital viewing system), after 7, 10, 14, and 21 days of incubation. In addition, all EQA strains were subjected to whole-genome sequencing and phenotypically characterized by the 7H10/7H11 agar proportion method (APM) and by use of MGIT960 mycobacterial growth indicator tubes. We concluded that the UKMYC5 plate is optimally read using the Vizion system after 14 days of incubation, achieving an interreader agreement of 97.9% and intra- and interlaboratory reproducibility rates of 95.6% and 93.1%, respectively. The mirrored box had a similar reproducibility. Strains classified as resistant by APM, MGIT960, or the presence of mutations known to confer resistance consistently showed elevated MICs compared to those for strains classified as susceptible. Finally, the UKMYC5 plate records intermediate MICs for one strain for which the APM measured MICs close to the applied critical concentration, providing early evidence that the UKMYC5 plate can quantitatively measure the magnitude of resistance to anti-TB compounds that is due to specific genetic variation.

Accuracy in Estimating Repetitions to Failure During Resistance Exercise.

Hackett, DA, Cobley, SP, Davies, TB, Michael, SW, and Halaki, M. Accuracy in estimating repetitions to failure during resistance exercise. J Strength Cond Res 31(8): 2162-2168, 2017-The primary aim of this study was to assess the accuracy in estimation of repetitions to failure (ERF) during resistance exercise. Furthermore, this investigation examined whether the accuracy in ERF was affected by training status, sex, or exercise type. Eighty-one adults (men, n = 53 and women, n = 28) with broad range of resistance training experience participated in this study. Subjects performed up to 10 sets of 10 repetitions at 70% 1 repetition maximum (1RM) and 80% 1RM for the chest press and leg press, respectively. At the completion of each set, subjects reported their ERF and then continued repetitions to failure to determine actual repetitions to failure (ARF). The accuracy (amount of error) of ERF was determined over an ARF 0-10. Significant differences were found for error of ERF among ARF (p < 0.001), with the error of ERF ∼1 repetition at ARF 0-5 compared with >2 repetitions at ARF 7-10. Greater accuracy was found for the chest press compared with leg press, with the error of ERF ≤1 repetition for ARF 0-5 and ARF 0-3, respectively (p = 0.012). Men were found to be more accurate than women at specific ARFs for the leg press (p = 0.008), whereas no interaction was found for the chest press. Resistance training experience did not affect the accuracy in ERF. These results suggest that resistance trainers can accurately estimate repetitions to failure when close to failure and that ERF could importantly be practically used for prescription and monitoring of resistance exercise.

Vertically aligned zinc oxide nanowires electrodeposited within porous polycarbonate templates for vibrational energy harvesting.

A piezoelectric nanogenerator has been fabricated using a simple, fast and scalable template-assisted electrodeposition process, by which vertically aligned zinc oxide (ZnO) nanowires were directly grown within a nanoporous polycarbonate (PC) template. The nanowires, having average diameter 184 nm and length 12 µm, are polycrystalline and have a preferred orientation of the [100] axis parallel to the long axis. The output power density of a nanogenerator fabricated from the as-grown ZnO nanowires still embedded within the PC template was found to be 151 ± 25 mW m(-3) at an impedance-matched load, when subjected to a low-level periodic (5 Hz) impacting force akin to gentle finger tapping. An energy conversion efficiency of ∼4.2% was evaluated for the electrodeposited ZnO nanowires, and the ZnO-PC composite nanogenerator was found to maintain good energy harvesting performance through 24 h of continuous fatigue testing. This is particularly significant given that ZnO-based nanostructures typically suffer from mechanical and/or environmental degradation that otherwise limits their applicability in vibrational energy harvesting. Our template-assisted synthesis of ZnO nanowires embedded within a protective polymer matrix through a single growth process is thus attractive for the fabrication of low-cost, robust and stable nanogenerators.

Elevated P3b latency variability in carriers of ZNF804A risk allele for psychosis.

Increased intra-subject variability (ISV) in reaction times (RTs) is a candidate endophenotype for several psychiatric and neurological conditions, including schizophrenia. ISV reflects the degree of variability in RTs and is thought to be an index of the stability of cognition. It is generally assumed to have the same underlying physiological basis across conditions, but recent evidence raises the possibility that the neural underpinnings of ISV vary with aetiology. Combining genetics with single-trial event-related potentials is an ideal method for investigating the neural basis of ISV in groups where ISV may vary for relatively homogenous reasons. Here we examine the association between P3b latency variability and a polymorphism on the ZNF804A gene associated with psychosis. Ninety-one healthy volunteers genotyped for rs1344706, a polymorphism on ZNF804A, had electroencephalographic data recorded while carrying out three n-back tasks. Data were analysed with a single-trial approach and latency variability of the P3b was compared between the AA homozygous risk group (N=30) and C allele carriers (N=61). P3b latencies were more variable for AA carriers than C carriers. Behavioural ISV, however, was not associated with genotype. The increase in neurophysiological variability, unaccompanied by increased behavioural variability, suggests that this risk gene is associated with an attenuated form of an endophenotype associated with the psychosis phenotype. The increase in both stimulus and response-locked variability also contrasts with previous work into attention-deficit hyperactivity disorder, where only response-locked P3b variability was elevated, suggesting that increased ISV may not signify the same underlying processes in all conditions with which it is associated.

Can enhanced recovery pathways improve outcomes of vaginal hysterectomy? Cohort control study.

STUDY OBJECTIVE: To assess the effect of enhanced recovery pathway implementation on patient outcomes after vaginal hysterectomy (VH) performed to treat benign indications. DESIGN: Case-control study examining outcome measures including length of stay, pain scores, postoperative morbidity, and readmission rates after implementation of the Enhanced Recovery after Surgery (ERAS) program for VH (Canadian Task Force classification II). SETTING: Teaching hospital. PATIENTS: Fifty patients who underwent VH after implementation of ERAS were compared with 50 control patients before ERAS. Patients were matched for age, indication for surgery, American Society of Anesthesiologists grade, and surgeon. INTERVENTION: ERAS pathway. MEASUREMENTS AND MAIN RESULTS: Length of stay, percentage of patients discharged within 24 hours, use of urinary catheter and vaginal packing, and readmission rates were determined. Perioperative expenditures were compared, and cost-effectiveness of ERAS was assessed. Median patient vs control age (49.0 vs 51.0 years), parity (2.0 vs 2.0), and body mass index (26.5 vs 28.3) were statistically comparable. After ERAS implementation, the median length of stay was reduced by 51.6% (22.0 vs 45.5 hours; p < .01), and the percentage of patients discharged within 24 hours was increased by 5-fold (78.0 vs 15.6%; p < .05). Frequency of catheter use (82.0% vs 95.6%) and use of vaginal packing (52.0 vs 82.2%) were significantly lower in the post-ERAS group, and these devices were removed earlier (14.5 vs 23.7 hours and 16.0 vs 23.0 hours, respectively; p < .05 in all cases). Attendance in the Accident and Emergency Department (12.0% vs 0%; p > .05) and inpatient readmission rate (4.0% vs 0%; p > .05) were similar in both groups. Despite having to start a "gynecology school" and employ a specialist Enhanced Recovery nurse, a cost savings of 9.25% per patient was demonstrated. CONCLUSION: The ERAS program in benign VH reduces length of stay by 51.6% and enables more women to be discharged within 24 hours, with no increase in patient readmissions rates.

Germ fate determinants protect germ precursor cell division by reducing septin and anillin levels at the cell division plane.

Animal cell cytokinesis, or the physical division of one cell into two, is thought to be driven by constriction of an actomyosin contractile ring at the division plane. The mechanisms underlying cell type-specific differences in cytokinesis remain unknown. Germ cells are totipotent cells that pass genetic information to the next generation. Previously, using formincyk-1(ts) mutant Caenorhabditis elegans 4-cell embryos, we found that the P2 germ precursor cell is protected from cytokinesis failure and can divide with greatly reduced F-actin levels at the cell division plane. Here, we identified two canonical germ fate determinants required for P2-specific cytokinetic protection: PIE-1 and POS-1. Neither has been implicated previously in cytokinesis. These germ fate determinants protect P2 cytokinesis by reducing the accumulation of septinUNC-59 and anillinANI-1 at the division plane, which here act as negative regulators of cytokinesis. These findings may provide insight into the regulation of cytokinesis in other cell types, especially in stem cells with high potency.

The plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies.

Plasmids carry genes conferring antimicrobial resistance and other clinically important traits, and contribute to the rapid dissemination of such genes. Previous studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to plasmids carrying antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream infections in Oxfordshire, UK. The bacteria had been originally isolated in 2009 (194 isolates) and 2018 (368 isolates), plus a stratified selection from intervening years (176 isolates). We demonstrate that plasmids are largely, but not entirely, constrained to a single host species, although there is substantial overlap between species of plasmid gene-repertoire. Most ARGs are carried by a relatively small number of plasmid groups with biological features that are predictable. Plasmids carrying ARGs (including those encoding carbapenemases) share a putative 'backbone' of core genes with those carrying no such genes. These findings suggest that future surveillance should, in addition to tracking plasmids currently associated with clinically important genes, focus on identifying and monitoring the dissemination of high-risk plasmid groups with the potential to rapidly acquire and disseminate these genes.

A multicentre observational study of paediatric head and neck abscesses.

INTRODUCTION: In winter of 2022/3 paediatric ENT surgeons across the UK observed that the incidence of severe abscesses in the head and neck and associated complications was higher than seen in previous years. We aimed to collate and evaluate data from across the UK to establish if this was a true rise in cases, and to describe the factors associated. METHODS: A multicentre retrospective data collection was undertaken from 13 units across the UK. Patients admitted between September 2022-February 2023 with a head and neck abscess including sinogenic, otogenic, deep and superficial neck abscesses were included. Demographic, disease specific, management and outcome data were collected. Hospital episode statistic data were also requested and analysed to allow for comparison with previous 10 years of head and neck abscesses. RESULTS: 262 patients with abscesses of the head and neck were admitted during the study period, 100 between September and November and 163 between December and February. Mastoid abscesses were the most common abscess across both groups. The rate of group A streptococcus + culture results rose significantly from 12 % in autumn group to 30 % in winter (p = 0.02). The rate of intracranial complications rose from 10 % to 18 % (p = 0.11) and the rate of venous thrombosis rose over the same timeframe from 3 % to 14 % (p = 0.01). DISCUSSION: This study demonstrated a statistically significant rise in the rate of group A streptococcus associated abscesses when comparing Autumn and Winter 2022/2023. Over the same timeframe a statistically significant rise in the proportion of patients with venous thromboses associated with H&N abscesses was noted. Interestingly, despite perceived national consensus regarding a spike in abscess incidence, the number of abscesses seen in winter 2022/2023 was in keeping with expected rates of paediatric H&N abscesses, based on pre covid year-on-year rise in incidence.