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While the benefits of early antiretroviral therapy (ART) initiation in perinatally infected infants are well documented, early initiation is not always possible in postnatal pediatric HIV infections. The timing of ART initiation is likely to affect the size of the latent viral reservoir established, as well as the development of adaptive immune responses, such as the generation of neutralizing antibody responses against the virus. How these parameters impact the ability of infants to control viremia and the time to viral rebound after ART interruption is unclear and has never been modeled in infants. To investigate this question we used an infant nonhuman primate Simian/Human Immunodeficiency Virus (SHIV) infection model. Infant Rhesus macaques (RMs) were orally challenged with SHIV.C.CH505 375H dCT and either given ART at 4-7 days post-infection (early ART condition), at 2 weeks post-infection (intermediate ART condition), or at 8 weeks post-infection (late ART condition). These infants were then monitored for up to 60 months post-infection with serial viral load and immune measurements. To gain insight into early after analytic treatment interruption (ATI), we constructed mathematical models to investigate the effect of time of ART initiation in delaying viral rebound when treatment is interrupted, focusing on the relative contributions of latent reservoir size and autologous virus neutralizing antibody responses. We developed a stochastic mathematical model to investigate the joint effect of latent reservoir size, the autologous neutralizing antibody potency, and CD4+ T cell levels on the time to viral rebound for RMs rebounding up to 60 days post-ATI. We find that the latent reservoir size is an important determinant in explaining time to viral rebound in infant macaques by affecting the growth rate of the virus. The presence of neutralizing antibodies can also delay rebound, but we find this effect for high potency antibody responses only. Finally, we discuss the therapeutic implications of our findings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Conway has served as a consultant for Excision BioTherapeutics and Merck. Dr. Permar serves a consultant for Moderna, Merck, Pfizer, GSK, Dynavax, and Hoopika on their CMV vaccine program and has led a sponsored program with Moderna and Merck on CMV vaccines., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Pulmonary fibrosis, a disabling lung disease, results from the fibrotic transformation of lung tissue. This fibrotic transformation leads to a deterioration of lung capacity, resulting in significant respiratory distress and a reduction in overall quality of life. Currently, the frontline treatment of pulmonary fibrosis remains limited, focusing primarily on symptom relief and slowing disease progression. Bacterial infections with Pseudomonas aeruginosa are contributing to a severe progression of idiopathic pulmonary fibrosis. Phytic acid, a natural chelator of zinc, which is essential for the activation of metalloproteinase enzymes involved in pulmonary fibrosis, shows potential inhibition of LasB, a virulence factor in P. aeruginosa, and mammalian metalloproteases (MMPs). In addition, phytic acid has anti-inflammatory properties believed to result from its ability to capture free radicals, inhibit certain inflammatory enzymes and proteins, and reduce the production of inflammatory cytokines, key signaling molecules that promote inflammation. To achieve higher local concentrations in the deep lung, phytic acid was spray dried into an inhalable powder. Challenges due to its hygroscopic and low melting (25 °C) nature were mitigated by converting it to sodium phytate to improve crystallinity and powder characteristics. The addition of leucine improved aerodynamic properties and reduced agglomeration, while mannitol served as carrier matrix. Size variation was achieved by modifying process parameters and were evaluated by tools such as the Next Generation Impactor (NGI), light diffraction methods, and scanning electron microscopy (SEM). An inhibition assay for human MMP-1 (collagenase-1) and MMP-2 (gelatinase A) allowed estimation of the biological effect on tissue remodeling enzymes. The activity was also assessed with respect to inhibition of bacterial LasB. The formulated phytic acid demonstrated an IC50 of 109.7 µg/mL for LasB with viabilities > 80 % up to 188 µg/mL on A549 cells. Therefore, inhalation therapy with phytic acid-based powder shows promise as a treatment for early-stage Pseudomonas-induced pulmonary fibrosis., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The axon initial segment (AIS) constitutes not only the site of action potential initiation, but also a hub for activity-dependent modulation of output generation. Recent studies shedding light on AIS function used predominantly post-hoc approaches since no robust murine in vivo live reporters exist. Here, we introduce a reporter line in which the AIS is intrinsically labeled by an ankyrin-G-GFP fusion protein activated by Cre recombinase, tagging the native Ank3 gene. Using confocal, superresolution, and two-photon microscopy as well as whole-cell patch-clamp recordings in vitro , ex vivo , and in vivo , we confirm that the subcellular scaffold of the AIS and electrophysiological parameters of labeled cells remain unchanged. We further uncover rapid AIS remodeling following increased network activity in this model system, as well as highly reproducible in vivo labeling of AIS over weeks. This novel reporter line allows longitudinal studies of AIS modulation and plasticity in vivo in real-time and thus provides a unique approach to study subcellular plasticity in a broad range of applications., Competing Interests: Conflict of interest The authors declare that they have no competing interests.

The presence of antibodies against HIV in infected children is associated with a greater capacity to control viremia in the absence of therapy. While the benefits of early antiretroviral treatment (ART) in infants are well documented, early ART may interfere with the development of antibody responses. In contrast to adults, early treated children lack detectable HIV-specific antibodies, suggesting a fundamental difference in HIV pathogenesis. Despite this potential adverse effect, early ART may decrease the size of the latent reservoir established early in infection in infants, which can be beneficial in viral control. Understanding the virologic and immunologic aspects of pediatric HIV is crucial to inform innovative targeted strategies for treating children living with HIV. In this study, we investigate how ART initiation time sets the stage for trade-offs in the latent reservoir establishment and the development of humoral immunity and how these, in turn, affect posttreatment dynamics. We also elucidate the biological function of antibodies in pediatric HIV. We employ mathematical modeling coupled with experimental data from an infant nonhuman primate Simian/Human Immunodeficiency Virus (SHIV) infection model. Infant Rhesus macaques (RMs) were orally challenged with SHIV.C.CH505 375H dCT four weeks after birth and started treatment at different times after infection. In addition to viral load measurements, antibody responses and latent reservoir sizes were measured. We estimate model parameters by fitting viral load measurements to the standard HIV viral dynamics model within a nonlinear fixed effects framework. This approach allows us to capture differences between rhesus macaques (RMs) that develop antibody responses or exhibit high latent reservoir sizes compared to those that do not. We find that neutralizing antibody responses are associated with increased viral clearance and decreased viral infectivity but decreased death rate of infected cells. In addition, the presence of detectable latent reservoir is associated with less robust immune responses. These results demonstrate that both immune response and latent reservoir dynamics are needed to understand post-rebound dynamics and point to the necessity of a comprehensive approach in tailoring personalized medical interventions.

Objective: To examine gender differences in Australian football (AF)-related concussion presentations to EDs in regional Australia., Methods: A prospective observational study of patients presenting to 1 of the 10 EDs in Western Victoria, Australia, with an AF-related concussion was conducted. Patients were part of a larger study investigating AF injuries over a complete AF season, including pre-season training and practice matches. Information regarding concussion injuries was extracted from patient medical records, including clinical features, concurrent injuries, mechanism and context of injury. Female and male data were compared with chi-squared and Fisher's exact tests. P < 0.05 was considered significant., Results: From the original cohort of 1635 patients with AF-related injuries (242 female and 1393 male), 231 (14.1%) patients were diagnosed with concussion. Thirty-eight (15.7%) females had concussions versus 193 (13.9%) males (P > 0.05). Females over the age of 16 were more likely to be concussed than males in the same age range (females n = 26, 68.4% vs males n = 94, 48.7%; P = 0.026). Neurosurgically significant head injury was rare (one case). Similar rates of concurrent injury were found between females 15 (39.5%) and males 64 (33.2%), with neck injury the single most common in 24 (10.3%) concussions. Sixty-nine patients (29%) were admitted for observation or to await the results of scans. The majority of concussions occurred in match play (87.9%). Females were more likely injured in contested ball situations (63.2% vs 37.3%; P < 0.05)., Conclusion: Concussion rates for community-level AF presentations to regional EDs were similar between genders. Serious head injury was rare, although hospital admission for observation was common. Concurrent injuries were common, with associated neck injury most often identified. Match play accounted for the majority of head injuries., (© 2024 Australasian College for Emergency Medicine.)

Viral dynamics of acute HIV infection and HIV rebound following suspension of antiretroviral therapy may be qualitatively similar but must differ given, for one, development of adaptive immune responses. Understanding the differences of acute HIV infection and viral rebound dynamics in pediatric populations may provide insights into the mechanisms of viral control with potential implications for vaccine design and the development of effective targeted therapeutics for infants and children. Mathematical models have been a crucial tool to elucidate the complex processes driving viral infections within the host. Traditionally, acute HIV infection has been modeled with a standard model of viral dynamics initially developed to explore viral decay during treatment, while viral rebound has necessitated extensions of that standard model to incorporate explicit immune responses. Previous efforts to fit these models to viral load data have underscored differences between the two infection stages, such as increased viral clearance rate and increased death rate of infected cells during rebound. However, these findings have been predicated on viral load measurements from disparate adult individuals. In this study, we aim to bridge this gap, in infants, by comparing the dynamics of acute infection and viral rebound within the same individuals by leveraging an infant nonhuman primate Simian/Human Immunodeficiency Virus (SHIV) infection model. Ten infant Rhesus macaques (RMs) orally challenged with SHIV.C.CH505 375H dCT and given ART at 8 weeks post-infection. These infants were then monitored for up to 60 months post-infection with serial viral load and immune measurements. We use the HIV standard viral dynamics model fitted to viral load measurements in a nonlinear mixed effects framework. We find that the primary difference between acute infection and rebound is the increased death rate of infected cells during rebound. We use these findings to generate hypotheses on the effects of adaptive immune responses. We leverage these findings to formulate hypotheses to elucidate the observed results and provide arguments to support the notion that delayed viral rebound is characterized by a stronger CD8+ T cell response.

Objective: To determine (i) the prevalence of overweight and obesity among children presenting to all EDs in a large regional Australian city and (ii) whether age, sex, socioeconomic status (SES) or hospital setting (public vs private) were associated with overweight and obesity., Methods: This prospective observational study included children aged ≥2 and <18 years who presented to any of three EDs over an 18 month period who had their height and weight measured. Age, sex and residential postcode were collected. Weight category was determined by sex and age standardised body mass index (BMI) z-score. Weight category was assessed by sex, age, SES and hospital setting with chi-squared tests, and ordinal logistic regression with cluster sandwich error estimators. Results were reported using odds ratios (OR) with 95% confidence intervals (CI)., Results: Data were collected for 3827 children, of which 11.6% were obese and 19.8% overweight. The prevalence of obesity was highest in those aged 8-14 years and in those from lower SES postcodes. The likelihood of obesity was higher in the public than the private hospitals (OR 0.66, 95% CI 0.51-0.86), whereas the likelihood of overweight was similar (OR 1.00, 95% CI 0.83-1.22)., Conclusions: Almost one-third of children who presented to EDs were overweight or obese. Obesity was particularly high in those aged 8-14 years and those from lower SES postcodes. In the evolving obesity crisis, the high proportion of children presenting to EDs above a healthy weight might represent an opportunity for EDs to identify and refer children for body weight and lifestyle management., (© 2024 Australasian College for Emergency Medicine.)

Background and Objectives: To assess the impact of Gadolinium-enhanced magnetic resonance imaging (MRI) sequences on Preoperative imaging evaluation and surgical planning parameters for osteosarcoma (OS) of the knee in pediatric and young adult patients., Methods: Thirty MRI scans of patients with OS about the knee were reviewed by five orthopedic oncologists. Key preoperative parameters (neurovascular bundle involvement, intra-articular tumor extension, extent of intramedullary extension) and surgical plans were evaluated based on non-contrast versus Gd contrast enhanced sequences. Assessment agreement, inter-rater agreement, and intrarater agreement between pre and postcontrast images were evaluated via Kappa statistics., Results: Moderate agreement was seen between non and contrast-enhanced assessment of neurovascular involvement and intra-articular tumor extension. Intrarater reproducibility was substantial for neurovascular bundle involvement (precontrast Kappa: 0.63, postcontrast Kappa: 0.69). Intrarater reproducibility was also substantial for precontrast (Kappa: 0.70) and moderate for postcontrast (Kappa: 0.50) assessment of intra-articular tumor extension. Planned resection length and choice of surgical approach were similar between sequences. The addition of Gd-enhanced sequences improved the inter-rater agreement across collected parameters., Conclusions: While some findings suggest that contrast enhanced sequences may not significantly alter the assessment of key preoperative planning parameters by orthopedic oncologists, they may help reduce variability among providers with differing experience levels., (© 2023 Wiley Periodicals LLC.)

An effective HIV-1 vaccine remains a critical unmet need for ending the AIDS epidemic. Vaccine trials conducted to date have suggested the need to increase the durability and functionality of vaccine-elicited antibodies to improve efficacy. We hypothesized that a conjugate vaccine based on the learned response to immunization with hepatitis B virus could be utilized to expand T cell help and improve antibody production against HIV-1. To test this, we developed an innovative conjugate vaccine regimen that used a modified vaccinia virus Ankara (MVA) co-expressing HIV-1 envelope (Env) and the hepatitis B virus surface antigen (HBsAg) as a prime, followed by two Env-HBsAg conjugate protein boosts. We compared the immunogenicity of this conjugate regimen to matched HIV-1 Env-only vaccines in two groups of 5 juvenile rhesus macaques previously immunized with hepatitis B vaccines in infancy. We found expansion of both HIV-1 and HBsAg-specific circulating T follicular helper cells and elevated serum levels of CXCL13, a marker for germinal center activity, after boosting with HBsAg-Env conjugate antigens in comparison to Env alone. The conjugate vaccine elicited higher levels of antibodies binding to select HIV Env antigens, but we did not observe significant improvement in antibody functionality, durability, maturation, or B cell clonal expansion. These data suggests that conjugate vaccination can engage both HIV-1 Env and HBsAg specific T cell help and modify antibody responses at early time points, but more research is needed to understand how to leverage this strategy to improve the durability and efficacy of next-generation HIV vaccines., (© 2023. The Author(s).)

Pregnancy is associated with a 5-26 times increased risk of invasive Haemophilus influenzae infection and subsequent adverse pregnancy outcomes. Incidence rate and outcome are published in some regions, but the characterisation of bacterial isolates is limited. We performed comparative genomic analyses of isolates from 12 pregnancy-associated cases, cultured from maternal bacteraemia in pregnancy (nine), postpartum bacteraemia (one), neonatal bacteraemia (one), and placental tissue (one). In two bacteraemia cases, identical isolates were also cultured from cervical swabs. Eight cases occurred early in pregnancy (gestational week 7-26), and seven of them resulted in miscarriage or neonatal death. All bacterial genomes were devoid of capsule loci, and they were evenly distributed in the major phylogenetic group I of the species. The conspicuous tropism of H. influenzae for pregnancy and placental tissue is associated with the species rather than specific clonal subtypes.

Background: Heavy menstrual bleeding (HMB), self-reported by 37% of adolescents, can be the first sign of a bleeding disorder (BD) during adolescence. The Dutch general practitioner (GP) guideline demands laboratory diagnostics and referral for patients at risk for a BD. How often adolescents consult the GP for HMB and which diagnostic and management strategies are used are unknown., Objectives: This study aims to estimate the incidence of HMB in adolescents in primary care and to identify diagnostic and management practices for HMB, considering the HMB GP guideline., Methods: Retrospective analyses of a GP network database containing over 200 Dutch GPs were performed. Adolescents aged 10 to 21 years, with a new diagnosis of HMB between 2010 and 2020, and a 6-month follow-up were eligible. The incidence rate and diagnostic and therapeutic strategy data were extracted., Results: We identified 1879 new diagnoses of HMB in adolescents. The average incidence rate was 7.91 per 1000 person-years. No diagnostic studies were performed in 67%. Laboratory studies were mainly restricted to hemoglobin levels (31%). Full coagulation screening occurred in 1.3%, and ferritin levels in 10%. Medication was prescribed in 65%; mostly hormonal treatment (56%) and/or nonsteroidal antiinflammatory drugs (NSAIDs) (18%). The referral rate was higher after >2 follow-up visits (6.7%) vs after 1 GP visit for HMB (1.6%; Odds ratio: 8.8; 95% CI: 5.1-15), mostly to gynecologists (>85%)., Conclusion: According to this GP database study, few adolescents visit their GP with HMB despite its high self-reported incidence. Most adolescents were prescribed hormonal contraception without further diagnostics. Referral was rare and mostly occurred after multiple follow-up visits., (© 2023 The Author(s).)

Valentine's influential norm-based multidimensional face-space model (nMDFS) predicts that perceived distinctiveness of a face increases with its distance to the norm. Occipito-temporal event-related potentials (ERPs) have been recently shown to respond selectively to variations in distance-to-norm (P200) or familiarity (N250, late negativity), respectively (Wuttke & Schweinberger, 2019). Despite growing evidence on interindividual differences in face perception skills at the behavioral level, little research has focused on their electrophysiological correlates. To reveal potential interindividual differences in face spaces, we contrasted high and low performers in face recognition in regards to distance-to-norm (P200) and familiarity (N250). We replicated both the P200 distance-to-norm and the N250 familiarity effect. Importantly, we observed: i) reduced responses in low compared to high performers of face recognition, especially in terms of smaller distance-to-norm effects in the P200, possibly indicating less 'expanded' face spaces in low compared to high performers; ii) increased N250 responses to familiar original faces in high performers, suggesting more robust face identity representations. In summary, these findings suggest the contribution of both early norm-based face coding and robust face representations to individual face recognition skills, and indicate that ERPs can offer a promising route to understand individual differences in face perception and their neurocognitive correlates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To synthesize the outcome measures used by randomized controlled trials (RCTs) for childhood glaucoma., Methods: MEDLINE, EMBASE, and Scopus were searched from inception to February 17, 2023. Randomized controlled trials and observational studies related to childhood glaucoma were included. Primary and secondary outcomes were extracted and the data was used to generate a literature review., Results: This review identified 42 unique reports pertaining to childhood glaucomas. Most of the studies originated from Egypt, India, and the USA. Intraocular pressure (IOP) outcomes were the most frequent outcomes studied, followed by clinical outcomes and safety outcomes. Clinical outcomes were the most common secondary outcomes studied, followed by IOP outcomes and safety outcomes., Conclusions: This systematic review found heterogenous outcomes with IOP outcomes as the most studied primary outcome. As the remaining outcomes were not consistently utilized, this review highlights the need for a consensus on studies of pediatric glaucoma., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Investigate the characteristics of wrist, hand and finger (WHF) injuries in Australian footballers presenting to EDs and determine if injury profiles differed between females and males, and between children and adults., Methods: In this prospective observational study that took place during an entire football season, patients attended 1 of 10 EDs in Victoria, Australia with a WHF injury sustained while playing Australian football. Data were extracted from patient medical records by trained researchers. Data included injury type (e.g. fracture), body part (e.g. metacarpal) and mechanism of injury. Males versus females, and children versus adults were compared using chi-squared tests or Fisher's exact tests., Results: In total, 528 patients had a WHF injury, of which 105 (19.9%) were female and 308 (59.2%) were children. Fractures and sprains were the most common injury types (45.3% and 38.6%, respectively). Fingers were more often injured than wrists or hands (62.5%, 23.5% and 15.0%, respectively). Ball contact was the most common mechanism of injury (38.1% of injuries). Females were more likely than males to (i) have a sprain/strain injury, (ii) injure a finger (rather than wrist or hand) and (iii) injure themselves through ball contact. Children were more likely to injure their wrists, have a sprain/strain injury, or be injured falling to the ground. Adults were more likely to dislocate a joint or injure their hands., Conclusions: Differences in injury type, location and mechanism between females and males, and children and adults, suggest an opportunity for customised injury prevention and management strategies by sex and age., (© 2023 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

Objectives: Reactive side-step cutting manoeuvres are linked to anterior cruciate ligament (ACL) injuries in Women's Australian Football League (AFLW) matches. We explored knee joint moments and ground reaction forces (GRFs) in AFLW players when performing anticipated and unanticipated side-stepping., Methods: Sixteen AFLW players (age=25.3±4.2 years; height=1.71±0.06 m; mass=68.4±4.7 kg) completed anticipated and unanticipated side-stepping trials during which full-body three-dimensional kinematics and kinetics were recorded. One-dimensional statistical parametric mapping paired t-tests were used to compare three-dimensional knee moments during weight acceptance and GRFs during the stance phase between anticipated and unanticipated conditions., Results: Unanticipated side-stepping incurred lower knee flexion (18%-39% of stance, p<0.01) and abduction (11%-24% of stance, p<0.01) moments. Braking and propulsive GRFs were lower and higher, respectively, across the majority of stance phase (6%-90% of stance, p<0.01) in unanticipated side-stepping. Vertical GRFs were lower in unanticipated side-stepping in the early stance phase (14%-29% of stance, p<0.01)., Conclusion: Contrary to existing literature, AFLW players exhibited knee joint moments associated with reduced ACL loading when performing unanticipated side-stepping. Players appeared to adopt a 'cautious' approach to the unanticipated side-step (ie, decelerating at the change of direction), by reducing braking and vertical GRFs in the early stance phase of cutting. This approach may be implausible to employ or detrimental to performance during matches. AFLW ACL injury prevention programmes may be enhanced with greater exposure to scenarios that replicate reactive match-play demands when aiming to improve side-stepping biomechanics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Investigate the economic consequences of injuries to female Australian footballers from a health sector and societal perspective., Methods: This prospective observational study invited 242 females to complete an online questionnaire 3-6 months following an Australian football injury which involved presentation to an ED in Victoria, Australia. The questionnaire inquired regarding healthcare use, time off work, return to playing football and extent of recovery following injury. Relevant information was also extracted from respondents' medical records regarding injury-type, body part injured, investigations and treatments. Healthcare costs were determined for each respondent's ED presentation, hospital admission/s (when relevant), and subsequent healthcare use. Societal costs were determined as lost income to the respondent and/or carer., Results: A total of 108 people responded to the questionnaire. Sprains/strains and fractures accounted for 84.2% of respondents' injuries. Sixteen respondents (14.8%) required admission to hospital at the time of injury and 81 (75.0%) required subsequent healthcare appointments following discharge from the ED or hospital. Time off work or school following the injury was common (64.8% of respondents) and 27.8% of respondents had a carer take time off work. More than 80% of respondents missed training and matches following the injury. The median healthcare cost per respondent was AUD$753 and the median cost due to work absence was AUD$1393. One-quarter of respondents reported a full recovery., Conclusions: Injuries to female Australian footballers can produce substantial healthcare and societal costs, which has important implications for healthcare provision and prioritising and implementing injury prevention programmes and post-injury rehabilitation., (© 2023 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

Large-scale, climate-induced synchrony in the productivity of fish populations is becoming more pronounced in the world's oceans. As synchrony increases, a population's "portfolio" of responses can be diminished, in turn reducing its resilience to strong perturbation. Here we argue that the costs and benefits of trait synchronization, such as the expression of growth rate, are context dependent. Contrary to prevailing views, synchrony among individuals could actually be beneficial for populations if growth synchrony increases during favorable conditions, and then declines under poor conditions when a broader portfolio of responses could be useful. Importantly, growth synchrony among individuals within populations has seldom been measured, despite well-documented evidence of synchrony across populations. Here, we used century-scale time series of annual otolith growth to test for changes in growth synchronization among individuals within multiple populations of a marine keystone species (Atlantic cod, Gadus morhua). On the basis of 74,662 annual growth increments recorded in 13,749 otoliths, we detected a rising conformity in long-term growth rates within five northeast Atlantic cod populations in response to both favorable growth conditions and a large-scale, multidecadal mode of climate variability similar to the East Atlantic Pattern. The within-population synchrony was distinct from the across-population synchrony commonly reported for large-scale environmental drivers. Climate-linked, among-individual growth synchrony was also identified in other Northeast Atlantic pelagic, deep-sea and bivalve species. We hypothesize that growth synchrony in good years and growth asynchrony in poorer years reflects adaptive trait optimization and bet hedging, respectively, that could confer an unexpected, but pervasive and stabilizing, impact on marine population productivity in response to large-scale environmental change., (© 2022 The Authors. Ecology published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

Soft tissue sarcomas (STS) are rare malignant tumors often associated with poor outcomes and high local recurrence rates. Current tools for intraoperative and definitive margin assessment include intraoperative frozen section and permanent pathology, respectively. Indocyanine green dye (ICG) is a historically safe fluorophore dye that has demonstrated efficacy for intraoperative margin assessment in the surgical management of both breast and gastrointestinal cancers. The utility of ICG in the surgical management of sarcoma surgery has primarily been studied in pre-clinical mouse models and warrants further investigation as a potential adjunct to achieving negative margins. This study is a prospective, non-randomized clinical study conducted on patients with confirmed or suspected STS. Patients younger than 18 years, with a prior adverse reaction to iodine or fluorescein, or with renal disease were excluded from the study. Intravenous ICG was infused approximately three hours prior to surgery at a dosage of 2.0-2.5 mg/kg, and following tumor resection, the excised tumor and tumor bed were imaged for fluorescence intensity. When scanning the tumor bed, a threshold of 77% calibrated to the region of maximum intensity in the resected tumor was defined as a positive ICG margin, according to published protocols from the breast cancer literature. ICG results were then compared with the surgeon's clinical impression of margin status and permanent pathology results. Out of 26 subjects recruited for the original study, 18 soft tissue sarcomas (STS) were included for analysis. Three subjects were excluded for having bone sarcomas, and five subjects were excluded due to final pathology, which was ultimately inconsistent with sarcoma. The average age of patients was 64.1 years old (range: 28-83), with an average ICG dose of 201.8 mg. In 56% (10/18) of patients, ICG margins were consistent with the permanent pathology margins, with 89% specificity. The use of ICG as an intraoperative adjunct to obtaining negative margins in soft tissue sarcoma surgery is promising. However, studies with larger sample sizes are warranted to further delineate the accuracy, optimal dosage, timing, and types of sarcoma in which this diagnostic tool may be most useful.

Assault is the leading preventable cause of death, traumatic brain injury (TBI), and associated mental health problems. The COVID-19 pandemic has had a profound impact on patterns of interpersonal violence across the world. In this retrospective cross-sectional study, we analysed medical records of 1232 assault victims (domestic violence: 111, random assault: 900, prison assault: 221) with head injuries who presented to the emergency department (ED) at St Vincent's Hospital in Melbourne, Australia, a city with one of the longest and most severe COVID-19 restrictions worldwide. We examined changes in prevalence in the assault group overall and in domestic violence, random assault, and prison assault victims, comparing data from 19.5 months before and after the first day of COVID-19 restrictions in Melbourne. Moreover, we investigated differences driven by demographic factors ( Who : age group, sex, and nationality) and clinical variables ( Where : assault location, and When : time of arrival to the ED and time from moment of injury until presentation at ED). Descriptive statistics and chi-square analyses were performed. We found the COVID-19 pandemic significantly affected the Where of assault-related TBI, with a shift in the location of assaults from the street to the home, and the increase at home being driven by random assaults on middle-aged adults. Overall, we observed that 86% of the random assault cases were males, whereas 74% of the domestic assault cases were females. Meanwhile, nearly half (44%) of the random assault victims reported alcohol consumption versus a fifth (20%) of domestic violence victims. These findings will have direct implications for developing screening tools and better preventive and ameliorative interventions to manage the sequelae of assault TBI, particularly in the context of future large-scale health crises or emergencies.

Objectives: Alcohol is the most widely consumed psychoactive substance in Australia and the consequences of alcohol consumption have enormous personal and social impacts. This study aimed to describe the principal diagnoses of emergency department (ED) presentations involving alcohol use in the previous 12 hours at eight hospitals in Victoria and the Australian Capital Territory, Australia., Methods: Twelve months' data (1 July 2018 - 30 June 2019) were collected from eight EDs, including demographics, ICD-10 codes, hospital location and self-reported drinking in the preceding 12 hours. The ten most common ICD-10 discharge codes were analysed based on age, sex and hospital geographic area., Results: ICD codes pertaining to mental and behavioural disorders due to alcohol use accounted for the highest proportion in most EDs. Suicide ideation/attempt was in the five highest ICD codes for all but one hospital. It was the second most common alcohol-related presentation for both males and females., Conclusions: Alcohol plays a major role in a range of presentations, especially in relation to mental health and suicide., Implications for Public Health: The collection of alcohol involvement in ED presentations represents a major step forward in informing the community about the burden of alcohol on their health resources., (© 2022 The Authors.)

Background: Replacement of cytology screening with HPV testing is recommended and essential for cervical cancer elimination. HPV testing for primary screening was implemented in 12 laboratories within 9 Latin American countries, as part of the ESTAMPA cervical cancer screening study. Our observations provide information on critical operational aspects for HPV testing implementation in diverse resource settings., Methods: We describe the implementation process of HPV testing in ESTAMPA, focusing on laboratory aspects. We assess the readiness of 12 laboratories to start HPV testing and their continuity capacity to maintain good quality HPV testing until end of recruitment or up to December 2021. Readiness was based on a checklist. Information from the study database; regular meetings and monitoring visits; and a questionnaire on laboratory operational aspects sent in May 2020 were used to assess continuity capacity . Compliance with seven basic requirements (readiness) and eight continuity requirements (continuity capacity) was scored (1 = compliant, 0 = not compliant) and totaled to classify readiness and continuity capacity as very limited, limited, moderate or high. Experiences, challenges, and enablers of the implementation process are also described., Results: Seven of 12 laboratories had high readiness , three moderate readiness , and of two laboratories new to HPV testing, one had limited readiness and the other very limited readiness . Two of seven laboratories with high readiness also showed high continuity capacity , one moderate continuity capacity , and the other four showed limited continuity capacity since they could not maintain good quality HPV testing over time. Among three laboratories with moderate readiness , one kept moderate continuity capacity and two reached high continuity capacity. The two laboratories new to HPV testing achieved high continuity capacity . Based on gained expertise, five laboratories have become part of national screening programs., Conclusion: High readiness of laboratories is an essential part of effective implementation of HPV testing. However, high readiness is insufficient to guarantee HPV testing high continuity capacity , for which a "culture of quality" should be established with regular training, robust monitoring and quality assurance systems tailored to local context. All efforts to strengthen HPV laboratories are valuable and crucial to guarantee effective implementation of HPV-based cervical screening., Competing Interests: Author MH was employed by SMS-Oncology, Amsterdam, Netherlands. Author FD was employed by Laboratorio de Patología Oncológica, SAC, Peru. The remaining 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 © 2022 Rol, Picconi, Ferrera, Sánchez, Hernández, Lineros, Peraza, Brizuela, Mendoza, Mongelós, Cabrera, Rodríguez de la Peña, Correa, Terán, Colque Reynaga, García, Ramírez, Hernández-Nevarez, Doimi, Ramón, Arias-Stella, Zúñiga, Villagra, Bobadilla, Cardinal, Valls, Lucas, Baena, Fleider, Venegas, Cruz-Valdez, Rodríguez, Calderón, Wiesner, Luciani, Broutet, Herrero and Almonte.)

Objective: To evaluate the impact of an etonogestrel implant training program within a primary care Internal Medicine residency training program., Study Design: We surveyed graduates of our primary care Internal Medicine residency program in the Bronx, New York who performed implant procedures though the first 32 months after implementation of a monthly faculty-supervised resident implant clinic. We assessed the number of implants placed and removed per graduate, and surveyed graduates' satisfaction with the implant training program, perceived competence with implant procedures, and intent and ability to perform implant procedures and barriers to performing implant procedures postgraduation., Results: Between July 2017 and February 2020, 14 residents placed a total of 34 devices and removed four. All 14 program graduates completed the survey in August 2020. All but one respondent felt this training was valuable and 11 felt competent placing implants without supervision. Although 10 planned to provide implants following graduation, none have been able to, largely because of credentialing and clinic-practice level barriers., Conclusions: The primary care Internal Medicine program graduates we surveyed (n = 14) valued our etonogestrel implant training program and perceived competence, particularly with implant placement. However, even those who intended to provide etonogestrel implants postgraduation were unable to do so., Implications: Internal Medicine residents trained to place and remove etonogestrel implants are most comfortable with implant placement. However, these physicians may face barriers related to credentialing and ambulatory practice scope when attempting to provide this care in clinical practice., (Copyright © 2022. Published by Elsevier Inc.)

Background: Endovascular revascularization (EVR) is a pillar of therapeutic management in patients with symptomatic lower extremity artery disease (LEAD). Due to lack of scientific evidence, the approach of EVR type and the devices used at the different anatomic vascular segments of the lower limbs vary substantially between operators and centers. We analyzed data from the RECcording COurses of vasculaR Diseases (RECCORD) registry to assess the current real-world EVR treatment patterns in relation to anatomic vascular segments in symptomatic LEAD patients in Germany., Patients and Methods: RECCORD is an ongoing, prospective, multicenter, all-comers and entirely web-based registry platform. Baseline demographic and periprocedural data of patients undergoing EVR for symptomatic LEAD were assessed and performed EVRs were grouped according to the intervened anatomic vascular segment. We analyzed four EVR groups comprising either the aorto-iliac, femoropopliteal, or infrapopliteal segments (all these EVRs with or without a further intervention in another anatomic segment) or the infrapopliteal segment alone., Results: A total of 2210 EVR segments (in 1639 patients) were analyzed. Of those 616 (27.9%) were aorto-iliacal, 1346 (60.9%) femoropopliteal, 248 (11.2%) infrapopliteal and 104 (4.7%) only infrapopliteal segments. Aorto-iliac EVR was associated with younger age, smoking, claudication and simple lesions, while the distal infrapopliteal EVRs were related to advanced age, diabetes, multiple comorbidities, limb threatening ischemia and complex lesions. The use of different EVR devices at the aorto-iliac, femoropopliteal, infrapopliteal and only infrapopliteal segments were: only ballon-angioplasty: 8.3%, 12.9%, 58.1% and 63.5%; stenting: 82.3%, 45.3%, 16.9% and 12.5%; drug-coated balloon: 11.2%, 55.0%, 19.4% and 19.2%., Conclusion: The RECCORD registry data demonstrate that in LEAD clinical and lesion characteristics are related to anatomic vascular segments. Despite the clear relationship between vascular segments and the current use of device types, prospective, segment-specific clinical studies are warranted to establish a consistent, evidence-based path for EVR in LEAD.

Objective: Neuroimaging studies of obsessive-compulsive disorder (OCD) patients have highlighted the important role of deep gray matter structures. Less work has however focused on subcortical shape in OCD patients., Methods: Here we pooled brain MRI scans from 412 OCD patients and 368 controls to perform a meta-analysis utilizing the ENIGMA-Shape protocol. In addition, we investigated modulating effects of medication status, comorbid anxiety or depression, and disease duration on subcortical shape., Results: There was no significant difference in shape thickness or surface area between OCD patients and healthy controls. For the subgroup analyses, OCD patients with comorbid depression or anxiety had lower thickness of the hippocampus and caudate nucleus and higher thickness of the putamen and pallidum compared to controls. OCD patients with comorbid depression had lower shape surface area in the thalamus, caudate nucleus, putamen, hippocampus, and nucleus accumbens and higher shape surface area in the pallidum. OCD patients with comorbid anxiety had lower shape surface area in the putamen and the left caudate nucleus and higher shape surface area in the pallidum and the right caudate nucleus. Further, OCD patients on medication had lower shape thickness of the putamen, thalamus, and hippocampus and higher thickness of the pallidum and caudate nucleus, as well as lower shape surface area in the hippocampus and amygdala and higher surface area in the putamen, pallidum, and caudate nucleus compared to controls. There were no significant differences between OCD patients without co-morbid anxiety and/or depression and healthy controls on shape measures. In addition, there were also no significant differences between OCD patients not using medication and healthy controls., Conclusions: The findings here are partly consistent with prior work on brain volumes in OCD, insofar as they emphasize that alterations in subcortical brain morphology are associated with comorbidity and medication status. Further work is needed to understand the biological processes contributing to subcortical shape., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objective: To identify behavioural drivers and barriers that may have contributed to changes in ED attendance during the first 10 months of the coronavirus disease 2019 (COVID-19) pandemic in Victoria., Methods: We conducted a mixed methods analysis of patients who attended one of eight participating EDs between 1 November 2019 and 31 December 2020. A random sample of patients were chosen after their visit and invited to participate in an online survey assessing behavioural drivers and barriers to attendance. The study timespan was divided into four periods based on local and world events to assess changes in attitudes and behaviours over this period., Results: A total of 5600 patients were invited to complete the survey and 606 (11%) submitted sufficient information for analysis. There were significant differences in participants' attitudes towards healthcare and EDs, levels of concern about contracting and spreading COVID-19 and the influence of mask wearing. Patients expressed more concern about the safety of an ED during the largest outbreak of COVID-19 infections than they did pre-COVID, but this difference was not sustained once community infection numbers dropped. General concerns about hospital attendance were higher after COVID than they were pre-COVID. A total of 27% of patients specifically stated that they had delayed their ED attendance., Conclusion: Patients expressed increased concerns around attending ED during the first 10 months of the 2020 COVID-19 pandemic and frequently cited COVID-19 as a reason for delaying their presentation. These factors would be amenable to mitigation via focussed public health messaging., (© 2022 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

To develop vaccines for certain key global pathogens such as HIV, it is crucial to elicit both neutralizing and non-neutralizing Fc-mediated effector antibody functions. Clinical evidence indicates that non-neutralizing antibody functions including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) contribute to protection against several pathogens. In this study, we demonstrated that conjugation of HIV Envelope (Env) antigen gp120 to a self-assembling nanofiber material named Q11 induced antibodies with higher breadth and functionality when compared to soluble gp120. Immunization with Q11-conjugated gp120 vaccine (gp120-Q11) demonstrated higher tier 1 neutralization, ADCP, and ADCC as compared to soluble gp120. Moreover, Q11 conjugation altered the Fc N-glycosylation profile of antigen-specific antibodies, leading to a phenotype associated with increased ADCC in animals immunized with gp120-Q11. Thus, this nanomaterial vaccine strategy can enhance non-neutralizing antibody functions possibly through modulation of immunoglobulin G Fc N-glycosylation.

Background: This study characterizes the outcomes and complications of surgical reconstruction of distal radioulnar joint (DRUJ) instability using the extensor retinaculum (Herbert sling). Our hypothesis was that extensor retinaculum reconstruction is a reliable method of DRUJ stabilization in adolescents., Methods: This was a retrospective study of pediatric patients treated surgically using the Herbert sling for DRUJ instability at a single institution. We identified 22 subjects who underwent surgery at an average of 16.2 years of age (range, 12-18 years). Medical records and available imaging were reviewed for all subjects, and patients were contacted to participate in the prospective completion of the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire., Results: Preoperative symptoms were more commonly pain (95%) than feelings of DRUJ instability (45%), although 100% had instability on physical examination. Eight (36%) patients demonstrated limited supination preoperatively. Twenty-one subjects (95%) noted prior injury to that wrist, 15 of which were distal radius fractures. Surgery consisted of stabilization of the DRUJ using extensor retinaculum, in concert with other procedures to address all potential causes of wrist pain. Postoperatively, DRUJ stability was maintained in 21 of 22 subjects. Of the 12 patients who provided functional outcome scores, median QuickDASH score was 7.6 (range, 0-45)., Conclusions: Distal radioulnar joint instability in adolescents is often preceded by fracture of the distal radius. Surgeons must maintain a high level of suspicion to appropriately diagnose DRUJ instability, which is often not an isolated pathoanatomical problem. The Herbert sling technique using extensor retinaculum can successfully confer DRUJ stability in this population.

Human cytomegalovirus (HCMV) is the most common congenital infection and a leading cause of stillbirth, neurodevelopmental impairment, and pediatric hearing loss worldwide. Development of a maternal vaccine or therapeutic to prevent congenital HCMV has been hindered by limited knowledge of the immune responses that protect against HCMV transmission in utero. To identify protective antibody responses, we measured HCMV-specific IgG binding and antiviral functions in paired maternal and cord blood sera from HCMV-seropositive transmitting (n = 41) and non-transmitting (n = 40) mother-infant dyads identified via a large, US-based, public cord blood bank. We found that high-avidity IgG binding to HCMV and antibody-dependent cellular phagocytosis (ADCP) were associated with reduced risk of congenital HCMV infection. We also determined that HCMV-specific IgG activation of FcγRI and FcγRII was enhanced in non-transmitting dyads and that increased ADCP responses were mediated through both FcγRI and FcγRIIA expressed on human monocytes. These findings suggest that engagement of FcγRI/FcγRIIA and Fc effector functions including ADCP may protect against congenital HCMV infection. Taken together, these data can guide future prospective studies on immune correlates against congenital HCMV transmission and inform HCMV vaccine and immunotherapeutic development.

Early initiation of antiretroviral therapy (ART) significantly improves clinical outcomes and reduces mortality of infants/children living with HIV. However, the ability of infected cells to establish latent viral reservoirs shortly after infection and to persist during long-term ART remains a major barrier to cure. In addition, while early ART treatment of infants living with HIV can limit the size of the virus reservoir, it can also blunt HIV-specific immune responses and does not mediate clearance of latently infected viral reservoirs. Thus, adjunctive immune-based therapies that are geared towards limiting the establishment of the virus reservoir and/or mediating the clearance of persistent reservoirs are of interest for their potential to achieve viral remission in the setting of pediatric HIV. Because of the differences between the early life and adult immune systems, these interventions may need to be tailored to the pediatric settings. Understanding the attributes and specificities of the early life immune milieu that are likely to impact the virus reservoir is important to guide the development of pediatric-specific immune-based interventions towards viral remission and cure. In this review, we compare the immune profiles of pediatric and adult HIV elite controllers, discuss the characteristics of cellular and anatomic HIV reservoirs in pediatric populations, and highlight the potential values of current cure strategies using immune-based therapies for long-term viral remission in the absence of ART in children living with HIV., Competing Interests: Author SP serves as a consultant for Moderna, Merck, Dynavax, Pfizer, and Hoopika CMV vaccine programs and leads a sponsored research program on CMV vaccines with Moderna and Merck. The remaining 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 © 2022 Berendam, Nelson, Yagnik, Goswami, Styles, Neja, Phan, Dankwa, Byrd, Garrido, Amara, Chahroudi, Permar and Fouda.)

Background: Surgeons are sometimes presented with patients with distal radius fractures who present in a delayed fashion or lose reduction after several weeks of attempted closed management. There are limited studies on delayed surgical treatment of distal radius fractures to assist providers in decision-making., Methods: We conducted a matched cohort study to compare radiographic outcomes and complications for patients with a distal radius fracture treated with delayed (3-5 weeks) or early (0-2 weeks) surgical fixation. Patients ages 18+ who underwent open reduction and internal fixation of distal radius fractures by a volar approach at 2 Level I trauma centers between 2003 and 2015 were eligible. We measured radiographic outcomes and reviewed medical records to determine operative approach and complications., Results: There were 25 cases and 50 controls matched for age (18-87), sex, and AO fracture type. The delayed group had surgery at a mean of 24.8 days from injury and the early group at 5.6 days. There was no statistically significant difference between the delayed and early cohorts in radiographic parameters on injury x-rays, in improvement in radiographic parameters on first postoperative x-rays, or in maintenance of radiographic parameters at union., Conclusion: We did not find significant differences in radiographic outcomes or complication rates between patients with delayed versus early surgical treatment for distal radius fracture. Providers treating patients with late presentation or late displacement have the option of surgical fixation beyond the first few weeks after injury., Level of Evidence: III (Retrospective matched cohort study).

Background: There is no clear consensus for the criteria for closed treatment of metacarpal neck fractures. Our objective was to determine whether closed reduction of pediatric fifth metacarpal neck fractures results in a clinically meaningful improvement in radiographic angulation., Methods: We performed a retrospective cohort study of pediatric patients with fifth metacarpal neck fractures treated with closed reduction. Radiographs were examined for sagittal fracture angulation measured post-reduction, 2 to 14 days post-reduction, and 21 to 35 days post-reduction. We compared the angulation for open versus closed physes, initial fracture angulation greater than or less than 50°, and immobilization in extension versus intrinsic-plus position., Results: Fifty-four subjects were included with an average age of 14.8 years at the time of injury and a mean initial fracture angulation of 42.7°. The improvement in fracture angulation was 8.3° (90% confidence interval [CI], 5.9-10.7) on post-reduction radiographs, 8.5° (90% CI, 6.1-10.9) at 2 to 14 days post-reduction, and 4.3° (90% CI, 1.4-7.2) at 21 to 35 days post-reduction. Subgroup analysis showed that patients with injury angle greater than or equal to 50° had significantly higher mean reductions than those with injury angle less than 50°. In this group, angulation improved 15.6° (90% CI, 8.5-22.7) post-reduction, 15.1° (90% CI, 10.1-20.1) at 2 to 14 days post-reduction, and 16.5° (90% CI, 10.4-22.6) at 21 to 35 days post-reduction., Conclusions: Closed reduction of pediatric fifth metacarpal neck fractures with initial fracture angulation less than 50° may not meaningfully improve sagittal alignment. For fractures with initial angulation greater than or equal to 50°, closed reduction resulted in clinically important, statistically significant, and lasting improvements of 16.5°.

Improved access to antiretroviral therapy (ART) and antenatal care has significantly reduced in utero and peripartum mother-to-child human immunodeficiency virus (HIV) transmission. However, as breast milk transmission of HIV still occurs at an unacceptable rate, there remains a need to develop an effective vaccine for the pediatric population. Previously, we compared different HIV vaccine strategies, intervals, and adjuvants in infant rhesus macaques to optimize the induction of HIV envelope (Env)-specific antibodies with Fc-mediated effector function. In this study, we tested the efficacy of an optimized vaccine regimen against oral simian-human immunodeficiency virus (SHIV) acquisition in infant macaques. Twelve animals were immunized with 1086.c gp120 protein adjuvanted with 3M-052 in stable emulsion and modified vaccinia Ankara (MVA) virus expressing 1086.c HIV Env. Twelve control animals were immunized with empty MVA. The vaccine prime was given within 10 days of birth, with booster doses being administered at weeks 6 and 12. The vaccine regimen induced Env-specific plasma IgG antibodies capable of antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). Beginning at week 15, infants were exposed orally to escalating doses of heterologous SHIV-1157(QNE)Y173H once a week until infected. Despite the induction of strong Fc-mediated antibody responses, the vaccine regimen did not reduce the risk of infection or time to acquisition compared to controls. However, among vaccinated animals, ADCC postvaccination and postinfection was associated with reduced peak viremia. Thus, nonneutralizing Env-specific antibodies with Fc effector function elicited by this vaccine regimen were insufficient for protection against heterologous oral SHIV infection shortly after the final immunization but may have contributed to control of viremia. IMPORTANCE Women of childbearing age are three times more likely to contract HIV infection than their male counterparts. Poor HIV testing rates coupled with low adherence to antiretroviral therapy (ART) result in a high risk of mother-to-infant HIV transmission, especially during the breastfeeding period. A preventative vaccine could curb pediatric HIV infections, reduce potential health sequalae, and prevent the need for lifelong ART in this population. The results of the current study imply that the HIV Env-specific IgG antibodies elicited by this candidate vaccine regimen, despite a high magnitude of Fc-mediated effector function but a lack of neutralizing antibodies and polyfunctional T cell responses, were insufficient to protect infant rhesus macaques against oral virus acquisition.

Objective: Magnetic resonance imaging (MRI) is often used in practice to investigate for cord or discoligamentous injury following blunt trauma and a normal computed tomography (CT). This study investigates the MRI findings and surgical outcomes of patients in this cohort., Methods: Retrospective analysis of patients following trauma with suspected cervical spine injury from 2016 to 2019. Inclusion criteria included patients receiving a normal CT of the cervical spine and subsequent MRI due to cervical spine injury symptomatology (persistent tenderness and/or neurology). Inclusion criteria included: age ≥16 years, alert and <72 h from CT to MRI. Mann-Whitney and χ 2 statistical analysis techniques were employed., Results: Two hundred and twenty-eight patients with persistent midline tenderness and/or persistent neurology following blunt trauma and negative CT report were included. One hundred and eighty-one patients received an MRI for persistent tenderness of which 35 revealed abnormal MRI findings. Twenty-one cases required no treatment, 14 cases were treated with a rigid collar with no patients requiring operative management. Forty-seven patients received an MRI for neurological symptoms following blunt trauma and negative CT, with 11 abnormal MRI findings. Management included no treatment (three cases), application of rigid collar (six cases) and operative management (two cases)., Conclusion: No alert neurologically intact patient with 'persistent tenderness only' received operative management following a normal CT examination. While MRI is sensitive for detecting soft tissue injuries, the prevalence for detecting clinically significant cervical spine injury in blunt trauma patients in the absence of neurology is low. The utility of MRI in this cohort is questionable considering prolonged spinal immobilisation is not without harm., (© 2021 Australasian College for Emergency Medicine.)

Different HIV vaccine regimens elicit distinct plasma antibody responses in both human and nonhuman primate models. Previous studies in human and non-human primate infants showed that adjuvants influenced the quality of plasma antibody responses induced by pediatric HIV envelope vaccine regimens. We recently reported that use of the 3M052-SE adjuvant and longer intervals between vaccinations are associated with higher magnitude of antibody responses in infant rhesus macaques. However, the impact of different adjuvants in HIV vaccine regimens on the developing infant B cell receptor (BCR) repertoire has not been studied. This study evaluated whether pediatric HIV envelope vaccine regimens with different adjuvants induced distinct antigen-specific memory B cell repertoires and whether specific immunoglobulin (Ig) immunogenetic characteristics are associated with higher magnitude of plasma antibody responses in vaccinated infant rhesus macaques. We utilized archived preclinical pediatric HIV vaccine studies PBMCs and tissue samples from 19 infant rhesus macaques immunized either with (i) HIV Env protein with a squalene adjuvant, (ii) MVA-HIV and Env protein co-administered using a 3-week interval, (iii) MVA-HIV prime/ protein boost with an extended 6-week interval between immunizations, or (iv) with HIV Env administered with 3M-052-SE adjuvant. Frequencies of vaccine-elicited HIV Env-specific memory B cells from PBMCs and tissues were similar across vaccination groups (frequency range of 0.06-1.72%). There was no association between vaccine-elicited antigen-specific memory B cell frequencies and plasma antibody titer or avidity. Moreover, the epitope specificity and Ig immunogenetic features of vaccine-elicited monoclonal antibodies did not differ between the different vaccine regimens. These data suggest that pediatric HIV envelope vaccine candidates with different adjuvants that previously induced higher magnitude and quality of plasma antibody responses in infant rhesus macaques were not driven by distinct antigen-specific memory BCR repertoires., Competing Interests: The authors have declared that no competing interests exist.

Understanding viral rebound in pediatric HIV-1 infection may inform the development of alternatives to lifelong antiretroviral therapy (ART) to achieve viral remission. We thus investigated viral rebound after analytical treatment interruption (ATI) in 10 infant macaques orally infected with SHIV.C.CH505 and treated with long-term ART. Rebound viremia was detected within 7 to 35 days of ATI in 9 of 10 animals, with posttreatment control of viremia seen in 5 of 5 Mamu-A*01+ macaques. Single-genome sequencing revealed that initial rebound virus was similar to viral DNA present in CD4+ T cells from blood, rectum, and lymph nodes before ATI. We assessed the earliest sites of viral reactivation immediately following ATI using ImmunoPET imaging. The largest increase in signal that preceded detectable viral RNA in plasma was found in the gastrointestinal (GI) tract, a site with relatively high SHIV RNA/DNA ratios in CD4+ T cells before ATI. Thus, the GI tract may be an initial source of rebound virus, but as ATI progresses, viral reactivation in other tissues likely contributes to the composition of plasma virus. Our study provides potentially novel insight into the features of viral rebound in pediatric infection and highlights the application of a noninvasive technique to monitor areas of HIV-1 expression in children.

Triangular fibrocartilage complex (TFCC) tears can cause ulnar-sided wrist pain in children and adolescents following acute rotational injury or prior distal radius fracture. Surgical treatment, guided by the Palmer classification, is considered after activity modification and occupational therapy. All concomitant wrist pathologies, such as distal radioulnar joint instability, ulnocarpal impaction, and distal radius malunion, must be recognized and addressed at the time of TFCC debridement or repair. This article reviews recent literature guiding clinical evaluation and surgical treatment of children and adolescents with TFCC injuries. The authors' techniques for arthroscopic-assisted outside-in repair of Palmer 1B and 1D tears are described., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Vascular access site complications (ASC) are among the most frequent complications of percutaneous cardiovascular procedures (PCP) and are associated with adverse outcome and high resources utilization. In this prospective study, we investigated patients with postprocedural clinical suspicion of ASC evaluated by duplex ultrasound (DUS) for the presence of ASC. We assessed the incidence, in-hospital outcome, treatment of complications and predictors for ASC. Overall, 12,901 patients underwent PCP during a 40 months period. Of those, 2890 (22.4%) patients had postprocedural clinical symptoms of ASC and were evaluated using DUS. An ASC was found in 206 of the DUS examined patients (corresponding to 7.1% of the 2890 DUS examined patients). In 6.7% of all valvular/TAVI procedures, an ASC was documented, while coronary, electrophysiological and peripheral PCP had a comparable and low rate of complications (1.2-1.5%). Pseudoaneurysm (PSA) was the most frequent ASC (67.5%), followed by arteriovenous fistula (13.1%), hematoma (7.8%) and others (11.7%). Of all PSA, 84 (60.4%) were treated surgically, 44 (31.6%) by manual compression and 11 (7.9%) conservatively. Three (0.02%) patients died due to hemorrhagic shock. In conclusion, femoral ASC are rare in the current era of PCP with PSA being the leading type of ASC. Nonetheless, patients with predisposing risk factors and postprocedural suspicious clinical findings should undergo a DUS to early detect and mitigate ASC-associated outcome.

Background: Exposure and response prevention is an effective treatment for obsessive-compulsive disorder (OCD), but it is unclear how symptom reduction is related to changes in the brain. We aimed to determine the effects of a 4-day concentrated exposure and response prevention program (Bergen 4-day treatment) on the static and dynamic functional connectome in patients with OCD., Methods: Thirty-four patients with OCD (25 unmedicated) underwent resting-state functional magnetic resonance imaging the day before the Bergen 4-day treatment, and 28 (21 unmedicated) were rescanned after 1 week. Twenty-eight healthy control subjects were also scanned for baseline comparisons and 19 of them were rescanned after 1 week. Static and dynamic graph measures were quantified to determine network topology at the global, subnetwork, and regional levels (including efficiency, clustering, between-subnetwork connectivity, and node flexibility in module allegiance). The Yale-Brown Obsessive Compulsive Scale was used to measure symptom severity., Results: Twenty-four patients (86%) responded to treatment. We found significant group × time effects in frontoparietal-limbic connectivity (η p 2  = 0.19, p = .03) and flexibility of the right subgenual anterior cingulate cortex (η p 2  = 0.18, p = .03), where, in both cases, unmedicated patients showed significant decreases while healthy control subjects showed no significant changes. Healthy control subjects showed increases in global and subnetwork efficiency and clustering coefficient, particularly in the somatomotor subnetwork., Conclusions: Concentrated exposure and response prevention in unmedicated patients with OCD leads to decreased connectivity between the frontoparietal and limbic subnetworks and less flexibility of the connectivity of the subgenual anterior cingulate cortex, suggesting a more independent and stable network topology. This may represent less limbic interference on cognitive control subnetworks after treatment., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: The subtypes of surface osteosarcomas include well-differentiated, low-grade parosteal osteosarcoma (POS), intermediate-grade periosteal osteosarcoma (PerOS), high-grade surface osteosarcoma (HGSO), and high-grade, dedifferentiated POS (dPOS). We aimed to determine disease progression, defined as local recurrence and metastatic disease, and overall (OS) and disease-specific survival (DSS). We identify outcome predictive factors and report functional results., Methods: This retrospective study evaluated patients with primary surface osteosarcoma at our hospital from 1992 to 2019. Fifty-one patients had a median follow-up of 6.1 years (range: 0.1-25.2). Histologic subtypes included 32 POS, 11 PerOS, 4 HGSO, and 3 dPOS. Bone and soft tissue margins were classified using the American Joint Committee on Cancer residual tumor classification (Rx = Not evaluable; R0 = negative margin; R1 = microscopic positive margin; and R2 = macroscopic positive margin) and the modified R classification (mRx = not evaluable; mR0 = negative margin >1 mm; mR1 = negative margin ≤1 mm; mR1-dir: Positive microscopic margin locally; mR2a: Positive macroscopic margin locally; mR2b: positive macroscopic margin distally; and mR2C: positive macroscopic margin locally and distally). Forty-one patients had functional outcomes., Results: Three POS patients developed recurrence: two had R0 margins and one an intralesional resection. Five patients developed lung metastases (POS: 3, dPOS: 2). Four patients died. The only significant disease progression predictor was age. OS at 10 years was 97%. 48 patients had negative bone margins (R0 or mR0 and mR1) and 47 patients had negative soft-tissue margins (R0 or mR0 and mR1). The average MSTS score was 88.43 (range: 34.29-100)., Conclusions: We advocate surgery for POS and believe R0 (mR0 and mR1 resections) or planned R1 (mR1-dir) to preserve function are acceptable. We favor chemotherapy and surgery for PerOS, though a chemotherapeutic response is highly variable. High-grade tumors are the most infrequent subtype, but HGSO and dPOS seem to portend a poorer prognosis. Good function can be obtained., (© 2021 Wiley Periodicals LLC.)

Background: Peripheral arterial occlusive disease (PAOD) is an atherosclerotic vascular disease with high morbidity and mortality. A consistent medication-based secondary prevention is part of the essential and evidence-based treatment of PAOD. The aim of this study was to ascertain the status quo of medicinal secondary prevention based on submitted prescriptions., Methods: In the time period from 2014 to 2017 patients with a confirmed PAOD coding (I70.2-/I73.9-) were identified based on secondary data of the Association of Statutory Health Insurance Physicians Westphalia-Lippe (KVWL). The prescriptions submitted with respect to platelet inhibitors, oral anticoagulants, lipid lowering therapy (LLT) and angiotensin-converting enzyme (ACE) inhibitors in the fourth quarter year after diagnosis coding were collated., Results: In the diagnosis period 2014/2015 a total of 238,397 patients had PAOD in the catchment area of the KVWL. The proportion of submitted prescriptions in the fourth quarter year after diagnosis was 25.9% for LLT, 13.6% for acetylsalicylic acid, 4.5% for clopidogrel, 5.5% for vitamin K antagonists (VKA), 3.5% for non-vitamin K‑dependent oral anticoagulants (NOAC) and 26.8% for ACE inhibitors. Over the course of the 3 years (n = 241,375 patients with PAOD 2016/2017) the proportion of submitted prescriptions for all substances except VKA increased (p < 0.001), whereby the largest relative increase was noted for NOAC (relative increase of 81.7%)., Conclusion: The guideline-conform medicinal secondary prevention in patients with PAOD in Germany is still in need of improvement. A consistent implementation of evidence-based medicinal secondary prevention harbors a great potential for improvement of the overall prognosis in patients with PAOD., (© 2020. The Author(s).)

Objective: Evaluation of an early discharge program for COVID-19-patients who still required additional oxygen support, supervised by their own general practitioner (GP) in a home setting. We evaluated safety and gathered experiences from patients, caregivers and GPs., Design: Cohort study (prospective and retrospective inclusion) METHOD: Adult COVID-19-patients admitted to one of the three Amsterdam hospitals, the Netherlands, were eligible when clinically stable for at least 48 hours, with a minimum oxygen saturation of 94% and a maximum of 3 l/min oxygen support. Patients were included from 23-10-2020 to 26-03-2021., Results: We included 113 patients, of whom 40 retrospectively . Median age was 58 years and median length of hospital stay 8 days. Four patients (3.7%) were readmitted within 14 days after discharge. Median duration of oxygen support at home was 8 days. Almost no home visits were conducted by GPs, but contact by telephone was regular (median 6 times in 2 weeks). All stakeholders reported feeling safe, able and confident while delivering the necessary (self) care. The program was graded by patients and GPs with an 8 (on a scale of 1 to 10)., Conclusion: Early discharge for COVID-19-patients with a necessity for oxygen support, under supervision of the GP, is safe and was positively evaluated by all stakeholders involved.

Background: Population segmentation and risk stratification are important strategies for allocating resources in public health, health care and social care. Social exclusion, which is defined as the cumulation of disadvantages in social, economic, cultural and political domains, is associated with an increased risk of health problems, low agency, and as a consequence, a higher need for health and social care. The aim of this study is to test social exclusion against traditional social stratifiers to identify high-risk/high-need population segments., Methods: We used data from 33,285 adults from the 2016 Public Health Monitor of four major cities in the Netherlands. To identify at-risk populations for cardiovascular risk, cancer, low self-rated health, anxiety and depression symptoms, and low personal control, we compared relative risks (RR) and population attributable fractions (PAF) for social exclusion, which was measured with the Social Exclusion Index for Health Surveys (SEI-HS), and four traditional social stratifiers, namely, education, income, labour market position and migration background., Results: The analyses showed significant associations of social exclusion with all the health indicators and personal control. Particular strong RRs were found for anxiety and depression symptoms (7.95) and low personal control (6.36), with corresponding PAFs of 42 and 35%, respectively. Social exclusion was significantly better at identifying population segments with high anxiety and depression symptoms and low personal control than were the four traditional stratifiers, while the two approaches were similar at identifying other health problems. The combination of social exclusion with a low labour market position (19.5% of the adult population) captured 67% of the prevalence of anxiety and depression symptoms and 60% of the prevalence of low personal control, as well as substantial proportions of the other health indicators., Conclusions: This study shows that the SEI-HS is a powerful tool for identifying high-risk/high-need population segments in which not only ill health is concentrated, as is the case with traditional social stratifiers, but also a high prevalence of anxiety and depression symptoms and low personal control are present, in addition to an accumulation of social problems. These findings have implications for health care practice, public health and social interventions in large cities., (© 2021. The Author(s).)

Objectives: To compare injury-profiles of females and males presenting to Emergency Departments (EDs) with an Australian Football injury., Design: Prospective observational study., Methods: All patients presenting to one of 10 EDs in Victoria, Australia, with an Australian Football injury were included in the study. Data were prospectively collected over a 10 month period, coinciding with a complete Australian Football season, including pre-season training and practice matches. Relevant information was extracted from patient medical records regarding injury-type, body part injured, investigations and treatments required. Female and male data were compared with chi-squared and Fisher's exact tests., Results: 1635 patients were included, of whom 242 (14.8%) were female. Females had a higher proportion of hand/finger injuries (34.3% v 23.4%), neck injuries (6.6% v 2.5%) and patella dislocations (2.9% v 0.6%). Males had a higher proportion of shoulder injuries (11.5% v 5.8%), skin lacerations (8.0% v 1.7%), and thorax/abdominal/pelvic injuries (5.7% v 2.1%). Concussion rates were similar between the genders, occurring in 14.1% of all patients. Anterior cruciate ligament injuries were infrequent (1.0%) and not significantly different between genders. Females received more imaging investigations (83.1% v 74.7%) and analgesia (62.4% v 48.5%). A higher proportion of males required admission to hospital (5.0% v 2.1%), usually for surgery., Conclusion: Australian Football injury profiles differed between females and males. Gender-specific injury prevention and management programs would be indicated based on the study findings., (Copyright © 2021 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Background: Post-contrast acute kidney injury (AKI) is a dreaded complication of endovascular revascularization using iodinated contrast medium in patients with peripheral artery disease and concomitant chronic kidney disease (CKD). This study sought to evaluate the incidence of AKI in patients with peripheral artery disease and CKD undergoing endovascular revascularization and using carbon dioxide (CO 2 ) as contrast medium., Methods and Results: From 04/2015 to 07/2018, all consecutive peripheral artery disease patients with CKD stage ≥ 3 referred for endovascular revascularization of symptomatic peripheral artery disease were prospectively included. During endovascular revascularization, CO 2 as contrast medium was manually injected and iodinated contrast medium was additionally used when needed. The reference group consisted of 211 cardiovascular risk factor-matched patients undergoing endovascular revascularization with iodinated contrast medium only. CO 2 -guided endovascular revascularization was performed in 102 patients, thereof 16 (15.7%) patients exclusively with CO 2 . Baseline CKD stage ≥ 4 and iodinated contrast medium volume > 50 ml were disproportionally associated with post-procedural post-contrast AKI. At CKD stage 4 the odds ratio for post-contrast AKI was 13.2 (95% CI 1.489-117.004; p = 0.02) for iodinated contrast medium volume 51-100 ml and 37.7 (95% CI 3.927-362.234; p = 0.002) for iodinated contrast medium volume > 100 ml. The corresponding values at CKD stage 5 were 23.7 (95% CI 2.666-210.583; p = 0.005) and 28.3 (95% CI 3.289-243.252; p = 0.002), respectively. Radiation (dose area product) was significantly higher in the CO 2 -endovascular revascularization group (6.025 ± 6.926 cGy*cm 2 vs. 4.281 ± 4.722 cGy*cm 2 , p = 0.009)., Conclusion: CO 2 is an applicable and safe alternative to iodinated contrast medium for endovascular revascularization in peripheral artery disease patients with concomitant CKD. Patients with CKD stage 4 or 5, being at highest risk for post-contrast AKI, should primarily be treated by CO 2 -guided endovascular revascularization.

Purpose: Population-based comparisons between minimally invasive surgery (MIS) (robotic surgery [RS] and laparoscopic surgery [LS]) and open surgery (OS) for managing endometrial cancer are lacking. This study aimed to compare surgical and oncologic outcomes between endometrial cancer patients who underwent surgical staging via MIS or OS., Materials and Methods: A population-based retrospective cohort study was performed using claims data from the Korean National Health Insurance database from January 2012 to December 2016. All patients who underwent hysterectomy under diagnosis of endometrial cancer were identified. Patients were classified into RS, LS, and OS groups. Operative and oncologic outcomes were compared among the three groups after adjustments for age group, risk group (adjuvant therapy status), modified Charlson comorbidity index, income level, insurance type, and index year using propensity scores obtained via the inverse probability of treatment weighted method., Results: After adjustment, 5,065 patients (RS, n=315; LS, n=3,248; OS, n=1,503) were analyzed. Patient demographics were comparable. Hospital stay, postoperative complications, and cost were more favorable in the RS and LS groups than in the OS group (all p < 0.001). Five-year overall survival was significantly longer in the RS and LS groups than in the OS group (94.8%, 91.9%, and 86.9%, respectively; p < 0.001). Moreover, the survival benefit of RS was shown in the subgroup analysis of low-risk endometrial cancer patients., Conclusion: Our study provides further evidence for the RS being a safe surgical alternative to the LS and OS, especially in low-risk endometrial cancer patients, offering surgical and oncologic outcomes equivalent to other surgical approaches.

Background: Obsessive-compulsive disorder (OCD) has been related to worse performance, abnormal brain activity, and functional connectivity during response inhibition. Whether these findings are indications of stable traits that contribute to the development of the disorder, or whether they are a result of the state severity of obsessions and anxiety, remains unclear since previous research mainly has employed cross-sectional designs. The present study aimed to assess longitudinal between- and within-person relationships between symptoms, task performance, right inferior frontal gyrus brain activation, and connectivity between the right amygdala and the right pre-supplementary motor area in 29 OCD patients before and after concentrated exposure and response prevention treatment. Method: Patients received exposure and response prevention delivered during 4 consecutive days, following the Bergen 4-day Treatment format. Patients performed a Stop Signal Task during 3T functional Magnetic Resonance Imaging the day before treatment, as well as 1 week and 3 months after treatment completion. Multilevel models were used to analyze disaggregated within- and between-person effects over time. Independent variables were scores on the symptom severity scales for OCD, anxiety, depression, and state distress during scanning. Dependent variables were reaction time for go trials, stop signal response time, task-related brain activation and connectivity. Results: A positive between-person effect was found for obsessive-compulsive, anxiety, and depressive symptom severity on go trial reaction time, indicating that patients with higher symptom scores on average respond slower during accurate go trials. We also found no significant between- or within-person relations between symptom severity and task-related activation or fronto-limbic connectivity. Conclusions: The between-person findings may point toward a general association between slower processing speed and symptom severity in OCD. Longitudinal studies should disaggregate between- and within-person effects to better understand variation over time., Competing Interests: OH has received speaker's honorarium by Benecke. The remaining 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 © 2021 Hagland, Thorsen, Ousdal, Gjestad, de Wit, Hansen, Hagen, Kvale and van den Heuvel.)

Daily burden and clinical toxicities associated with antiretroviral therapy (ART) emphasize the need for alternative strategies to induce long-term human immunodeficiency virus (HIV) remission upon ART cessation. Broadly neutralizing antibodies (bNAbs) can both neutralize free virions and mediate effector functions against infected cells and therefore represent a leading immunotherapeutic approach. To increase potency and breadth, as well as to limit the development of resistant virus strains, it is likely that bNAbs will need to be administered in combination. It is therefore critical to identify bNAb combinations that can achieve robust polyfunctional antiviral activity against a high number of HIV strains. In this study, we systematically assessed the abilities of single bNAbs and triple bNAb combinations to mediate robust polyfunctional antiviral activity against a large panel of cross-clade simian-human immunodeficiency viruses (SHIVs), which are commonly used as tools for validation of therapeutic strategies targeting the HIV envelope in nonhuman primate models. We demonstrate that most bNAbs are capable of mediating both neutralizing and nonneutralizing effector functions against cross-clade SHIVs, although the susceptibility to V3 glycan-specific bNAbs is highly strain dependent. Moreover, we observe a strong correlation between the neutralization potencies and nonneutralizing effector functions of bNAbs against the transmitted/founder SHIV CH505. Finally, we identify several triple bNAb combinations comprising of CD4 binding site-, V2-glycan-, and gp120-gp41 interface-targeting bNAbs that are capable of mediating synergistic polyfunctional antiviral activities against multiple clade A, B, C, and D SHIVs. IMPORTANCE Optimal bNAb immunotherapeutics will need to mediate multiple antiviral functions against a broad range of HIV strains. Our systematic assessment of triple bNAb combinations against SHIVs will identify bNAbs with synergistic, polyfunctional antiviral activity that will inform the selection of candidate bNAbs for optimal combination designs. The identified combinations can be validated in vivo in future passive immunization studies using the SHIV challenge model., (Copyright © 2021 American Society for Microbiology.)

Competing Interests: Conflict of interestThe authors declare that they have no competing interest.