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Abstract This Scientific Report was carried out in the context of the self‐task mandate (M‐2023‐00097) of the EFSA's Scientific Committee on ‘Guidance on the use of biomarkers of effect in regulatory risk assessment of chemicals’. In the first phase, the project on biomarkers of effect started with a feasibility study (EFSA‐Q‐2024‐00128), with the intention to look closer at definitions and descriptions of biomarkers of effect, as well as to explore several concepts related to the context of application and other scientific principles to be further considered for its development. In addition, relevant activities, initiatives and knowledge in this area were collected and analysed within a complementary mapping study. The outcome of this phase aimed to create a structured basis for future guidance, to identify challenges and to recommend a way forward for its development. The recommendations refer especially to terminologies, the scope of the guidance and several scientific and technical aspects of the selection and interpretation of biomarkers of effect that need to be addressed in future guidance. Moreover, further recommendation refers to the collaborative process to be established with other regulatory organisations that should support the harmonisation and reduce divergencies in the application of methodologies across organisations or sectors.

Abstract Over recent decades, our understanding of climate change has accelerated greatly, but unfortunately, observable impacts have increased in tandem. Both mitigation and adaptation have not progressed at the level or scale warranted by our collective knowledge on climate change. More effective approaches to engage people on current and future anthropogenic climate change effects are urgently needed. Here, we show how species whose distributions are shifting in response to climate change, that is, ‘species‐on‐the‐move’, present an opportunity to engage people with climate change by linking to human values, and our deep connections with the places in which we live, in a locally relevant yet globally coherent narrative. Species‐on‐the‐move can impact ecosystem structure and function, food security, human health, livelihoods, culture and even the climate itself through feedback to the climate system, presenting a wide variety of potential pathways for people to understand that climate change affects them personally as individuals. Citizen science focussed on documenting changes in biodiversity is one approach to foster a deeper engagement on climate change. However, other possible avenues, which may offer potential to engage people currently unconnected with nature, include arts, games or collaborations with rural agriculture (e.g. new occurrences of pest species) or fisheries organisations (e.g. shifting stocks) or healthcare providers (e.g. changing distributions of disease vectors). Through the importance we place on the aspects of life impacted by the redistribution of species around us, species‐on‐the‐move offer emotional pathways to connect with people on the complex issue of climate change in profound ways that have the potential to engender interest and action on climate change. Read the free Plain Language Summary for this article on the Journal blog.

This article explores how museums can help empower people to engage constructively with climate change, through applying a range of time-related concepts to their exhibitions and events. Museums are mostly collections of the past. Climate change now and future presents particular challenges as it is perceived to be psychologically distant. The link between this distance and effective climate action is complex and presents an opportunity for museums, as sites where psychological distance can be explored in safe, consequence-free ways. This paper explores how we can use museums to help develop understanding within the rhetoric of climate change to assist visitors with their personal or collective response to the climate challenge. Time-related concepts including Foucault’s heterotopia, long-term thinking as advocated in the History Manifesto and the ‘Big Here and Long Now’, are explored in relation to museums as potential tools for constructive climate change engagement.

O trauma dentoalveolar é uma adversidade frequente para o sistema de saúde e necessita de diagnóstico e intervenção precoce. A gravidade dessas lesões pode variar de acordo com a sua classificação, de simples trincas em esmalte a avulsões do órgão dental e fraturas ósseas. Sendo assim, o objetivo deste trabalho é relatar um caso clínico de trauma dentoalveolar associado a fratura do bloco ósseo em região anterior de maxila, tratado tardiamente por meio de redução bidigital e esplintagem. Paciente do sexo masculino, vítima de acidente automobilístico, compareceu ao serviço de emergência 04 dias após o trauma. Durante o exame físico maxilofacial foi possível observar presença de mobilidade em bloco anterior de maxila e luxação lateral dos dentes anteriores. Na tomografia de face foi possível analisar a presença de linha de fratura em tábua vestibular e palatina da região anterior da maxila, assim como luxação lateral envolvendo as unidades 12, 11, 21 e 22. Apesar do longo período pós-trauma, o tratamento proposto foi a redução fechada, associada a instalação de contenção semirrígida, proporcionando estabilidade ao segmento fraturado e ambiente propício para correta cicatrização óssea. O manejo inicial do trauma dental tem grande influência no prognostico, no entanto, foi possível observar por meio desse caso, que o tratamento tardio apresenta resultados satisfatórios, auxiliando no reestabelecimento da função e estética do paciente de forma menos invasiva.

La lutte contre le changement climatique exige une créativité radicale et de nouvelles formes de relations, d’institutions et de pratiques. Reimagining Museums for Climate Action a été lancé le 18 mai 2020, à l’occasion de la Journée internationale des musées 2020, sous la forme d’un concours international d’idées et de design visant à (re)imaginer et à (re)concevoir radicalement l’institution muséale, afin de contribuer à un avenir plus équitable et plus durable à l’ère du changement climatique. Le concours a suscité un intérêt considérable, avec 264 contributions de 48 pays. Huit lauréats ont reçu chacun 2 500 £ pour transformer leurs idées en expositions qui seront présentées au Centre scientifique de Glasgow avant et pendant la COP26. L’exposition présente également un large éventail d’idées parmi les soumissions, visant à fournir au secteur des musées et à la société une source d’innovation et d’inspiration pour atteindre les objectifs de la Convention-cadre sur les changements climatiques et de l’Accord de Paris.

Dorfman, E. (ed.) The Future of Natural History Museums, Routledge, paperback, £31.99, pp. 268.

Objective: We describe our preliminary experience with coronary computed tomography angiography (CCTA) in emergency department (ED) patients with low- to intermediate-risk chest pain. Methods: A convenience cohort of patients with low- to intermediate-risk acute chest pain presenting to a suburban ED in 2009 were prospectively enrolled if the attending physician ordered a CCTA for possible coronary artery disease. Demographic and clinician data were entered into structured data collection sheets required before any imaging. The results of CCTA were classified as normal, nonobstructive (1%-50% stenosis), and obstructive (>50% stenosis). Outcomes included hospital admission and death within a 6-month follow-up period. Results: In 2009, 507 patients with ED chest pain had a CCTA while in the ED. The median (interquartile range) age was 54 (47-62) years; 51.5% were female. Thrombolysis in myocardial infarction risk scores were 0 (42.6%), 1 (42.2%), 2 (11.8%), 3 (2.4%), and 4 (1.0%). The results of CCTA were normal (n = 363), nonobstructive (n = 123), and obstructive (n = 21). Admission rates by CCTA results were obstructive (90.5%), nonobstructive (4.9%), and normal (3.0%). None of the patients with normal or nonobstructive CCTA died within the 6-month follow-up period (0%; 95% confidence interval, 0-0.9%). Conclusions: Many ED patients with low- to intermediate-risk chest pain have a normal or nonobstructive CCTA and may be safely discharged from the ED without any associated mortality within the following 6 months. [ABSTRACT FROM AUTHOR]

We show that Hill’s equation with white noise potential has a sequence of Dirichlet eigenvalues /lambda n that behaves almost like in the classical case, in the sense that /lambda n - n2/pi 2 has a logarithmic growth coming from a sequence of Gaussian random variables.

This paper presents the first published listing of the holdings of type specimens of mollusc in The Manchester Museum (University of Manchester, UK), the fourth largest mollusc collection in Britain. Type material relating to 480 taxa are included in the present catalogue, mainly coming from the collections of A Abercrombie (India), RD Darbishire, Prof. AC Haddon (Torres Straits), Rev. J Hadfield (Lifu, Loyalty Islands), LJ Shackleford (especially Marginella), GC Spence (especially African land snails and Urocoptis and many specimens from M Connolly and HB Preston), FW Townsend (Persian Gulf), syntype material from the Scottish National Antarctic Expedition (1902-1904) and that received from the Smithsonian Institution in 1973 in exchange. There is undoubtedly more type material within the collection which is not identified as such as yet.

The association between hygiene and prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study of experimental infection with the hookworm Necator americanus was undertaken among a group of otherwise healthy people with celiac disease to test the potential of the helminth to suppress the immunopathology induced by gluten.In a 21-week, double-blinded, placebo-controlled study, we explored the effects of N. americanus infection in 20 healthy, helminth-naïve adults with celiac disease well controlled by diet. Staged cutaneous inoculations with 10 and 5 infective 3(rd) stage hookworm larvae or placebo were performed at week-0 and -12 respectively. At week-20, a five day oral wheat challenge equivalent to 16 grams of gluten per day was undertaken. Primary outcomes included duodenal Marsh score and quantification of the immunodominant α-gliadin peptide (QE65)-specific systemic interferon-γ-producing cells by ELISpot pre- and post-wheat challenge.Enteric colonisation with hookworm established in all 10 cases, resulting in transiently painful enteritis in 5. Chronic infection was asymptomatic, with no effect on hemoglobin levels. Although some duodenal eosinophilia was apparent, hookworm-infected mucosa retained a healthy appearance. In both groups, wheat challenge caused deterioration in both primary and several secondary outcomes.Experimental N. americanus infection proved to be safe and enabled testing its effect on a range of measures of the human autoimmune response. Infection imposed no obvious benefit on pathology.ClinicalTrials.gov NCT00671138.

The sphingosine-1-phosphate-5 (S1P 5 ) receptor is one of the five membrane G protein-coupled receptors that are activated by the lysophospholipid, sphingosine-1-phosphate, resulting in regulation of many cellular processes. S1P 5 receptors are located on oligodendrocytes and are proposed to influence oligodendrocyte physiology. Understanding S1P 5 modulation during processes such as remyelination could have potential applications for demyelinating CNS disorders such as multiple sclerosis (MS). Herein, we report the synthesis and preliminary evaluation of a series of fluorinated 6-arylaminobenzamides as positron emission tomography (PET) ligands of S1P 5 . Pharmacokinetic screening and binding evaluation using a [ 35 S]GTPγS assay led to the discovery of TEFM78, a selective and high affinity agonist of S1P 5 . Radiosynthesis of [ 18 F]TEFM78 allowed pilot PET imaging studies in an animal model, which showed that [ 18 F]TEFM78 can cross the blood brain barrier with good uptake in rat brain and spinal cord., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Women have historically been underrepresented in surgical leadership and in specialty organizations. This study longitudinally examines representation of women across committee leadership within the American Pediatric Surgical Association (APSA)., Methods: Annual APSA committee chair and vice-chair rosters (2003-2023) were obtained. If not self-reported in the membership roster, gender was classified based upon review of publicly available data. Proportions of women who served as chairs and vice-chairs were quantified by committee and by year., Results: Overall, the proportion of women serving as APSA committee chairs and vice-chairs increased from 11% to 48% during the study period (p = 0.001). In examining each position, the proportion of women chairs increased from 12% to 40% (p = 0.042), while women vice-chairs increased from 10% to 58% (p = 0.009). The committees with the highest cumulative proportion of women chairs were Benjy Brooks (100%), Diversity Equity & Inclusion (100%), Finance (100%), Global Pediatric Surgery (67%), and Wellness (67%). Four committees- Trauma, Access to Surgery for Kids, Practice, and Professional Development - were not led by a woman chair in the entire study period. Additionally, five committees that traditionally have had significant impact on organizational workflow and agendas all had cumulative proportions of women chairs of less than 50% - Education (33%), Publications (28.6%), Outcomes (19%), Surgical Quality & Safety (18.8%) and Program (9.5%)., Conclusion: These results demonstrate encouraging trends in the gender diversity of APSA leadership. However, this progress does not appear to be evenly distributed; leadership of key committees continues to lack substantial women's representation., Level of Evidence: III., Competing Interests: Conflicts of interest The authors have no disclosures or competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Impostor phenomenon (IP) is defined as feeling inadequacy, self-doubt, and the tendency to attribute achievement to external causes. We sought to examine IP rates among pediatric surgeons and to identify IP-associated factors, based on the hypothesis that pediatric surgeons experience imposterism, especially in the first few years of practice., Design: Anonymous survey, including the validated Clance IP Scale (CIPS), distributed to pediatric surgeons. CIPS scores indicated degree of IP characteristics: 21-40= "few," 41-60="moderate," 61-80="frequent," 81-100="intense." Demographic, training, and practice-based characteristics were collected. Univariate statistics were used to compare differences between groups and logistic regression to further understand associations., Setting: Survey study distributed via email to the American Pediatric Surgical Association (January 2023-February 2023)., Participants: 1129 surveys were sent. We received 337 responses (29.8%) and analyzed data from 319 respondents, after exclusion of incomplete responses and fellows., Results: The median CIPS score for analyzed respondents was 52 (IQR 40-65), moderate imposterism. Female respondents were more likely to have IP compared to males (OR 3.52 [CI 2.13-5.73], p < 0.01). Junior attendings (<5y practice) had increased odds of IP (OR 2.88, CI 1.71-4.93) compared to midcareer and senior attendings (p < 0.001). Using multiple logistic regression, the addition of junior attending status plus female gender was even more predictive of imposterism [AUC 0.722; CI 0.661-0.782; p < 0.0001]. There was no relationship between IP and fellowship or practice-based characteristics., Conclusions: IP is prevalent among pediatric surgeons, particularly junior surgeons, and females. We did not find a relationship with IP and fellowship or practice-based characteristics but did find higher IP in respondents who did not feel they had support in practice. We underscore both intrapersonal and interpersonal characteristics impact IP in the pediatric surgeon. We suggest interventions that foster inclusion and mentorship be employed to help mitigate possible negative outcomes of IP., (Copyright © 2024 Association of Program Directors in Surgery. All rights reserved.)

Intrinsically disordered proteins (IDPs) are important drug targets as they are key actors within cell signaling networks. However, the conformational plasticity of IDPs renders them challenging to characterize, which is a bottleneck in developing small molecule drugs that bind to IDPs and modulate their behavior. In relation to this, ion mobility mass spectrometry (IM-MS) is a useful tool to investigate IDPs, as it can reveal their conformational preferences. It can also offer important insights in drug discovery, as it can measure binding stoichiometry and unveil conformational shifts of IDPs exerted by the binding of small drug-like molecules. Herein, we have used IM-MS to investigate the effect of drug lead EPI-001 on the disordered N-terminal domain of the androgen receptor (AR-NTD). Despite structural heterogeneity rendering the NTD a challenging region of the protein to drug, this domain harbors most, if not all, of the transcriptional activity. We quantify the stoichiometry of EPI-001 binding to various constructs corresponding to functional domains of AR-NTD and show that it binds to separate constructs containing transactivation unit (TAU)-1 and TAU-5, respectively, and that 1-2 molecules bind to a larger construct containing both sequences. We also identify a conformational shift upon EPI-001 binding to the TAU-5, and to a much lesser extent with TAU-1 containing constructs. This work provides novel insight on the interactions of EPI-001 with the AR-NTD, and the structural alterations that it exerts, and positions IM-MS as an informative tool that will enhance the tractability of IDPs, potentially leading to better therapies., (© 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

Objective: Presenting at academic conferences is an important means of disseminating research, networking, and building a professional reputation, but the quality of presentations at conferences is often suboptimal. This project describes the design, implementation, and evaluation of a presentation coaching program offered by an academic surgical society to presenters at its annual meeting., Design: Oral presenters were paired with a coach and encouraged to meet independently, yet coaching was unstructured. During the conference, program committee members rated all presentations. Afterwards, an online survey collected perspectives about the program from both participants and nonparticipants. Responses were analyzed with summary statistics and inductive coding. Presentation scores among participants and nonparticipants were compared via t-test., Setting: This project occurred as part of the American Pediatric Surgical Association (APSA) 2024 Annual Meeting., Participants: Senior APSA members were recruited to serve as coaches, and all presenters were invited to participate. Of 164 total presenters, 26 (15.9%) participated in the coaching program and were paired with 24 coaches., Results: Almost all participants (92.3%) were trainees, including students, residents or fellows. The survey had 38 responses (23.2% overall response rate), including 17 participants (65.4%) and 21 non-participants (15.2%). Most participants met with their coach once (58.8%) or twice (29.4%), usually via video call (82.4%). Presenters cited various motivations to participate in the program, and numerous benefits. Nearly all participants (94.1%) were extremely satisfied with their experience in the coaching program. The mean ± standard deviation presentation score among trainees who participated was 3.88 ± 0.45 of 5, compared to 3.79 ± 0.51 among trainees who did not (p = 0.49)., Conclusions: Having senior surgical society members serve as volunteer coaches is a feasible and well-regarded approach to help conference attendees, particularly trainees, prepare for their oral presentations. Participants especially appreciated the opportunity to meet senior society members., (Copyright © 2025 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: In 2022, firearms injured or killed more than 6000 American children. Significant disparities exist in injury risk. We hypothesized that analyzing an injury's time, date, and location could help identify additional risk and protective factors in the pediatric population., Methods: We performed a retrospective analysis of the 2003-2020 National Violent Death Reporting System. The National Violent Death Reporting System currently collects data from all 50 states, the District of Columbia, and Puerto Rico. Demographic (age, sex, race/ethnicity) and incident (date, time, location) data were abstracted. Inclusion criteria were pediatric victims (age≤18) of fatal firearm injuries. Records with missing values were excluded. Chi-squared tests were used to test the association between victim demographics and time, date, or location. Significance was P < 0.05., Results: Nine thousand fifty-eight children (male: 83.5% [n = 7559]), age: 17 yrs old (interquartile range: 15-18 years old), Black: 64.1% [n = 5810]) were eligible. 6161 (68.1%) of children had not completed high school. 3308 (36.5%) fatal injuries occurred after school or at night (1601-2359 h). 3678 (40.6%) injuries occurred at home. Black children were significantly more likely to be injured during the summer months (June - August, P < 0.01), after school or at night (P < 0.001), and along a street (P < 0.001). Hispanic children were more likely to be killed after school or at night (P < 0.001) and along a street (P < 0.001). There was no seasonal variation in this demographic. Compared to other times of the day, there was a significant increase in weekend (Friday-Sunday) morning (0000- 0800) injuries. (P < 0.001)., Conclusions: Firearm violence disproportionately impacts Black children. There are significant associations with the time and season. Interventions during those times such as extended academic engagement or after school programs beyond the traditional school day and school year may afford opportunities which could mitigate exposure to firearm violence., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study identified failures in emergency inter-hospital transfer, or re-triage, at high-level trauma centers receiving severely injured patients., Summary Background Data: The re-triage process averages four hours despite the fact timely re-triage within two hours mitigates injury-associated mortality. Non-trauma and low-level trauma centers reported most critical failures were in finding an accepting high-level trauma center. Critical failures at high-level trauma centers have not been assessed., Methods: This was an observational cross-sectional study at nine high-level adult trauma centers and three high-level pediatric trauma centers. Failure Modes Effects Analysis (FMEA) of the re-triage process was conducted in four phases. Phase 1 purposively sampled trauma coordinators followed by snowball sampling of clinicians, operations, and leadership to ensure representative participation. Phase 2 mapped each re-triage step. Phase 3 identified failures at each step. Phase 4 scored each failure on impact, frequency, and safeguards for detection. Standardized rubrics were used in Phase 4 to rate each failure's impact (I), frequency (F), and safeguard for detection (S) to calculate their Risk Priority Number (RPN) (I x F x S). Failures were rank ordered for criticality., Results: A total of 64 trauma coordinators, surgeons, emergency medicine physicians, nurses, operations and quality managers across twelve high-level trauma centers participated. There were 178failures identified at adult and pediatric high-level trauma centers. The most critical failures were: Insufficient trained transport staff (RPN=648); Issues transmitting imaging from sending to receiving centers (RPN=400); Incomplete exchange of clinical information(RPN=384)., Conclusions: The most critical failures were limited transportation and incomplete exchange of clinical, radiological and arrival timing information. Further investigation of these failures that includes several regions is needed to determine the reproducibility of these findings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Homicide is a leading cause of death for American children. We hypothesized demographics and homicide circumstances would differ by victim age., Methods: We performed a retrospective analysis of the 2003-2020 National Violent Death Reporting System. The National Violent Death Reporting System collects data from nearly all 50 states, the District of Columbia, and Puerto Rico. Demographics (age, sex, race, and ethnicity), homicide year, and weapon type were abstracted. Inclusion criteria were pediatric victims (age < 18). Two groups: 0-4 y old (young cohort [YC]) and 13-17 y old (teen cohort [TC]) were compared. Chi-squared tests, p-test, and t-tests with significance P < 0.05 were used to determine the association between victim demographics, cohort, and homicide mechanism., Results: 10,569 pediatric (male: 70.2% [n = 7424], median age: 12 y old [interquartile range 1-16], black: 52.7% [n = 5573]) homicides met inclusion. Homicides demonstrated a bimodal age distribution (YC: 40.9% [n = 4320] versus TC: 48.9% [n = 5164]). Gender and race were both associated with homicide victimhood (P < 0.001). TC homicides were more likely to be male (YC: 57.8% [n = 2496] versus TC: 83.7% [n = 4320], P < 0.001) and black (YC: 40.1% [n = 1730] versus TC: 65.0% [n = 3357], P < 0.001). Pediatric homicides increased from 2018 (n = 1049) to 2020 (n = 1597), with only TC demonstrating a significant increase (2018: n = 522 versus 2020: n = 971, P < 0.001). Homicide mechanism was significantly associated with age (Blunt: YC: 57.5% [n = 2484] versus TC: 2.9% [n = 148], P < 0.001; Penetrating: YC: 7.9% [n = 340] versus TC: 92.8% [n = 4794], P < 0.001)., Conclusions: Pediatric homicides demonstrate distinct demographic characteristics and homicide mechanisms between two at risk age cohorts. Age-based education and intervention strategies may increase injury prevention programs' efficacy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A one-pot procedure for the oxidative amidation of aldehydes via the in situ generation of reactive nitrile imine (NI) intermediates has been developed. Distinct from our progenitor processes, mechanistic and control experiments revealed that the NI undergoes rapid oxidation to an acyl diazene species, which then facilitates N -acylation of an amine. A range of substrates have been explored, including application in the synthesis of pharmaceutically relevant compounds.

Firearm injuries have become the leading cause of death among American children. Here we review the scope of the problem, and the pivotal role pediatric surgeons have in preventing pediatric firearm injury. Specific methods for screening and counseling are reviewed, as well as how to overcome barriers. Community and hospital resources as well as organizational efforts are discussed. Finally, a path for surgeon advocacy is outlined as is a call to action for the pediatric surgeon, as we are uniquely poised to identify pediatric patients and deliver timely interventions to reduce the impact of firearm violence. LEVEL OF EVIDENCE: Level IV., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Musculoskeletal discomfort is widely experienced by surgeons across multiple surgical specialties. Developing technologies and new minimally invasive techniques add further complexity and ergonomic stressors. These stressors differentially affect male and female surgeons, but little is known about the role these sex disparities play in surgical ergonomic stress. We reviewed existing literature to better understand how ergonomic stress varies between male and female surgeons., Study Design: A literature search was performed via PubMed including but not limited to the following topics: ergonomics, surgeons, female surgeons, women surgeons, pregnancy, and operating room. A review of available quantitative data was performed., Results: Female surgeons endure more pronounced ergonomic discomfort than their male counterparts, with added ergonomic stress associated with pregnancy., Conclusions: A 4-fold method is proposed to overcome ergonomic barriers, including (1) improved education on prevention and treatment of ergonomic injury for active surgeons and trainees, (2) increased departmental and institutional support for ergonomic solutions for surgeons, (3) partnerships with industry to study innovative ergonomic solutions, and (4) additional research on the nature of surgical ergonomic challenges and the differential effects of surgical ergonomics on female surgeons., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Neuroinflammation is associated with a number of brain diseases, making it a common feature of cerebral pathology. Among the best-known biomarkers for neuroinflammation in Positron Emission Tomography (PET) research is the 18 kDa translocator protein (TSPO). This study aims to investigate the binding kinetics of a novel TSPO PET radiotracer, [ 18 F]LW223, in mice and specifically assess its volume of non-displaceable binding ( V ND ) in brain as well as investigate the use of simplified analysis approaches for quantification of [ 18 F]LW223 PET data. Adult male mice were injected with [ 18 F]LW223 and varying concentrations of LW223 (0.003-0.55 mg/kg) to estimate V ND of [ 18 F]LW223. Dynamic PET imaging with arterial input function studies and radiometabolite studies were conducted. Simplified quantification methods, standard uptake values ( SUV ) and apparent volume of distribution ( V Tapp ), were investigated. [ 18 F]LW223 had low V ND in the brain (<10% of total binding) and low radiometabolism (∼15-20%). The 2-tissue compartment model provided the best fit for [ 18 F]LW223 PET data, although its correlation with SUV 90-120min or V Tapp allowed for [ 18 F]LW223 brain PET data quantification in healthy animals while using simpler experimental and analytical approaches. [ 18 F]LW223 has the required properties to become a successful TSPO PET radiotracer., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A patent for TSPO binders has been submitted (application GB1810312.7, PCT/EP2019/066546 and WO2019243616A1). No other potential conflicts of interest relevant to this article exist.

The 18 kDa translocator protein is a well-known biomarker of neuroinflammation, but also plays a role in homeostasis. PET with 18 kDa translocator protein radiotracers [ 11 C]PBR28 in humans and [ 18 F]GE180 in mice has demonstrated sex-dependent uptake patterns in the healthy brain, suggesting sex-dependent 18 kDa translocator protein expression, although humans and mice had differing results. This study aimed to assess whether the 18 kDa translocator protein PET radiotracer [ 18 F]LW223 exhibited sexually dimorphic uptake in healthy murine brain and peripheral organs. Male and female C57Bl6/J mice (13.6 ± 5.4 weeks, 26.8 ± 5.4 g, mean ± SD) underwent 2 h PET scanning post-administration of [ 18 F]LW223 (6.7 ± 3.6 MBq). Volume of interest and parametric analyses were performed using standard uptake values (90-120 min). Statistical differences were assessed by unpaired t -test or two-way ANOVA with Šidak's test (alpha = 0.05). The uptake of [ 18 F]LW223 was significantly higher across multiple regions of the male mouse brain, with the most pronounced difference detected in hypothalamus ( P < 0.0001). Males also exhibited significantly higher [ 18 F]LW223 uptake in the heart when compared to females ( P = 0.0107). Data support previous findings on sexually dimorphic 18 kDa translocator protein radiotracer uptake patterns in mice and highlight the need to conduct sex-controlled comparisons in 18 kDa translocator protein PET imaging studies., Competing Interests: A patent for TSPO binders has been submitted (application GB1810312.7, PCT/EP2019/066546 and WO2019243616). No other potential conflicts of interest relevant to this article exist., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Injury from a firearm is now the leading cause of death of children and youth under age 19 in the United States (U.S.) [1] and the incidence of these deaths continues to increase each year [2]. For every death from firearm violence, there are several young people who have been injured by a bullet but not killed. As pediatric surgeons, we are on the front lines of treating these young patients. We have the unforgettable memories of delivering the horrible news to parents in "quiet rooms." [3]. As these injuries fall within our scope of practice, it is incumbent on us as professionals to work to prevent these injuries, apply best practices and work for the best pathways to recovery for our patients who do survive. There is a diverse community of pediatric surgeons tackling this public health problem in a variety of ways [4]. In a pre-meeting symposium at the APSA 2023 Annual meeting, we brought together a community of pediatric surgeons working on this critical area. The following summarizes the presentations of the symposium, with topics including Risk Factors, Injury Prevention, Treatment, Public Initiatives, and National Collaborative Efforts. TYPE OF STUDY: Review Article, Proceedings of a Symposium. LEVEL OF EVIDENCE: 1 through 4 all presented., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Firearm violence is now endemic to certain US neighborhoods. Understanding factors that impact a neighborhood's susceptibility to firearm violence is crucial for prevention. Using a nationally standardized measure to characterize community-level firearm violence risk has not been broadly studied but could enhance prevention efforts. Thus, we sought to examine the association between firearm violence and the social, structural, and geospatial determinants of health, as defined by the Social Vulnerability Index (SVI)., Study Design: In this cross-sectional study, we merged 2018 SVI data on census tract with shooting incidents between 2015 and 2021 from Baltimore, Chicago, Los Angeles, New York City, and Philadelphia. We used negative binomial regression to associate the SVI with shooting incidents per 1,000 people in a census tract. Moran's I statistics and spatial lag models were used for geospatial analysis., Results: We evaluated 71,296 shooting incidents across 4,415 census tracts. Fifty-five percent of shootings occurred in 9.4% of census tracts. In all cities combined, a decile rise in SVI resulted in a 37% increase in shooting incidents (p < 0.001). A similar relationship existed in each city: 30% increase in Baltimore (p < 0.001), 50% in Chicago (p < 0.001), 28% in Los Angeles (p < 0.001), 34% in New York City (p < 0.001), and 41% in Philadelphia (p < 0.001). Shootings were highly clustered within the most vulnerable neighborhoods., Conclusions: In 5 major US cities, firearm violence was concentrated in neighborhoods with high social vulnerability. A tool such as the SVI could be used to inform prevention efforts by directing resources to communities most in need and identifying factors on which to focus these programs and policies., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The androgen receptor (AR) is central to prostate cancer pathogenesis and has been extensively validated as a drug target. However, small-molecule anti-androgen therapies remain limited due to resistance and will eventually fail to suppress tumor growth, resulting in progression to castration-resistant prostate cancer (CRPC). The intrinsically disordered N-terminal domain (NTD) is crucial for AR transactivation and has been investigated as a suitable target in the presence of ligand binding domain mutations. A screening campaign identified biaryl isoxazole compound 7 as a weak inhibitor of the AR NTD. A library of biaryl analogues were synthesized, and their biological activities were assessed in a VCaP cell-based luciferase reporter gene assay. A structure-activity relationship (SAR) study revealed that indazole analogue 16 exhibited increased potency and favorable physicochemical properties with a benchmarked pharmacokinetic profile, providing a suitable starting point for further optimization of 16 as a CRPC therapeutic in the presence of AR mutations., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Purpose: Despite trends toward equal gender representation among medical school graduates, surgical trainees and fellows, diversity in higher levels of pediatric surgery is largely unstudied. This study aims to quantify gender diversity among leadership of pediatric surgical associations and societies across the globe., Methods: National and international pediatric surgical organizations were identified from the websites of the American Pediatric Surgical Association (APSA) and World Federation of Associations of Pediatric Surgery (WOFAPS). Compositional gender data of current and past organizational leadership was collected by examining publicly available archives of executive membership rosters. If roster pictures were not available, member names were input into social media sites and other search engines to ensure accurate gender denotation. Univariate analyses of organizational metrics and aggregate data of 5-year time intervals were performed via Fischer's Exact Test with significance of p < 0.05., Results: Nineteen pediatric surgical organizations were included for study analysis. Of 189 current organizational leaders, 50 (26.4%) are women. Eight organizations (42.1%) have less than 20% of leadership positions filled by women members, while two executive boards have no women members. Four organizations (22.2%) have a current woman seated as president/chairperson. Historical gender distribution stratified by organization demonstrates a range of 0-7.8% (p = 0.99), with one organization having yet to elect a woman president/chairperson. Longitudinally, women presidential representation remained consistently low (5-11%) across all time intervals from 1993 to 2022 (p = 0.35)., Conclusions: Despite advances in diversity in medical school graduates, surgical training, and workforce recruitment, there are still significant disparities in gender representation within pediatric surgery societal leadership., Level of Evidence: IV., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Hospital-based violence intervention programs (HVIPs) have shown promise in preventing reinjury and enhancing recovery from violent injuries, including those related to firearms. Historically, HVIPs have primarily focused on at-risk adolescents and young adults. The aim of this study is to perform a scoping review of HVIPs targeting children under the age of 18, describe the evidence supporting these programs, and deduce the potential impact of expanding HVIPs to younger children., Methods: A scoping review was performed utilizing PubMed database with search terms "violence intervention program" and pediatric, or children, or youth. Articles were screened for youth-inclusive violence programs, and the literature was analyzed for program descriptions, evidence supporting interventions, and barriers to evaluation., Results: 36 studies (covering 23 programs) were identified that met criteria (including patients ≤18 years old), with only 4 programs including children under 10. Many HVIPs utilize brief hospital interventions with longitudinal wraparound outpatient services. Despite heterogeneity in programs and studied outcomes, many HVIPs demonstrated positive outcomes, such as reduction of risk factors, decreased reinjury, decreased violent behaviors, decreased criminal justice involvement, and positive attitude or behavioral changes. Only a few studies reported increased odds of enrollment and positive impact in younger patients specifically., Conclusions: Children are an impressionable population in which HVIPs may have significant impact; however, there remains a gap in targeted programs. Given that firearm injuries are the leading cause of death in children and adolescents, priority should be given to piloting, implementing, and evaluating HVIPs among younger age groups., Level of Evidence: Level IV., Competing Interests: Conflict of interest The authors have no related conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In sub-Saharan Africa, despite the implementation of multiple control interventions, the prevalence of malaria infection and clinical cases remains high. The primary tool for vector control against malaria in this region is the use of long-lasting insecticide-treated nets (LLINs) combined or not with indoor residual spraying (IRS) to achieve a synergistic effect in protection. The objective of this study was to assess the effectiveness of LLINs, with or without IRS, protected against Plasmodium falciparum infection and uncomplicated clinical cases (UCC) of malaria in Benin. A case-control study was conducted, encompassing all age groups, in the urban area of Djougou and the rural area of Cobly. A cross-sectional survey was conducted that included 2080 individuals in the urban area and 2770 individuals in the rural area. In the urban area, sleeping under LLINs did not confer significant protection against malaria infection and UCC when compared to no intervention. However, certain neighbourhoods benefited from a notable reduction in infection rates ranging from 65% to 85%. In the rural area, the use of LLINs alone, IRS alone, or their combination did not provide additional protection compared to no intervention. IRS alone and LLINs combined with IRS provided 61% and 65% protection against malaria infection, respectively, compared to LLINs alone. The effectiveness of IRS alone and LLINs combined with IRS against UCC was 52% and 54%, respectively, when compared to LLINs alone. In both urban and rural areas, the use of LLINs alone, IRS alone, and their combination did not demonstrate significant individual protection against malaria infection and clinical cases when compared to no intervention. In the conditions of this study, LLINs combined or not with IRS are not effective enough to eliminate malaria. In addition to the interventions, this study identified factors associated with malaria in Benin as housing design, neglected social groups like gender-marginalised individuals and adolescents, and socio-economic conditions acting as barriers to effective malaria prevention. Addressing these factors is crucial in order to facilitate malaria elimination efforts in sub-Saharan Africa.

The androgen receptor (AR) has been shown to be a key determinant in the pathogenesis of castration-resistant prostate cancer (CRPC). The current standard of care therapies targets the ligand-binding domain of the receptor and can afford improvements to life expectancy often only in the order of months before resistance occurs. Emerging preclinical and clinical compounds that inhibit receptor activity via differentiated mechanisms of action which are orthogonal to current antiandrogens show promise for overcoming treatment resistance. In this review, we present an authoritative summary of molecules that noncompetitively target the AR. Emerging small molecule strategies for targeting alternative domains of the AR represent a promising area of research that shows significant potential for future therapies. The overall quality of lead candidates in the area of noncompetitive AR inhibition is discussed, and it identifies the key chemotypes and associated properties which are likely to be, or are currently, positioned to be first in human applications., (© 2023 The Authors. Medicinal Research Reviews published by Wiley Periodicals LLC.)

We report the use of N -2,4-dinitrophenyltetrazoles as latent active esters (LAEs) in the synthesis of amide bonds. Activating the tetrazole generates an HOBt-type active ester without the requirement for exogenous coupling agents. The methodology was widely applicable to a range of substrates, with up to quantitative yields obtained. The versatility and functional group tolerance were exemplified with the one-step synthesis of various pharmaceutical agents and the N -acylation of resin-bound peptides.

Background: Despite a global decrease in malaria burden worldwide, malaria remains a major public health concern, especially in Benin children, the most vulnerable group. A better understanding of malaria's spatial and age-dependent characteristics can help provide durable disease control and elimination. This study aimed to analyze the spatial distribution of Plasmodium falciparum malaria infection and disease among children under five years of age in Benin, West Africa., Methods: A cross-sectional epidemiological and clinical survey was conducted using parasitological examination and rapid diagnostic tests (RDT) in Benin. Interviews were done with 10,367 children from 72 villages across two health districts in Benin. The prevalence of infection and clinical cases was estimated according to age. A Bayesian spatial binomial model was used to estimate the prevalence of malaria infection, and clinical cases were adjusted for environmental and demographic covariates. It was implemented in R using Integrated Nested Laplace Approximations (INLA) and Stochastic Partial Differentiation Equations (SPDE) techniques., Results: The prevalence of P. falciparum infection was moderate in the south (34.6%) of Benin and high in the northern region (77.5%). In the south, the prevalence of P. falciparum infection and clinical malaria cases were similar according to age. In northern Benin children under six months of age were less frequently infected than children aged 6-11, 12-23, 24-60 months, (p < 0.0001) and had the lowest risk of malaria cases compared to the other age groups (6-12), (13-23) and (24-60): OR = 3.66 [2.21-6.05], OR = 3.66 [2.21-6.04], and OR = 2.83 [1.77-4.54] respectively (p < 0.0001). Spatial model prediction showed more heterogeneity in the south than in the north but a higher risk of malaria infection and clinical cases in the north than in the south., Conclusion: Integrated and periodic risk mapping of Plasmodium falciparum infection and clinical cases will make interventions more evidence-based by showing progress or a lack in malaria control., (© 2022. The Author(s).)

We report how the rearrangement of highly reactive nitrile imines derived from N -2-nitrophenyl hydrazonyl bromides can be harnessed for the facile construction of amide bonds. This amidation reaction was found to be widely applicable to the synthesis of primary, secondary, and tertiary amides and was used as the key step in the synthesis of the lipid-lowering agent bezafibrate. The orthogonality and functional group tolerance of this approach was exemplified by the N -acylation of unprotected amino acids.

Introduction: Since 2006, the U.S. Navy has conducted six Pacific Partnership (PP) missions throughout Southeast Asia on board the U.S. Naval Ship Mercy (T-AH 19). This study describes trends in overall and surgical specialty operative volumes to better understand the burden of surgical disease treated during these humanitarian and civic assistance (HCA) operations. This information can assist medical planners and surgical leaders involved in future humanitarian missions., Materials and Methods: Following approval from the Naval Medical Center San Diego Institutional Review Board, a retrospective review of surgical case data was performed for the six PP missions from 2006 to 2018. Data collected included patient demographics, Current Procedural Terminology codes, and surgical specialty. The primary outcome was surgical case volume per specialty. Secondary outcomes included surgical staffing per mission and overall trends in operative volume., Results: A total of 3,826 operative procedures were performed during the study period. Mission years in which case volume for both general surgery and ophthalmology were below their respective medians were associated with the least total surgical services to host nations (HNs). The number of active duty Navy surgeons varied with each mission; however, the staffing for a PP mission generally included at least two general surgeons, one ophthalmologist, one plastic surgeon, one pediatric surgeon, one orthopedic surgeon, one otolaryngologist, one oral surgeon, one urologist, and one obstetrician-gynecologist. Case volume per surgeon was highest in 2006 (50 cases per surgeon) and decreased after 2006, reaching an all-time low during the 2018 PP mission (10 cases per surgeon). Pediatric surgery and plastic surgery had the highest average case volumes per surgeon at 58 and 46 cases per surgeon, respectively, while oromaxillofacial surgery and neurosurgery had the lowest average case volumes per surgeon at 9 and 14 cases per surgeon, respectively., Conclusions: Operative volume on military HCA missions is greatly influenced by the priorities of the HN, the mission focus, the number of individuals from the HN that present for screening, and the availability of personnel and resources available on the hospital ship. Future mission planning should optimize general surgery and ophthalmology staffing and essential equipment, as total mission case volumes were highly dependent upon the productivity of these two specialties. Careful determination of the surgical needs of HNs should serve as a guide for the selection of subspecialists to maximize effectiveness in future military HCA missions., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: About 5% of women are pregnant at substance use disorder (SUD) treatment entry, and pregnant women with SUD often belong to marginalized groups experiencing social, economic, and health care barriers associated with stigma from prenatal substance use. Pregnant women in SUD treatment have high rates of trauma and posttraumatic stress disorder (PTSD). This study sought to (1) examine the lived experiences of pregnant individuals with PTSD symptoms in SUD treatment and (2) understand the roles of systematic or contextual barriers to the pursuit of prenatal abstinence., Methods: We draw upon in-depth semi-structured interviews to examine relationships between SUD, psychological trauma/PTSD experience, social resources, and lived experiences among patients in prenatal SUD treatment with PTSD symptoms. Our sample was pregnant patients ( N  = 13) with prior DSM-5 Criterion A trauma and current PTSD symptoms enrolled in a comprehensive program integrating prenatal care, substance use counseling, medication for opioid use disorder and case management at three sites affiliated with an urban academic medical center in New Mexico., Results: Using thematic analysis, four main themes identified structural forces influencing alcohol and drug use: (a) lack of access or ability to obtain resources, (b) substance use to cope with negative affect, (c) social stigma, and (d) interpersonal relationships., Conclusions: Despite receiving high-quality integrated prenatal and SUD care, these pregnant patients with PTSD symptoms in SUD treatment still experienced substantial social and structural hurdles to achieving abstinence during pregnancy., Competing Interests: None., (© 2021 The Authors. Published by Elsevier B.V.)

Background: Although not routinely assessed, prenatal posttraumatic stress disorder (PTSD) is associated with poor maternal mental health and mother-infant bonding. Prenatal PTSD may also be associated with birth weight and gestational age outcomes, but this remains unclear. This systematic review and meta-analysis investigated the association of prenatal PTSD with risk of low birth weight (LBW) or preterm birth (PTB) (dichotomous medically-defined cut-offs) or with birth weight (BW) or gestational age (GA) (continuous variables)., Methods: A comprehensive literature search was conducted in Web of Science, MedLine, PubMed, and PsychInfo. Data were collected and processed according to Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Study quality was assessed with the Newcastle-Ottowa Quality Assessment Scale. Pooled effect sizes were estimated with random-effects models (correlation for continuous and odds ratios for dichotomous outcomes)., Results: Sixteen studies with 51,470 participants (prenatal PTSD 8%) were included in 4 meta-analyses. Maternal prenatal PTSD was associated with higher risks of LBW (OR = 1.96; 95% CI, 1.26, 3.03; P = .003), PTB (OR = 1.42; 95% CI, 1.16, 1.73; P = .001), and reduced GA (r = -0.04; 95% CI, -0.06, -0.01; P = .002)., Limitations: Different designs across studies, variety of PTSD assessment practices, and a small pool of studies were noted., Conclusions: Findings suggest prenatal PTSD presents increased risks of LBW, PTB, and reduced GA. Evidence of physical harm to neonates from prenatal PTSD provides a powerful rationale to increase prenatal PTSD screening and identify effective prenatal interventions to improve maternal and child outcomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)