Primary Care Interventions to Prevent Child Maltreatment: US Preventive Services Task Force Recommendation Statement.

Importance: Child maltreatment, which includes child abuse and neglect, can have profound effects on health, development, survival, and well-being throughout childhood and adulthood. The prevalence of child maltreatment in the US is uncertain and likely underestimated. In 2021, an estimated 600 000 children were identified by Child Protective Services as experiencing abuse or neglect and an estimated 1820 children died of abuse and neglect. Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate benefits and harms of primary care-feasible or referable behavioral counseling interventions to prevent child maltreatment in children and adolescents younger than 18 years without signs or symptoms of maltreatment. Population: Children and adolescents younger than 18 years who do not have signs or symptoms of or known exposure to maltreatment. Evidence Assessment: The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of primary care interventions to prevent child maltreatment in children and adolescents younger than 18 years without signs or symptoms of or known exposure to maltreatment. Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of primary care interventions to prevent child maltreatment. (I statement).

Investigation of Head Kinematics and Brain Strain Response During Soccer Heading Using a Custom-Fit Instrumented Mouthguard.

Association football, also known as soccer in some regions, is unique in encouraging its participants to intentionally use their head to gain a competitive advantage, including scoring a goal. Repetitive head impacts are now being increasingly linked to an inflated risk of developing long-term neurodegenerative disease. This study investigated the effect of heading passes from different distances, using head acceleration data and finite element modelling to estimate brain injury risk. Seven university-level participants wore a custom-fitted instrumented mouthguard to capture linear and angular acceleration-time data. They performed 10 headers within a laboratory environment, from a combination of short, medium, and long passes. Kinematic data was then used to calculate peak linear acceleration, peak angular velocity, and peak angular acceleration as well as two brain injury metrics: head injury criterion and rotational injury criterion. Six degrees of freedom acceleration-time data were also inputted into a widely accepted finite element brain model to estimate strain-response using mean peak strain and cumulative strain damage measure values. Five headers were considered to have a 25% concussion risk. Mean peak linear acceleration equalled 26 ± 7.9 g, mean peak angular velocity 7.20 ± 2.18 rad/s, mean peak angular acceleration 1730 ± 611 rad/s2, and 95th percentile mean peak strain 0.0962 ± 0.252. Some of these data were similar to brain injury metrics reported from American football, which supports the need for further investigation into soccer heading.

Rapid disintegration and weakening of ice shelves in North Greenland.

The glaciers of North Greenland are hosting enough ice to raise sea level by 2.1 m, and have long considered to be stable. This part of Greenland is buttressed by the last remaining ice shelves of the ice sheet. Here, we show that since 1978, ice shelves in North Greenland have lost more than 35% of their total volume, three of them collapsing completely. For the floating ice shelves that remain we observe a widespread increase in ice shelf mass losses, that are dominated by enhanced basal melting rates. Between 2000 and 2020, there was a widespread increase in basal melt rates that closely follows a rise in the ocean temperature. These glaciers are showing a direct dynamical response to ice shelf changes with retreating grounding lines and increased ice discharge. These results suggest that, under future projections of ocean thermal forcing, basal melting rates will continue to rise or remain at high level, which may have dramatic consequences for the stability of Greenlandic glaciers.

Interpopulation differences and temporal synchrony in rates of adult survival between two seabird colonies that differ in population size and distance to foraging grounds.

Understanding the processes that drive interpopulation differences in demography and population dynamics is central to metapopulation ecology. In colonial species, populations are limited by local resource availability. However, individuals from larger colonies will travel greater distances to overcome density-dependent competition. Consequently, these individuals may also experience greater carry-over effects and interpopulation differences in demography. To test this prediction, we use mark-recapture data collected over four decades from two breeding colonies of a seabird, the Manx shearwater (Puffinus puffinus), that exhibit strong spatial overlap throughout the annual cycle but differ in population size and maximum foraging distances. We quantify interpopulation differences and synchrony in rates of survival and assess whether local mean wind speeds act to strengthen or disrupt synchrony. In addition, we examine whether the imputed interpopulation differences in survival can generate population-level consequences. The colony where individuals travel further during the breeding season had slightly lower and more variable rates of survival, indicative of individuals experiencing greater carry-over effects. Fluctuations in survival were highly synchronous between the colonies, but neither synchronous, nor asynchronous, variation could be strongly attributed to fluctuations in local mean wind speeds. Finally, we demonstrate that the imputed interpopulation differences in rates of survival could lead to considerable differences in population growth. We hypothesise that the observed interpopulation differences in rates of adult survival reflect carry-over effects associated with foraging distances during the breeding season. More broadly, our results highlight that breeding season processes can be important for understanding interpopulation differences in the demographic rates and population dynamics of long-lived species, such as seabirds.

Inhibiting Anti-angiogenic VEGF165b Activates a Novel miR-17-20a-Calcipressin-3 Pathway that Revascularizes Ischemic Muscle in Peripheral Artery Disease.

Background: VEGF165a increases the expression of microRNA-17-92 cluster, promoting developmental, retinal, and tumor angiogenesis. We have previously shown that VEGF165b, an alternatively spliced VEGF-A isoform, inhibits the VEGFR-STAT3 pathway in ischemic endothelial cells (ECs) to decrease their angiogenic capacity. In ischemic macrophages (Møs), VEGF165b inhibits VEGFR1 to induce S100A8/A9 expression, which drives M1-like polarization. Our current study aims to determine whether VEGF165b inhibition promotes perfusion recovery by regulating the miR-17-92 cluster in preclinical PAD. Methods: Hind limb ischemia (HLI) induced by femoral artery ligation and resection was used as a preclinical PAD model. Hypoxia serum starvation (HSS) was used as an in vitro PAD model. VEGF165b was inhibited/neutralized by an isoform-specific VEGF165b antibody. Results: Systematic analysis of miR-17-92 cluster members (miR-17-18a-19a-19b-20a-92) in experimental-PAD models showed that VEGF165b-inhibition induces miRNA-17-20a (within miR-17-92 cluster) in HSS-ECs and HSS-bone marrow derived macrophages (BMDMs) vs. respective normal and/or isotype matched IgG controls to enhance perfusion-recovery. Consistent with the bioinformatics analysis that revealed RCAN3 as a common target of miR-17 and miR-20a, Argonaute-2 pull-down assays showed decreased miR-17-20a expression and higher RCAN3 expression in the RISC complex of HSS-ECs and HSS-BMDMs vs. the respective controls. Inhibiting miR-17-20a induced RCAN3 levels to decrease ischemic angiogenesis and promoted M1-like polarization to impair perfusion recovery. Finally, using STAT3 inhibitors, S100A8/A9 silencers and VEGFR1-deficient ECs and Møs, we show that VEGF165b inhibition activates the miR-17-20a-RCAN3 pathway independent of VEGFR1-STAT3 or VEGFR1-S100A8/A9 in ischemic ECs and ischemic Møs, respectively. Conclusion: Our data revealed a hereunto unrecognized therapeutic 'miR-17-20a-RCAN3' pathway in the ischemic vasculature that is VEGFR1-STAT3/S100A8/A9 independent and is activated only upon VEGF165b inhibition in PAD.

Chornobyl radiation spikes are not due to military vehicles disturbing soil.

On 25th February 2022, increased gamma radiation dose rates were reported within the Chornobyl Exclusion Zone (CEZ). This coincided with Russian military vehicles entering the Ukrainian part of the CEZ from neighbouring Belarus. It was speculated that contaminated soil resuspension by vehicle movements or a leak from the Chornobyl Nuclear Power Plant complex may explain these spikes in radiation dose rates. The gamma dose rate monitoring network in the CEZ provides a crucial early warning system for releases of radioactivity to the environment and is part of the international safeguards for nuclear facilities. With the potential for further military action in the CEZ and concerns over nuclear safety, it is essential that such anomalous readings are investigated. We evaluate the hypotheses suggested to explain the apparent gamma dose rate increases, demonstrating that neither military vehicle-induced soil resuspension nor a leak from the Chornobyl Nuclear Power Plant are plausible. However, disruption of the Chornobyl base-station's reception of wireless signals from the gamma dose rate monitoring network in the CEZ may potentially explain the dose rate increases recorded.

Machine learned interatomic potential for dispersion strengthened plasma facing components.

Tungsten (W) is a material of choice for the divertor material due to its high melting temperature, thermal conductivity, and sputtering threshold. However, W has a very high brittle-to-ductile transition temperature, and at fusion reactor temperatures (≥1000 K), it may undergo recrystallization and grain growth. Dispersion-strengthening W with zirconium carbide (ZrC) can improve ductility and limit grain growth, but much of the effects of the dispersoids on microstructural evolution and thermomechanical properties at high temperatures are still unknown. We present a machine learned Spectral Neighbor Analysis Potential for W-ZrC that can now be used to study these materials. In order to construct a potential suitable for large-scale atomistic simulations at fusion reactor temperatures, it is necessary to train on ab initio data generated for a diverse set of structures, chemical environments, and temperatures. Further accuracy and stability tests of the potential were achieved using objective functions for both material properties and high temperature stability. Validation of lattice parameters, surface energies, bulk moduli, and thermal expansion is confirmed on the optimized potential. Tensile tests of W/ZrC bicrystals show that although the W(110)-ZrC(111) C-terminated bicrystal has the highest ultimate tensile strength (UTS) at room temperature, observed strength decreases with increasing temperature. At 2500 K, the terminating C layer diffuses into the W, resulting in a weaker W-Zr interface. Meanwhile, the W(110)-ZrC(111) Zr-terminated bicrystal has the highest UTS at 2500 K.

Functional Laryngeal Assessment in Patients with Tracheostomy Following COVID-19 a Prospective Cohort Study.

To explore laryngeal function of tracheostomised patients with COVID-19 in the acute phase, to identify ways teams may facilitate and expedite tracheostomy weaning and rehabilitation of upper airway function. Consecutive tracheostomised patients underwent laryngeal examination during mechanical ventilation weaning. Primary outcomes included prevalence of upper aerodigestive oedema and airway protection during swallow, tracheostomy duration, ICU frailty scores, and oral intake type. Analyses included bivariate associations and exploratory multivariable regressions. 48 consecutive patients who underwent tracheostomy insertion as part of their respiratory wean following invasive ventilation in a single UK tertiary hospital were included. 21 (43.8%) had impaired airway protection on swallow (PAS ≥ 3) with 32 (66.7%) having marked airway oedema in at least one laryngeal area. Impaired airway protection was associated with longer total artificial airway duration (p = 0.008), longer tracheostomy tube duration (p = 0.007), multiple intubations (p = 0.006) and was associated with persistent ICU acquired weakness at ICU discharge (p = 0.03). Impaired airway protection was also an independent predictor for longer tracheostomy tube duration (p = 0.02, Beta 0.38, 95% CI 2.36 to 27.16). The majority of our study patients presented with complex laryngeal findings which were associated with impaired airway protection. We suggest a proactive standardized scoring and review protocol to manage this complex group of patients in order to maximize health outcomes and ICU resources. Early laryngeal assessment may facilitate weaning from invasive mechanical ventilation and liberation from tracheostomy, as well as practical and objective risk stratification for patients regarding decannulation and feeding.

Optimizing the Application Timing and Dosage of Metarhizium brunneum (Hypocreales: Clavicipitaceae) as a Biological Control Agent of Aedes aegypti (Diptera: Culicidae) Larvae.

Aedes aegypti (Diptera: Culicidae) is the principal vector of dengue and other viruses that cause disease among 100 to 400 million people each year. The recent development of widespread insecticidal resistance has led to the rapid development of biological control solutions aimed at larval control. While the efficacy of Metarhizium brunneum has been shown against Aedes larvae, the impact of larval population dynamics will need to be determined to formulate effective control strategies. In this study, larvae were subjected to four concentrations of M. brunneum (105, 106, 107, 108 conidia ml-1). Larvae were found to be susceptible to M. brunneum with dose-dependent efficacy. When constant larval immigration was added as a parameter, peak mortality was consistently found to occur on the fourth day, before a significant reduction in control efficacy linked to a decline in conidial availability within the water column. This suggests that M. brunneum treatments should be applied at a concentration 1 × 107 conidia ml-1 every four days to effectively control mosquito larvae in the field, regardless of the fungal formulation, water volume, or larval density. Understanding fungal-mosquito dynamics is critical in developing appropriate control programs as it helps optimize the fungal control agent's dose and frequency of application.

Temporal endurance of exercise-induced benefits on hippocampus-dependent memory and synaptic plasticity in female mice.

Exercise facilitates hippocampal neurogenesis and neuroplasticity that in turn, promotes cognitive function. Our previous studies have demonstrated that in male mice, voluntary exercise enables hippocampus-dependent learning in conditions that are normally subthreshold for long-term memory formation in sedentary animals. Such cognitive enhancement can be maintained long after exercise has ceased and can be re-engaged by a subsequent subthreshold exercise session, suggesting exercise-induced benefits are temporally dynamic. In females, the extent to which the benefits of exercise can be maintained and the mechanisms underlying this maintenance have yet to be defined. Here, we examined the exercise parameters required to initiate and maintain the benefits of exercise in female C57BL/6J mice. Using a subthreshold version of the hippocampus-dependent task called object-location memory (OLM) task, we show that 14d of voluntary exercise enables learning under subthreshold acquisition conditions in female mice. Following the initial exercise, a 7d sedentary delay results in diminished performance, which can be re-facilitated when animals receive 2d of reactivating exercise following the sedentary delay. Assessment of estrous cycle reveals enhanced wheel running activity during the estrus phase relative to the diestrus phase, whereas estrous phase on training or test had no effect on OLM performance. Utilizing the same exercise parameters, we demonstrate that 14d of exercise enhances long-term potentiation (LTP) in the CA1 region of the hippocampus, an effect that persists throughout the sedentary delay and following the reactivating exercise session. Previous studies have proposed exercise-induced BDNF upregulation as the mechanism underlying exercise-mediated benefits on synaptic plasticity and cognition. However, our assessment of hippocampal Bdnf mRNA expression following memory retrieval reveals no difference between exercise conditions and control, suggesting that persistent Bdnf upregulation may not be required for maintenance of exercise-induced benefits. Together, our data indicate that 14d of voluntary exercise can initiate long-lasting benefits on neuroplasticity and cognitive function in female mice, establishing the first evidence on the temporal endurance of exercise-induced benefits in females.

Ensuring robust radiological risk assessment for wildlife: insights from the International Atomic Energy Agency EMRAS and MODARIA programmes.

In response to changing international recommendations and national requirements, a number of assessment approaches, and associated tools and models, have been developed over the last circa 20 years to assess radiological risk to wildlife. In this paper, we summarise international intercomparison exercises and scenario applications of available radiological assessment models for wildlife to aid future model users and those such as regulators who interpret assessments. Through our studies, we have assessed the fitness for purpose of various models and tools, identified the major sources of uncertainty and made recommendations on how the models and tools can best be applied to suit the purposes of an assessment. We conclude that the commonly used tiered or graded assessment tools are generally fit for purpose for conducting screening-level assessments of radiological impacts to wildlife. Radiological protection of the environment (or wildlife) is still a relatively new development within the overall system of radiation protection and environmental assessment approaches are continuing to develop. Given that some new/developing approaches differ considerably from the more established models/tools and there is an increasing international interest in developing approaches that support the effective regulation of multiple stressors (including radiation), we recommend the continuation of coordinated international programmes for model development, intercomparison and scenario testing.

Towards an ecological modelling approach for assessing ionizing radiation impact on wildlife populations.

The emphasis of the international system of radiological protection of the environment is to protect populations of flora and fauna. Throughout the MODARIA programmes, the United Nations' International Atomic Energy Agency (IAEA) has facilitated knowledge sharing, data gathering and model development on the effect of radiation on wildlife. We present a summary of the achievements of MODARIA I and II on wildlife dose effect modelling, extending to a new sensitivity analysis and model development to incorporate other stressors. We reviewed evidence on historical doses and transgenerational effects on wildlife from radioactively contaminated areas. We also evaluated chemical population modelling approaches, discussing similarities and differences between chemical and radiological impact assessment in wildlife. We developed population modelling methodologies by sourcing life history and radiosensitivity data and evaluating the available models, leading to the formulation of an ecosystem-based mathematical approach. This resulted in an ecologically relevant conceptual population model, which we used to produce advice on the evaluation of risk criteria used in the radiological protection of the environment and a proposed modelling extension for chemicals. This work seeks to inform stakeholder dialogue on factors influencing wildlife population responses to radiation, including discussions on the ecological relevance of current environmental protection criteria. The area of assessment of radiation effects in wildlife is still developing with underlying data and models continuing to be improved. IAEA's ongoing support to facilitate the sharing of new knowledge, models and approaches to Member States is highlighted, and we give suggestions for future developments in this regard.

Investigation of discordant sibling pairs from hereditary breast cancer families and analysis of a rare PMS1 variant.

BACKGROUND: It is likely that additional genes for hereditary breast cancer can be identified using a discordant sib pair design. Using this design we identified individuals harboring a rare PMS1 c.605G>A variant previously predicted to result in loss of function. OBJECTIVES: A family-based design and predictive algorithms were used to prioritize candidate variants possibly associated with an increased risk of hereditary breast cancer. Functional analyses were performed for one of the candidate variants, PMS1 c.605G>A. METHODS: 1) 14 discordant sister-pairs from hereditary breast cancer families were identified. 2) Whole exome sequencing was performed and candidate risk variants identified. 3) A rare PMS variant was identified in 2 unrelated affected sisters but no unaffected siblings. 4) Functional analysis of this variant was carried out using targeted mRNA sequencing. RESULTS: Genotype-phenotype correlation did not demonstrate tracking of the variant with cancer in the family. Functional analysis revealed no difference in exon 6 incorporation, which was validated by analyzing PMS1 allele specific expression. CONCLUSIONS: The PMS1 c.605G>A variant did not segregate with disease, and there was no variant-dependent impact on PMS1 exon 6 splicing, supporting this variant is likely benign. Functional analyses are imperative to understanding the clinical significance of predictive algorithms.

Pediatric malnutrition screening and assessment tools: Analyzing the gaps.

Pediatric healthcare professionals know that children who are malnourished have worse clinical outcomes than do their well-nourished peers. The body of evidence in the literature on the topic of pediatric malnutrition (PMN) is growing and supports this conclusion. The goal of this article is to present the current state of practice related to PMN screening, the use of malnutrition risk screening (MNRS) tools, malnutrition assessment, and the use of malnutrition assessment tools. The purpose is also to discuss best practice for MNRS and assessment and to consider the gaps in practice where additional work is needed.

HDAC3 Activity within the Nucleus Accumbens Regulates Cocaine-Induced Plasticity and Behavior in a Cell-Type-Specific Manner.

Epigenetic mechanisms regulate processes of neuroplasticity critical to cocaine-induced behaviors. This includes the Class I histone deacetylase (HDAC) HDAC3, known to act as a negative regulator of cocaine-associated memory formation within the nucleus accumbens (NAc). Despite this, it remains unknown how cocaine alters HDAC3-dependent mechanisms. Here, we profiled HDAC3 expression and activity in total NAc mouse tissue following cocaine exposure. Although chronic cocaine did not affect expression of Hdac3 within the NAc, chronic cocaine did affect promoter-specific changes in HDAC3 and H4K8Ac occupancy. These changes in promoter occupancy correlated with cocaine-induced changes in expression of plasticity-related genes. To causally determine whether cocaine-induced plasticity is mediated by HDAC3's deacetylase activity, we overexpressed a deacetylase-dead HDAC3 point mutant (HDAC3-Y298H-v5) within the NAc of adult male mice. We found that disrupting HDAC3's enzymatic activity altered selective changes in gene expression and synaptic plasticity following cocaine exposure, despite having no effects on cocaine-induced behaviors. In further assessing HDAC3's role within the NAc, we observed that chronic cocaine increases Hdac3 expression in Drd1 but not Drd2-cells of the NAc. Moreover, we discovered that HDAC3 acts selectively within D1R cell-types to regulate cocaine-associated memory formation and cocaine-seeking. Overall, these results suggest that cocaine induces cell-type-specific changes in epigenetic mechanisms to promote plasticity important for driving cocaine-related behaviors.SIGNIFICANCE STATEMENT Drugs of abuse alter molecular mechanisms throughout the reward circuitry that can lead to persistent drug-associated behaviors. Epigenetic regulators are critical drivers of drug-induced changes in gene expression. Here, we demonstrate that the activity of an epigenetic enzyme promotes neuroplasticity within the nucleus accumbens (NAc) critical to cocaine action. In addition, we demonstrate that these changes in epigenetic activity drive cocaine-seeking behaviors in a cell-type-specific manner. These findings are key in understanding and targeting cocaine's impact of neural circuitry and behavior.

Systemic HDAC3 inhibition ameliorates impairments in synaptic plasticity caused by simulated galactic cosmic radiation exposure in male mice.

Deep space travel presents a number of measurable risks including exposure to a spectrum of radiations of varying qualities, termed galactic cosmic radiation (GCR) that are capable of penetrating the spacecraft, traversing through the body and impacting brain function. Using rodents, studies have reported that exposure to simulated GCR leads to cognitive impairments associated with changes in hippocampus function that can persist as long as one-year post exposure with no sign of recovery. Whether memory can be updated to incorporate new information in mice exposed to GCR is unknown. Further, mechanisms underlying long lasting impairments in cognitive function as a result of GCR exposure have yet to be defined. Here, we examined whether whole body exposure to simulated GCR using 6 ions and doses of 5 or 30 cGy interfered with the ability to update an existing memory or impact hippocampal synaptic plasticity, a cellular mechanism believed to underlie memory processes, by examining long term potentiation (LTP) in acute hippocampal slices from middle aged male mice 3.5-5 months after radiation exposure. Using a modified version of the hippocampus-dependent object location memory task developed by our lab termed "Objects in Updated Locations" (OUL) task we find that GCR exposure impaired hippocampus-dependent memory updating and hippocampal LTP 3.5-5 months after exposure. Further, we find that impairments in LTP are reversed through one-time systemic subcutaneous injection of the histone deacetylase 3 inhibitor RGFP 966 (10 mg/kg), suggesting that long lasting impairments in cognitive function may be mediated at least in part, through epigenetic mechanisms.

Dysphagia presentation and management following COVID-19: an acute care tertiary centre experience.

OBJECTIVES: As the pathophysiology of COVID-19 emerges, this paper describes dysphagia as a sequela of the disease, including its diagnosis and management, hypothesised causes, symptomatology in relation to viral progression, and concurrent variables such as intubation, tracheostomy and delirium, at a tertiary UK hospital. RESULTS: During the first wave of the COVID-19 pandemic, 208 out of 736 patients (28.9 per cent) admitted to our institution with SARS-CoV-2 were referred for swallow assessment. Of the 208 patients, 102 were admitted to the intensive treatment unit for mechanical ventilation support, of which 82 were tracheostomised. The majority of patients regained near normal swallow function prior to discharge, regardless of intubation duration or tracheostomy status. CONCLUSION: Dysphagia is prevalent in patients admitted either to the intensive treatment unit or the ward with COVID-19 related respiratory issues. This paper describes the crucial role of intensive swallow rehabilitation to manage dysphagia associated with this disease, including therapeutic respiratory weaning for those with a tracheostomy.

Precision measurement of the neutral pion lifetime.

The explicit breaking of the axial symmetry by quantum fluctuations gives rise to the so-called axial anomaly. This phenomenon is solely responsible for the decay of the neutral pion π0 into two photons (γγ), leading to its unusually short lifetime. We precisely measured the decay width Γ of the [Formula: see text] process. The differential cross sections for π0 photoproduction at forward angles were measured on two targets, carbon-12 and silicon-28, yielding [Formula: see text], where stat. denotes the statistical uncertainty and syst. the systematic uncertainty. We combined the results of this and an earlier experiment to generate a weighted average of [Formula: see text] Our final result has a total uncertainty of 1.50% and confirms the prediction based on the chiral anomaly in quantum chromodynamics.