Children's toys no longer: a porcine model study of the lethality of modern air rifles.

AIMS: We observed modern spring-loaded air rifles reaching velocities similar to small-bore rifles, raising concerns about their potential lethality. After encountering two life-threatening thoracic injuries in our practice, we conducted a study to assess the injuries that a commonly available air rifle could cause in a porcine cadaver model. METHODS: We conducted shooting experiments from 5 and 10 metres away using a .22 calibre spring-loaded airgun, firing five shots into the anterolateral chest on the left side at both distances. Additionally, we repeated the experiment with ten shots into 10% ballistics gel behind an explanted chest wall to evaluate chest wall penetration reliability. RESULTS: Out of the ten combined shots, six resulted in lethal or potentially lethal injuries, including multiple cardiac injuries. Moreover, we observed chest wall penetration in 9 out of 10 shots, with an average penetration depth of 106mm. Non-life-threatening injuries appeared to be influenced by shot location rather than an inability to penetrate the chest wall. CONCLUSION: Our study raises significant concerns about the potential lethality of unrestricted air rifles in New Zealand. With muzzle velocities comparable to small-bore rifles, these firearms should be reconsidered in terms of regulation and possibly restricted to gun license holders.

Remotely supervised at-home delivery of taVNS for autism spectrum disorder: feasibility and initial efficacy.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has potential clinical application for autism spectrum disorder (ASD). At-home sessions are necessary to allow delivery of repeated sessions, and remove burden on patients for daily visits, and reduce costs of clinic delivery. Our objective was to validate a protocol for remote supervised administration for home delivery of taVNS using specially designed equipment and platform. Methods: An open-label design was followed involving administration by caretakers to 12 patients with ASD (ages:7-16). Daily 1-h sessions over 2 weeks were administered under remote supervision. The primary outcome was feasibility, which was assessed by completion rate, stimulation tolerability, and confirmation of programmed stimulation delivery. The secondary measures were initial efficacy assessed by Childhood Anxiety Sensitivity Index-Revised (CASI-R), Parent Rated Anxiety Scale for Youth with ASD (PRAS-ASD), and Clinician Global Impression (CGI) scales. Sleep measures were also tracked using Cleveland Adolescent Sleep Questionnaire (CASQ). Results: Across 132 sessions, we obtained an 88.5% completion rate. A total of 22 expected adverse events were reported with headache being the most common followed by transient pain, itchiness, and stinging at the electrode site. One subject dropped out of the study unrelated to the stimulation or the study. Average scores of anxiety (CASI-R, PRAS-ASD, and CGI) and sleepiness (CASQ) were all improved at the 2 week time point. While not powered to determine efficacy, benefits were suggested in this open label pilot. Conclusion: Remotely supervised, proxy-administered, at-home delivery of taVNS is feasible in patients with ASD. Initial efficacy supports pursuing larger scale trials.

The History of Water in Martian Magmas From Thorium Maps.

Water inventories in Martian magmas are poorly constrained. Meteorite-based estimates range widely, from 102 to >104 ppm H2O, and are likely variably influenced by degassing. Orbital measurements of H primarily reflect water cycled and stored in the regolith. Like water, Th behaves incompatibly during mantle melting, but unlike water Th is not prone to degassing and is relatively immobile during aqueous alteration at low temperature. We employ Th as a proxy for original, mantle-derived H2O in Martian magmas. We use regional maps of Th from Mars Odyssey to assess variations in magmatic water across major volcanic provinces and through time. We infer that Hesperian and Amazonian magmas had ∼100-3,000 ppm H2O, in the lower range of previous estimates. The implied cumulative outgassing since the Hesperian, equivalent to a global H2O layer ∼1-40 m deep, agrees with Mars' present-day surface and near-surface water inventory and estimates of sequestration and loss rates.

Implementation of maternal and perinatal death surveillance and response (MPDSR) in humanitarian settings: insights and experiences of humanitarian health practitioners and global technical expert meeting attendees.

BACKGROUND: Maternal and perinatal death surveillance and response (MPDSR) is a system of identifying, analysing and learning lessons from such deaths in order to respond and prevent future deaths, and has been recommended by WHO and implemented in many low-and-middle income settings in recent years. However, there is limited documentation of experience with MPDSR in humanitarian settings. A meeting on MPDSR in humanitarian settings was convened by WHO, UNICEF, CDC and Save the Children, UNFPA and UNHCR on 17th-18th October 2019, informed by semi-structured interviews with a range of professionals, including expert attendees. CONSULTATION FINDINGS: Interviewees revealed significant obstacles to full implementation of the MPDSR process in humanitarian settings. Many obstacles were familiar to low resource settings in general but were amplified in the context of a humanitarian crisis, such as overburdened services, disincentives to reporting, accountability gaps, a blame approach, and politicisation of mortality. Factors more unique to humanitarian contexts included concerns about health worker security and moral distress. There are varying levels of institutionalisation and implementation capacity for MPDSR within humanitarian organisations. It is suggested that if poorly implemented, particularly with a punitive or blame approach, MPDSR may be counterproductive. Nevertheless, successes in MPDSR were described whereby the process led to concrete actions to prevent deaths, and where death reviews have led to improved understanding of complex and rectifiable contextual factors leading to deaths in humanitarian settings. CONCLUSIONS: Despite the challenges, examples exist where the lessons learnt from MPDSR processes have led to improved access and quality of care in humanitarian contexts, including successful advocacy. An adapted approach is required to ensure feasibility, with varying implementation being possible in different phases of crises. There is a need for guidance on MPDSR in humanitarian contexts, and for greater documentation and learning from experiences.

Parental understanding and attitudes following pharmacogenomic testing for pediatric neuropsychiatric patients.

Aim: This study explores parental understanding and attitudes around pharmacogenomic results in their child(ren). Patients and methods: In-depth interviews with parents whose child(ren) had received a pharmacogenomic testing panel for management of neuropsychiatric medications were completed. Interviews were analyzed for themes and accuracy of understanding of results. Results: In 18 parents interviewed, 49/63 (78%) of statements made regarding results were accurate. Differences in understanding were seen by clinic, number of medications and result type. Parents expected results to guide prescribing and perceived the greatest utility in results that could impact current care. Results predicting normal drug metabolism may create mixed feelings. Conclusion: Parents perceive utility in pharmacogenomic testing for their children. Challenges exist in understanding probabilistic and multifactorial information about pharmacogenomic results.

A call to safeguard sexual and reproductive health information and services during Ebola outbreaks.

The recent Ebola virus disease (EVD) outbreaks in 2021 exemplify how sexual and reproductive health services are too often considered unessential during health emergencies. Bleeding for reasons other than EVD, such as pregnancy complications or rape, can be construed as EVD symptoms, reinforcing fear and stigmatisation, and delaying timely access to adequate care. In this commentary, we urgently call on all humanitarian actors to integrate the Minimum Initial Services Package for Sexual and Reproductive Health in Crisis Situations into current and future EVD preparedness and response efforts.

Global climate disruption and regional climate shelters after the Toba supereruption.

The Toba eruption ∼74,000 y ago was the largest volcanic eruption since the start of the Pleistocene and represents an important test case for understanding the effects of large explosive eruptions on climate and ecosystems. However, the magnitude and repercussions of climatic changes driven by the eruption are strongly debated. High-resolution paleoclimate and archaeological records from Africa find little evidence for the disruption of climate or human activity in the wake of the eruption in contrast with a controversial link with a bottleneck in human evolution and climate model simulations predicting strong volcanic cooling for up to a decade after a Toba-scale eruption. Here, we use a large ensemble of high-resolution Community Earth System Model (CESM1.3) simulations to reconcile climate model predictions with paleoclimate records, accounting for uncertainties in the magnitude of Toba sulfur emissions with high and low emission scenarios. We find a near-zero probability of annual mean surface temperature anomalies exceeding 4 °C in most of Africa in contrast with near 100% probabilities of cooling this severe in Asia and North America for the high sulfur emission case. The likelihood of strong decreases in precipitation is low in most of Africa. Therefore, even Toba sulfur release at the upper range of plausible estimates remains consistent with the muted response in Africa indicated by paleoclimate proxies. Our results provide a probabilistic view of the uneven patterns of volcanic climate disruption during a crucial interval in human evolution, with implications for understanding the range of environmental impacts from past and future supereruptions.

Reconciling early Deccan Traps CO2 outgassing and pre-KPB global climate.

A 2 to 4 °C warming episode, known as the Latest Maastrichtian warming event (LMWE), preceded the Cretaceous-Paleogene boundary (KPB) mass extinction at 66.05 ± 0.08 Ma and has been linked with the onset of voluminous Deccan Traps volcanism. Here, we use direct measurements of melt-inclusion CO2 concentrations and trace-element proxies for CO2 to test the hypothesis that early Deccan magmatism triggered this warming interval. We report CO2 concentrations from NanoSIMS and Raman spectroscopic analyses of melt-inclusion glass and vapor bubbles hosted in magnesian olivines from pre-KPB Deccan primitive basalts. Reconstructed melt-inclusion CO2 concentrations range up to 0.23 to 1.2 wt% CO2 for lavas from the Saurashtra Peninsula and the Thakurvadi Formation in the Western Ghats region. Trace-element proxies for CO2 concentration (Ba and Nb) yield estimates of initial melt concentrations of 0.4 to 1.3 wt% CO2 prior to degassing. Our data imply carbon saturation and degassing of Deccan magmas initiated at high pressures near the Moho or in the lower crust. Furthermore, we find that the earliest Deccan magmas were more CO2 rich, which we hypothesize facilitated more efficient flushing and outgassing from intrusive magmas. Based on carbon cycle modeling and estimates of preserved lava volumes for pre-KPB lavas, we find that volcanic CO2 outgassing alone remains insufficient to account for the magnitude of the observed latest Maastrichtian warming. However, accounting for intrusive outgassing can reconcile early carbon-rich Deccan Traps outgassing with observed changes in climate and atmospheric pCO2.

Retrospective Review of Pharmacogenetic Testing at an Academic Children's Hospital.

There is limited evidence to support pharmacogenetic (PGx) testing in children. We conducted a retrospective review of PGx testing among 452 patients at an academic children's hospital to determine the potential utility of PGx in diseases of childhood and to identify targets for future pediatric pharmacogenetic research. An actionable gene-drug pair associated with the 28 genes tested (Clinical Pharmacogenetics Implementation Consortium (CPIC) level A or B, Pharmacogenomics Knowledge Base (PharmGKB) level 1A or B, or US Food and Drug Administration (FDA) recommendation and a PharmGKB level) was present in 98.7% of patients. We identified 203 actionable gene-drug-diagnosis groups based on the indications for each actionable drug listed in Lexicomp. Among patients with an actionable gene-drug-diagnosis group, 49.3% had a diagnosis where the drug was a therapeutic option and PGx could be used to guide treatment selection. Among patients with an associated diagnosis, 30.9% had a prescription for the actionable drug allowing PGx guided dosing. Three genes (CYP2C19, CYP2D6, and CYP3A5) accounted for all the gene-drug-diagnosis groups with matching diagnoses and prescriptions. The most common gene-drug-diagnosis groups with matching diagnoses and prescriptions were CYP2C19-citalopram-escitalopram-depression 3.3% of patients tested; CYP2C19-dexlansoprazole-gastritis-esophagitis 3.1%; CYP2C19-omeprazole-gastritis-esophagitis 2.4%; CYP2D6-atomoxetine-attention deficit hyperactivity disorder 2.2%; and CYP2C19-citalopram-escitalopram-obsessive-compulsive disorder 1.5%. PGx could be used to guide selection of current treatment options or medication dosing in almost half (48.7%) of pediatric patients tested. Mood disorders and gastritis/esophagitis are promising targets for future study of PGx testing because of the high prevalence of these diagnoses and associated actionable gene-drug pairs in the pediatric population.

Problematic Child Mealtime Behavior and Caregiver Mobile Phone Use.

OBJECTIVE: To evaluate the associations of caregiver mobile phone problematic use and child problematic mealtime behaviors (PMBs) to improve understanding of the possible implications of caregiver mobile phone problematic use. METHODS: Surveys were administered to caregivers of children aged 3 to 8 years. The survey included demographics, a validated measure for caregiver mobile phone problematic use (Mobile Phone Problematic Use Scale-10 [MPPUS-10]), and a validated measure for the perception of child PMB (Meals in our Household [MIOH]). The bivariate associations between child and caregiver characteristics, mobile phone problematic use, and PMBs of children were analyzed. Partial correlations examined these relations while controlling for significant (p ≤ 0.05) covariates. RESULTS: Eighty-four caregivers (mean age 32.6 years, 63% white, 21% ≤ high school completion) participated. The correlation of MIOH problematic behavior total with MPPUS-10 was significant (r = 0.33, p ≤ 0.01). Significantly correlated caregiver variables with MPPUS-10 included age (r = -0.25, p = 0.02) and female sex (p = 0.01). No significant caregiver variables were noted for PMB. Child's age was significantly correlated with PMB (r = -0.27, p = 0.01). MPPUS-10 and PMB correlation remained significant when controlling for significant covariates. CONCLUSION: A positive correlation existed between MPPUS-10 and PMB. Understanding the potential association between caregiver mobile phone problematic use and child PMB strengthens the pediatricians' ability to counsel about the implications of caregiver mobile phone problematic use when discussing child PMB.

Maternal health after Ebola: unmet needs and barriers to healthcare in rural Sierra Leone.

Sierra Leone has the world's highest estimated maternal mortality. Following the 2014-16 Ebola outbreak, we described health outcomes and health-seeking behaviour amongst pregnant women to inform health policy. In October 2016-January 2017, we conducted a sequential mixed-methods study in urban and rural areas of Tonkolili District comprising: household survey targeting women who had given birth since onset of the Ebola outbreak; structured interviews at rural sites investigating maternal deaths and reporting; and in-depth interviews (IDIs) targeting mothers, community leaders and health workers. We selected 30 clusters in each area: by random GPS points (urban) and by random village selection stratified by population size (rural). We collected data on health-seeking behaviours, barriers to healthcare, childbirth and outcomes using structured questionnaires. IDIs exploring topics identified through the survey were conducted with a purposive sample and analysed thematically. We surveyed 608 women and conducted 29 structured and 72 IDIs. Barriers, including costs of healthcare and physical inaccessibility of healthcare facilities, delayed or prevented 90% [95% confidence interval (CI): 80-95] (rural) vs 59% (95% CI: 48-68) (urban) pregnant women from receiving healthcare. Despite a general preference for biomedical care, 48% of rural and 31% of urban women gave birth outside of a health facility; of those, just 4% and 34%, respectively received skilled assistance. Women expressed mistrust of healthcare workers (HCWs) primarily due to payment demanded for 'free' healthcare. HCWs described lack of pay and poor conditions precluding provision of quality care. Twenty percent of women reported labour complications. Twenty-eight percent of villages had materials to record maternal deaths. Pregnant women faced important barriers to care, particularly in rural areas, leading to high preventable mortality and morbidity. Women wanted to access healthcare, but services available were often costly, unreachable and poor quality. We recommend urgent interventions, including health promotion, free healthcare access and strengthening rural services to address barriers to maternal healthcare.

Global drainage patterns and the origins of topographic relief on Earth, Mars, and Titan.

Rivers have eroded the topography of Mars, Titan, and Earth, creating diverse landscapes. However, the dominant processes that generated topography on Titan (and to some extent on early Mars) are not well known. We analyzed drainage patterns on all three bodies and found that large drainages, which record interactions between deformation and erosional modification, conform much better to long-wavelength topography on Titan and Mars than on Earth. We use a numerical landscape evolution model to demonstrate that short-wavelength deformation causes drainage directions to diverge from long-wavelength topography, as observed on Earth. We attribute the observed differences to ancient long-wavelength topography on Mars, recent or ongoing generation of long-wavelength relief on Titan, and the creation of short-wavelength relief by plate tectonics on Earth.

PCDH19-related epileptic encephalopathy in a male mosaic for a truncating variant.

Variants in the X-linked gene PCDH19 are associated with early infantile epileptic encephalopathy-9. This unusual condition spares hemizygous males except for psychiatric and behavioral abnormalities, and for this reason is also known as female limited epilepsy. Some cases are due to de novo PCDH19 variants, but may also be paternally inherited. Our patient is a 6-year-old male with epileptic encephalopathy. Exome sequencing revealed apparent heterozygosity in PCDH19 for a novel nonsense variant, c.605C>A (p.Ser202*), inconsistent with expectations for a male. Testing of other tissues revealed a mixture of mutant and normal alleles. These results are consistent with somatic mosaicism for p.Ser202*. This is the second male with somatic mosaicism for PCDH19 deficiency, providing further support for cellular interference as the pathogenic mechanism for this condition, which leads to this unusual mode of inheritance in which females are more severely affected than males. © 2016 Wiley Periodicals, Inc.

Clinical and Pharmacologic Considerations for Guanfacine Use in Very Young Children.

OBJECTIVE: Guanfacine, in the immediate release form, remains a commonly used medication for the treatment of clinically significant hyperactivity, impulsivity, or disruptive behaviors. This article reviews the available literature regarding guanfacine use in very young children (<6 years of age), and explores some of the factors that may uniquely impact the clinical pharmacology of guanfacine in very young children and that deserve consideration when it is used in this patient population. METHODS: The authors performed electronic literature searches in PubMed through October 2015 using the terms attention-deficit/hyperactivity disorder, guanfacine, and alpha agonists. We also performed an informal review of the literature and used selected articles from relevant reference lists. The result was a broad, qualitative review of the literature, with a focus on specific factors regarding guanfacine use in very young children. RESULTS: Despite the fact that guanfacine is commonly used in very young children, there is a paucity of published studies that looked specifically at its use in this population. In reviewing the pharmacology of guanfacine, there are specific factors that may play a unique role in its disposition in very young children. CONCLUSIONS: Guanfacine is an important medication option in very young children; however, there is a significant pharmacologic "information gap," and further research is needed to help establish appropriate, safe, and effective dosing of guanfacine in this population.

Ebola viral disease and pregnancy.

Ebola viral disease's interaction with pregnancy is poorly understood and remains a particular challenge for medical and para-medical personnel responding to an outbreak. This review article is written with the benefit of hindsight and experience from the largest recorded Ebola outbreak in history. We have provided a broad overview of the issues that arise for pregnant women and for the professionals treating them during an Ebola outbreak. The discussion focuses on the specifics of Ebola infection in pregnancy and possible management strategies, including the delivery of an infected woman. We have also discussed the wider challenges posed to pregnant women and their carers during an epidemic, including the identification of suspected Ebola-infected pregnant women and the impact of the disease on pre-existing health services. This paper outlines current practices in the field, as well as highlighting the gaps in our knowledge and the paramount need to protect the health-care workers directly involved in the management of pregnant women.

Treating our youngest patients: psychotropic medications in early childhood.

Over the past several decades there have been multiple studies indicating that infants, toddlers and preschoolers who develop emotional and behavioral problems may not simply outgrow their problems. Early intervention is ideal, and may help to maximize long-term functioning. When other interventions fail or do not fully address the symptoms, psychotropic medications can be very helpful, even in the preschool years. With limited scientific research in this population, the use of psychotropic medications in very young children can be challenging. The judicious use of these agents in this population will be discussed, including weighing the risks and benefits of prescribing to these most vulnerable patients.