Letter From William W. Tracy and A. J. Lester to William McKinley, March 20, 1897

In this copy of a typed letter to President McKinley, William Tracy and A. J. Lester endorse Francis Mairs Huntington-Wilson for the position of Second Secretary of the Embassy in Paris.https://digitalcommons.ursinus.edu/fmhw_early_career/1006/thumbnail.jp

Congenital hallux valgus occurs in Fibrodysplasia Ossificans Progressiva and BMPR1B- associated dysplasia: an important distinction

Background: Fibrodysplasia Ossificans Progressiva (FOP; OMIM #135100) is an ultrarare genetic disorder characterised by congenital bilateral hallux valgus (CBHV), intermittent soft tissue swellings and progressive heterotopic ossification. We report a three-month-old girl with great toe abnormalities similar to FOP, in whom comprehensive clinical workup and genetic investigations illustrates an alternative diagnosis. Case presentation: A three-month-old girl presented with CBHV. The antenatal period was unremarkable, she was born by spontaneous vaginal delivery with an uneventful subsequent course, except for maternal concern of her bent toes which received reassurance from several health professionals. Her mother’s persisting concerns were explored via the internet and social media leading her to request referral to an expert bone centre for consideration of FOP. On examination, she was thriving, there was no dysmorphism, subcutaneous lumps, skeletal or extra-skeletal deformity except for shortened great toes with lateral deviation of the proximal and distal phalanges. FOP was a feasible diagnosis, for which CBHV is highlighted as an early sign. A cautionary potential diagnosis of FOP was counselled, including advice to defer intramuscular immunisations until genetic results available. Genetic investigation was undertaken through rapid whole genomic sequencing (WGS), with analysis of data from a skeletal dysplasia gene panel, which demonstrated no ACVR1variants. The only finding was a heterozygous variant of unknown significance in BMPR1B (c1460T>A, p.(Val487Asp)), which encodes a bone morphogenic receptor involved in brachydactyly syndromes A1, A2 and D and acromesomelic dysplasia 3 (only the latter being an autosomal recessive condition). Conclusion: This report highlights that CBHV serves as a vital diagnostic indicator of FOP and affected infants should be considered and investigated for FOP, including precautionary management whilst awaiting genetic studies. The second educational aspect is that CBHV may not represent a generalised skeletal disorder, or one much less significant than FOP. Receptor-ligand BMP and Activins mediated interactions are instrumental in the intricate embryology of the great toe. Recognition of non-FOP conditions caused by alterations in different genes are likely to increase with new genomic technology and large gene panels, enhancing understanding of bone signaling pathways

Prenatal exposure to metal mixtures and newborn neurobehavior in the Rhode Island Child Health Study

Background: Prenatal exposure to metals can affect the developing fetus and negatively impact neurobehavior. The associations between individual metals and neurodevelopment have been examined, but little work has explored the potentially detrimental neurodevelopmental outcomes associated with the combined impact of coexisting metals. The objective of this study is to evaluate prenatal metal exposure mixtures in the placenta to elucidate the link between their combined effects on newborn neurobehavior. Method: This study included 192 infants with available placental metal and NICU Network Neurobehavioral Scale data at 24 hours-72 hours age. Eight essential and nonessential metals (cadmium, cobalt, copper, iron, manganese, molybdenum, selenium, zinc) detected in more than 80% of samples were tested for associations with atypical neurobehavior indicated by NICU Network Neurobehavioral Scale using logistic regression and in a quantile g-computation analysis to evaluate the joint association between placental metal mixture and neurobehavioral profiles. Results: Individually, a doubling of placental cadmium concentrations was associated with an increased likelihood of being in the atypical neurobehavioral profile (OR = 2.39; 95% CI = 1.05 to 5.71). In the mixture analysis, joint effects of a quartile increase in exposure to all metals was associated with 3-fold increased odds of newborns being assigned to the atypical profile (OR = 3.23; 95% CI = 0.92 to 11.36), with cadmium having the largest weight in the mixture effect. Conclusions: Prenatal exposure to relatively low levels of a mixture of placental metals was associated with adverse newborn neurobehavior. Examining prenatal metal exposures as a mixture is important for understanding the harmful effects of concomitant exposures in the vulnerable populations

Duplication of the EFNB1 Gene in Familial Hypertelorism: Imbalance in Ephrin-B1 Expression and Abnormal Phenotypes in Humans and Mice

Familial hypertelorism, characterized by widely spaced eyes, classically shows autosomal dominant inheritance (Teebi type), but some pedigrees are compatible with X-linkage. No mechanism has been described previously, but clinical similarity has been noted to craniofrontonasal syndrome (CFNS), which is caused by mutations in the X-linked EFNB1 gene. Here we report a family in which females in three generations presented with hypertelorism, but lacked either craniosynostosis or a grooved nasal tip, excluding CFNS. DNA sequencing of EFNB1 was normal, but further analysis revealed a duplication of 937 kb including EFNB1 and two flanking genes: PJA1 and STARD8. We found that the X chromosome bearing the duplication produces ∼1.6-fold more EFNB1 transcript than the normal X chromosome and propose that, in the context of X-inactivation, this difference in expression level of EFNB1 results in abnormal cell sorting leading to hypertelorism. To support this hypothesis, we provide evidence from a mouse model carrying a targeted human EFNB1 cDNA, that abnormal cell sorting occurs in the cranial region. Hence, we propose that X-linked cases resembling Teebi hypertelorism may have a similar mechanism to CFNS, and that cellular mosaicism for different levels of ephrin-B1 (as well as simple presence/absence) leads to craniofacial abnormalities. Hum Mutat 32:1–9, 2011. © 2011 Wiley-Liss, Inc

Apparently synonymous substitutions in FGFR2affect splicing and result in mild Crouzon syndrome

BACKGROUND: Mutations of fibroblast growth factor receptor 2 (FGFR2) account for a higher proportion of genetic cases of craniosynostosis than any other gene, and are associated with a wide spectrum of severity of clinical problems. Many of these mutations are highly recurrent and their associated features well documented. Crouzon syndrome is typically caused by heterozygous missense mutations in the third immunoglobulin domain of FGFR2. CASE PRESENTATION: Here we describe two families, each segregating a different, previously unreported FGFR2 mutation of the same nucleotide, c.1083A>G and c.1083A>T, both of which encode an apparently synonymous change at the Pro361 codon. We provide experimental evidence that these mutations affect normal FGFR2 splicing and document the clinical consequences, which include a mild Crouzon syndrome phenotype and reduced penetrance of craniosynostosis. CONCLUSIONS: These observations add to a growing list of FGFR2 mutations that affect splicing and provide important clinical information for genetic counselling of families affected by these specific mutations

Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Preterm birth remains a common cause of neonatal mortality, with a disproportionately high burden in low-income and middle-income countries. Meta-analyses of low-dose aspirin to prevent pre-eclampsia suggest that the incidence of preterm birth might also be decreased, particularly if initiated before 16 weeks of gestation. METHODS: ASPIRIN was a randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin (81 mg daily) initiated between 6 weeks and 0 days of pregnancy, and 13 weeks and 6 days of pregnancy, in nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy. Participants were enrolled at seven community sites in six countries (two sites in India and one site each in the Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia). Participants were randomly assigned (1:1, stratified by site) to receive aspirin or placebo tablets of identical appearance, via a sequence generated centrally by the data coordinating centre at Research Triangle Institute International (Research Triangle Park, NC, USA). Treatment was masked to research staff, health providers, and patients, and continued until 36 weeks and 7 days of gestation or delivery. The primary outcome of incidence of preterm birth, defined as the number of deliveries before 37 weeks\u27 gestational age, was analysed in randomly assigned women with pregnancy outcomes at or after 20 weeks, according to a modified intention-to-treat (mITT) protocol. Analyses of our binary primary outcome involved a Cochran-Mantel-Haenszel test stratified by site, and generalised linear models to obtain relative risk (RR) estimates and associated confidence intervals. Serious adverse events were assessed in all women who received at least one dose of drug or placebo. This study is registered with ClinicalTrials.gov, NCT02409680, and the Clinical Trial Registry-India, CTRI/2016/05/006970. FINDINGS: From March 23, 2016 to June 30, 2018, 14 361 women were screened for inclusion and 11 976 women aged 14-40 years were randomly assigned to receive low-dose aspirin (5990 women) or placebo (5986 women). 5780 women in the aspirin group and 5764 in the placebo group were evaluable for the primary outcome. Preterm birth before 37 weeks occurred in 668 (11·6%) of the women who took aspirin and 754 (13·1%) of those who took placebo (RR 0·89 [95% CI 0·81 to 0·98], p=0·012). In women taking aspirin, we also observed significant reductions in perinatal mortality (0·86 [0·73-1·00], p=0·048), fetal loss (infant death after 16 weeks\u27 gestation and before 7 days post partum; 0·86 [0·74-1·00], p=0·039), early preterm delivery (\u3c34 \u3eweeks; 0·75 [0·61-0·93], p=0·039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0·38 [0·17-0·85], p=0·015). Other adverse maternal and neonatal events were similar between the two groups. INTERPRETATION: In populations of nulliparous women with singleton pregnancies from low-income and middle-income countries, low-dose aspirin initiated between 6 weeks and 0 days of gestation and 13 weeks and 6 days of gestation resulted in a reduced incidence of preterm delivery before 37 weeks, and reduced perinatal mortality. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development

Children's claims to knowledge regarding their mental health experiences and practitioners' negotiation of the problem.

The objective was to identify how children's knowledge positions were negotiated in child mental health assessments and how this was managed by the different parties.The child psychiatry data consisted of 28 video-recorded assessments. A conversation analysis was undertaken to examine the interactional detail between the children, parents, and practitioners.The findings indicated that claims to knowledge were managed in three ways. First, practitioners positioned children as 'experts' on their own health and this was sometimes accepted. Second, some children resisted this epistemic position, claiming not to have the relevant knowledge. Third, some children's claims to knowledge were negotiated and sometimes contested by adult parties who questioned their competence to share relevant information about their lives in accordance with the assessment agenda.Through question design, the practitioner was able to position the child as holding relevant knowledge regarding their situation. The child was able to take up this position or resist it in various ways.This has important implications for debates regarding children's competence to contribute to mental health interventions. Children are often treated as agents with limited knowledge, yet in the mental health assessment they are directly questioned about their own lives

'Here be dragons, here be savages, here be bad plumbing: Australian media representations of sport and terrorism

As 'Propaganda Theorists argue, an examination of key discourses can enhance our understanding of how economic, political and social debate is shaped by mainstream media reporting. In this essay we present content and discourse analysis of Australian media reporting on the nexus of sport and terrorism. Examining newspaper reports over a five-year period, from 1996-2001, which included the 11 September 2001 terrorist tragedy in the United States (9/11), provides useful insights into how public discourse might be influenced with regard to sport and terrorism interrelationships. The results of the media analysis suggest that hegemonic tropes are created around sport and terrorism. The distilled message is one of good and evil, with homilies of sport employed in metaphors for western society and its values. The reactions and responses of sport administrators and athletes to terrorist acts and the threat of terrorism to sport are used to exemplify these ideals, providing newspaper readers a context within which to localize meaning and relevance

Development and Psychometric Validation of the Pandemic-Related Traumatic Stress Scale for Children and Adults

To assess the public health impact of the COVID-19 pandemic on mental health, investigators from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) research program developed the Pandemic-Related Traumatic Stress Scale (PTSS). Based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) acute stress disorder symptom criteria, the PTSS is designed for adolescent (13–21 years) and adult self-report and caregiver-report on 3–12-year-olds. To evaluate psychometric properties, we used PTSS data collected between April 2020 and August 2021 from non-pregnant adult caregivers (n = 11,483), pregnant/postpartum individuals (n = 1,656), adolescents (n = 1,795), and caregivers reporting on 3–12-year-olds (n = 2,896). We used Mokken scale analysis to examine unidimensionality and reliability, Pearson correlations to evaluate relationships with other relevant variables, and analyses of variance to identify regional, age, and sex differences. Mokken analysis resulted in a moderately strong, unidimensional scale that retained nine of the original 10 items. We detected small to moderate positive associations with depression, anxiety, and general stress, and negative associations with life satisfaction. Adult caregivers had the highest PTSS scores, followed by adolescents, pregnant/postpartum individuals, and children. Caregivers of younger children, females, and older youth had higher PTSS scores compared to caregivers of older children, males, and younger youth, respectively