Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort.

PURPOSE: Genome-wide sequencing is increasingly being performed during pregnancy to identify the genetic cause of congenital anomalies. The interpretation of prenatally identified variants can be challenging and is hampered by our often limited knowledge of prenatal phenotypes. To better delineate the prenatal phenotype of Coffin-Siris syndrome (CSS), we collected clinical data from patients with a prenatal phenotype and a pathogenic variant in one of the CSS-associated genes. METHODS: Clinical data was collected through an extensive web-based survey. RESULTS: We included 44 patients with a variant in a CSS-associated gene and a prenatal phenotype; 9 of these patients have been reported before. Prenatal anomalies that were frequently observed in our cohort include hydrocephalus, agenesis of the corpus callosum, hypoplastic left heart syndrome, persistent left vena cava, diaphragmatic hernia, renal agenesis, and intrauterine growth restriction. Anal anomalies were frequently identified after birth in patients with ARID1A variants (6/14, 43%). Interestingly, pathogenic ARID1A variants were much more frequently identified in the current prenatal cohort (16/44, 36%) than in postnatal CSS cohorts (5%-9%). CONCLUSION: Our data shed new light on the prenatal phenotype of patients with pathogenic variants in CSS genes.

Lead pollution recorded in Greenland ice indicates European emissions tracked plagues, wars, and imperial expansion during antiquity.

Lead pollution in Arctic ice reflects midlatitude emissions from ancient lead-silver mining and smelting. The few reported measurements have been extrapolated to infer the performance of ancient economies, including comparisons of economic productivity and growth during the Roman Republican and Imperial periods. These studies were based on sparse sampling and inaccurate dating, limiting understanding of trends and specific linkages. Here we show, using a precisely dated record of estimated lead emissions between 1100 BCE and 800 CE derived from subannually resolved measurements in Greenland ice and detailed atmospheric transport modeling, that annual European lead emissions closely varied with historical events, including imperial expansion, wars, and major plagues. Emissions rose coeval with Phoenician expansion, accelerated during expanded Carthaginian and Roman mining primarily in the Iberian Peninsula, and reached a maximum under the Roman Empire. Emissions fluctuated synchronously with wars and political instability particularly during the Roman Republic, and plunged coincident with two major plagues in the second and third centuries, remaining low for >500 years. Bullion in silver coinage declined in parallel, reflecting the importance of lead-silver mining in ancient economies. Our results indicate sustained economic growth during the first two centuries of the Roman Empire, terminated by the second-century Antonine plague.

Improved sub-seasonal forecasts to support preparedness action for meningitis outbreak in Africa.

West African countries are hit annually by meningitis outbreaks which occur during the dry season and are linked to atmospheric variability. This paper describes an innovative co-production process between the African Centre of Meteorological Applications for Development (ACMAD; forecast producer) and the World Health Organisation Regional Office for Africa (WHO AFRO; forecast user) to support awareness, preparedness and response actions for meningitis outbreaks. Using sub-seasonal to seasonal (S2S) forecasts, this co-production enables ACMAD and WHO AFRO to build initiative that increases the production of useful climate services in the health sector. Temperature and relative humidity forecasts are combined with dust forecasts to operationalize a meningitis early warning system (MEWS) across the African meningitis belt with a two-week lead time. To prevent and control meningitis, the MEWS is produced from week 1 to 26 of the year. This study demonstrates that S2S forecasts have good skill at predicting dry and warm atmospheric conditions precede meningitis outbreaks. Vigilance levels objectively defined within the MEWS are consistent with reported cases of meningitis. Alongside developing a MEWS, the co-production process provided a framework for analysis of climate and environmental risks based on reanalysis data, meningitis burden, and health service assessment, to support the development of a qualitative roadmap of country prioritization for defeating meningitis by 2030 across the WHO African region. The roadmap has enabled the identification of countries most vulnerable to meningitis epidemics, and in the context of climate change, supports plans for preventing, preparing, and responding to meningitis outbreaks.

Configurations of identity among sexual minority youth: context, desire, and narrative.

Youth with same-sex desire undergo a process of narrative engagement as they construct configurations of identity that provide meaning and coherence with available sexual taxonomies. This article presents a theoretical analysis and four case studies centering on the relationship among context, desire, and identity for youth with same-sex desire. Through an interpretive, holistic analysis of the personal narratives of youth, we examine the integration of same-sex desire, behavior, and identity in the general life story and the selective appropriation of elements of "master narratives" of sexual identity development. Narratives were characterized by challenges to integrate desire, behavior, and identity into a configuration that conformed to the received sexual taxonomy. Implications for theory and further research on sexual identity development are discussed.

"Mostly straight" young women: variations in sexual behavior and identity development.

Researchers have begun to explore and identify various gradations in sexual orientation identity, paying attention to alternative sexual identity categories and attempting to clarify potential subtypes of same-sex sexuality, particularly among women. This study utilizes both quantitative and qualitative data to explore the behavioral experiences and identity development processes among women of a particular sexual identity subtype, "mostly straight." Participants were 349 female college students whose primary sexual identities included exclusively straight, mostly straight, bisexual, and lesbian. Results indicated that, on most behavioral variables, mostly straight women fell directly between and were significantly different from exclusively straight and bisexual/lesbian women. Mostly straight women were also distinct from exclusively straight women but were similar to bisexual women and lesbians on several quantitative measures of identity. Narratives about sexual identity development for mostly straight women revealed the complexities of sexual identity exploration, uncertainty, and commitment within this population. As a whole, this study encourages researchers to begin to recognize and examine mostly straight as a distinct sexual identity subtype in young women.

Processes of sexual orientation questioning among heterosexual women.

Because very little is known about heterosexual identity development, this study assesses and describes sexual orientation questioning processes of heterosexual-identified women and offers a comparison of these processes with those employed by their sexual-minority counterparts. Participants included 333 female college students (ages 18-23; M = 19.2): 228 participants primarily identified as "exclusively straight/heterosexual," and 105 participants indicated a sexual-minority identity. Sixty-seven percent of exclusively heterosexual respondents (n = 154) indicated having thought about or questioned their sexual orientation. The processes by which heterosexual participants described questioning their sexual orientation were coded for the presence of five emergent categories using an inductive thematic coding methodology. These five categories included unelaborated questioning (19%), other-sex experiences (16%), exposure to sexual minorities (26%), assessment of same-sex attraction (48%), and evaluations of same-sex behavior (26%). Several unifying and differentiating themes emerged between sexual orientation groups. Results from this study suggest that contemporary young women's heterosexuality is not necessarily an unexamined identity; indeed, the large majority of young women in this sample were deliberately identifying as heterosexual after contemplating alternative possibilities.