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Fetal structural anomalies, which are detected by ultrasonography, have a range of genetic causes, including chromosomal aneuploidy, copy number variations (CNVs; which are detectable by chromosomal microarrays), and pathogenic sequence variants in developmental genes. Testing for aneuploidy and CNVs is routine during the investigation of fetal structural anomalies, but there is little information on the clinical usefulness of genome-wide next-generation sequencing in the prenatal setting. We therefore aimed to evaluate the proportion of fetuses with structural abnormalities that had identifiable variants in genes associated with developmental disorders when assessed with whole-exome sequencing (WES). In this prospective cohort study, two groups in Birmingham and London recruited patients from 34 fetal medicine units in England and Scotland. We used whole-exome sequencing (WES) to evaluate the presence of genetic variants in developmental disorder genes (diagnostic genetic variants) in a cohort of fetuses with structural anomalies and samples from their parents, after exclusion of aneuploidy and large CNVs. Women were eligible for inclusion if they were undergoing invasive testing for identified nuchal translucency or structural anomalies in their fetus, as detected by ultrasound after 11 weeks of gestation. The partners of these women also had to consent to participate. Sequencing results were interpreted with a targeted virtual gene panel for developmental disorders that comprised 1628 genes. Genetic results related to fetal structural anomaly phenotypes were then validated and reported postnatally. The primary endpoint, which was assessed in all fetuses, was the detection of diagnostic genetic variants considered to have caused the fetal developmental anomaly. The cohort was recruited between Oct 22, 2014, and June 29, 2017, and clinical data were collected until March 31, 2018. After exclusion of fetuses with aneuploidy and CNVs, 610 fetuses with structural anomalies and 1202 matched parental samples (analysed as 596 fetus-parental trios, including two sets of twins, and 14 fetus-parent dyads) were analysed by WES. After bioinformatic filtering and prioritisation according to allele frequency and effect on protein and inheritance pattern, 321 genetic variants (representing 255 potential diagnoses) were selected as potentially pathogenic genetic variants (diagnostic genetic variants), and these variants were reviewed by a multidisciplinary clinical review panel. A diagnostic genetic variant was identified in 52 (8·5%; 95% CI 6·4–11·0) of 610 fetuses assessed and an additional 24 (3·9%) fetuses had a variant of uncertain significance that had potential clinical usefulness. Detection of diagnostic genetic variants enabled us to distinguish between syndromic and non-syndromic fetal anomalies (eg, congenital heart disease only vs a syndrome with congenital heart disease and learning disability). Diagnostic genetic variants were present in 22 (15·4%) of 143 fetuses with multisystem anomalies (ie, more than one fetal structural anomaly), nine (11·1%) of 81 fetuses with cardiac anomalies, and ten (15·4%) of 65 fetuses with skeletal anomalies; these phenotypes were most commonly associated with diagnostic variants. However, diagnostic genetic variants were least common in fetuses with isolated increased nuchal translucency (≥4·0 mm) in the first trimester (in three [3·2%] of 93 fetuses). WES facilitates genetic diagnosis of fetal structural anomalies, which enables more accurate predictions of fetal prognosis and risk of recurrence in future pregnancies. However, the overall detection of diagnostic genetic variants in a prospectively ascertained cohort with a broad range of fetal structural anomalies is lower than that suggested by previous smaller-scale studies of fewer phenotypes. WES improved the identification of genetic disorders in fetuses with structural abnormalities; however, before clinical implementation, careful consideration should be given to case selection to maximise clinical usefulness. UK Department of Health and Social Care and The Wellcome Trust.

The Deepwater Horizon (DWH) oil spill was the largest accidental release of crude oil into the sea in history, and represents the most extensive use of chemical dispersants to treat an oil spill. Following the spill, extensive studies were conducted to determine the potential acute and sublethal toxic effects of crude oil and dispersants on a range of planktonic, nektonic, and benthic marine organisms. Organisms such as phytoplankton, zooplankton, and fish were examined via controlled laboratory studies, while others, such as deep-sea benthic invertebrates, which are difficult to sample, maintain, and study in the laboratory, were assessed through field studies. Laboratory studies with marine fishes focused on the sublethal effects of oil and dispersants, and early life history stages were generally found to be more sensitive to these toxins than adults. Field studies in the vicinity of the DWH spill indicate a significant reduction in abundance and diversity of benthic meiofauna and macrofauna as well as visual damage to deep-sea corals. Overall, studies indicate that while the responses of various marine species to oil and dispersants are quite variable, a general picture is emerging that chemical dispersants may be more toxic to some marine organisms than previously thought, and that small oil droplets created by dispersant use and directly consumed by marine organisms are often more toxic than crude oil alone.

To assess the potential impact of the Deepwater Horizon oil spill on offshore ecosystems, 11 sites hosting deep-water coral communities were examined 3 to 4 mo after the well was capped. Healthy coral communities were observed at all sites >20 km from the Macondo well, including seven sites previously visited in September 2009, where the corals and communities appeared unchanged. However, at one site 11 km southwest of the Macondo well, coral colonies presented widespread signs of stress, including varying degrees of tissue loss, sclerite enlargement, excess mucous production, bleached commensal ophiuroids, and covering by brown flocculent material (floc). On the basis of these criteria the level of impact to individual colonies was ranked from 0 (least impact) to 4 (greatest impact). Of the 43 corals imaged at that site, 46% exhibited evidence of impact on more than half of the colony, whereas nearly a quarter of all of the corals showed impact to >90% of the colony. Additionally, 53% of these corals’ ophiuroid associates displayed abnormal color and/or attachment posture. Analysis of hopanoid petroleum biomarkers isolated from the floc provides strong evidence that this material contained oil from the Macondo well. The presence of recently damaged and deceased corals beneath the path of a previously documented plume emanating from the Macondo well provides compelling evidence that the oil impacted deep-water ecosystems. Our findings underscore the unprecedented nature of the spill in terms of its magnitude, release at depth, and impact to deep-water ecosystems.

The sexual and reproductive health (SRH) needs of youths in sub-Saharan Africa are not being fully met, as evidenced by high rates of unintended pregnancies and sexually transmitted infections in this population. Understanding service needs and preferences of sub-Saharan African youths aged 10–24 years is critical for improving access and SRH outcomes and the focus of this systematic review of qualitative research. Four databases were searched with key words to identify relevant studies, supplemented by citation search, with an update in June 2023. The eligibility criteria were clear and developed a priori. Twenty included studies from seven countries underwent quality appraisal using the Critical Appraisal Skills Programme (CASP). A meta-ethnographic approach was used to synthesise concepts across studies by the researchers. Four key themes were generated: information needs; service needs; social needs; and delivery preferences . Information needs encompassed desires for age-appropriate education on contraception, safer sex, bodily changes, and healthy relationships to fill knowledge gaps. Social needs consisted of life skills training, vocational development, substance use rehabilitation, and support systems to foster healthy behaviours. Service needs included accessible youth-friendly sexual health services, preventative care, sexually transmitted Infections (STI) management, and contraception; and delivery preferences including competent providers who maintain privacy and confidentiality, convenient youth-oriented settings, free or low-cost provisions, and youth involvement in service design. In conclusion, the identified themes emphasise the diverse nature of SRH needs and preferences among sub-Saharan African youths. Insights from their unique priorities and unmet needs inform policy development and intervention strategies. Tailored awareness campaigns, youth-centred training for providers, youth-friendly and confidential SRH models, comprehensive education, and engaging youth in developing relevant solutions may improve acceptability, access, and health outcomes. These efforts could address barriers around stigma, costs, and lack of knowledge, contributing to enhanced SRH and wellbeing. Fulfilling youth SRH needs in sub-Saharan Africa requires commitment across sectors to evidence-based, youth-focused strategies placing their perspectives at the centre.

Black lives are systematically undervalued by constitutional enforcement remedies. Section 1983 adopts, wholesale, the damages scheme from torts, which not only permits, but encourages, the consideration of race and gender to calculate actuarially \"accurate\" damages figures. Given that Blacks earn seventy-five percent of what white men earn on average, it's no surprise that this results in significantly lower damages awards. This Note argues that the use of racebased actuarial tables in constitutional torts is both unconstitutional and theoretically unsound. Yet, plaintiffs rarely challenge this practice and often even stipulate to its use. This presents a puzzle—why does a bad practice go unchallenged? Furthermore, the largely unchallenged adoption of race-based actuarial tables is symptomatic of constitutional law's broader, unquestioned embrace of the corrective justice framework. Corrective justice's appeal is that it ostensibly allows judges to focus on the narrow task of returning plaintiffs to a prior baseline rather than requiring legislative-type determinations of whether that \"baseline\" is normatively desirable. But, when the legal dispute turns on a government actor's violations of a citizen's constitutional rights, the harms and benefits exchanged between plaintiff and defendant are more complex and indeterminate than between purely private parties. The complicated relationship between parties in constitutional torts makes corrective justice's determinate inquiry uncertain and unsatisfactory. Indeed, the selection of a prior baseline requires judges to engage in value-laden choices about which harms and benefits — among the innumerable exchanged between citizen and government — are counted toward the plaintiffs baseline. Thus, this Note reveals that the purported normative neutrality that commends corrective justice in private torts is a mere illusion in the constitutional tort context. Finally, this Note argues that distributive justice emerges as a viable alternative framework for developing constitutional tort remedies. Under that framework, remedial schemes should be premised on moving toward a more ideal distribution rather than limited to returning plaintiffs to a particular baseline. While distributive justice is often rejected in tort litigation, the framework has much to offer in the constitutional tort context. Yet, much of constitutional law and scholarship has overlooked distributive justice and adopted a narrow, tort-like version of corrective justice—a doubly value-laden choice. This Note demonstrates that selecting between the two frameworks should be a contested question—one that has broader implications for our understanding of constitutional law.

Introduction Bolus track and test bolus are the most commonly used contrast timing protocols to undertake computed tomography pulmonary angiography (CTPA). The aim of this study was to compare test bolus and bolus track contrast enhancement protocols in terms of enhancement of the pulmonary vessels and aorta, radiation dose and suboptimal scan rate to determine the optimal technique for CTPA. Methods A total of 200 CTPA examinations (100 using each protocol) performed between January and February 2021 were assessed retrospectively. All scans were performed on a 2x128 Dual Source Siemens Drive Scanner. CT attenuation was measured in Hounsfield Units (HU), with measurements taken from the main pulmonary trunk, right pulmonary artery and left pulmonary artery, ascending and descending aorta. The mean effective dose was calculated from the dose‐length product (DLP). The suboptimal scan rate was calculated as the percentage of examinations below 210HU. Results The average HU of the pulmonary arteries was 358 HU ± SD 129.2 in the test bolus group and increased to 394 HU ± SD 133.9 in the bolus track group with a P value of ≤0.05. The average HU of the aorta was 235 HU ± SD 82.8 in the test bolus group and increased to 319 HU ± SD 91.8 in the bolus track group with a P value of <0.001. Although not statistically significant, the mean effective dose was reduced by 4.2% for the bolus track protocol (2.4 mSv vs. 2.5 mSv, P > 0.05). Fewer suboptimal scans were performed with the bolus track protocol (5 scans <210HU Bolus Track vs. 9 scans <210HU Test Bolus). Conclusion The bolus track protocol results in increased enhancement of the pulmonary arteries and aorta, with the added benefits of a lower suboptimal scan rate and lower effective dose. A comparison of test bolus and bolus track contrast enhancement protocols in terms of enhancement of pulmonary vessels and aorta, radiation dose and suboptimal scan rate to determine the optimal technique for computed tomography pulmonary angiography (CTPA). The results of this study justify the use of the bolus track protocol when performing CTPA's with a similar contrast injection rate and scan parameters.

Honey bee (Apis mellifera) health has been severely impacted by multiple environmental stressors including parasitic infection, pesticide exposure, and poor nutrition. The decline in bee health is therefore a complex multifactorial problem which requires a holistic investigative approach. Within the exposome paradigm, the combined exposure to the environment, drugs, food, and individuals' internal biochemistry affects health in positive and negative ways. In the context of the exposome, honey bee hive infection with parasites such as Nosema ceranae is also a form of environmental exposure. In this study, we hypothesized that exposure to xenobiotic pesticides and other environmental chemicals increases susceptibility to N. ceranae infection upon incidental exposure to the parasite. We further queried whether these exposures could be linked to changes in conserved metabolic biological pathways. From 30 hives sampled across 10 sites, a total of 2,352 chemical features were found via gas chromatography-time of flight mass spectrometry (GC-TOF) in extracts of honey bees collected from each hive. Of these, 20 pesticides were identified and annotated, and found to be significantly associated with N. ceranae infection. We further determined that infected hives were linked to a greater number of xenobiotic exposures, and the relative concentration of the exposures were not linked to the presence of a N. ceranae infection. In the exposome profiles of the bees, we also found chemicals inherent to known biological metabolic pathways of Apis mellifera and identified 9 dysregulated pathways. These findings have led us to posit that for hives exposed to similar chemicals, those that incur multiple, simultaneous xenobiotic stressors have a greater incidence of infection with N. ceranae. Mechanistically, our results suggests the overwhelming nature of these exposures negatively affects the biological functioning of the bee, and could explain how the decline in bee populations is associated with pesticide exposures.

Analysis of cell free fetal (cff) DNA in maternal plasma is used routinely for non invasive prenatal diagnosis (NIPD) of fetal sex determination, fetal rhesus D status and some single gene disorders. True positive results rely on detection of the fetal target being analysed. No amplification of the target may be interpreted either as a true negative result or a false negative result due to the absence or very low levels of cffDNA. The hypermethylated RASSF1A promoter has been reported as a universal fetal marker to confirm the presence of cffDNA. Using methylation-sensitive restriction enzymes hypomethylated maternal sequences are digested leaving hypermethylated fetal sequences detectable. Complete digestion of maternal sequences is required to eliminate false positive results. cfDNA was extracted from maternal plasma (n = 90) and digested with methylation-sensitive and insensitive restriction enzymes. Analysis of RASSF1A, SRY and DYS14 was performed by real-time PCR. Hypermethylated RASSF1A was amplified for 79 samples (88%) indicating the presence of cffDNA. SRY real time PCR results and fetal sex at delivery were 100% accurate. Eleven samples (12%) had no detectable hypermethylated RASSF1A and 10 of these (91%) had gestational ages less than 7 weeks 2 days. Six of these samples were male at delivery, five had inconclusive results for SRY analysis and one sample had no amplifiable SRY. Use of this assay for the detection of hypermethylated RASSF1A as a universal fetal marker has the potential to improve the diagnostic reliability of NIPD for fetal sex determination and single gene disorders.

Prior to Hurricane Isaac making landfall along the Gulf of Mexico coast in August 2012, local and state officials were concerned that the hurricane would mobilize submerged oiled-materials from the Deepwater Horizon (DWH) spill. In this study, we investigated materials washed ashore following the hurricane to determine if it affected the chemical composition or density of oil-containing sand patties regularly found on Gulf Coast beaches. While small changes in sand patty density were observed in samples collected before and after the hurricane, these variations appear to have been driven by differences in sampling location and not linked to the passing of Hurricane Isaac. Visual and chemical analysis of sand patties confirmed that the contents was consistent with oil from the Macondo well. Petroleum hydrocarbon signatures of samples collected before and after the hurricane showed no notable changes. In the days following Hurricane Isaac, dark-colored mats were also found on the beach in Fort Morgan, AL, and community reports speculated that these mats contained oil from the DWH spill. Chemical analysis of these mat samples identified n-alkanes but no other petroleum hydrocarbons. Bulk and δ13C organic carbon analyses indicated mat samples were comprised of marshland peat and not related to the DWH spill. This research indicates that Hurricane Isaac did not result in a notable change the composition of oil delivered to beaches at the investigated field sites. This study underscores the need for improved communications with interested stakeholders regarding how to differentiate oiled from non-oiled materials. This is especially important given the high cost of removing oiled debris and the increasing likelihood of false positives as oiled-materials washing ashore from a spill become less abundant over time.