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Siblings of those with autism spectrum disorder (ASD) have increased likelihood of ASD or related subclinical traits. Here, studying 253 ASD families, D’Abate et al. test the predictive value of genomic copy number variation involving ASD-associated loci, with confirmation in a second cohort.

Pleuropulmonary blastoma (PPB) is a childhood mesenchymal pleural-based tumor that is associated with a germline mutation in DICER1 gene in familial PPB. It occurs most commonly in children between the ages of 2 and 5. Approximately 25% of patients have familial cancer syndrome which can include different combinations of PPB, lung cysts, thyroid tumors, cystic nephroma, Wilms tumor, embryonal rhabdomyosarcoma, ovarian Sertoli-Leydig cell tumors, juvenile granulosa cell tumor, gynandroblastoma, medulloblastoma, other childhood central nervous system tumors, nasal chondral mesenchymal hamartoma, and small bowel polyps. Our case report presents a child diagnosed with PPB with maternal history of bilateral ovarian Sertoli-Leydig cell tumors and papillary carcinoma of the thyroid. Molecular analysis performed on the patient and mother showed a specific gene change (c. 2830) in the DICER1 gene. The patient underwent surgical resection of the tumor and five cycles of chemotherapy. Despite this aggressive treatment, she eventually succumbed to brain metastases and was made comfort care after suffering a massive brain hemorrhage several months after the initial diagnosis of her disease.

This paper details a computational fluid dynamic (CFD) study of a constantly loaded actuator disc model featuring different boundary conditions; these boundary conditions were defined to represent a channel and a duct flow. The simulations were carried out using the commercially available CFD software ANSYS-CFX. The data produced were compared to the one-dimensional (1D) momentum equation as well as previous numerical and experimental studies featuring porous discs in a channel flow. The actuator disc was modelled as a momentum loss using a resistance coefficient related to the thrust coefficient (CT). The model showed good agreement with the 1D momentum theory in terms of the velocity and pressure profiles. Less agreement was demonstrated when compared to previous numerical and empirical data in terms of velocity and turbulence characteristics in the far field. These models predicted a far larger velocity deficit and a turbulence peak further downstream. This study therefore demonstrates the usefulness of the duct boundary condition (for computational ease) for representing open channel flow when simulating far field effects as well as the importance of turbulence definition at the inlet.

Objectives Informing research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.Design In the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.Setting UK stroke services.Participants 3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.Results Of those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.Conclusion It is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration number ISRCTN83290762; Post-results.

We present results from the James Webb Space Telescope Director’s Discretionary Time Early Release Science program 1328 targeting the nearby, luminous infrared galaxy, VV 114. We use the MIRI and NIRSpec instruments to obtain integral-field spectroscopy of the heavily obscured eastern nucleus (V114E) and surrounding regions. The spatially resolved, high-resolution spectra reveal the physical conditions in the gas and dust over a projected area of 2–3 kpc that includes the two brightest IR sources, the NE and SW cores. Our observations show for the first time spectroscopic evidence that the SW core hosts an active galactic nucleus as evidenced by its very low 6.2 μ m and 3.3 μ m polycyclic aromatic hydrocarbon equivalent widths (0.12 and 0.017 μ m, respectively) and mid- and near-IR colors. Our observations of the NE core show signs of deeply embedded star formation including absorption features due to aliphatic hydrocarbons, large quantities of amorphous silicates, as well as HCN due to cool gas along the line of sight. We detect elevated [Fe ii ]/Pf α consistent with extended shocks coincident with enhanced emission from warm H _2 , far from the IR-bright cores and clumps. We also identify broadening and multiple kinematic components in both H _2 and fine structure lines caused by outflows and previously identified tidal features.

We present mid-infrared spectroscopic observations of the nucleus of the nearby Seyfert galaxy NGC 7469 taken with the MIRI instrument on the James Webb Space Telescope (JWST) as part of Directors Discretionary Time Early Release Science program 1328. The high-resolution nuclear spectrum contains 19 emission lines covering a wide range of ionization. The high-ionization lines show broad, blueshifted emission reaching velocities up to 1700 km s ^−1 and FWHM ranging from ∼500 to 1100 km s ^−1 . The width of the broad emission and the broad-to-narrow line flux ratios correlate with ionization potential. The results suggest a decelerating, stratified, AGN-driven outflow emerging from the nucleus. The estimated mass outflow rate is 1–2 orders of magnitude larger than the current black hole accretion rate needed to power the AGN. Eight pure rotational H _2 emission lines are detected with intrinsic widths ranging from FWHM ∼125 to 330 km s ^−1 . We estimate a total mass of warm H _2 gas of ∼1.2 × 10 ^7 M _⊙ in the central 100 pc. The PAH features are extremely weak in the nuclear spectrum, but a 6.2 μ m PAH feature with an equivalent width of ∼0.07 μ m and a flux of 2.7 × 10 ^−17 W m ^−2 is detected. The spectrum is steeply rising in the mid-infrared, with a silicate strength of ∼0.02, significantly smaller than seen in most PG QSOs but comparable to other Seyfert 1s. These early MIRI mid-infrared IFU data highlight the power of JWST to probe the multiphase interstellar media surrounding actively accreting supermassive black holes.

In Nepal and many developing countries around the world, roads are vehicles for development for communities in rural areas. By reducing travel time on foot, opportunities are opened for quicker transportation of goods and better access to employment, education, health care and markets. Roads also fuel migration and numerous social changes, both positive and negative. Poorly constructed roads in mountainous areas of Nepal have increased erosion and landslide risk as they often cut through fragile geology, destabilizing slopes and altering local hydrological conditions, with costs to lives and livelihoods. The convergence of the newly constituted decentralized Nepali government with China's Belt and Road Initiative is likely to bring more roads to rural communities. The new provincial government administrations now have the opportunity to develop policies and practices, which can realign the current trend of poorly engineered, inefficient and hazardous road construction toward a more sustainable trajectory. This commentary provides an overview of some of the obstacles along the way for a more sustainable road network in Nepal and illustrates how good governance, development and landslide risk are intertwined. The opinion presented in this brief commentary lends little hope that Nepal's current pathway of unsustainable road construction will provide the country with the much-needed sustainable road network, unless checks and balances are put in place to curb noncompliance with existing laws and policies.

There is little research about what parents of children with diabetes want and need from their health-care providers as they negotiate life with diabetes. Sixty-three parents of children with type 1 diabetes were interviewed. Interviews were tape-recorded and transcribed verbatim, and a content analysis of text data was conducted. Three themes emerged describing what they wanted in their relationships with diabetes providers: laying the foundation, providing clinical care, and engaging families as partners. Collectively, these data provide vivid insights into the parent''s perspective regarding their needs from diabetes providers as well as their perceptions of interactions that were unhelpful or worse, hurtful or undermining. [Copyright &y& Elsevier]

AbstractPredictors of study retention and scheduled visit attendance in the University of North Carolina Center for AIDS Research (UNC CFAR) prospective clinical cohort of HIV-infected patients enrolled between 1 January 2001 and 1 January 2008 are reported. At study entry, 1636 participants were 32% female, 58% were African-American, 49% had not received HIV care elsewhere, 71% were receiving or initiated combination antiretroviral therapy, and 26% were diagnosed with AIDS, with median (quartiles) age of 40 (34; 47) years, distance to clinic of 45 (21; 70) miles, HIV-1 RNA of 1396 (200; 26,750) copies/ml, and CD4 of 374 (182; 602) cells/mm3. Participants contributed a median of 7 (4; 13) scheduled visits and 2.25 (1.0; 3.9) years alive under follow-up. During 6134 person-years of follow-up, 414 participants dropped out and 145 died. Accounting for differences in death by participant characteristics, the 6-year cumulative probability of retention was 67% [95% confidence limits (CL): 65, 70%], with 6.75 (95% CL: 6.13, 7.43) drop outs per 100 person-years. In a multivariable Cox proportional hazards model, retention was higher among participants who were insured, had not received HIV care elsewhere, had controlled HIV viremia, and were living in nonurban areas or proximate to the clinic. In a multivariable modified Poisson regression model that accounted for differences in drop out and death by participant characteristics, visit attendance was higher among older, AIDS-diagnosed, immune compromised, and cART-initiated participants. The UNC CFAR clinical cohort has ample enrollment with retention and visit attendance modestly influenced by factors such as disease severity. [ABSTRACT FROM AUTHOR]

The importance of estuarine wetlands to ecosystem services such as primary productivity and flood attenuation, as well as their function as habitat for threatened species has prompted efforts to restore tidal flows to degraded wetlands. We tracked the response of estuarine vegetation to tidal-flow reinstatement over 12 years (1995–2007) in a wetland of the Hunter estuary, Australia. This site provides important habitat for migratory shorebird species, which favour shallow tidal pools and saltmarsh over mangrove forest. Increased tidal flows following culvert removal reduced shorebird roost habitat by 17% because of mangrove encroachment on saltmarsh and shallow tidal pools. Saltmarsh occurred in areas with a spring tidal range <0.3 m, hydroperiod <1.0 and elevation >0.4 above the Australian height datum (mAHD), whereas mangrove occupied areas with spring tidal range >0.3 m, hydroperiod <0.45 and elevation <0.4 mAHD. By using these parameters, it is possible to exclude mangrove from saltmarsh areas and to establish saltmarsh at lower elevations in the tidal frame than would occur under natural conditions, effectively expanding saltmarsh area. These measures can be useful where landward migration of estuarine communities is restricted by infrastructure; however, they should not be considered a substitute for conservation of remnant saltmarsh or establishment of landward buffer zones. [ABSTRACT FROM AUTHOR]

The bio-electrospray technique has been recently pioneered to manipulate living, immortalised and primary cells, including a wide range of stem cells. Studies have demonstrated that the creation of viable, fully functional in vitromicroenvironments is possible using this technique. By modifying the bio-electrospray procedure (referred to as cell electrospinning), a variety of microenvironment morphologies have been fabricated. Because bio-electrospraying of biological material is a relatively new technique, it is important to determine if there are any unwanted consequences to the manipulated cells as a result of the procedure. Here, we establish the validity of the process using a heterogeneous, living population of hematopoietic stem/progenitor cells, using a functional in vitroassay and in vivomouse model to investigate for side-effects that previous in vitroassays may not have detected. Our studies demonstrate that these bio-protocols have no obvious negative effects, thus indicating significant promise for utility in biological sciences and for a plethora of healthcare applications. [ABSTRACT FROM AUTHOR]

Cytochrome c6A is a unique dithio-cytochrome of green algae and plants. It has a very similar core structure to that of bacterial and algal cytochromes c6, but is unable to fulfil the same function of transferring electrons from cytochrome f to Photosystem I. A key feature of cytochrome c6A is that its haem midpoint potential is more than 200 mV below that of cytochrome c6 (Em≈+340 mV) despite both cytochromes having histidine and methionine residues as axial haem-iron ligands. One salient difference between the haem pockets is that a valine residue in cytochrome c6A replaces a highly conserved glutamine residue in cytochrome c6. This difference has been probed using site-directed mutagenesis, X-ray crystallography and protein film voltammetry studies. It has been found that the stereochemistry of the glutamine residue within the haem pocket has a destabilizing effect and is responsible for tuning the haem's midpoint potential by over 100 mV. This large effect may have contributed to the evolution of a new biological function for cytochrome c6A. [ABSTRACT FROM AUTHOR]

In vivobioimaging of transgenic luciferase in the lung and nose is an expedient method by which to continually measure expression of this marker gene after gene transduction. Its substrate, luciferin, is typically injected into the peritoneal cavity before bioimaging. Here we demonstrate that, compared with intraperitoneal injection, intranasal instillation of luciferin confers approximately an order of magnitude increase in luciferase bioluminescence detection in both lung and nose. This effect was observed after administration of viral vectors based on adenovirus type 5, adeno-associated virus type 8, and gp64-pseudotyped HIV lentivirus and, to a lesser extent, after nonviral polyethylenimine (PEI)–DNA delivery. Detection increased relative to the concentration of luciferin; however, a standard concentration of 15 mgml was well beyond the saturation point. Compared with intraperitoneal injection, intranasal instillation yields about a 10-fold increase in sensitivity with an approximate 30-fold reduction in luciferin usage when bioimaging in the nasal and pulmonary airways of mice. [ABSTRACT FROM AUTHOR]

Photosynthesis by marine diatoms contributes substantially to global biogeochemical cycling and ecosystem productivity. It is widely accepted that diatoms are extremely sensitive to changes in Fe availability, with numerous in situ experiments demonstrating rapid growth and increased export of elements (e.g. C, Si and Fe) from surface waters as a result of Fe addition. Less is known about the effects of Fe enrichment on the phenotypes of diatoms, such as associated changes in nutritional value – furthermore, data on taxon-specific responses are almost non-existent. Enhanced supply of nutrient-rich waters along the coast of the subantarctic Kerguelen Island provide a valuable opportunity to examine the responses of phytoplankton to natural Fe enrichment. Here we demonstrate the use of synchrotron radiation Fourier Transform Infrared (SR-FTIR) microspectroscopy to analyse changes in the macromolecular composition of diatoms collected along the coast and plateau of Kerguelen Island, Southern Ocean. SR-FTIR microspectroscopy enabled the analysis of individual diatom cells from mixed communities of field-collected samples, thereby providing insight into in situ taxon-specific responses in relation to changes in Fe availability. Phenotypic responses were taxon-specific in terms of intraspecific variability and changes in proteins, amino acids, phosphorylated molecules, silicate/silicic acid and carbohydrates. In contrast to some previous studies, silicate/silicic acid levels increased under Fe enrichment, in conjunction with increases in carbohydrate stores. The highly abundant taxon Fragilariopsis kerguelensis displayed a higher level of phenotypic plasticity than Pseudo-nitzschia spp., while analysis of the data pooled across all measured taxa showed different patterns in macromolecular composition compared to those for individual taxon. This study demonstrates that taxon-specific responses to Fe enrichment may not always be accurately reflected by bulk community measurements, highlighting the need for further research into taxon-specific phenotypic responses of phytoplankton to environmental change.

Background: Despite positive outcomes in controlled trials, organizations have been slow to adopt health literacy practices. The purpose of the Communicate to CARE (Clear Communication, Achieve Understanding with Teach-Back, Receptive to our patient family needs, Empathetic care delivery) study was to use theories and strategies from implementation science to scale up health literacy practices in a pediatric Ears, Nose, and Throat (ENT) clinic. Brief Description of Activity: Expanding on previous efforts that simply reflected on barriers, the CARE team identified barriers within the local context pre-implementation to select strategies to directly address barriers during health literacy implementation. The RE-AIM framework was used to evaluate the reach, effectiveness, adoption, implementation, and maintenance of health literacy practices. Implementation: Over 18 months, the CARE team delivered multiple implementation strategies, including external facilitator, microlessons, preparing champions, audit and feedback, local consensus discussions, and small test of change. We tailored health literacy practices to clinic team roles to accommodate the clinic workflow. Results: ENT team mean ratings on acceptability, appropriateness, and feasibility remained >4 indicating a high likelihood of successful implementation. Caregiver always ratings significantly increased from baseline to 12 months for easy-to-understand medication instructions (74%–96%), test results (54%–96%), know what to do if had questions (89%–96%), and encouraged to talk about health problems (76%–90%). Caregiver ratings dropped slightly at 18 months, indicating a need for booster training. While one third of caregivers reported Teach-Back practice across all time periods, the ENT team reported increased practice from baseline (42%), 6 (61%) and 12 months (70%). Lessons Learned: Over the first 12 months, the external facilitator delivered implementation strategies with weekly contact, tapering contact over the final 6 months. The local champion became engaged in the CARE study through a quality improvement project with meaningful outcomes for the clinic and an incentivization program for scholarly endeavors. Lunch and learn sessions helped build relationships between the CARE and ENT team to discuss and problem solve issues. The 5-item CAHPS health literacy composite proved to be sensitive to changes during implementation of health literacy practices. Integrating these items into standard follow up surveys with patients and families would help realize the return on investment for health literacy implementation. [HLRP: Health Literacy Research and Practice. 2024;8(3):e166–e174.]

Abstract Spouses may affect each other’s sleeping behaviour. In 47,420 spouse-pairs from the UK Biobank, we found a weak positive phenotypic correlation between spouses for self-reported sleep duration (r = 0.11; 95% CI = 0.10, 0.12) and a weak inverse correlation for chronotype (diurnal preference) (r = −0.11; −0.12, −0.10), which replicated in up to 127,035 23andMe spouse-pairs. Using accelerometer data on 3454 UK Biobank spouse-pairs, the correlation for derived sleep duration was similar to self-report (r = 0.12; 0.09, 0.15). Timing of diurnal activity was positively correlated (r = 0.24; 0.21, 0.27) in contrast to the inverse correlation for chronotype. In Mendelian randomization analysis, positive effects of sleep duration (mean difference=0.13; 0.04, 0.23 SD per SD) and diurnal activity (0.49; 0.03, 0.94) were observed, as were inverse effects of chronotype (−0.15; −0.26, −0.04) and snoring (−0.15; −0.27, −0.04). Findings support the notion that an individual’s sleep may impact that of their partner, promoting opportunities for sleep interventions at the family-level.

Abstract Background Down syndrome (DS) is one of the most common genetic causes of intellectual disability, and it is associated with an increased incidence of numerous co-occurring conditions. Autism spectrum disorder (ASD) is common in persons with DS, with rates reported as high as 39%. However, little is known regarding co-occurring conditions in children with both DS and ASD. Methods A single-center retrospective review of prospective longitudinally collected clinical data was performed. Any patient with a confirmed diagnosis of DS evaluated at a large, specialized Down Syndrome Program in a tertiary pediatric medical center between March 2018 and March 2022 was included. A standardized survey which included demographic and clinical questions was administered during each clinical evaluation. Results In total, 562 individuals with DS were included. The median age was 10 years (IQR: 6.18–13.92). Of this group, 72 (13%) had a co-occurring diagnosis of ASD (DS+ASD). Individuals with DS+ASD were more likely to be male (OR 2.23, CI 1.29–3.84) and had higher odds of a current or prior diagnosis of constipation (OR 2.19, CI 1.31–3.65), gastroesophageal reflux (OR 1.91, CI 1.14–3.21), behavioral feeding difficulties (OR 2.71, CI 1.02–7.19), infantile spasms (OR 6.03, CI 1.79–20.34) and scoliosis (OR 2.73, CI 1.16–6.40). There were lower odds of congenital heart disease in the DS+ASD group (OR 0.56, CI 0.34–0.93). There was no observed difference in prematurity or Neonatal Intensive Care Unit complications between groups. Individuals with DS+ASD had similar odds of having a history of congenital heart defect requiring surgery to those with DS only. Furthermore, there was no difference in rates of autoimmune thyroiditis or celiac disease. There was also no difference in rates of diagnosed co-occurring neurodevelopmental or mental health conditions in this cohort, including anxiety disorders and attention-deficit/hyperactivity disorder. Conclusions This study identifies a variety of medical conditions which are more frequent in children with DS+ASD than DS alone, providing important information for the clinical management of these patients. Future research should investigate the role of some of these medical conditions in the development of ASD phenotypes, and whether there may be distinct genetic and metabolic contributions towards these conditions.