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Background: Congenital Heart Disease (CHD) is the most common congenital abnormality. Survival rates are over 90%, however infants with CHD remain at high risk of attention and executive function impairments. These abilities are difficult to assess in toddlers because clinical assessments rely on language abilities which are commonly delayed in CHD. Our aim was to characterise visual attention in toddlers with CHD compared to controls and identify associations with parent‐rated effortful control. Methods: Thirty toddlers with CHD (19 male, median (IQR) age at assessment 22.2 (22–23.1) months) and 66 controls from the developing human connectome project (36 male, age at assessment 22 (21.5–23.8) months) using eye‐tracking tasks designed to assess multiple components of visual attention. Analyses of co‐variance and regressions were used to identify differences between groups and relationships between gaze behaviours and parent‐rated effortful control. Results: Toddlers with CHD were less accurate when switching behaviours (set‐shifting) [median (IQR) 79%, (28–100)] compared to controls [100% (86–100), pFDR = 0.032], with worse accuracy associated with lower parent‐rated effortful control in CHD but not controls (interaction pFDR = 0.028). Reaction times were slower during selective [CHD 1243 ms (986–1786), controls 1065 ms (0851–1397), pFDR<0.001] and exogenous attention tasks [CHD 312 ms (279–358), control 289 (249–331), (pFDR = 0.032) and endogenous attention was less mature (prolonged looks at facial stimuli CHD 670 ms (518–885), control 500 ms (250–625), (pFDR = 0.006). These results were unrelated to differences in cognition or socioeconomic status. In contrast, the allocation of attentional resources was preserved in CHD. Conclusions: We identified a profile of altered attention and early executive functioning development in CHD. Eye‐tracking may provide clinically feasible, early objective measures of attention and executive function development in CHD. [ABSTRACT FROM AUTHOR]

Visual observation data collected by protected species observers (PSOs) is required per regulations stipulated in Notices to Lessees (NTLs) and geophysical survey Permits (Form BOEM-0328) issued to seismic operators in the Gulf of Mexico (GOM). Here, data collected by certified and trained PSOs during seismic surveys conducted between 2002–2015 were compiled and analyzed to assess utility in assessing marine mammal responses to seismic noise and effectiveness of required mitigation measures. A total of 3,886 agency-required bi-weekly PSO Effort and Sightings reports were analyzed comprising 598,319 hours of PSO visual effort and 15,117 visual sighting records of marine mammals. The observed closest point of approach (CPA) distance was statistically compared across five species groupings for four airgun activity levels (full, minimum source, ramp up, silent). Whale and dolphin detections were significantly farther from airgun array locations during full power operations versus silence, indicating some avoidance response to full-power operations. Dolphin CPA distances were also significantly farther from airguns operating at minimum source than silence. Blackfish were observed significantly farther from the airgun array during ramp up versus both full and minimum source activities. Blackfish were observed significantly closer to the airgun array during silent activities versus at full, minimum source, and ramp up activities. Beaked whales had the largest mean CPA for detection distance compared to all other species groups. Detection distances for beaked whales were not significantly differences between full and silent operations; however, the sample size was very low. Overall results are consistent with other studies indicating that marine mammals may avoid exposure to airgun sounds based on observed distance from the seismic source during specified source activities. There was geographic variability in sighting rates associated with specific areas of interest within the GOM. This study demonstrates that agency required PSO reports provide a robust and useful data set applicable to impact assessments; management, policy and regulatory decision making; and qualitative input for regional scientific, stock assessment and abundance studies. However, several improvements in content and consistency would facilitate finer-scale analysis of some topics (e.g., effort associated with specific activities, observer biases, sound field estimation) and support statistical comparisons that could provide further insight into marine mammal responses and mitigation efficacy. [ABSTRACT FROM AUTHOR]

Demyelination in the central nervous system (CNS) resulting from injury or disease can cause loss of nerve function and paralysis. Cell therapies intended to promote remyelination of axons are a promising avenue of treatment, with mesenchymal stromal cells (MSCs) a prominent candidate. We have previously demonstrated that MSCs derived from human olfactory mucosa (hOM-MSCs) promote myelination to a greater extent than bone marrow-derived MSCs (hBM-MSCs). However, hOM-MSCs were developed using methods and materials that were not good manufacturing practice (GMP)-compliant. Before considering these cells for clinical use, it is necessary to develop a method for their isolation and expansion that is readily adaptable to a GMP-compliant environment. We demonstrate here that hOM-MSCs can be derived without enzymatic tissue digestion or cell sorting and without culture antibiotics. They grow readily in GMP-compliant media and express typical MSC surface markers. They robustly produce CXCL12 (a key secretory factor in promoting myelination) and are pro-myelinating in in vitro rodent CNS cultures. GMP-compliant hOM-MSCs are comparable in this respect to those grown in non-GMP conditions. However, when assessed in an in vivo model of demyelinating disease (experimental autoimmune encephalitis, EAE), they do not significantly improve disease scores compared with controls, indicating further pre-clinical evaluation is necessary before their advancement to clinical trials. [ABSTRACT FROM AUTHOR]

Much remains to be determined about the participation of ubiquitin receptors in proteasomal degradation and their potential as therapeutic targets. Suppression of the ubiquitin receptor S5A/PSMD4/hRpn10 alone stabilises p53/TP53 but not the key p53 repressor MDM2. Here, we observed S5A and the ubiquitin receptors ADRM1/PSMD16/hRpn13 and RAD23A and B functionally overlap in MDM2 degradation. We provide further evidence that degradation of only a subset of ubiquitinated proteins is sensitive to S5A knockdown because ubiquitin receptor redundancy is commonplace. p53 can be upregulated by S5A modulation while degradation of substrates with redundant receptors is maintained. Our observations and analysis of Cancer Dependency Map (DepMap) screens show S5A depletion/loss substantially reduces cancer cell line viability. This and selective S5A dependency of proteasomal substrates make S5A a target of interest for cancer therapy. [ABSTRACT FROM AUTHOR]

ABSTRACT Shell growth, survival, and physiology were compared between diploid Suminoe (Crassostrea ariakensis) and eastern oysters (Crassostrea virginica) under conditions simulating a U.S. subtropical estuary. Two age groups (4 mo [...]

Infants born with congenital heart disease (CHD) are at increased risk of neurodevelopmental difficulties in childhood. The extent to which perioperative factors, cardiac physiology, brain injury severity, socioeconomic status, and home environment influence early neurodevelopment is not clear. Sixty‐nine newborns with CHD were recruited from St Thomas' Hospital. Infants underwent presurgical magnetic resonance imaging on a 3‐Tesla scanner situated on the neonatal unit. At 22 months, children completed the Bayley Scales of Infant and Toddler Development‐3rd edition and parents completed the cognitively stimulating parenting scale to assess cognitive stimulation at home. Level of maternal education and total annual household income were also collected. Hospital records were reviewed to calculate days on the intensive care unit post‐surgery, time on bypass during surgery, and days to corrective or definitive palliative surgical intervention. In the final analysis of 56 infants, higher scores on the cognitively stimulating parenting scale were associated with higher cognitive scores at age 22 months, correcting for gestational age at birth, sex, and maternal education. There were no relationships between outcome scores and clinical factors; socioeconomic status; or brain injury severity. Supporting parents to provide a stimulating home environment for children may promote cognitive development in this high‐risk population. [ABSTRACT FROM AUTHOR]

Objectives: Neurodevelopmental impairment has become the most important comorbidity in infants with congenital heart disease (CHD). We aimed to (1) investigate the burden of brain lesions in infants with CHD prior to surgery and (2) explore clinical factors associated with injury.Study Design: Prospective observational study.Setting: Single centre UK tertiary neonatal intensive care unit.Patients: 70 newborn infants with critical or serious CHD underwent brain MRI prior to surgery.Main Outcome Measures: Prevalence of cerebral injury including arterial ischaemic strokes (AIS), white matter injury (WMI) and intracranial haemorrhage.Results: Brain lesions were observed in 39% of subjects (95% CI 28% to 50%). WMI was identified in 33% (95% CI 23% to 45%), subdural haemorrhage without mass effect in 33% (95% CI 23% to 45%), cerebellar haemorrhage in 9% (95% CI 4% to 18%) and AIS in 4% (95% CI 1.5% to 12%). WMI was distributed widely throughout the brain, particularly involving the frontal white matter, optic radiations and corona radiata. WMI exhibited restricted diffusion in 48% of cases. AIS was only observed in infants with transposition of the great arteries (TGA) who had previously undergone balloon atrial septostomy (BAS). AIS was identified in 23% (95% CI 8% to 50%) of infants with TGA who underwent BAS, compared with 0% (95% CI 0% to 20%) who did not.Conclusions: Cerebral injury in newborns with CHD prior to surgery is common. [ABSTRACT FROM AUTHOR]

Chemokines are members of a large family of chemotactic cytokines that signal through their receptors to mediate leukocyte recruitment during inflammation and homeostasis. The chemokine receptor CXCR2 has largely been associated with neutrophil recruitment. However, there is emerging evidence of roles for chemokines and their receptors in processes other than leukocyte migration. We have previously demonstrated that CXCR2 knockout (KO) mice have thinner skin compared to wild‐type mice. Herein we demonstrate that this is due to a thinner subcutaneous adipose layer, as a result of fewer and smaller individual adipocytes. We observe a similar phenotype in other fat depots and present data that suggests this may be due to reduced expression of adipogenesis related genes associated with adipocyte specific CXCR2 signaling. Interestingly, this phenotype is evident in female, but not male, CXCR2 KO mice. These findings expand our understanding of nonleukocyte related chemokine receptor functions and help to explain some previously observed adipose‐related phenotypes in CXCR2 KO mice. Study demonstrates that adipose tissue in CXCR2 KO mice is smaller compared to wild type mice, as a result of fewer and smaller individual adipocytes. [ABSTRACT FROM AUTHOR]

Dams are continuing to age and deteriorate that affect the service life of the dams in the U.S. Risk assessment is required to understand the behavior of dams and to prioritize the remedial actions and maintenance, and yet it is quite challenging to do risk assessment since it requires extensive current and historical data from in situ instrumentation on dams and detailed design, construction, and operation information. Currently, the required data for risk assessment resides in various paper-based and digital documents that hinder the capabilities of risk assessors to gather, analyze, and visualize the data flexibly from various engineering perspectives such as geotechnical, hydrologic, geologic, and structural. As a result, getting a holistic view of a dam's current condition and its behavior over time becomes a time and resource intensive task. There is a need for an integrated shared knowledge repository for dams to streamline the risk assessment process. The research described in this paper provides requirements for developing such a shared knowledge repository for risk assessment of embankment dams that would support the information needs of various engineering domains and the means and methods for integrated assessment, visualization, and data analytics to understand the risk of internal erosion. [ABSTRACT FROM AUTHOR]

The article examines the reasons for the high cost of biological drugs and ways to increase access to biopharmaceuticals. It states that biological therapies come from living material and have a highly complex chemical structure. Some of the factors that contribute to the high cost of biological drugs include the complex manufacturing processes, high costs of research and development, and the perceived value of drugs to patients. Examples of hurdles faced by potential generic manufacturers of biological therapies are outlined.