To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
For African American emerging adult men, developmental challenges are evident in their escalating substance abuse and depressive symptoms; this is particularly true for men from low-resource communities. The present study tests a developmental model linking childhood adversity and contemporaneous contextual stressors to increases in emerging adults’ substance use and depressive symptoms, indirectly, via increases in defensive/hostile relational schemas and social developmental risk factors (e.g., risky peers and romantic partners, lack of involvement in school or work). We also advance exploratory hypotheses regarding DNA methylation in the oxytocin receptor gene (OXTR) as a moderator of the effects of stress on relational schemas. Hypotheses were tested with three waves of data from 505 rural African American men aged 19–25 years. Adverse childhood experiences predicted exposure to emerging adult contextual stressors. Contextual stressors forecast increases in defensive/hostile relational schemas, which increased social developmental risk factors. Social developmental risk factors proximally predicted increases in substance abuse and depressive symptoms. OXTR DNA methylation moderated the effects of contextual stressors on defensive/hostile relational schemas. Findings suggest that early exposures to stress carry forward to affect the development of social developmental risk factors in emerging adulthood, which place rural African American men at risk for increased substance abuse and depressive symptoms during the emerging adult years.
Many studies demonstrate that marriage protects against risky alcohol use and moderates genetic influences on alcohol outcomes; however, previous work has not considered these effects from a developmental perspective or in high-risk individuals. These represent important gaps, as it cannot be assumed that marriage has uniform effects across development or in high-risk samples. We took a longitudinal developmental approach to examine whether marital status was associated with heavy episodic drinking (HED), and whether marital status moderated polygenic influences on HED. Our sample included 937 individuals (53.25% female) from the Collaborative Study on the Genetics of Alcoholism who reported their HED and marital status biennially between the ages of 21 and 25. Polygenic risk scores (PRS) were derived from a genome-wide association study of alcohol consumption. Marital status was not associated with HED; however, we observed pathogenic gene-by-environment effects that changed across young adulthood. Among those who married young (age 21), individuals with higher PRS reported more HED; however, these effects decayed over time. The same pattern was found in supplementary analyses using parental history of alcohol use disorder as the index of genetic liability. Our findings indicate that early marriage may exacerbate risk for those with higher polygenic load.
We analyze optimal budget allocations to acquire protected areas for carbon storage while balancing risk and return from protection under economic growth uncertainty in a local community. Our study is the first to explore how risk of uncertain economic growth affects cost of protected area acquisition using real estate values at the parcel level, enabling us to estimate the site-specific opportunity cost of carbon storage. The Pareto optimal trade-off frontier between the expected carbon storage benefit and its variance provides a continuum of risk-return combinations. The pattern of the trade-off relationship implies that risk mitigation is less costly in terms of foregone expected benefit when risk is higher than when it is lower. Our results also find that the difference in cluster-specific budget allocations between the strong economic growth scenario and the weak economic growth scenario subsequently decreases between the point of expected benefit maximization and the point of variance minimization. Our findings of optimal hectares of land for protected area acquisition for carbon storage and corresponding benefits and costs serve as an empirically informed knowledge base to help a local community prioritize acquisition of potential protected areas for carbon storage under economic growth uncertainty.
OBJECTIVES/GOALS: The primary aim of this observational study was to explore minute by minute differences in children’s in-school PA accumulation while attending a nature-based compared to a traditional Pre-K program. METHODS/STUDY POPULATION: Participants from a single Pre-K program wore an accelerometer at the waist during school for two consecutive weekdays in the winter, chosen for consistent weather conditions. In this program, one day was spent at a nature-based site, and one day at a traditional classroom location. Accelerometer data was analyzed using Butte (2014) vector magnitude activity thresholds summed by minute across each day. Paired-sample t-tests were applied on a minute-by-minute basis at a significance of p<0.001 to determine the point(s) at which PA accumulation diverged between settings. Direct observation (DO) conducted by a trained researcher also documented activities children engaged in each school day. RESULTS/ANTICIPATED RESULTS: In-school PA differed significantly between settings beginning at minute 37 of classroom time. Based on results obtained through DO, this coincided with the end of unstructured free play time and the start of structured activities across both days. In a traditional classroom setting, structured activities included classroom-based learning, while the nature-based setting incorporated a 10-minute outdoor walk prior to the start of classroom learning. This walking period altered the trajectory of total in-school PA accumulation between program locations, with participants maintaining a significantly greater PA accumulation while in a nature-based setting through the end of the school period. DISCUSSION/SIGNIFICANCE OF IMPACT: Compared to a traditional setting, nature-based programs allow for more active structured periods in school. A 10-minute teacher-led walk can significantly improve the trajectory of children’s PA accumulation throughout the remainder of a school day.
The aim of this study was to examine whether the presence of risk alleles of the norepinephrine transporter gene (SLC6A2) polymorphisms is associated with differences in regional cerebral blood flow (rCBF) measured by 99mTc-HMPAO single photon emission computerized tomography in a Korean sample of ADHD.
The present study included 24 children with ADHD (9.5±2.4 years), consisting of 20 boys and 4 girls, aged 6-16 years. We investigated the G1287A and -3081(A/T) polymorphisms of the SLC6A2. The rCBF was compared between the ADHD subjects with and without risk alleles at the G1287A polymorphism and at the -3081(A/T) polymorphism. Image analyses were performed with voxelwise t-statistics using SPM2.
1) The ADHD subjects with the A allele (risk allele) at the G1287A polymorphism showed reduced perfusion in the left middle frontal gyrus, left inferior parietal lobule, precuneus, right superior frontal gyrus, and right superior parietal lobule as compared with ADHD subjects without the A allele (p< 0.001).
2) The ADHD subjects with the A allele at the G1287A polymorphism showed increased perfusion in the right middle frontal gyrus, right middle temporal gyrus, right superior temporal gyrus, right fusiform gyrus, right precentral gyrus, and right anterior lobe of cerebellum as compared with ADHD subjects without the A allele (p< 0.001).
3) No significant perfusion differences were found between ADHD subjects with and without the T allele (risk allele) at the -3081(A/T) polymorphism.
Our findings suggest that the SLC6A2 G1287A polymorphism might exert differential effects on rCBF in children with ADHD.
Schizophrenia is highly familial neuropsychiatric disorder with heritability estimated at 60-90%. Even unaffected first-degree relatives of schizophrenia manifested some neuropsychological abnormalities as well as neurologic soft sign and morphologic anomalies. the aim of this study was to evaluate personality profile in first-degree relatives of schizophrenia compared to their schizophrenia probands and healthy controls and whether personality profile might be endophenotype of schizophrenia.
The subjects were 97 first-degree relatives of schizophrenia, 48 their schizophrenia probands, and 106 healthy controls, who completed Temperament and Character Inventory (TCI) scale. Relatives were further divided into presumed carriers and pesumed non-carriers by schizophrenia genetic loading. Group difference in TCI scores were compared by general linear model using age and gender as covariates.
1. There were significant group differences in HA scores between healthy controls, relatives, and probands after controlling age and gender, in that HA scores were increased by healthy controls, relatives, and probands in order.
2. Presumed carriers have higher HA scores than presumed non-carriers and healthy controls.
3. Proband group showed significantly lower RD and lower P in temperament dimension and lower SD, lower C, and higher ST in character dimension compared to other groups.
We found that HA scores of first-degree relatives of schizophrenia is intermediate level between schizophrenia probands and healthy controls. Considering increase of HA with schizophrenia genetic loading, HA may be potential endophenotype of schizophrenia. Further research with longitudinal follow up is needed to elucidate the clinical implication of high HA observed in schizophrenia family.
There are two major forms of long-term depression (LTD) of synaptic transmission in the central nervous system, which require activation of either N-methyl-D-aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). In synapses in the perirhinal cortex we have directly compared the Ca2+ signalling mechanisms involved in NMDAR-LTD and mGluR-LTD. Whilst both forms of LTD involve Ca2+ release from intracellular stores the Ca2+ sensors involved are different; NMDAR-LTD involves calmodulin, whilst mGluR-LTD involves the neuronal Ca2+ sensor (NCS) protein NCS-1. In addition, there is a specific requirement for IP3 and PKC as well as protein interacting with C-kinase (PICK-1) in mGluR-LTD. NCS-1 binds directly to PICK1, via its BAR domain, in a Ca2+-dependent manner. Furthermore, the NCS-1-PICK1 association is stimulated by activation of mGluRs, but not NMDARs, and introduction of a PICK1 BAR domain fusion protein specifically blocks mGluR-LTD. Thus, NCS-1 is a component of a novel mechanism involved in mGluR-LTD.
Identifying early risk factors for the development of social anxiety symptoms has important translational implications. Accurately identifying which children are at the highest risk is of critical importance, especially if we can identify risk early in development. We examined continued risk for social anxiety symptoms at the transition to adolescence in a community sample of children (n = 112) that had been observed for high fearfulness at age 2 and tracked for social anxiety symptoms from preschool through age 6. In our previous studies, we found that a pattern of dysregulated fear (DF), characterized by high fear in low threat contexts, predicted social anxiety symptoms at ages 3, 4, 5, and 6 years across two samples. In the current study, we re-evaluated these children at 11–13 years of age by using parent and child reports of social anxiety symptoms, parental monitoring, and peer relationship quality. The scores for DF uniquely predicted adolescents’ social anxiety symptoms beyond the prediction that was made by more proximal measures of behavioral (e.g., kindergarten social withdrawal) and concurrent environmental risk factors (e.g., parental monitoring, peer relationships). Implications for early detection, prevention, and intervention are discussed.
Micronutrient supplementation is recommended in Ebola Virus Disease (EVD). However, there is limited data on its therapeutic impacts. This study evaluated the association between vitamin A supplementation and mortality outcomes in EVD patients.
This retrospective cohort study accrued patients with EVD admitted to five International Medical Corps run Ebola Treatment Units (ETU) in two countries from 2014-2015. Protocolized treatments with antimicrobials and micronutrients were used at all ETUs. However, due to resource limitations and care variations, only a subset of patients received vitamin A. Standardized data on demographics, clinical characteristics, malaria status, and Ebola virus RT-PCR cycle threshold (CT) values were collected. The outcome of interest was mortality compared between cases treated with 200,000 International Units of vitamin A on care days one and two and those not. Propensity scores (PS) based on the first 48-hours of care were derived using the covariates of age, duration of ETU function, malaria status, CT values, symptoms of confusion, hemorrhage, diarrhea, dysphagia, and dyspnea. Treated and non-treated cases were matched 1:1 based on nearest neighbors with replacement. Covariate balance met predefined thresholds. Mortality proportions between cases treated and untreated with vitamin A were compared using generalized estimating equations to calculate relative risks (RR) with associated 95% confidence intervals (CI).
There were 424 cases analyzed, with 330 (77.8%) being vitamin A-treated cases. The mean age was 30.5 years and 57.0% were female. The most common symptoms were diarrhea (86%), anorexia (81%), and vomiting (77%). Mortality proportions among cases untreated and treated with vitamin A were 71.9% and 55.0%, respectively. In a propensity-matched analysis, mortality was significantly lower among cases receiving vitamin A (RR = 0.77 95%; CI:0.59-0.99; p = 0.041).
Early vitamin A supplementation was associated with reduced mortality in EVD patients and should be provided routinely during future epidemics.
Antimicrobial stewardship (AS) involves the appropriate selection of antimicrobials. Antimicrobial stewardship programs are mandated in hospitals and are expanding to involve outpatient arenas. Multiple articles have been published describing the need for AS education for medical and pharmacy students, beginning early in the students’ career to develop into competent AS practitioners. Additionally, publications have described the role and impact of medical and pharmacy trainees on AS programs. Here, we review the published evidence describing medical and pharmacy trainees’ involvement in AS and call for future research in this area.
The present model is devoted for the steady stagnation point flow of a Williamson micropolar nanofluid with magneto-hydrodynamics and thermal radiation effects passed over a horizontal porous stretching sheet. The fluid is considered to be gray, absorbing-emitting but non-scattering medium. The Cogley-Vincent-Gilles formulation is adopted to simulate the radiation component of heat transfer. By applying similarity analysis, the governing partial differential equations are transformed into a set of non-linear ordinary differential equations and they are solved by using the bvp4c package in MATLAB. Numerical computations are carried out for various values of the physical parameters. The effects of momentum, microrotation, temperature and nanoparticle volume fraction profiles together with the reduced skin friction coefficient, reduced Nusselt number and reduced Sherwood number of both active and passive controls on the wall mass flux are graphically presented. The present results are compared with previously obtained solutions and they are in good agreement. Results show that the skin friction is increasing functions of the Williamson parameter in both stretching and shrinking surfaces.
Background:ATP8A2 mutations have only recently been associated with human disease. We present the clinical features from the largest cohort of patients with this disorder reported to date. Methods: An observational study of 9 unreported and 2 previously reported patients with biallelic ATP8A2 mutations was carried out at multiple centres. Results: The mean age of the cohort was 9.4 years old (range: 2.5-28 yrs). All patients demonstrated developmental delay, severe hypotonia and movement disorders: chorea/choreoathetosis (100%), dystonia (27%) or facial dyskinesia (18%). Hypotonia was apparent at birth (70%) or before 6 months old (100%). Optic atrophy was observed in 75% of patients who had a funduscopic examination. MRI of the brain was normal for most patients with a small proportion showing mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Epilepsy was seen in two older patients. Conclusions:ATP8A2 gene mutations have emerged as a cause of a novel phenotype characterized by developmental delay, severe hypotonia and hyperkinetic movement disorders. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation. Early recognition of the cardinal features of this condition will facilitate diagnosis of this disorder.
We report on the astrometric registration of VLBI images of the SiO and H2O masers in OH 231.8+4.2, the iconic Proto-Planetary Nebula also known as the Calabash nebula, using the KVN and Source/Frequency Phase Referencing. This, for the first time, robustly confirms the alignment of the SiO masers, close to the AGB star, which drives the bi-lobe structure with the water masers in the out-flow.
We estimated the heritabilities (h2) and genetic and phenotypic correlations among individual and groups of fatty acids, as well as their correlations with six important carcass and meat-quality traits in Korean Hanwoo cattle. Meat samples were collected from the longissimus dorsi muscles of 1000 Hanwoo steers that were 30-month-old (progeny of 85 proven Hanwoo bulls) to determine intramuscular fatty acid profiles. Phenotypic data on carcass weight (CWT), eye muscle area (EMA), back fat thickness (BFT), marbling score (MS), Warner–Bratzler shear force (WBSF) and intramuscular fat content (IMF) were also investigated using this half-sib population. Variance and covari.ance components were estimated using restricted maximum likelihood procedures under univariate and pairwise bivariate animal models. Oleic acid (C18:1n-9) was the most abundant fatty acid, accounting for 50.69% of all investigated fatty acids, followed by palmitic (C16:0; 27.33%) and stearic acid (C18:0; 10.96%). The contents of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) were 41.64%, 56.24% and 2.10%, respectively, and the MUFA/SFA ratio, PUFA/SFA ratio, desaturation index (DI) and elongation index (EI) were 1.36, 0.05, 0.59 and 0.66, respectively. The h2 estimates for individual fatty acids ranged from very low to high (0.03±0.14 to 0.63±0.14). The h2 estimates for SFAs, MUFAs, PUFAs, DI and EI were 0.53±0.14, 0.49±0.14, 0.23±0.10, 0.51±0.13 and 0.53±0.13, respectively. The genetic and phenotypic correlations among individual fatty acids and fatty acid classes varied widely (−0.99 to 0.99). Notably, C18:1n-9 had favourable (negative) genetic correlations with two detrimental fatty acids, C14:0 (−0.76) and C16:0 (−0.92). Genetic correlations of individual and group fatty acids with CWT, EMA, BFT, MS, WBSF and IMF ranged from low to moderate (both positive and negative) with the exception of low-concentration PUFAs. Low or near-zero phenotypic correlations reflected potential non-genetic contributions. This study provides insights on genetic variability and correlations among intramuscular fatty acids as well as correlations between fatty acids and carcass and meat-quality traits, which could be used in Hanwoo breeding programmes to improve fatty acid compositions in meat.
High-grade gliomas are deadly cancers, and current standard-of-care has demonstrated limited success. The ability to specifically target glioma cells can allow for the development of improved theranostic agents leading to better detection methods, as well as safer anti-cancer therapies. Brevican (Bcan), a CNS-specific protein is upregulated in glioma cells and correlates with tumor progression. Particularly, a Bcan isoform lacking normal glycosylation, called B/bDg is a unique glioma marker and is not expressed in non-cancerous tissues. Therefore, B/bDg represents a valuable target for anti-cancer strategies. We describe here the discovery of novel high-affinity B/bDg-targeted peptides using rapid combinatorial library screening approaches and a microfluidic sorting device of our own design. Briefly, a one-bead-one-compound (OBOC) peptide library was screened against small magnetic particles decorated with B/bDg. Positive “hit” beads labeled with magnetic particles were isolated using an inexpensive but yet, accurate and high-throughput in-house microfluidic magnetic-activated sorter. These hits were exposed to cells expressing B/bDg, and beads with the highest cell association were isolated and sequenced. Seven novel peptides were identified. Cell uptake analyses and blocking studies revealed that 5 of these peptides displayed specific uptake in B/bDg-overexpressing cells. These candidates displayed nano-/micromolar binding affinity for recombinant B/bDg protein. Further analyses of these candidates using confocal microscopy revealed increased peptide binding/uptake in patient-derived glioma stem cells (GSCs) compared with primary human astrocytes. We plan to incorporate these onto multi-functional BBB-penetrating nanoparticles loaded with imaging agents or a drug payload to translate them into highly selective and efficacious brain cancer theranostic agents.
Coaxially nested intense
sheared flow realized an upgraded stable mirror plasma regime. After such an external control of high vorticity formation due to electron cyclotron heating, significantly unstable plasmas appeared. Thereby, the associated cross-field transport caused a crash of plasmas. Its generalized physics and interpretation could prepare or extend to another possibility of stability in a field-reversed configuration (FRC), for instance. Such underlying physics bases of vorticity formation were essentially or partially performed in tokamaks and stellarators (solved problems). Nevertheless, it remains to be seen whether this mirror-based experimental evidence is applicable or not to open ended FRC devices. This open issue may give a solution of one of unsolved important problems, and possibly provide more generalized and externally controllable opportunities for not only FRC but wider plasma confinement improvements.
Sparganosis is one of the top three tissue-dwelling heterologous helminthic diseases, along with cysticercosis and paragonimiasis, in Korea. Due to a lack of effective early diagnosis and treatment methods, this parasitic disease is regarded as a public health threat. This study evaluated reactivity, against sparganum extracts, of sera from inhabitants of Cheorwon-gun, Goseong-gun and Ongjin-gun in Korea. The sera from 836 subjects were subjected to enzyme-linked immunosorbent assay and immunoblot analysis. The sera from 18 (5.8%) and 15 (5.1%) inhabitants in Cheorwon-gun (n = 312) and Goseong-gun (n = 294), respectively, exhibited highly positive reactions to the sparganum antigen, whereas only two (0.9%) inhabitants in Ongjin-gun (n = 230) showed positivity. We sought antigenic proteins for serodiagnosis of positive sera by immunoproteomic approaches. Total sparganum lysates were separated by two-dimensional electrophoresis and then subjected to immunoblot analysis with mixed sparganosis-positive sera. We found seven antigenic spots and identified paramyosin as an antigenic protein by liquid chromatography–mass spectrometry. By two-dimensional (2D)-based mass analysis and immunoblotting against sparganosis-positive sera, paramyosin was identified as a candidate antigen for serodiagnosis of sparganosis.