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A recent hypothesis postulates the existence of an ‘immune-metabolic depression’ (IMD) dimension characterized by metabolic dysregulations. Combining data on metabolomics and depressive symptoms, we aimed to identify depressions associated with an increased risk of adverse metabolic alterations.
Clustering data were from 1094 individuals with major depressive disorder in the last 6 months and measures of 149 metabolites from a 1H-NMR platform and 30 depressive symptoms (IDS-SR30). Canonical correlation analyses (CCA) were used to identify main independent metabolite-symptom axes of variance. Then, for the replication, we examined the association of the identified dimensions with metabolites from the same platform and cardiometabolic diseases in an independent population-based cohort (n = 6572).
CCA identified an overall depression dimension and a dimension resembling IMD, in which symptoms such as sleeping too much, increased appetite, and low energy level had higher relative loading. In the independent sample, the overall depression dimension was associated with lower cardiometabolic risk, such as (i.e. per s.d.) HOMA-1B −0.06 (95% CI −0.09 – −0.04), and visceral adipose tissue −0.10 cm2 (95% CI −0.14 – −0.07). In contrast, the IMD dimension was associated with well-known cardiometabolic diseases such as higher visceral adipose tissue 0.08 cm2 (95% CI 0.04–0.12), HOMA-1B 0.06 (95% CI 0.04–0.09), and lower HDL-cholesterol levels −0.03 mmol/L (95% CI −0.05 – −0.01).
Combining metabolomics and clinical symptoms we identified a replicable depression dimension associated with adverse metabolic alterations, in line with the IMD hypothesis. Patients with IMD may be at higher cardiometabolic risk and may benefit from specific treatment targeting underlying metabolic dysregulations.
Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.
To evaluate the impact of state-mandated policies for pulse oximetry screening on healthcare utilisation, with a focus on use of echocardiograms.
Data sources/study setting:
Healthcare Cost and Utilisation Project, Statewide Inpatient Databases from 2008 to 2014 from six states.
We defined pre- and post-mandate cohorts based on dates when pulse oximetry became mandated in each state. Linear segmented regression models for interrupted time series assessed associations between implementation of the screening and changes in rate of newborns with Critical CHD-negative echocardiogram results. We also evaluated the changes in rate of newborns who underwent echocardiogram but were not diagnosed with any health issues that could cause hypoxemia.
We identified 5967 critical CHD-negative echocardiograms (2847 and 3120 in the pre- and post-mandate periods, respectively). Our models detected a statistically significant increasing trend in rate of critical CHD-negative echocardiograms in the pre-mandate period (Incidence Rate Ratio: 1.08, p = 0.02), but did not detect any statistical differences in changes between pre- and post-mandate periods (Incidence Rate Ratio: 0.93, p = 0.14). Among non-Whites, an increasing trend of Critical CHD-negative echocardiogram during the pre-mandate period was detected (Incidence Rate Ratio 1.12, p < 0.01) and was attenuated during the post-mandate period (Incidence Rate Ratio 0.89, p = 0.02). Similar results were observed in the sensitivity analyses among both Whites and non-Whites.
Results suggest that mandatory state screening policies are associated with reductions in false-positive screening rates for hypoxemic conditions, with reductions primarily attributed to trends among non-Whites.
OBJECTIVES/GOALS: Utilize polymer-based fiber scaffolds and machine learning methods applied to patient biomarker data to enhance and personalize T cell expansion and production for T cell therapy in chronic lymphocytic leukemia. METHODS/STUDY POPULATION: Scaffolds are 1) generated from a co-polymer blend of PDMS and PCL with controlled fiber diameters and pore size, 2) coated with activating antibodies to CD3 and CD28, and 3) used to stimulate T cells from both healthy donors and CLL patients. CLL patients have pre-annotated mutation burdens and clinical biomarkers. T cell populations will be analyzed for exhaustion markers and phenotypes before, during, and after expansion. Cell functionality will be measured by cytokine secretion, cell cycle analysis, and fold expansion, with respect to platform parameters, and analyzed with inputs of disease markers and exhaustion profile of isolated T cells using regression and random forest classifiers. RESULTS/ANTICIPATED RESULTS: We previously showed that engineering the mechanical rigidity of activating substrates can enhance and rescue T cell expansion from exhausted populations. Now we aim to study a broader range of compositions and geometry of scaffolds with respect to capacity to expand CLL T cells. Preliminary data with fiber diameters ranging from 300 nm to 6 um confirm the effect of geometry in modulating expansion. A biorepository of T cells from 80 CLL patients have been isolated concurrently. Anticipated results include correlating exhaustion profile of T cells with clinical biomarkers and identifying markers associated with expansion on panel of platform parameters. DISCUSSION/SIGNIFICANCE OF IMPACT: T cell therapy has shown particular promise in treating blood cancers, yet significant percentage of T cells isolated from patients undergoing treatments are unresponsive to activation. A powerful tool is to predict if and how patient T cells can be robustly expanded on a personalized approach.
To examine relationships between suicidal ideation, self-harm, and suicide attempts, including the timing of the phenomena.
Subjects and methods
The British National Psychiatric Morbidity Survey (NPMS) 2000, a randomised cross-sectional survey of the British population (n = 8,580), included detailed questions about suicidal phenomena.
Suicidal phenomena were common in the survey population: a fifth had experienced tedium vitae, and nearly one in six had had death wishes or considered suicide. 4.4% of the study population had attempted suicide at some time. The relationships between individual elements of suicidality, though not absolute, were strong. The relationships tended to be hierarchical. The results suggested that suicidal thinking represents a strong indicator of vulnerability to suicidal acts, less so to self-harm. Although suicidal phenomena were more common in women, the relationship of the different elements were not affected by gender.
Studies in non clinical populations allow full appreciation of the nature and burden of suicidality. The topic of suicide is sensitive, so there may have been under-reporting, although the level of missing data was around 0.1%. Nevertheless, the sample was large and closely representative of the whole British populace.
Suicidality is common in the British population. The strong relationships between elements of suicidality are clinically important.
The network approach to psychopathology posits that mental disorders can be conceptualized and studied as causal systems of mutually reinforcing symptoms. This approach, first posited in 2008, has grown substantially over the past decade and is now a full-fledged area of psychiatric research. In this article, we provide an overview and critical analysis of 363 articles produced in the first decade of this research program, with a focus on key theoretical, methodological, and empirical contributions. In addition, we turn our attention to the next decade of the network approach and propose critical avenues for future research in each of these domains. We argue that this program of research will be best served by working toward two overarching aims: (a) the identification of robust empirical phenomena and (b) the development of formal theories that can explain those phenomena. We recommend specific steps forward within this broad framework and argue that these steps are necessary if the network approach is to develop into a progressive program of research capable of producing a cumulative body of knowledge about how specific mental disorders operate as causal systems.
The Netherlands Twin Register (NTR) is a national register in which twins, multiples and their parents, siblings, spouses and other family members participate. Here we describe the NTR resources that were created from more than 30 years of data collections; the development and maintenance of the newly developed database systems, and the possibilities these resources create for future research. Since the early 1980s, the NTR has enrolled around 120,000 twins and a roughly equal number of their relatives. The majority of twin families have participated in survey studies, and subsamples took part in biomaterial collection (e.g., DNA) and dedicated projects, for example, for neuropsychological, biomarker and behavioral traits. The recruitment into the NTR is all inclusive without any restrictions on enrollment. These resources — the longitudinal phenotyping, the extended pedigree structures and the multigeneration genotyping — allow for future twin-family research that will contribute to gene discovery, causality modeling, and studies of genetic and cultural inheritance.
The Rio Grande Cone is a major fanlike depositional feature in the continental slope of the Pelotas Basin, Southern Brazil. Two representative sediment cores collected in the Cone area were retrieved using a piston core device. In this work, the organic matter (OM) in the sediments was characterized for a continental vs. marine origin using chemical proxies to help constrain the origin of gas in hydrates. The main contribution of OM was from marine organic carbon based on the stable carbon isotope (δ13C-org) and total organic carbon/total nitrogen ratio (TOC:TN) analyses. In addition, the 14C data showed important information about the origin of the OM and we suggest some factors that could modify the original organic matter and therefore mask the “real” 14C ages: (1) biological activity that could modify the carbon isotopic composition of bulk terrestrial organic matter values, (2) the existence of younger sediments from mass wasting deposits unconformably overlying older sediments, and (3) the deep-sediment-sourced methane contribution due to the input of “old” (>50 ka) organic compounds from migrating fluids.
Objectives: The current study examines whether psychosocial outcomes following pediatric traumatic brain injury (TBI) vary as a function of children’s rejection sensitivity (RS), defined as their disposition to be hypersensitive to cues of rejection from peers. Methods: Children ages 8–13 with a history of severe TBI (STBI, n=16), complicated mild/moderate TBI (n=35), or orthopedic injury (OI, n=49) completed measures assessing self-esteem and RS on average 3.28 years post-injury (SD=1.33, range=1.25–6.34). Parents reported on their child’s emotional and behavioral functioning and social participation. Results: Regression analyses found moderation of group differences by RS for three outcomes: social participation, self-perceptions of social acceptance, and externalizing behavior problems. Conditional effects at varying levels of RS indicated that externalizing problems and social participation were significantly worse for children with STBI at high levels of RS, compared to children with OI. Social participation for the STBI group remained significantly lower than the OI group at mean levels of RS, but not at low levels of RS. At high levels of RS, self-perceptions of social acceptance were lower for children with moderate TBI compared to OI, but group differences were not significant at mean or low levels of RS. No evidence of moderation was found for global self-worth, self-perceptions of physical appearance or athletic ability, or internalizing problems. Conclusions: The findings highlight the salient nature of social outcomes in the context of varying levels of RS. These findings may have implications for the design of interventions to improve social outcomes following TBI. (JINS, 2017, 23, 451–459)
Composite copper oxide–copper bromide films were electrodeposited on gas diffusion layer (GDL) supports under controlled potential from aqueous copper salt solutions in the presence of a complexing/surfactant agent such as lactate. The solution pH was adjusted to target simultaneous deposition of cubic nanostructures composed of copper, oxygen, and bromine elements. The film composition and morphology were carefully tuned for enhanced electrochemical conversion of CO2 to hydrocarbons. Hydrocarbon products, predominantly ethylene and minor amounts of methane, ethane, and propylene were observed along with inevitable H2 co-generation. Importantly, CO gas was not detected during CO2 electrolyses. Low temperatures (3–5 °C) enhanced the conversion of CO intermediate to C2H4. The durability and electroactivity of these composite films were maintained for extended periods (up to 10 h) of CO2 electrolysis by periodic in situ application of anodic pulses to regenerate the cathode surface.
A monolithic fuel design based on U–Mo alloy has been selected as the fuel type for conversion of United States’ high-performance research reactors (USHPRRs) from highly enriched uranium (HEU) to low-enriched uranium (LEU). In this fuel design, a thin layer of zirconium is used to eliminate the direct interaction between the U–Mo fuel meat and the aluminum-alloy cladding during irradiation. The co-rolling process used to bond the Zr barrier layer to the U–Mo foil during fabrication alters the microstructure of both the U–10Mo fuel meat and the U–Mo/Zr interface. This work studied the effects of post-rolling annealing treatment on the microstructure of the co-rolled U–Mo fuel meat and the U–Mo/Zr interaction layer. The U–Mo/Zr interaction-layer thickness increased with the annealing temperature with an Arrhenius constant for growth of 184kJ/mole, consistent with a previous diffusion-couple study. The phases in the U–Mo/Zr interaction layer produced by co-rolling, however, differ from those reported in the previous diffusion-couple study.
This research explored gender and cross-cultural similarities and differences in the motivational profiles of Indigenous Papua New Guinean (PNG) and Indigenous and non-Indigenous Australians. Secondary students (N = 1,792) completed self-report motivational measures. Invariance testing demonstrated that the Inventory of School Motivation (McInerney, Yeung, & McInerney, 2001) measure was invariant across both gender and Indigenous and non-Indigenous groups. Structural equation modelling (SEM) results explicated that males were significantly more performance orientated than females in all three groups examined; however, the disparity between genders was most apparent in non-Indigenous Australians. Diverging from previous findings with non-Indigenous students, the current study found that PNG and Australian Indigenous males endorsed mastery goals more strongly than Indigenous females. In contrast, non-Indigenous females were more mastery orientated than non-Indigenous males. Finally, the two Indigenous groups endorsed social goals more strongly than the non-Indigenous Australians. The current findings highlight the importance of assessing gender and group differences, as broad statements relating to student motivation do not appear to be applicable in all cultural contexts.
We present the first measurement of the evolution of the apparent projected shape of galaxy clusters from 0.2≲ z≲2. We measure the ellipticities (εcl) of homogeneously selected galaxy clusters over this wide redshift range. We confirm the predictions of N-body simulations that clusters are more elongated at higher redshift, finding the mean projected ellipticity changes linearly from 0.36±0.01 to 0.25±0.01 over that range. The fraction of relaxed clusters (defined as having εcl<0.2) is 9+5-3% at z∼1.8, steadily increasing to 42+7-6% by z∼0.3. Because more spherical clusters have a higher degree of virialization, our result shows significant evolution in the degree of cluster virialization over cosmic time.
It has been postulated that aging is the consequence of an accelerated accumulation of somatic DNA mutations and that subsequent errors in the primary structure of proteins ultimately reach levels sufficient to affect organismal functions. The technical limitations of detecting somatic changes and the lack of insight about the minimum level of erroneous proteins to cause an error catastrophe hampered any firm conclusions on these theories. In this study, we sequenced the whole genome of DNA in whole blood of two pairs of monozygotic (MZ) twins, 40 and 100 years old, by two independent next-generation sequencing (NGS) platforms (Illumina and Complete Genomics). Potentially discordant single-base substitutions supported by both platforms were validated extensively by Sanger, Roche 454, and Ion Torrent sequencing. We demonstrate that the genomes of the two twin pairs are germ-line identical between co-twins, and that the genomes of the 100-year-old MZ twins are discerned by eight confirmed somatic single-base substitutions, five of which are within introns. Putative somatic variation between the 40-year-old twins was not confirmed in the validation phase. We conclude from this systematic effort that by using two independent NGS platforms, somatic single nucleotide substitutions can be detected, and that a century of life did not result in a large number of detectable somatic mutations in blood. The low number of somatic variants observed by using two NGS platforms might provide a framework for detecting disease-related somatic variants in phenotypically discordant MZ twins.