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The deleterious effects of adversity are likely intergenerational, such that one generation’s adverse experiences can affect the next. Epidemiological studies link maternal adversity to offspring depression and anxiety, possibly via transmission mechanisms that influence offspring fronto-limbic connectivity. However, studies have not thoroughly disassociated postnatal exposure effects nor considered the role of offspring sex. We utilized infant neuroimaging to test the hypothesis that maternal childhood maltreatment (CM) would be associated with increased fronto-limbic connectivity in infancy and tested brain-behavior associations in childhood. Ninety-two dyads participated (32 mothers with CM, 60 without; 52 infant females, 40 infant males). Women reported on their experiences of CM and non-sedated sleeping infants underwent MRIs at 2.44 ± 2.74 weeks. Brain volumes were estimated via structural MRI and white matter structural connectivity (fiber counts) via diffusion MRI with probabilistic tractography. A subset of parents (n = 36) reported on children’s behaviors at age 5.17 ± 1.73 years. Males in the maltreatment group demonstrated greater intra-hemispheric fronto-limbic connectivity (b = 0.96, p= 0.008, [95%CI 0.25, 1.66]), no differences emerged for females. Fronto-limbic connectivity was related to somatic complaints in childhood only for males (r = 0.673, p = 0.006). Our findings suggest that CM could have intergenerational associations to offspring brain development, yet mechanistic studies are needed.
OBJECTIVES/GOALS: In vitro models that mimic the human respiratory system are needed to assess the toxicity of inhaled contaminants. Therefore, our goal is to establish a Dosimetric Aerosol in-Vitro Inhalation Device (DAVID) that delivers aerosols in different patterns to human lung cells cultured at an air-liquid interface (ALI). METHODS/STUDY POPULATION: The collection unit of DAVID was modified in this study to accommodate different deposition patterns (spots, annular ring, rectangle & circle). CuO aerosols of varying concentrations were generated using a 6-jet Collison nebulizer for varying time periods to achieve different doses. To quantify the doses that were delivered to cells, the samples were digested with nitric acid & analyzed by Inductively Coupled Plasma-Optical Emission Spectrometry. Following the exposure of A549 cells to CuO aerosols, cytotoxicity and mRNA expression (i.e., HMOX1 & IL-8) will be assessed via LDH and RT-qPCR to determine the effect of regional (mass deposited/area of the pattern) and global (mass deposited/area of the cell culture insert) doses in cells. RESULTS/ANTICIPATED RESULTS: The deposition areas covered by rectangular, spot, annular ring, and circular patterns are estimated to be 6, 17, 27 and 85% of the insert’s surface area, onto which cells are cultured. Results for the patterns tested (spots and annular ring) show that both the regional and global doses were greater for spots than annular ring. Also, the regional doses were higher than global doses. Irrespective of the patterns, the global doses were the same for nebulizer suspensions of 0.1-1 mg/mL. Statistical analysis by ANOVA revealed there was no significant difference in doses between replicate inserts used in the same trial. We anticipate that regional doses with aerosol deposition to a larger surface area of the cell culture insert will correspond with higher cytotoxicity and mRNA expression of HMOX1 and IL-8 in cells. DISCUSSION/SIGNIFICANCE: There are limited in vitro exposure systems that can efficiently deliver aerosols to lung cells, while also mimicking inhalation by humans. In addition to addressing this knowledge gap, we will show the role of regional & global doses in studying cellular response & the ability of DAVID to deliver aerosols in different deposition patterns.
Modeling and forecasting of mortality rates are closely related to a wide range of actuarial practices, such as the designing of pension schemes. To improve the forecasting accuracy, age coherence is incorporated in many recent mortality models, which suggests that the long-term forecasts will not diverge infinitely among age groups. Despite their usefulness, misspecification is likely to occur for individual mortality models when applied in empirical studies. The reliableness and accuracy of forecast rates are therefore negatively affected. In this study, an ensemble averaging or model averaging (MA) approach is proposed, which adopts age-specific weights and asymptotically achieves age coherence in mortality forecasting. The ensemble space contains both newly developed age-coherent and classic age-incoherent models to achieve the diversity. To realize the asymptotic age coherence, consider parameter errors, and avoid overfitting, the proposed method minimizes the variance of out-of-sample forecasting errors, with a uniquely designed coherent penalty and smoothness penalty. Our empirical data set include ten European countries with mortality rates of 0–100 age groups and spanning 1950–2016. The outstanding performance of MA is presented using the empirical sample for mortality forecasting. This finding robustly holds in a range of sensitivity analyses. A case study based on the Italian population is finally conducted to demonstrate the improved forecasting efficiency of MA and the validity of the proposed estimation of weights, as well as its usefulness in actuarial applications such as the annuity pricing.
Previous research has indicated that attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk for dementia, but studies are scarce and inconclusive. We aimed to investigate the association between ADHD, and dementia and mild cognitive impairment (MCI). Additionally, we aimed to investigate the impact of comorbid conditions, educational attainment, head injuries, other developmental disorders, and sex on the association.
Methods
The study population consisted of 3,591,689 individuals born between 1932 and 1963, identified from Swedish population-based registers. Cases of ADHD, dementia and MCI were defined according to ICD diagnostic codes and ATC codes for medication prescriptions. A Cox proportional hazards model was used to test the associations between ADHD, and dementia and MCI.
Results
Individuals with ADHD had an increased risk for dementia and MCI. After adjusting for sex and birth year, a hazard ratio (HR) was 2.92 (95% confidence interval 2.40–3.57) for dementia, and 6.21 (5.25–7.35) for MCI. Additional adjustment for psychiatric disorders (depression, anxiety, substance use disorder, and bipolar disorder) substantially attenuated the associations, HR = 1.62 (1.32–1.98) for dementia, and 2.54 (2.14–3.01) for MCI. Common metabolic disorders (hypertension, type 2 diabetes, and obesity), sleep disorders, head injuries, educational attainment, and other developmental disorders, had a limited impact on the association. The association between ADHD and dementia was stronger in men.
Conclusions
ADHD is a potential risk factor for dementia and MCI, although the risk significantly attenuates after controlling for psychiatric disorders. Further research is needed to confirm these findings and to explore underlying mechanisms of the associations.
This paper investigates a high-dimensional vector-autoregressive (VAR) model in mortality modeling and forecasting. We propose an extension of the sparse VAR (SVAR) model fitted on the log-mortality improvements, which we name “spatially penalized smoothed VAR” (SSVAR). By adaptively penalizing the coefficients based on the distances between ages, SSVAR not only allows a flexible data-driven sparsity structure of the coefficient matrix but simultaneously ensures interpretable coefficients including cohort effects. Moreover, by incorporating the smoothness penalties, divergence in forecast mortality rates of neighboring ages is largely reduced, compared with the existing SVAR model. A novel estimation approach that uses the accelerated proximal gradient algorithm is proposed to solve SSVAR efficiently. Similarly, we propose estimating the precision matrix of the residuals using a spatially penalized graphical Lasso to further study the dependency structure of the residuals. Using the UK and France population data, we demonstrate that the SSVAR model consistently outperforms the famous Lee–Carter, Hyndman–Ullah, and two VAR-type models in forecasting accuracy. Finally, we discuss the extension of the SSVAR model to multi-population mortality forecasting with an illustrative example that demonstrates its superiority in forecasting over existing approaches.
To investigate homocysteine (Hcy) and folate levels, prevalence of hyperhomocysteinaemia (HHcy) and folate deficiency, which are affected by lifestyles in urban, agricultural and stock-raising populations.
Design:
This is a cross-sectional study.
Setting:
Urban, agricultural and stock-raising regions in Emin, China.
Participants:
Totally 1926 subjects – 885 (45·9 %) from urban, 861 (44·7 %) from agricultural and 180 (9·4 %) from stock-raising regions – were obtained using multistage stratified random sampling. Inclusion criteria encompassed inhabitants aged ≥15 years who resided at the current address for ≥6 months and agreed to participate in the study. Surveys on health behaviour questionnaires and physical examinations were conducted and blood samples collected.
Results:
The folate level of subjects from the stock-raising region was the lowest, followed by those from the agricultural region, and the highest in those from the urban region (3·48 v. 6·50 v. 7·12 ng/ml, P < 0·001), whereas mean Hcy showed no significant difference across regions. The OR for HHcy in stock-raising regions was 1·90 (95 % CI 1·11, 3·27) compared with the urban region after adjusting for all possible covariates. The OR for folate deficiency in stock-raising and agriculture regions was 11·51 (95 % CI 7·09, 18·67) and 1·91 (95 % CI 1·30, 2·82), respectively, compared with the urban region after adjusting for all possible covariates.
Conclusions:
HHcy and folate deficiency are highly prevalent in stock-raisers, which is of important reference for HHcy control in Xinjiang, with a possibility of extension to others with approximate lifestyles.
This article is a summary of perspectives on training curricula from child and adolescent psychiatry trainees globally. We aimed to identify the relative strengths, weaknesses and gaps in learning needs from a trainee's perspective. The 20 early-career child psychiatrists who contributed are from 16 countries and represent all the five continents. We could identify some global challenges as well as local/regional challenges that need to be addressed to develop competent child psychiatrists.
The cao vit gibbon Nomascus nasutus, also known as eastern black crested gibbon, is categorized as Critically Endangered on the IUCN Red List and was considered one of the world's 25 most threatened primates. The only known population occurs along the border between China and Viet Nam. Accurate information on population size and dynamics is critical for the species’ conservation, but population surveys conducted in only one country may over- or underestimate total population size because the home ranges of cao vit gibbon groups often cross the international border. In 2007 and 2016 we conducted two collaborative transboundary censuses of the cao vit gibbon populations in the Trung Khanh Cao Vit Gibbon Species and Habitat Conservation Area in Viet Nam and the Bangliang Gibbon National Nature Reserve in China. The results showed a population size of 102–110 in 2007, which increased to 107–136 in 2016. Our results indicate that previous surveys conducted separately in Viet Nam and China underestimated the global population size of this species. According to our more comprehensive surveys, the gibbon population is increasing slowly. The gibbons and their habitat are legally protected in both countries. Hunting and charcoal making have not been reported in this area since 2007. As habitat carrying capacity is a limiting factor, habitat restoration is required. However, lack of funding to protect the cao vit gibbon remains a challenge.
The Chinese Crested Tern Thalasseus bernsteini (CCT) is likely the most critically endangered seabird species in Asia. The Matsu, Penghu, Jiushan, and Wuzhishan Archipelagos along the China coastline, plus Yeonggwang County in South Korea, are the five areas where this species is currently confirmed to breed. According to census and historical data collected in the Matsu Archipelago from 2004 to 2017, there was an average of 10 ± 4 adult CCT individuals at the Matsu Islands Tern Refuge (MITR) during the breeding season. CCT nested only in association with Greater Crested Terns T. bergii (GCT) among seven protected islands in the MITR, and the numbers of observed breeding individuals of the two species were positively correlated (r = 0.59, P < 0.001). We used generalized linear models to examine the effects of chlorophyll-a concentrations in surrounding marine habitats, typhoon frequency, and in-season shifts in colony location on inter-annual variation in numbers of breeding individuals and productivity (chick:adult ratios) of both CCT and GCT at the MITR from 2004 to 2017. Average chlorophyll-a concentrations during July-August obtained from the MODIS satellite were positively correlated with the annual maximum number of GCT at the MITR, but not that of CCT. In addition, we found that nest abandonment events during early incubation at the mixed-species colonies were associated with in-season shifts in colony location and delayed nesting chronology, thereby extending nesting into the peak typhoon season during July and August. The effects of in-season colony shifts on nesting chronology and the additive effects of typhoons caused a significant decline in CCT breeding success during the study period. We propose more rigorous monitoring to ascertain the root causes of in-season colony shifts of terns and then determine possible solutions. Additionally, creating educational programmes to increase public awareness towards seabird conservation could prove beneficial.
Low-field magnetic stimulation (LFMS) has mood-elevating effect, and the increase of brain-derived neurotrophic factor (BDNF) is associated with antidepressant treatment. We evaluated the effects and association with BDNF of rhythmic LFMS in the treatment of major depressive disorder (MDD).
Methods
A total of 22 MDD patients were randomized to rhythmic alpha stimulation (RAS) or rhythmic delta stimulation (RDS), with 5 sessions per week, lasting for 6 weeks. Outcomes assessments included the 17-item Hamilton Depression Rating Scale (HAMD–17), the Hamilton Anxiety Rating Scale (HAMA), and the Clinical Global Impressions–Severity scale (CGI–S) at baseline and at weeks 1, 2, 3, 4, and 6. Serum BDNF level was measured at baseline and at weeks 2, 4, and 6.
Results
HAMD–17, HAMA, and CGI–S scores were significantly reduced with both RAS and RDS. RAS patients had numerically greater reductions in HAMD–17 scores than RDS patients (8.9 ± 7.4 vs. 6.2 ± 6.2, effect size [ES]=0.40), while RDS patients had greater improvement in HAMA scores (8.2 ± 8.0 vs. 5.3 ± 5.8, ES=0.42). RAS was associated with clinically relevant advantages in response (54.5% vs. 18.2%, number-needed-to-treat [NNT]=3) and remission (36.4% vs. 9.1%, NNT=4). BDNF increased significantly during the 6-week study period (p<0.05), with greater increases in RAS at weeks 4 and 6 (ES=0.66—0.76) and statistical superiority at week 2 (p=0.034, ES=1.23). Baseline BDNF in the 8 responders (24.8±9.0 ng/ml) was lower than in the 14 nonresponders (31.1±7.3 ng/ml, p=0.083, ES=–0.79), and BDNF increased more in responders (8.9±7.8 ng/ml) than in nonresponders (1.8±3.5 ng/ml, p=0.044). The change in BDNF at week 2 was the most strongly predicted response (p=0.016).
Conclusions
Rhythmic LFMS was effective for MDD. BDNF may moderate/mediate the efficacy of LFMS.
Recent Genome-Wide Association Studies (GWAS) have identified four low-penetrance ovarian cancer susceptibility loci. We hypothesized that further moderate- or low-penetrance variants exist among the subset of single-nucleotide polymorphisms (SNPs) not well tagged by the genotyping arrays used in the previous studies, which would account for some of the remaining risk. We therefore conducted a time- and cost-effective stage 1 GWAS on 342 invasive serous cases and 643 controls genotyped on pooled DNA using the high-density Illumina 1M-Duo array. We followed up 20 of the most significantly associated SNPs, which are not well tagged by the lower density arrays used by the published GWAS, and genotyping them on individual DNA. Most of the top 20 SNPs were clearly validated by individually genotyping the samples used in the pools. However, none of the 20 SNPs replicated when tested for association in a much larger stage 2 set of 4,651 cases and 6,966 controls from the Ovarian Cancer Association Consortium. Given that most of the top 20 SNPs from pooling were validated in the same samples by individual genotyping, the lack of replication is likely to be due to the relatively small sample size in our stage 1 GWAS rather than due to problems with the pooling approach. We conclude that there are unlikely to be any moderate or large effects on ovarian cancer risk untagged by less dense arrays. However, our study lacked power to make clear statements on the existence of hitherto untagged small-effect variants.
Layer-structured polypyrrole/montmorillonite (PPy/MMT) naoncomposite films were synthesized by the electrodeposition method. The fabricated free-standing films consist of about 0∼2 wt% Na+-montmorillonite (NMMT). The thickness of films could be controlled by deposition time. X-ray diffraction (XRD) and scanning electron microscope (SEM) were used to observe the microstructure of the films. After MMT was introduced into the PPy matrix, the interspace between PPy chains decreased, according to the XRD results. The layered structure of the films was observed from the SEM images. Tensile and nanoindentation test results showed that the mechanical properties of the composite films were improved at low clay loading. The electrical conductivity of the films with 1.2 wt% MMT loading was increased from 3.6 to 51 S/cm, probably because of the restricted growth of PPy chains in the interspace of MMT layers.
To enhance the detection of bacterial meningitis in an East Asian surveillance study, we employed cerebrospinal fluid (CSF) bacterial culture, latex agglutination (LA) and polymerase chain reaction–enzyme immunoassay (PCR–EIA) testing for Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (Sp). The sensitivity and specificity of CSF PCR–EIA testing was compared to LA and culture. A meningitis case was defined by one positive result for any of the three tests. The sensitivity of H. influenzae CSF PCR–EIA, LA, and culture was 100%, 40% and 57·5% respectively; and for Sp CSF PCR–EIA, LA and culture, the sensitivity was 100%, 58·3% and 66·7%, respectively. Hib and Sp specificity was 100% by each method. CSF PCR–EIA was more sensitive than culture or LA for the detection of Hib and Sp meningitis cases increasing their incidence by 74% and 50% compared to culture respectively. CSF PCR–EIA should be included for the detection of bacterial meningitis in surveillance studies.
Lithium has been intercalated chemically and electrochemically in LnNb3O9 (Ln = La, Nd) perovskite-type phases and LiW3O9F which can be considered as a hexagonal tungsten bronze derivative.
The crystallographic formula of the LnNb3O9 starting material is □3/2 (Ln□1/2 )Nb3O9. In both systems, solid solutions are observed in the fir part of the intercalation reaction. While almost all perovskite cavities are filled in the neodymium phases, the higher ionic character of the La-O bonds prevents practically the Li intercalation in the □' sites.
In the LiW3O9F phase two lithium atoms can be electrochemically intercalated via a single phase mechanism. The reaction is completely reversible. For higher amounts of intercalation (x > 3), irreversible structural modifications occur.
In both systems the unit cell parameter variation is negligible during intercalation. This behavior results from the blocking up of the framework by Ln3+ ions in LnNb3O9 phases or by the stacking of the three octahedra triangular arrangement in the hexagonal tungsten bronze structure.
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