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1.
Singapore Med J ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32241065

RESUMO

In this paper, we aimed to provide professional guidance to practising gastrointestinal (GI) endoscopists for the safe conduct of GI endoscopy procedures during the current coronavirus disease 2019 (COVID-19) pandemic and future outbreaks of similar severe respiratory tract infections in Singapore. It draws on the lessons learnt during the severe acute respiratory syndrome (SARS) epidemic and available published data concerning the COVID-19 pandemic. It addresses measures before, during and after endoscopy that must be considered for both non- infected and infected patients, and provides recommendations for practical implementation.

2.
Nucleic Acids Res ; 48(6): 3134-3155, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32083649

RESUMO

While G/U pairs are present in many RNAs, the lack of molecular studies to characterize the roles of multiple G/U pairs within a single RNA limits our understanding of their biological significance. From known RNA 3D structures, we observed that the probability a G/U will form a Watson-Crick (WC) base pair depends on sequence context. We analyzed 17 G/U pairs in the 359-nucleotide genome of Potato spindle tuber viroid (PSTVd), a circular non-coding RNA that replicates and spreads systemically in host plants. Most putative G/U base pairs were experimentally supported by selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE). Deep sequencing PSTVd genomes from plants inoculated with a cloned master sequence revealed naturally occurring variants, and showed that G/U pairs are maintained to the same extent as canonical WC base pairs. Comprehensive mutational analysis demonstrated that nearly all G/U pairs are critical for replication and/or systemic spread. Two selected G/U pairs were found to be required for PSTVd entry into, but not for exit from, the host vascular system. This study identifies critical roles for G/U pairs in the survival of an infectious RNA, and increases understanding of structure-based regulation of replication and trafficking of pathogen and cellular RNAs.

3.
Sci Total Environ ; 718: 137282, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32086087

RESUMO

Trace metals and nutrients attached on road deposited sediments (RDS) are the main source of non-point pollution to urban waterbodies causing ecological degradation and eutrophication problems. Mathematical models of the pollutant build-up process on road surfaces can be used to develop remediation measures. However, there was lack of research on the pollutant build-up process of various sized particles during a long dry period. This research investigated the build-up behaviors of specific pollutants in size-fractioned particles during 41 antecedent dry-weather days (ADDs), which was the longest build-up period ever studied. This research revealed that the pollution concentration exhibited a mono-growth behavior, while the pollutant mass followed a cyclic behavior during the study period. The time to peak and the build-up cycle of various pollutant mass were all highly associated with the particle characteristics, and the mass and concentration levels of pollutants in various sized particles were different. Furthermore, two important phenomena were found in this study: the bioavailability of phosphorus as well as the enrichment factors of metals all increased along with time during the build-up process. These findings provide new insights in non-point source pollution build-up and improve the water quality modelling.

4.
Biomed Res Int ; 2020: 3289023, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32090079

RESUMO

The use of genetic testing to identify individuals with hereditary cancer syndromes has been widely adopted by clinicians for management of inherited cancer risk. The objective of this study was to develop and validate a 34-gene inherited cancer predisposition panel using targeted capture-based next-generation sequencing (NGS). The panel incorporates genes underlying well-characterized cancer syndromes, such as BRCA1 and BRCA2 (BRCA1/2), along with more recently discovered genes associated with increased cancer risk. We performed a validation study on 133 unique specimens, including 33 with known variant status; known variants included single nucleotide variants (SNVs) and small insertions and deletions (Indels), as well as copy-number variants (CNVs). The analytical validation study achieved 100% sensitivity and specificity for SNVs and small Indels, with 100% sensitivity and 98.0% specificity for CNVs using in-house developed CNV flagging algorithm. We employed a microarray comparative genomic hybridization (aCGH) method for all specimens that the algorithm flags as CNV-positive for confirmation. In combination with aCGH confirmation, CNV detection specificity improved to 100%. We additionally report results of the first 500 consecutive specimens submitted for clinical testing with the 34-gene panel, identifying 53 deleterious variants in 13 genes in 49 individuals. Half of the detected pathogenic/likely pathogenic variants were found in BRCA1 (23%), BRCA2 (23%), or the Lynch syndrome-associated genes PMS2 (4%) and MLH1 (2%). The other half were detected in 9 other genes: MUTYH (17%), CHEK2 (15%), ATM (4%), PALB2 (4%), BARD1 (2%), CDH1 (2%), CDKN2A (2%), RAD51C (2%), and RET (2%). Our validation studies and initial clinical data demonstrate that a 34-gene inherited cancer predisposition panel can provide clinically significant information for cancer risk assessment.

5.
BMC Psychiatry ; 19(1): 420, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881956

RESUMO

BACKGROUND: Previous research suggests that the 17-item Hamilton Depression Rating Scale (HAM-D17) is less sensitive in detecting differences between active treatment and placebo for major depressive disorder (MDD) than is the HAM-D6 scale, which focuses on six core depression symptoms. Whether HAM-D6 shows greater sensitivity when comparing two active MDD treatment arms is unknown. METHODS: This post hoc analysis used data from the intent-to-treat (ITT) cohort (N = 1541) of the Genomics Used to Improve DEpression Decisions (GUIDED) trial, a rater- and patient-blinded randomized controlled trial. GUIDED compared combinatorial pharmacogenomics-guided care with treatment as usual (TAU) in patients with MDD. Percent of symptom improvement, response rate and remission rate from baseline to week 8 were evaluated using both scales. Analyses were performed for the full cohort and for the subset of patients who at baseline were taking medications predicted by the test to have moderate or significant gene-drug interactions. A Mokken scale analysis was conducted to compare the homogeneity of HAM-D17 with that of HAM-D6. RESULTS: At week 8, the guided-care arm demonstrated statistically significant benefit over TAU when the HAM-D6 (∆ = 4.4%, p = 0.023) was used as the continuous measure of symptom improvement, but not when using the HAM-D17 (∆ = 3.2%, p = 0.069). Response rates increased significantly for guided-care compared with TAU when evaluated using both HAM-D6 (∆ = 7.0%, p = 0.004) and HAM-D17 (∆ = 6.3%, p = 0.007). Remission rates also were significantly greater for guided-care versus TAU using both measures (HAM-D6 ∆ = 4.6%, p = 0.031; HAM-D17 ∆ = 5.5%, p = 0.005). Patients in the guided-care arm who at baseline were taking medications predicted to have gene-drug interactions showed further increased benefit over TAU at week 8 for symptom improvement (∆ = 7.3%, p = 0.004) response (∆ = 10.0%, p = 0.001) and remission (∆ = 7.9%, p = 0.005) using HAM-D6. All outcomes showed continued improvement through week 24. Mokken scale analysis demonstrated the homogeneity and unidimensionality of HAM-D6, but not of HAM-D17, across treatment arms. CONCLUSIONS: The HAM-D6 scale identified a statistically significant difference in symptom improvement between combinatorial pharmacogenomics-guided care and TAU, whereas the HAM-D17 did not. The demonstrated utility of pharmacogenomics-guided treatment over TAU as detected by the HAM-D6 highlights its value for future biomarker-guided trials comparing active treatment arms. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02109939. Registered 10 April 2014.

6.
J Geriatr Psychiatry Neurol ; : 891988719892341, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31842673

RESUMO

OBJECTIVE: We compared economic outcomes when elderly patients with neuropsychiatric disorders received psychotropic medications guided by a combinatorial pharmacogenomic (PGx) test. METHODS: This is a subanalysis of a 1-year prospective assessment of medication cost for patients with neuropsychiatric disorders receiving combinatorial PGx testing. Pharmacy claims were used to compare per member per year (PMPY) medication cost for patients ≥65 and <65 years old when medications were congruent or incongruent with the PGx test. Polypharmacy was also assessed. RESULTS: Congruent prescribing was associated with savings of US$3497 PMPY (P < .001) for patients ≥65 years and US$2467 PMPY (P < .001) for patients <65, compared to incongruent prescribing. Congruent prescribing in patients ≥65 treated by primary care providers was associated with US$4113 PMPY (P = .026) in savings, while congruent prescribing by psychiatrists was associated with US$120 PMPY (P = .719). Congruent prescribing was also associated with one fewer neuropsychiatric medication for patients ≥65 (P = .070). CONCLUSION: Congruence with PGx testing was associated with medication cost savings in elderly patients.

7.
BMC Med Educ ; 19(1): 415, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706306

RESUMO

BACKGROUND: Struggling medical students is an under-researched in medical education. It is known, however, that early identification is important for effective remediation. The aim of the study was to determine the predictive effect of medical school admission tools regarding whether a student will struggle academically. METHODS: Data comprise 700 students from the University of New South Wales undergraduate medical program. The main outcome of interest was whether these students struggled during this 6-year program; they were classified to be struggling they failed any end-of-phase examination but still graduated from the program. Discriminate Function Analysis (DFA) assessed whether their pre-admission academic achievement, Undergraduate Medicine Admission Test (UMAT) and interview scores had predictive effect regarding likelihood to struggle. RESULTS: A lower pre-admission academic achievement in the form of Australian Tertiary Admission Rank (ATAR) or Grade Point Average (GPA) were found to be the best positive predictors of whether a student was likely to struggle. Lower UMAT and poorer interview scores were found to have a comparatively much smaller predictive effect. CONCLUSION: Although medical admission tests are widely used, medical school rarely use these data for educational purposes. The results of this study suggest admission test data can predict who among the admitted students is likely to struggle in the program. Educationally, this information is invaluable. These results indicate that pre-admission academic achievement can be used to predict which students are likely to struggle in an Australian undergraduate medicine program. Further research into predicting other types of struggling students as well as remediation methods are necessary.

8.
J Pharmacokinet Pharmacodyn ; 46(6): 617-626, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31667657

RESUMO

Cardiac safety assessment is a key regulatory requirement for almost all new drugs. Until recently, one evaluation aspect was via a specifically designated, expensive, and resource intensive thorough QTc study, and a by-time-point analysis using an intersection-union test (IUT). ICH E14 Q&A (R3) (http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E14/E14_Q_As_R3__Step4.pdf) allows for analysis of the PK-QTc relationship using early Phase I data to assess QTc liability. In this paper, we compared the cardiac risk assessment based on the early Phase I analysis with that from a thorough QTc study across eleven drug candidate programs, and demonstrate that the conclusions are largely the same. The early Phase I analysis is based upon a linear mixed effect model with known covariance structure (Dosne et al. in Stat Med 36(24):3844-3857, 2017). The treatment effect was evaluated at the supratherapeutic Cmax as observed in the thorough QTc study using a non-parametric bootstrap analysis to generate 90% confidence intervals for the treatment effect, and implementation of the standardized methodology in R and SAS software yielded consistent results. The risk assessment based on the concentration-response analysis on the early Phase I data was concordant with that based on the standard analysis of the thorough QTc study for nine out of the eleven drug candidates. This retrospective analysis is consistent with and supportive of the conclusion of a previous prospective analysis by Darpo et al. (Clin Pharmacol Ther 97(4):326-335, 2015) to evaluate whether C-QTc analysis can detect QTc effects in a small study with healthy subjects.

9.
J Clin Psychiatry ; 80(6)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31721487

RESUMO

OBJECTIVE: The objective of the Genomics Used to Improve DEpression Decisions (GUIDED) trial was to evaluate the utility of pharmacogenomic testing to improve outcomes among patients with major depressive disorder (MDD) who had not responded to at least 1 prior medication trial. The objective of the present analysis was to assess outcomes for the subset of patients expected to benefit from combinatorial pharmacogenomic testing because they were taking medications with predicted gene-drug interactions. METHODS: Participants (enrolled from April 14, 2014, to February 10, 2017) had an inadequate response to at least 1 psychotropic medication in the current episode of MDD. Patients were randomized to treatment as usual (TAU) or the guided-care arm, in which clinicians had access to a combinatorial pharmacogenomic test report to inform medication selection. Patients and raters were blinded to study arm through week 8. The following outcomes were assessed using the 17-item Hamilton Depre​ssion Rating Scale (HDRS-17): symptom improvement (percent change in HDRS-17 score), response (≥ 50% decrease in HDRS-17 score), and remission (HDRS-17 score ≤ 7). In the GUIDED trial, the primary endpoint of symptom improvement did not reach significance in the intent-to-treat cohort (P = .069). Here, a post hoc analysis of patients who were taking medications subject to gene-drug interactions at baseline as predicted by combinatorial pharmacogenomic testing (N = 912) is presented. RESULTS: Among participants taking medications subject to gene-drug interactions at baseline, outcomes at week 8 were significantly improved for those in the guided-care arm compared to TAU (symptom improvement: 27.1% versus 22.1%, P = .029; response: 27.0% versus 19.0%, P = .008; remission: 18.2% versus 10.7%, P = .003). When patients who switched medications were assessed, all outcomes were significantly improved in the guided-care arm compared to TAU (P = .011 for symptom improvement, P = .011 for response, P = .008 for remission). CONCLUSIONS: By identifying and focusing on the patients with predicted gene-drug interactions, use of a combinatorial pharmacogenomic test significantly improved outcomes among patients with MDD who had at least 1 prior medication failure. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02109939​.

10.
Prehosp Emerg Care ; : 1-5, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31580180

RESUMO

Background and Purpose: Thrombectomy for large vessel occlusion acute ischemic stroke (AIS-LVO) may benefit patients up to 24 hour since last known normal (LKN). Prehospital tools, like the Cincinnati Stroke Triage Assessment Tool (C-STAT), are used to select hospital destination for suspected AIS-LVO patients. The objective of this study was to estimate the potential impact of the expanded thrombectomy time window on suspected AIS-LVO cases transported to the regional comprehensive stroke center (CSC). Methods: From June to November 2015, C-STAT was performed by prehospital providers following a positive prehospital Cincinnati Prehospital Stroke Scale (CPSS) stroke screen in suspected stroke/TIA patients. There was no preferential triage based on C-STAT results. Final diagnoses, including the presence of AIS-LVO was ascertained via medical record review. Impact of positive C-STAT cases on CSC volumes was estimated for up to 24 hours since LKN. Results: Of 158 patients with prehospital suspicion for stroke/TIA, 105 were CPSS positive within 24 hours of onset and had complete C-STAT and clinical data available for analysis. Forty-six percent (17/37) of C-STAT + were non-strokes. C-STAT sensitivity and specificity for LVO were 71% (95% CI 36-92) and 67% (95% CI 58-80), respectively. C-STAT triage would increase transport of prehospital suspected stroke cases to the CSC by 11% (12/105) within six hours and 21% (22/105) within 24 hours. Of 37 C-STAT + patients, only 5 (13.5%) had LVO as final diagnosis. Conclusions: Preferential triage of prehospital suspected stroke patients using C-STAT would increase the number of patients transported to the CSC by 11% within six hours and an additional 10% from six to 24 hours. For every patient with LVO as final diagnosis, approximately an additional 6 non-LVO patients would be triaged to a CSC.

11.
Psychol Med ; : 1-10, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31658909

RESUMO

BACKGROUND: Polygenic scores (PGS) are widely used to characterize genetic liability for heritable mental disorders, including attention-deficit/hyperactivity disorder (ADHD). However, little is known about the effects of a low burden of genetic liability for ADHD, including whether this functions as a low risk or protective factor for ADHD and related functional outcomes in later life. The current study examines the association of low ADHD PGS and functional outcomes in adulthood. METHODS: Participants were from Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health) (N = 7088; mean age = 29, s.d. = 1.74). ADHD PGS was computed from an existing genome-wide association study, and adult functional outcomes, including cognition, educational attainment, mental health, and physical health were assessed during in-home interviews. RESULTS: Individuals at the lowest end of the ADHD PGS distribution (i.e. lowest 20th percentile) had the lowest probabilities of ADHD, exhibiting a 17-19% reduction in risk for ADHD relative to the observed 8.3% prevalence rate of ADHD in Add Health. Furthermore, individuals with low ADHD PGS had higher cognitive performance, greater levels of educational attainment, and lower BMI relative to individuals representing the rest of the ADHD PGS distribution, including those who were in the medium and high-PGS groups. CONCLUSIONS: Findings indicate that psychiatric PGS likely capture far more than just the risk and the absence of risk for a psychiatric outcome; where one lies along the PGS distribution may predict diverging functional consequences, for better and for worse.

12.
Endosc Int Open ; 7(10): E1207-E1213, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31579701

RESUMO

Background and study aims Published data on blue laser imaging (BLI) for detection and differentiation of colonic polyps are limited compared to narrow band imaging (NBI). This study investigated whether BLI can increase the detection rate of colonic polyps and adenomas when compared to white light imaging (WLI), and examined use of NICE (NBI International Colorectal Endoscopic) and JNET (Japan NBI Expert Team) classifications with BLI. Patients and methods Patients aged 50 years and above referred for colonoscopy were randomized to BLI or WLI on withdrawal. Detected polyps were characterized using NICE and JNET classifications under BLI mode and correlated with histology. Primary outcome was adenoma detection rate. Secondary outcomes were utility of NICE and JNET classifications to predict histology using BLI. Results A total of 182 patients were randomized to BLI (92) or WLI (90). Comparing BLI with WLI, the polyp detection rate was 59.8 % vs 40.0 %, P  = 0.008, and the adenoma detection rate was 46.2 % vs 27.8 %, P  = 0.010. NICE 1 and JNET 1 diagnosed hyperplastic polyps with sensitivity of 87.18 % and specificity of 84.35 %. NICE 2 diagnosed low- (LGD) or high-grade dysplasia (HGD) with sensitivity of 92.31 % and specificity of 77.45 %. JNET 2A diagnosed LGD with sensitivity of 91.95 %, and specificity of 74.53 %. Four cases of focal HGD all had JNET 2A morphology. Conclusion BLI increased adenoma detection rate compared to WLI. NICE and JNET classifications can be applied when using BLI for endoscopic diagnosis of HP and LGD but histological confirmation remains crucial.

13.
J Allergy Clin Immunol Pract ; 7(7): 2154-2155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31495423
14.
Clin Cancer Res ; 25(23): 6995-7003, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31444250

RESUMO

PURPOSE: Anti-CD19 chimeric antigen receptor (CAR) T cells represent a novel immunotherapy and are highly effective in treating relapsed/refractory B-cell non-Hodgkin's lymphoma (B-NHL). How tumor microenvironment influences clinical response to CAR T therapy remains of great interest. PATIENTS AND METHODS: A phase I, first-in-human, dose-escalation study of anti-CD19 JWCAR029 was conducted in refractory B-NHL (NCT03355859) and 10 patients received CAR T cells at an escalating dose of 2.5 × 107(n = 3), 5 × 107(n = 4), and 1 × 108(n = 3) cells. Core needle biopsy was performed on tumor samples collected from diffuse large B-cell lymphoma patients on Day -6 (1 day before lymphodepletion) and on Day 11 after CAR T-cell infusion when adequate CAR T-cell expansion was detected. RESULTS: The overall response rate was 100%, with 6 of 9 (66.7%) evaluable patients achieving complete remission. The most common adverse events of grade 3 or higher were neutropenia (10/10, 100%), anemia (3/10, 30%), thrombocytopenia (3/10, 30%), and hypofibrinogenemia (2/10, 20%). Grade 1 cytokine release syndrome occurred in all patients and grade 3 neurotoxicity in 1 patient. The average peak levels of peripheral blood CAR T cells and cytokines were similar in 3 different dose levels, but CAR T cells were significantly higher in patients achieved complete remission on Day 29. Meanwhile, RNA sequencing identified gene expression signatures differentially enriched in complete and partial remission patients. Increased tumor-associated macrophage infiltration was negatively associated with remission status. CONCLUSIONS: JWCAR029 was effective and safe in treating refractory B-NHL. The composition of the tumor microenvironment has a potential impact in CAR T therapy response.

15.
Sci Total Environ ; 696: 133788, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31445237

RESUMO

The build-up of urban road deposited sediments is the key to study the quality of stormwater and the associated receiving waterbody in urban catchments. In the past, many sediment build-up field studies were conducted between 7 and 20days. It is generally assumed that the cumulative amount of pollutants reaches equilibrium and be represented as a mono-growth curve such as the power function. However, the dry period between two rain events in many areas in Northern China may be much longer than 20days, especially for spring and fall seasons. This research was conducted for 41days during a long dry period in 2017 in Tianjin, a megacity of China. The variability of the road sediment build-up process and the intrinsic and extrinsic factors which influence the process variability were investigated. It has been found that the normally used mono-growth curve (such as the power function) may be suitable for the short-term build-up process in area with less interference (sparse human activity area, R2>0.6). The double-bell shaped curve (sin function) fits better for the 41-day study, a longer period build-up study (R2>0.9). An "unexpected" phenomenon at which the particulate load was rapidly decreased in the first three sampling days was observed. This remarkable phenomenon can undoubtedly be well represented by the sin function instead of the power function. Compared to the power function, the goodness of fit of the sin function is increased by 30%-130%. Particle size, as an important characteristic affecting the behavior of particles, was considered in the build-up model. This research may bring people's attention to study the long-term road sediment build-up process and their impacts on the receiving water quality.

16.
Singapore Med J ; 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363784

RESUMO

INTRODUCTION: Spontaneous bacterial peritonitis (SBP) is the commonest complication of liver cirrhosis. Timely and appropriate treatment of SBP is crucial, particularly with the rising worldwide prevalence of multidrug-resistant organisms (MDROs). We aimed to investigate the clinical outcomes of SBP in Singapore. METHODS: All cirrhotic patients with SBP diagnosed between January 2014 and December 2017 were included. Nosocomial SBP (N-SBP) was defined as SBP diagnosed more than 48 hours after hospitalisation. Clinical outcomes were analysed as categorical outcomes using univariate and multivariate analysis. RESULTS: There were 33 patients with 39 episodes of SBP. Their mean age was 64.5 years and 69.7% were male. The commonest aetiology of cirrhosis was hepatitis B (27.3%). The Median Model for End-stage Liver Disease (MELD) score was 17, 33.3% had acute-on-chronic liver failure and 60.6% had septic shock at presentation. N-SBP occurred in 25.6% of SBP cases. N-SBP was more commonly associated with MDROs, previous antibiotic use in the past three months (p = 0.014) and longer length of stay (p = 0.011). The 30-day and 90-day mortality among SBP patients was 30.8% and 51.3%, respectively. MELD score > 20 was a predictor for 30-day mortality. N-SBP and MELD score > 20 were predictors for 90-day mortality. CONCLUSION: N-SBP was significantly associated with recent antibiotic use, longer hospitalisation, more resistant organisms and poorer survival among patients with SBP. N-SBP and MELD score predict higher mortality in SBP. Judicious use of antibiotics may reduce N-SBP and improve survival among cirrhotic patients.

18.
J Child Psychol Psychiatry ; 60(11): 1191-1199, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31044437

RESUMO

BACKGROUND: Children with ADHD frequently engage in higher rates of externalizing behaviors in adulthood relative to children without. However, externalizing behaviors vary across development. Little is known about how this risk unfolds across development. Phenotypic and polygenic models of childhood ADHD were used to predict individual differences in adult externalizing trajectories. Supportive parenting, school connectedness, and peer closeness were then examined as causal mechanisms. METHODS: Data were from the National Longitudinal Study of Adolescent to Adult Health (N = 7,674). Externalizing behavior was measured using data from age 18 to 32 and modeled using latent class growth analysis. Child ADHD was measured using retrospective self-report (phenotypic model) and genome-wide polygenic risk scores (polygenic model). Multiple mediation models examined the direct and indirect effects of the phenotypic and polygenic models (separately) on externalizing trajectories through the effects of adolescent supportive parenting, school connectedness, and peer closeness. RESULTS: Phenotypic and polygenic models of ADHD were associated with being in the High Decreasing (3.2% of sample) and Moderate (16.1%) adult externalizing trajectories, but not the severe Low Increasing trajectory (2.6%), relative to the Normal trajectory (78.2%). Associations between both models of ADHD on the High Decreasing and Moderate trajectories were partially mediated through the effects of school connectedness, but not supportive parenting or peer closeness. CONCLUSIONS: Findings shed light on how childhood ADHD affects downstream psychosocial processes that then predict specific externalizing outcomes in adulthood. They also reinforce the importance of fostering a strong school environment for adolescents with (and without) ADHD, as this context plays a critical role in shaping the development of externalizing behaviors in adulthood.

19.
Endosc Ultrasound ; 8(4): 255-260, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31115385

RESUMO

Background and Objective: EUS-guided fine-needle biopsy (EUS-FNB) with acquisition of tissue core is possible with the use of 19G fine-needle aspiration (FNA) and dedicated biopsy needles. Published data of direct comparisons between biopsy needles are more limited compared to the abundant data comparing EUS-FNA with EUS-FNB. We performed a retrospective study to determine the difference in histologic yield between 19G FNA needle and EUS-FNB needles in patients with solid masses. Materials and Methods: Consecutive patients who underwent EUS-FNB of solid masses from January 2014 to July 2018 were identified from a database. The difference in histologic yield between needles was analyzed. Results: A total of 159 patients underwent 179 EUS-FNB procedures (median of 2 needle passes [range: 1-4]). The use of 19G FNA, 19G, 20G, and 22G FNB needles allowed acquisition of a histologic core in 67.4% (29/43), 72.5% (29/40), 82.1% (46/56), and 75.9% (22/29), respectively (P = 0.368). A significant difference in the yield of histologic core was detected when 19G FNA needle was compared with 22G Acquire™ FNB needle (67.4% [29/43] vs. 94.1% [16/17], P = 0.032). The presence of histologic core was significantly associated with a positive diagnosis (95.6% vs. 30.2%, P < 0.0001). Conclusion: EUS-FNB with acquisition of histologic core improved the diagnostic yield. Dedicated FNB needles appeared to achieve a higher yield of histologic core compared to 19G FNA needles.

20.
PLoS Genet ; 15(4): e1007973, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30946739

RESUMO

Facial attractiveness is a complex human trait of great interest in both academia and industry. Literature on sociological and phenotypic factors associated with facial attractiveness is rich, but its genetic basis is poorly understood. In this paper, we conducted a genome-wide association study to discover genetic variants associated with facial attractiveness using 4,383 samples in the Wisconsin Longitudinal Study. We identified two genome-wide significant loci, highlighted a handful of candidate genes, and demonstrated enrichment for heritability in human tissues involved in reproduction and hormone synthesis. Additionally, facial attractiveness showed strong and negative genetic correlations with BMI in females and with blood lipids in males. Our analysis also suggested sex-specific selection pressure on variants associated with lower male attractiveness. These results revealed sex-specific genetic architecture of facial attractiveness and provided fundamental new insights into its genetic basis.


Assuntos
Beleza , Face/anatomia & histologia , Variação Genética , Adolescente , Alelos , Feminino , Estudo de Associação Genômica Ampla , Humanos , Estudos Longitudinais , Masculino , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Caracteres Sexuais
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