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Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
ABSTRACT IMPACT: Despite its importance in systemic diseases such as diabetes, the eye is notably difficult to examine for non-specialists; this study introduces a fully automated approach for eye disease screening, coupling a deep learning algorithm with a robotically-aligned optical coherence tomography system to improve eye care in non-ophthalmology settings. OBJECTIVES/GOALS: This study aims to develop and test a deep learning (DL) method to classify images acquired from a robotically-aligned optical coherence tomography (OCT) system as normal vs. abnormal. The long-term goal of our study is to integrate artificial intelligence and robotic eye imaging to fully automate eye disease screening in diverse clinical settings. METHODS/STUDY POPULATION: Between August and October 2020, patients seen at the Duke Eye Center and healthy volunteers (age ≥18) were imaged with a custom, robotically-aligned OCT (RAOCT) system following routine eye exam. Using transfer learning, we adapted a preexisting convolutional neural network to train a DL algorithm to classify OCT images as normal vs. abnormal. The model was trained and validated on two publicly available OCT datasets and two of our own RAOCT volumes. For external testing, the top-performing model based on validation was applied to a representative averaged B-scan from each of the remaining RAOCT volumes. The model’s performance was evaluated against a reference standard of clinical diagnoses by retina specialists. Saliency maps were created to visualize the areas contributing most to the model predictions. RESULTS/ANTICIPATED RESULTS: The training and validation datasets included 87,697 OCT images, of which 59,743 were abnormal. The top-performing DL model had a training accuracy of 96% and a validation accuracy of 99%. For external testing, 43 eyes of 27 subjects were imaged with the robotically-aligned OCT system. Compared to clinical diagnoses, the model correctly labeled 18 out of 22 normal averaged B-scans and 18 out of 21 abnormal averaged B-scans. Overall, in the testing set, the model had an AUC for the detection of pathology of 0.92, an accuracy of 84%, a sensitivity of 86%, and a specificity of 82%. For the correctly predicted scans, saliency maps identified the areas contributing most to the DL algorithm’s predictions, which matched the regions of greatest clinical importance. DISCUSSION/SIGNIFICANCE OF FINDINGS: This is the first study to develop and apply a DL model to images acquired from a self-aligning OCT system, demonstrating the potential of integrating DL and robotic eye imaging to automate eye disease screening. We are working to translate this technology for use in emergency departments and primary care, where it will have the greatest impact.
The proximity required of a thorough biomicroscopic slit-lamp examination may put ophthalmologists at increased risk for respiratory-borne infection with SARS-CoV-2. Conjunctivitis has been described in a few patients with COVID-19 and other coronavirus syndromes. Although SARS-CoV-2 has been detected in the conjunctival secretions or tears of patients with COVID-19 and conjunctivitis, transmission of infection through respiratory droplets to ophthalmologists without eye protection or masks may be the bigger concern.
Many family characteristics were reported to increase the risk of bipolar disorder (BPD). The development of BPD may be mediated through different pathways, involving diverse risk factor profiles. We evaluated the associations of family characteristics to build influential causal-pie models to estimate their contributions on the risk of developing BPD at the population level. We recruited 329 clinically diagnosed BPD patients and 202 healthy controls to collect information in parental psychopathology, parent-child relationship, and conflict within family. Other than logistic regression models, we applied causal-pie models to identify pathways involved with different family factors for BPD. The risk of BPD was significantly increased with parental depression, neurosis, anxiety, paternal substance use problems, and poor relationship with parents. Having a depressed mother further predicted early onset of BPD. Additionally, a greater risk for BPD was observed with higher numbers of paternal/maternal psychopathologies. Three significant risk profiles were identified for BPD, including paternal substance use problems (73.0%), maternal depression (17.6%), and through poor relationship with parents and conflict within the family (6.3%). Our findings demonstrate that different aspects of family characteristics elicit negative impacts on bipolar illness, which can be utilized to target specific factors to design and employ efficient intervention programs.
Prior research on body-image-related issues has mainly focused on the relationship between overall body satisfaction and health-related outcomes, particularly among Western women. However, there is still a paucity of information on whether body satisfaction with specific body parts is differentially associated with body-image-related mental distress, especially across gay, bisexual, and heterosexual men in Taiwan.
Objectives
To Identify the differences by sexual orientation regarding the relationship between satisfaction with specific body parts and body-image-related mental distress among Taiwanese men.
Aims
To develop effective interventions to reduce mental distress related to body dissatisfaction in men.
Methods
A total of 665 male participants were recruited via a popular electronic bulletin board system frequented by Taiwanese youth.
Results
Increased levels of satisfaction with weight were significantly associated with lower odds of body-image-related mental distress across gay, bisexual, and heterosexual men (AOR=0.38, 0.31, and 0.56, respectively). Gay men who were more satisfied with their height (AOR=0.57) and body fat (AOR=0.28), as well as heterosexual men who were more satisfied with their facial features (AOR=0.51), muscle (AOR=0.53), and body fat (AOR=0.55), were significantly less likely to have body-image-related mental distress than their counterparts.
Conclusions
Higher levels of satisfaction with various specific body parts were associated with reduced risk of body-image-related mental distress. Further, these associations varied differentially across gay, bisexual, and heterosexual men. Future research may explore the possible mechanisms through which satisfaction with specific body parts influences men's body-image-related mental distress. Accordingly, interventions could be tailored for men of different sexual orientations.
The ability of the aorta to buffer blood flow and provide diastolic perfusion (Windkessel function) is a determinant of cardiovascular health. We have reported cardiac dysfunction indicating downstream vascular abnormalities in young adult baboons who were intrauterine growth restricted (IUGR) at birth as a result of moderate maternal nutrient reduction. Using 3 T MRI, we examined IUGR offspring (eight male, eight female; 5.7 years; human equivalent 25 years) and age-matched controls (eight male, eight female; 5.6 years) to quantify distal descending aortic cross-section (AC) and distensibility (AD). ANOVA showed decreased IUGR AC/body surface area (0.9±0.05 cm2/m2v. 1.2±0.06 cm2/m2, M±s.e.m., P<0.005) and AD (1.7±0.2 v. 4.0±0.5×10−3/mmHg, P<0.005) without sex difference or group-sex interaction, suggesting intrinsic vascular pathology and impaired development persisting in adulthood. Future studies should evaluate potential consequences of these changes on coronary perfusion, afterload and blood pressure.
Eating disorders (EDs) have long-term physical and mental impacts on those affected. However, few population-based studies have estimated the prevalence of EDs. We aimed to estimate the lifetime and 12-month prevalence rates of EDs using DSM-IV criteria, and to examine differences against the DSM-5 criteria for anorexia.
Method
A nationally representative sample of 10 038 residents in Switzerland was interviewed, and prevalence rates for anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) were assessed using WHO Composite International Diagnostic Interviews (WHO-CIDI).
Results
The lifetime prevalence rate for any ED was found to be 3.5%. Lifetime prevalence estimates for AN, BN, and/or BED were 1.2%, 2.4%, and 2.4%, respectively, among women and 0.2%, 0.9%, and 0.7%, respectively, among men. Utilizing the DSM-5 criteria, the prevalence of AN in women increased by more than 50%, from 1.2% to 1.9%. Among those meeting the criteria for any ED, only 49.4% of men and 67.9% of women had ever sought professional help about their problems with eating or weight.
Conclusions
The higher prevalence of BN we detected relative to other studies should prompt further monitoring for a possible increasing trend. The female v. male ratios, especially for bulimia and BED, are decreasing. Given that more than half of those affected have never consulted any professional about their problems with eating or weight, routine inquiries about eating and weight by clinicians, school teachers/psychologists, and family members may help those who are at risk, especially among men.
Substantial geographic coverage in paleontological study is essential in testing evolutionary models of phyletic gradualism and punctuated equilibrium. We present a multivariate morphometric study of the late Neogene planktonic foraminiferal clade Globoconella using specimens from four Deep Sea Drilling Project sites (DSDP 284, 207A, 208, and 588) along a latitudinal traverse in the southwest Pacific.
During the Late Miocene (7 Ma to 5 Ma), populations of the ancestral species Globorotalia (Globoconella) conomiozea formed a geographic cline showing continuous morphological variation from the temperate sites (DSDP 284 and 207A) to the warm subtropical sites (DSDP 208 and 588). Populations living to the south had higher conical angle and fewer chambers in the final whorl compared to the northern populations. Nevertheless, populations across the entire cline exhibited a coherent, directional trend towards having larger conical angle and fewer chambers through time. At the Miocene/Pliocene boundary, the intensification of the Tasman Front (Subtropical Divergence) possibly isolated the peripheral populations in the warm subtropics from the central stocks of the temperate water masses. The evolutionary trends became decoupled: the central populations gradually lost their keel and transformed into G. (G.) sphericomiozea, while the peripheral populations in the warm subtropical areas retained their keel and evolved into a flattened species, G. (G.) pliozea.
The gradual transformation of G. (G.) conomiozea terminalis (a form retaining a keel) into G. (G.) sphericomiozea (a form lacking a keel) occurred during an interval of about 0.2 m.y., with all measured morphologic variables showing continuous and steady changes. The evolution of the central populations follows the model of phyletic gradualism. In peripheral populations, the origin of the descendant species G. (G.) pliozea from the ancestor G. (G.) conomiozea terminalis occurred very rapidly within an interval of less than 0.01 m.y. The population size of G. (G.) pliozea was small at the incipient stage at about 5.05 Ma, but increased rapidly to become dominant during the next 0.2 m.y. when the ancestral species G. (G.) conomiozea terminalis became locally extinct. Following speciation, G. (G.) pliozea exhibited morphological stasis for about 0.6 m.y., until the central stock form G. (G.) puncticulata migrated back to the warm subtropics; during the next 0.5 m.y. of their sympatry, there is no sign of hybridization between these two sister species. The evolution of G. (G.) pliozea follows the model of punctuated equilibrium.
The evolution of the Globoconella clade shows both phyletic gradualism and punctuated equilibrium. These two “alternative” evolutionary models complement each other rather than being mutually exclusive. Both models are indispensable towards providing a complete picture of the evolution of Globoconella.
This study had 2 objectives: (1) to describe the epidemiology of catheter-related bloodstream infections (CRBSI) in patients with end-stage renal disease (ESRD) who have no access to scheduled dialysis and (2) to evaluate whether a positive culture of the heparin-lock solution is associated with subsequent development of bacteremia.
DESIGN
Retrospective observational cohort design for objective 1; and prospective cohort design for objective 2.
SETTING AND PARTICIPANTS
The study was conducted in a 770-bed public academic tertiary hospital in Dallas, Texas. The participants were patients with ESRD undergoing scheduled or emergent hemodialysis.
METHODS
We reviewed the records of 147 patients who received hemodialysis between January 2011 and May 2011 and evaluated the rate of CRBSI in the previous 5 years. For the prospective study, we cultured the catheter heparin-lock solution in 62 consecutive patients between June 2012 and August 2012 and evaluated the incidence of CRBSI at 6 months.
RESULTS
Of the 147 patients on emergent hemodialysis, 125 had a tunneled catheter, with a CRBSI rate of 2.61 per 1,000 catheter days. The predominant organisms were Gram-negative rods (GNR). In the prospective study, we found that the dialysis catheter was colonized more frequently in patients on emergent hemodialysis than in those on scheduled hemodialysis. Colonization with GNR or Staphylococcus aureus was associated with subsequent CRBSI at 6 months follow-up.
CONCLUSIONS
Patients undergoing emergent hemodialysis via tunneled catheter are predisposed to Gram-negative CRBSI. Culturing the heparin-lock solution may predict subsequent episodes of CRBSI if it shows colonization with GNR or Staphylococcus aureus. Prevention approaches in this population need to be studied further.
Infect. Control Hosp. Epidemiol. 2016;37(3):301–305
The association between Kawasaki disease (KD) and Attention deficit hyperactivity disorder (ADHD) has rarely been studied. In this study, we investigated the hypothesis that KD may increase the risk of ADHD using a nationwide Taiwanese population-based claims database.
Methods.
Our study cohort consisted of patients who were diagnosed with KD between January 1997 and December 2005 (N = 651). For a comparison cohort, five age- and gender-matched control patients for every patient in the study cohort were selected using random sampling (N = 3255). The cumulative incidence of ADHD was 3.89/1000 (from 0.05 to 0.85) in this study. All subjects were tracked for 5 years from the date of cohort entry to identify whether or not they had developed ADHD. Cox proportional hazard regression analysis was performed to evaluate 5-year ADHD-free survival rates.
Results.
Of all patients, 83 (2.1%) developed ADHD during the 5-year follow-up period, of whom 21 (3.2%) had KD and 62 (1.9%) were in the comparison cohort. The patients with KD seemed to be at an increased risk of developing ADHD (crude hazard ratio (HR): 1.71; 95% confidence interval (CI) = 1.04–2.80; p < 0.05). However, after adjusting for gender, age, asthma, allergic rhinitis, atopic dermatitis and meningitis, the adjusted hazard ratios (AHR) of the ADHD in patients with KD showed no association with the controls (AHR: 1.59; 95% CI = 0.96–2.62; p = 0.07). We also investigated whether or not KD was a gender-dependent risk factor for ADHD, and found that male patients with KD did not have an increased risk of ADHD (AHR: 1.62; 95% CI = 0.96–2.74; p = 0.07) compared with the female patients.
Conclusions.
The findings of this population-based study suggest that patients with KD may not have an increased risk of ADHD and whether or not there is an association between KD and ADHD remains uncertain.
We studied the association between drinking water, agriculture and sporadic human campylobacteriosis in one region of British Columbia (BC), Canada. We compared 2992 cases of campylobacteriosis to 4816 cases of other reportable enteric diseases in 2005–2009 using multivariate regression. Cases were geocoded and assigned drinking water source, rural/urban environment and socioeconomic status (SES) according to the location of their residence using geographical information systems analysis methods. The odds of campylobacteriosis compared to enteric disease controls were higher for individuals serviced by private wells than municipal surface water systems (odds ratio 1·4, 95% confidence interval 1·1–1·8). In rural settings, the odds of campylobacteriosis were higher in November (P = 0·014). The odds of campylobacteriosis were higher in individuals aged ⩾15 years, especially in those with higher SES. In this region of BC, campylobacteriosis risk, compared to other enteric diseases, seems to be mediated by vulnerable drinking water sources and rural factors. Consideration should be given to further support well-water users and to further study the microbiological impact of agriculture on water.
This study focuses on nanoindentation creep in polycarbonate (PC) and syndiotactic polystyrene (sPS) throughout the transient and steady-state regions. The viscoelastic Burgers model is used to explain transient creep data, while the power-law creep model is used to interpret steady-state creep data. The Newtonian shear viscosity of the Maxwell element and Young’s modulus of the Kelvin element are greater for the creep period than for the preload period, and an opposite trend is noted in the Newtonian shear viscosity of the Kelvin element and Young’s modulus of the Maxwell element. The fact that the Young’s moduli of Maxwell and Kelvin elements in the creep period are different from those in the preload period implies that a stress-induced mesomorphic structure forms or that crystallization occurs in nanoindentation creep. While the strain rate increases with decreasing preload period, the stress exponent factor is almost the same for all preload periods.
Background: The Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-NAB) offers information on the clinical diagnosis of Alzheimer's disease (AD) and gives a profile of cognitive functioning. This study explores the effects of age, education and gender on participants' performance on eight subtests in the Chinese-Cantonese version of the CERAD-NAB.
Methods: The original English version of the CERAD-NAB was translated and content-validated into a Chinese-Cantonese version to suit the Hong Kong Chinese population. The battery was administered to 187 healthy volunteers aged 60 to 94 years. Participants were excluded if they had neurological, medical or psychiatric disorders (including dementia). Stepwise multiple linear regression analyses were performed to assess the relative contribution of the demographic variables to the scores on each subtest.
Results: The Cantonese version of CERAD-NAB was shown to have good content validity and excellent inter-rater reliability. Stepwise multiple regression analyses revealed that performances on seven and four out of eight subtests in the CERAD-NAB were significantly influenced by education level and age, respectively. Age and education had significant effects on participants' performance on many tests. Gender also showed a significant effect on one subtest.
Conclusions: The preliminary data will serve as an initial phase for clinical interpretation of the CERAD-NAB for Cantonese-speaking Chinese elders.
Outlined here is a technique for sub-wavelength infrared surface imaging performed using a phase matched optical parametric oscillator laser and an atomic force microscope as the detection mechanism. The technique uses a novel surface excitation illumination approach to perform simultaneously chemical mapping and AFM topography imaging with an image resolution of 200 nm. This method was demonstrated by imaging polystyrene micro-structures.
To establish the Fe status of pregnant women and their neonates in the Republic of Seychelles.
Design
A prospective study.
Setting
Republic of Seychelles.
Subjects
Pregnant women were recruited and blood samples taken at enrolment and post-delivery along with cord blood samples. Ferritin and soluble transferrin receptor (sTfR) were measured in maternal (n 220) and cord blood (n 123) samples.
Results
Maternal Fe deficiency (ferritin < 15 ng/ml, sTfR > 28 nmol/l) was present in 6 % of subjects at enrolment and in 20 % at delivery. There was no significant decrease in maternal ferritin. A significant increase in sTfR was observed between enrolment and delivery (P < 0·001). Maternal BMI and use of Fe supplements at 28 weeks’ gestation were associated with improved maternal Fe status at delivery, whereas parity had a negative effect on sTfR and ferritin at delivery.
Conclusions
Fe status of pregnant Seychellois women was, on average, within normal ranges. The incidence of Fe deficiency throughout pregnancy in this population was similar to that in a Westernised population. Increased awareness of the importance of adequate Fe intake during pregnancy, particularly in multiparous women, is warranted.
This work studied the Rayleigh-Bénard convection under the first-order slip boundary conditions in both hydrodynamic and thermal fields. The variation principle was applied to find the critical Rayleigh number of instability. The exteneded relations of the critical Rayleigh number (Rc) and the wavenumber (ac) under partially slip boundary conditions were derived. The numerical results showed that both Rc and ac are decreasing with increasing the Knudsen number. The dependence of Rc on the Knudsen number (K) shows that when K≤10−3, the boundary can be considered as nonslip, while K≥10, it can be considered as free boundaries. The maximum change rate occurs when the Knudsen number is around 0.1, indicating that the system would be affected significantly in that range.
The coupling of hydromagnetic Alfvén waves is studied numerically in a dipolc-field model of the magnetosphere. The two coupled hydromagnetic equations derived by Radoski are solved as an implicit boundary-value problem, namely the boundary conditions at the magnetopause are determined self-consistently. Thus the calculated wave-field distribution inside the magnetosphere can match all known linear characteristic features of the stormtime Pc5 waves observed on 14/15 November 1979 from satellites. A set of proper boundary conditions is found, excellent agreement between the numerical results and observations is demonstrated. Based on the very limited spatial coverage (L ≈ 6·6 and within a latitudinal region ( −10°, 10°)), of the data provided by the satellites, the theoretical model can successfully reconstruct the global micropulsations in the magnetosphere and identify the source regions of hydromagnetic waves.
A purely growing instability characterized by a four-wave interaction has been analysed in a uniform, magnetized plasma. Up-shifted and down-shifted upper-hybrid waves and a non-oscillatory mode can be excited by a pump wave of ordinary rather than extraordinary polarization in the case of ionospheric heating. The differential Ohmic heating force dominates over the ponderomotive force as the wave–wave coupling mechanism. The beating current at zero frequency produces a significant stabilizing effect on the excitation of short-scale modes by counterbalancing the destabilizing effect of the differential Ohmic heating. The effect of ionospheric inhomogeneity is estimated, showing a tendency to raise the thresholds of the instability. When applied to ionospheric heating experiments, the present theory can explain the excitation of field-aligned plasma lines and ionospheric irregularities with a continuous spectrum ranging from metre-scale to hundreds of metre-scale. Further, the proposed mechanism may become a competitive process to the parametric decay instability and be responsible for the overshoot phenomena of the plasma line enhancement at Arecibo.