Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.

Conversions between metabolically unhealthy and healthy obesity from midlife to late-life.

INTRODUCTION: Metabolically healthy obesity may be a transient phenotype, but studies with long follow-up, especially covering late-life, are lacking. We describe conversions between cross-categories of body mass index (BMI) and metabolic health in 786 Swedish twins with up to 27 years of follow-up, from midlife to late-life. METHODS: Metabolic health was defined as the absence of metabolic syndrome (MetS). We first visualized conversions between BMI-metabolic health phenotypes in 100 individuals with measurements available at ages 50-64, 65-79, and ≥80. Next, we modeled conversion in metabolic health status by BMI category in the full sample using Cox proportional hazards regression. RESULTS: The proportion of individuals with MetS and with overweight or obesity increased with age. However, one-fifth maintained a metabolically healthy overweight or obesity across all three age categories. Among those metabolically healthy at baseline, 59% converted to MetS during follow-up. Conversions occurred 56% more often among individuals with metabolically healthy obesity, but not overweight, compared to normal weight. Among those with MetS at baseline, 60% regained metabolic health during follow-up, with no difference between BMI categories. CONCLUSIONS: Conversions between metabolically healthy and unhealthy status occurred in both directions in all BMI categories. While conversions to MetS were more common among individuals with obesity, many individuals maintained or regained metabolic health during follow-up.

Association between cytomegalovirus seropositivity and all-cause mortality: An original cohort study.

To examine the association between cytomegalovirus (CMV) seropositivity and all-cause mortality in a nationwide cohort of US adults. We obtained data from the National Health and Nutrition Examination Survey III (1988-1994), including 16,547 participants aged 18-90 years old with CMV serology assessments. Mortality status was ascertained until December 2019 using the National Death Index linkage data. The Cox proportional hazard model was applied to estimate the association between CMV seropositivity and mortality. During a median follow-up of 26.3 years, 6,930 deaths were recorded. CMV seropositivity was associated with a higher hazard of all-cause mortality after adjusting for attained age, sex, and ethnicity (HR: 1.22, 95% CI: 1.10, 1.36, p < 0.001). The magnitude of the association attenuated slightly after adjusting further for body mass index, family income, smoking status, diabetes, and self-reported cancer history (HR = 1.11, 95% CI: 1.00, 1.23, p = 0.04). While the association was observed for both men and women, it was only statistically significant among non-Hispanic white people (HR: 1.16, 95% CI: 1.06, 1.26, p = 0.001) but not among other ethnic populations. CMV seropositivity might be an independent risk factor for all-cause mortality among US adults. If the findings are validated in an independent population, further research is needed to unveil the biological mechanisms driving the increased mortality with CMV seropositivity.

Olfactory Dysfunction and Long-Term Trajectories of Sleep Disorders among early Parkinson's Disease: Findings from a Longitudinal Cohort.

BACKGROUND: Previous studies have suggested a connection between impaired olfactory function and an increased risk of rapid eye movement sleep behavior disorder (RBD) in individuals diagnosed with Parkinson's disease (PD). However, there is a gap in knowledge regarding the potential impact of olfactory dysfunction on the long-term patterns of sleep disorders among early PD patients. METHODS: Data from the Parkinson's Progression Markers Initiative program included 589 participants with assessments of sleep disorders using the Epworth Sleepiness Scale (ESS) and RBD Screening Questionnaire (RBDSQ). Olfactory dysfunction at baseline was measured using the University of Pennsylvania Smell Identification Test. Trajectories of sleep disorders over a 5-year follow-up were identified using group-based trajectory modeling, and the relationship between olfactory dysfunction and sleep disorder trajectories was examined through binomial logistic regression. RESULTS: Two distinct trajectories of sleep disorders over the 5-year follow-up period were identified, characterized by maintaining a low or high ESS score and a low or high RBDSQ score. An inversion association was observed between olfactory function measures and trajectories of excessive daytime sleepiness (odds ratio [OR] = 0.97, 95% confidence interval [CI] 0.95, 1.00, p = 0.038), after controlling for potential covariates. Similarly, olfactory function showed a significant association with lower trajectories of probable RBD (OR = 0.96, 95% CI 0.94, 0.98, p = 0.001) among early PD individuals. Consistent findings were replicated across alternative analytical models. CONCLUSIONS: Our findings indicated that olfactory dysfunction was associated with unfavorable long-term trajectories of sleep disorders among early PD.

Associations between Sleep Disorders and Impulsive-Compulsive Behaviors in Parkinson's Disease: A Prospective Cohort Study.

OBJECTIVE: To examine the associations of excessive daytime sleepiness (EDS) and probable rapid eye movement sleep behavior disorder (pRBD), respectively, with impulsive-compulsive behaviors (ICB) over a 5-year follow-up in patients with early Parkinson's disease (PD). METHODS: The Parkinson's Progression Markers Initiative is a multicenter cohort study based on an ongoing and open-ended registry. Longitudinal associations of sleep disorders with ICB over 5-year follow-up visits were estimated using generalized linear mixed-effects models among PD participants. RESULTS: A total of 825 PD participants were enrolled at baseline. The study sample had a median baseline age of 63.1 (interquartile range [IQR]: 55.6-69.3) years and comprised 496 (61.5%) men. Among them, 201 (24.9%) had ICB at baseline. In the generalized mixed-effects models, EDS (odds ratio [OR] =1.09, 95% confidence interval [CI] 1.05, 1.12) and RBD (OR=1.07, 95% CI 1.03, 1.12) were substantially associated with higher odds of developing ICB over time in PD patients, after multivariate adjustment including age, gender, family history, GDS score, STAI-Y score, MDS-UPDRS part III score, LEDD, and disease duration. Consistent results were observed when stratifying by age at baseline, gender, and PD family history. CONCLUSIONS: The study findings suggest a longitudinal association between EDS and pRBD with an increased risk of developing ICB in patients with Parkinson's disease. The findings emphasize the significance of evaluating and addressing sleep disorders in PD patients as a potential approach to managing ICB.

Metabolic profiling of smoking, associations with type 2 diabetes and interaction with genetic susceptibility.

BACKGROUND: Smokers are at increased risk of type 2 diabetes (T2D), but the underlying mechanisms are unclear. We investigated if the smoking-T2D association is mediated by alterations in the metabolome and assessed potential interaction with genetic susceptibility to diabetes or insulin resistance. METHODS: In UK Biobank (n = 93,722), cross-sectional analyses identified 208 metabolites associated with smoking, of which 131 were confirmed in Mendelian Randomization analyses, including glycoprotein acetyls, fatty acids, and lipids. Elastic net regression was applied to create a smoking-related metabolic signature. We estimated hazard ratios (HR) of incident T2D in relation to baseline smoking/metabolic signature and calculated the proportion of the smoking-T2D association mediated by the signature. Additive interaction between the signature and genetic risk scores for T2D (GRS-T2D) and insulin resistance (GRS-IR) on incidence of T2D was assessed as relative excess risk due to interaction (RERI). FINDINGS: The HR of T2D was 1·73 (95% confidence interval (CI) 1·54 - 1·94) for current versus never smoking, and 38·3% of the excess risk was mediated by the metabolic signature. The metabolic signature and its mediation role were replicated in TwinGene. The metabolic signature was associated with T2D (HR: 1·61, CI 1·46 - 1·77 for values above vs. below median), with evidence of interaction with GRS-T2D (RERI: 0·81, CI: 0·23 - 1·38) and GRS-IR (RERI 0·47, CI: 0·02 - 0·92). INTERPRETATION: The increased risk of T2D in smokers may be mediated through effects on the metabolome, and the influence of such metabolic alterations on diabetes risk may be amplified in individuals with genetic susceptibility to T2D or insulin resistance.

Association between physical activity and psychosocial status in adults with epilepsy: Results from the 2022 National health Interview survey.

OBJECTIVE: The study aimed to investigate the association between physical activity and the four dimensions of psychosocial status in adults with epilepsy. METHODS: The data of individuals with epilepsy utilized in this cross-sectional study were derived from the 2022 National Health Interview Survey(NHIS). Physical activity was analyzed based on walking, moderate or vigorous intensity physical activity and the 2018 Physical Activity Guidelines (PAG) for Americans. The psychosocial status of the participants was assessed using self-report questionnaires that evaluated life satisfaction, symptoms of depression and anxiety, and social functioning. A multivariate ordinal regression model was employed to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) following adjustment for potential confounding factors. RESULTS: In total of 424 individuals with epilepsy(mean age:48.0 years; male: 40.6 %) were included in this study. About 39.9 % of the participants met the 2018 PAG for aerobic activity. After controlling for potential confounding factors, individuals who adhered to the 2018 PAG for aerobic activity were found to have a higher likelihood of reporting increased life satisfaction (OR, 0.39; 95 % CI: 0.21, 0.71), decreased symptoms of depression (OR, 0.53; 95 % CI: 0.30, 0.94), and improved social functioning (OR, 0.42; 95 % CI: 0.24, 0.74). However, no significant association was observed between physical activity and anxiety symptoms among individuals with epilepsy. CONCLUSIONS: This study emphasizes that moderate to vigorous physical activity enhances psychosocial health in individuals with epilepsy. Nevertheless, it is important to note that a causal relationship cannot be inferred from these findings, and further verification through randomized controlled trials is necessary.

Cognition as mediator of pulmonary function and risk of sarcopenia among older adults.

BACKGROUND: The relationship between lung function and sarcopenia remains ambiguous. The primary aim of this study was to investigate the potential association between lung function and sarcopenia in the older adults, as well as to examine the mediating role of cognitive function in this relationship. METHODS: The participants were selected from a nationally representative population-based cohort in China. The peak expiratory flow (PEF) measurement was used to evaluate the lung function in older persons. The sarcopenia was diagnosed using the guidelines of the Asian Working Group for Sarcopenia (AWGS) in 2019. The Cox proportional hazard model was utilized to perform primary analyses of the relationship between PEF and sarcopenia. The mediating effect of cognitive function was evaluated using the counterfactual mediation method. RESULTS: This cohort study included 4,011 older adults (average age, 66.6 years; 53.3% males). During a follow-up period of 3.86 years, 349 individuals were diagnosed with sarcopenia. After adjusting for potential confounders, each one-standard-deviation increase in PEF was associated with a 28% reduction in the risk of sarcopenia (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.63, 0.80). There was a significant mediation of cognition for the association between PEF and incident sarcopenia, and the proportion mediated was 12.2% (95% CI: 4.5%, 23.1%). CONCLUSIONS: Older adults with impaired lung function are more likely to develop sarcopenia. Nevertheless, cognition can explain only a small portion of this association. Thus, other potential pathways between lung function and sarcopenia must be elucidated.

Childhood adiposity and novel subtypes of adult-onset diabetes: a Mendelian randomisation and genome-wide genetic correlation study.

AIMS/HYPOTHESIS: We investigated whether the impacts of childhood adiposity on adult-onset diabetes differ across proposed diabetes subtypes using a Mendelian randomisation (MR) design. METHODS: We performed MR analysis using data from European genome-wide association studies of childhood adiposity, latent autoimmune diabetes in adults (LADA, proxy for severe autoimmune diabetes), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD). RESULTS: Higher levels of childhood adiposity had positive genetically predicted effects on LADA (OR 1.62, 95% CI 1.05, 2.52), SIDD (OR 2.11, 95% CI 1.18, 3.80), SIRD (OR 2.76, 95% CI 1.60, 4.75) and MOD (OR 7.30, 95% CI 4.17, 12.78), but not MARD (OR 1.06, 95% CI 0.70, 1.60). CONCLUSIONS/INTERPRETATION: Childhood adiposity is a risk factor not only for adult-onset diabetes primarily characterised by obesity or insulin resistance, but also for subtypes primarily characterised by insulin deficiency or autoimmunity. These findings emphasise the importance of preventing childhood obesity.

In Situ Cross-Linking Strategy to Enable Highly Stable Perovskite Solar Cells.

The perovskite solar cells (PSCs) have achieved great success in power conversion efficiency due to their excellent optoelectrical properties of perovskite. However, the instability of PSCs severely impedes their commercialization. Recently, in situ cross-linking strategy has been proposed to mitigate stability issues of PSCs, enabling highly efficient and stable PSCs. Here, the critical factors that lead to the degradation of PSCs are first outlined. Then, a comprehensive review of in situ cross-linking strategy in perovskite to enhance the moisture, thermal, illumination, and bending stress resistance properties of PSCs is presented. Furthermore, the detailed mechanism underlying these advantageous effects is discussed pertaining to crystallization regulation, immobilization of ions, water resistance, and release of unfavorable stress. Finally, the current challenges and further development trends of in situ cross-linking strategy in PSCs and extension to other optoelectronic devices are prospected.

Telomere length and its association with systemic lupus erythematosus in an Asian population: A Mendelian randomization study.

OBJECTIVES: To investigate whether shorter telomere length is a causal risk factor for systemic lupus erythematosus (SLE) in the Asian population. METHODS: We applied the two-sample Mendelian randomization (MR) method to the pooled statistics from a genome-wide association study (GWAS) of 6,707 SLE cases and 16,047 controls. We selected nine single-nucleotide polymorphisms (SNPs) with genome-wide significance as instrumental variables for telomere length. The main analysis was carried out by the random-effects inverse-variance weighted (IVW) method. Horizontal pleiotropy was evaluated by the intercept of MR-Egger regression. RESULTS: A potentially causal relationship between longer genetically predicted telomere length and increased risk of systemic lupus erythematosus (OR = 1.72, 95%CI: 1.21, 2.46, p = 0.01) was observed. The MR-Egger regression demonstrated an intercept proximal to zero (intercept = 0.017, p = 0.69), which does not provide evidence of the presence of horizontal pleiotropy. CONCLUSIONS: Our findings provided evidence supporting a potential causal relationship between longer telomere length and increased risk of systemic lupus erythematosus.

Assessment of automatic rib fracture detection on chest CT using a deep learning algorithm.

OBJECTIVES: To evaluate deep neural networks for automatic rib fracture detection on thoracic CT scans and to compare its performance with that of attending-level radiologists using a large amount of datasets from multiple medical institutions. METHODS: In this retrospective study, an internal dataset of 12,208 emergency room (ER) trauma patients and an external dataset of 1613 ER trauma patients taking chest CT scans were recruited. Two cascaded deep neural networks based on an extended U-Net architecture were developed to segment ribs and detect rib fractures respectively. Model performance was evaluated with a 95% confidence interval (CI) on both the internal and external dataset, and compared with attending-level radiologist readings using t test. RESULTS: On the internal dataset, the AUC of the model for detecting fractures at per-rib level was 0.970 (95% CI: 0.968, 0.972) with sensitivity of 93.3% (95% CI: 92.0%, 94.4%) at a specificity of 98.4% (95% CI: 98.3%, 98.5%). On the external dataset, the model obtained an AUC of 0.943 (95% CI: 0.941, 0.945) with sensitivity of 86.2% (95% CI: 85.0%, 87.3%) at a specificity of 98.8% (95% CI: 98.7%, 98.9%), compared to the sensitivity of 70.5% (95% CI: 69.3%, 71.8%) (p < .0001) and specificity of 98.8% (95% CI: 98.7%, 98.9%) (p = 0.175) by attending radiologists. CONCLUSIONS: The proposed DL model is a feasible approach to identify rib fractures on chest CT scans, at the very least, reaching a level on par with attending-level radiologists. KEY POINTS: • Deep learning-based algorithms automatically detected rib fractures with high sensitivity and reasonable specificity on chest CT scans. • The performance of deep learning-based algorithms reached comparable diagnostic measures with attending level radiologists for rib fracture detection on chest CT scans. • The deep learning models, similar to human readers, were susceptible to the inconspicuity and ambiguity of target lesions. More training data was required for subtle lesions to achieve comparable detection performance.

Causal inference and observational data.

Observational studies using causal inference frameworks can provide a feasible alternative to randomized controlled trials. Advances in statistics, machine learning, and access to big data facilitate unraveling complex causal relationships from observational data across healthcare, social sciences, and other fields. However, challenges like evaluating models and bias amplification remain.

An Energy-Efficient Flexible Multi-Modal Wireless Sweat Sensing System Based on Laser Induced Graphene.

Real-time sweat monitoring is vital for athletes in order to reflect their physical conditions, quantify their exercise loads, and evaluate their training results. Therefore, a multi-modal sweat sensing system with a patch-relay-host topology was developed, which consisted of a wireless sensor patch, a wireless data relay, and a host controller. The wireless sensor patch can monitor the lactate, glucose, K+, and Na+ concentrations in real-time. The data is forwarded via a wireless data relay through Near Field Communication (NFC) and Bluetooth Low Energy (BLE) technology and it is finally available on the host controller. Meanwhile, existing enzyme sensors in sweat-based wearable sports monitoring systems have limited sensitivities. To improve their sensitivities, this paper proposes a dual enzyme sensing optimization strategy and demonstrates Laser-Induced Graphene (LIG)-based sweat sensors decorated with Single-Walled Carbon Nanotubes (SWCNT). Manufacturing an entire LIG array takes less than one minute and costs about 0.11 yuan in materials, making it suitable for mass production. The in vitro test result showed sensitivities of 0.53 µA/mM and 3.9 µA/mM for lactate and glucose sensing, and 32.5 mV/decade and 33.2 mV/decade for K+ and Na+ sensing, respectively. To demonstrate the ability to characterize personal physical fitness, an ex vivo sweat analysis test was also performed. Overall, the high-sensitivity lactate enzyme sensor based on SWCNT/LIG can meet the requirements of sweat-based wearable sports monitoring systems.

Birthweight, BMI in adulthood and latent autoimmune diabetes in adults: a Mendelian randomisation study.

AIMS/HYPOTHESIS: Observational studies have found an increased risk of latent autoimmune diabetes in adults (LADA) associated with low birthweight and adult overweight/obese status. We aimed to investigate whether these associations are causal, using a two-sample Mendelian randomisation (MR) design. In addition, we compared results for LADA and type 2 diabetes. METHODS: We identified 43 SNPs acting through the fetal genome as instrumental variables (IVs) for own birthweight from a genome-wide association study (GWAS) of the Early Growth Genetics Consortium (EGG) and the UK Biobank. We identified 820 SNPs as IVs for adult BMI from a GWAS of the UK Biobank and the Genetic Investigation of ANthropometric Traits consortium (GIANT). Summary statistics for the associations between IVs and LADA were extracted from the only GWAS involving 2634 cases and 5947 population controls. We used the inverse-variance weighted (IVW) estimator as our primary analysis, supplemented by a series of sensitivity analyses. RESULTS: Genetically determined own birthweight was inversely associated with LADA (OR per SD [~500 g] decrease in birthweight 1.68 [95% CI 1.01, 2.82]). In contrast, genetically predicted BMI in adulthood was positively associated with LADA (OR per SD [~4.8 kg/m2] increase in BMI 1.40 [95% CI 1.14, 1.71]). Robust results were obtained in a range of sensitivity analyses using other MR estimators or excluding some IVs. With respect to type 2 diabetes, the association with birthweight was not stronger than in LADA while the association with adult BMI was stronger than in LADA. CONCLUSIONS/ INTERPRETATION: This study provides genetic support for a causal link between low birthweight, adult overweight/obese status and LADA.

Association between COVID-19 and telomere length: A bidirectional Mendelian randomization study.

Several traditional observational studies suggested an association between COVID-19 and leukocyte telomere length (LTL), a biomarker for biological age. However, whether there was a causal association between them remained unclear. We aimed to investigate whether genetically predicted COVID-19 is related to the risk of LTL, and vice versa. We performed bidirectional Mendelian randomization (MR) study using summary statistics from the genome-wide association studies of critically ill COVID-19 (n = 1 388 342) and LTL (n = 472 174) of European ancestry. The random-effects inverse-variance weighted estimation method was applied as the primary method with several other estimators as complementary methods. Using six single-nucleotide polymorphisms (SNPs) of genome-wide significance as instrumental variables for critically ill COVID-19, we did not find a significant association of COVID-19 on LTL (ß = 0.0075, 95% confidence interval [CI]: -0.018 to 0.021, p = 0.733). Likewise, using 97 SNPs of genome-wide significance as instrumental variables for LTL, we did not find a significant association of LTL on COVID-19 (odds ratio = 1.00, 95% CI: 0.79-1.28, p = 0.973). Comparable results were obtained using MR-Egger regression, weighted median, and weighted mode approaches. We did not find evidence to support a causal association between COVID-19 and LTL in either direction.

Adiposity and the risk of dementia: mediating effects from inflammation and lipid levels.

While midlife adiposity is a risk factor for dementia, adiposity in late-life appears to be associated with lower risk. What drives the associations is poorly understood, especially the inverse association in late-life. Using results from genome-wide association studies, we identified inflammation and lipid metabolism as biological pathways involved in both adiposity and dementia. To test if these factors mediate the effect of midlife and/or late-life adiposity on dementia, we then used cohort data from the Swedish Twin Registry, with measures of adiposity and potential mediators taken in midlife (age 40-64, n = 5999) or late-life (age 65-90, n = 7257). Associations between body-mass index (BMI), waist-hip ratio (WHR), C-reactive protein (CRP), lipid levels, and dementia were tested in survival and mediation analyses. Age was used as the underlying time scale, and sex and education included as covariates in all models. Fasting status was included as a covariate in models of lipids. One standard deviation (SD) higher WHR in midlife was associated with 25% (95% CI 2-52%) higher dementia risk, with slight attenuation when adjusting for BMI. No evidence of mediation through CRP or lipid levels was present. After age 65, one SD higher BMI, but not WHR, was associated with 8% (95% CI 1-14%) lower dementia risk. The association was partly mediated by higher CRP, and suppressed when high-density lipoprotein levels were low. In conclusion, the negative effects of midlife adiposity on dementia risk were driven directly by factors associated with body fat distribution, with no evidence of mediation through inflammation or lipid levels. There was an inverse association between late-life adiposity and dementia risk, especially where the body's inflammatory response and lipid homeostasis is intact.

Basal metabolic rate and risk of multiple sclerosis: a Mendelian randomization study.

To determine the relationship between basal metabolic rate (BMR) and multiple sclerosis (MS) susceptibility, we analyzed genome-wide association study (GWAS) summary statistics data from the International Multiple Sclerosis Genetics Consortium on a total of 115,803 participants of European descent, including 47,429 patients with MS and 68,374 controls. We selected 378 independent genetic variants strongly associated with BMR in a GWAS involving 454,874 participants as instrumental variables to examine a potential causal relationship between BMR and MS. A genetically predicted higher BMR was associated with a greater risk of MS (odds ratio [OR]: 1.283 per one standard deviation increase in BMR, 95% confidence interval [CI]: 1.108-1.486, P = 0.001). Moreover, we used the lasso method to eliminate heterogeneity (Q statistic = 384.58, P = 0.370). There was no pleiotropy in our study and no bias was found in the sensitivity analysis using the leave-one-out test. We provide novel evidence that a higher BMR is an independent causal risk factor in the development of MS. Further work is warranted to elucidate the potential mechanisms.

The Spectrum-Beamformer for Conventional B-Mode Ultrasound Imaging System: Principle, Validation, and Robustness.

Fast and efficient imaging techniques are important for real-time ultrasound imaging. The delay and sum (DAS) beamformer is the most widely-used strategy in focused ultrasound imaging (FUI) modality. However, calculating the time delays and coherently summing the amplitude response in DAS is computationally expensive and generally require a high-performance processor to realize real-time processing. In this study, an efficient spectrum beamformer, namely full-matrix capture (FMC)-stolt, is proposed in FUI system with a linear phased array. The imaging performance of FMC-stolt was validated with the point-scatter simulation and in vitro point and cyst phantoms, and then compared with that of five beamformers, that is, Multiline acquisition (MLA), retrospective transmit beamforming (RTB) in the FUI modality, as well as DAS, Garcia's frequency-wavenumber (f-k), Lu's f-k in the coherent plane wave compounding imaging (CPWCI) modality, under specific conditions. We show that the imaging performance of FMC-stolt is better than MLA-DAS in non-transmit-focal regions, and comparable with RTB-DAS at all imaging depths. FMC-stolt also shows better discontinuity alleviation than MLA and RTB. In addition, FMC-stolt has similar imaging characteristics (e.g., off-axis resolution, computational cost) as the f-k beamformers. The computational complexity and actual computational time indicate that FMC-stolt is comparable to Garcia's f-k, Lu's f-k, and faster than RTB and CPWCI-DAS if the transmitting numbers are close for FUI and CPWCI. The study demonstrates that the proposed FMC-stolt could achieve good reconstruction speed while preserving high-quality images and thus provide a choice for software beamforming for conventional B-mode ultrasound imaging, especially for hand-held devices with limited performance processors.

Lipids, Apolipoproteins, and the Risk of Parkinson Disease.

RATIONALE: A complete picture of the associations of the most common lipid fractions, including total cholesterol (TC), LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), triglycerides, and apolipoproteins, with the risk of Parkinson disease (PD), is lacking. OBJECTIVE: To assess the associations of lipids and apolipoproteins with the future risk of PD. METHODS AND RESULTS: In the AMORIS (Apolipoprotein-Related Mortality Risk) Study, we enrolled ≈600 000 participants during 1985 to 1996 in Stockholm, Sweden, with repeated measurements of TC, LDL-C, HDL-C, triglycerides, ApoB (apolipoprotein B), and ApoA-I (apolipoprotein A-I). The cohort was followed until the end of 2011, and incident cases of PD were identified through the Swedish Patient Register. We first used Cox models to estimate the associations of these biomarkers with later risk of PD. We further applied a Mendelian randomization analysis for TC, LDL-C, and triglycerides using the GWAS (Genome-wide association study) summary statistics from the public PD GWAS data and 23andMe PD cohorts with >800 000 individuals. One SD increase of TC was associated with a lower hazard of PD (hazard ratio, 0.90; 95% CI, 0.87-0.94). Similar associations were observed for LDL-C (hazard ratio, 0.93; 95% CI, 0.88-0.98), triglycerides (hazard ratio, 0.94; 95% CI, 0.90-0.97), and ApoB (hazard ratio, 0.91; 95% CI, 0.85-0.97). A clear dose-response relation was also noted when using these biomarkers as categorical variables. A causal inverse association of TC, LDL-C, and triglycerides with PD risk was further suggested by the Mendelian randomization analysis. CONCLUSIONS: Our findings reinforce that higher levels of TC, LDL-C, and triglycerides are associated with a lower future risk of PD and further suggest that these associations may be causal. The findings for ApoB in relation to PD risk are novel, and whether such association is causal needs to be examined.