Heat Kernel Bounds on Metric Measure Spaces and Some Applications

Let $(X,d,\mu)$ be a $RCD^\ast(K, N)$ space with $K\in \mathbb{R}$ and $N\in [1,\infty]$. For $N\in [1,\infty)$, we derive the upper and lower bounds of the heat kernel on $(X,d,\mu)$ by applying the parabolic Harnack inequality and the comparison principle, and then sharp bounds for its gradient, which are also sharp in time. When $N=\infty$, we also establish a sharp upper bound of the heat kernel by using the dimension free Harnack inequality. For applications, we study the large time behavior of the heat kernel, the stability of solutions to the heat equation, and show the $L^p$ boundedness of (local) Riesz transforms.Comment: 27pp,Section 6 was removed, to appear in Potential Ana

The Interpretation of Problem Based Learning: A Case Study

 Currently, there are a large number of higher education institutions transforming their traditional educational approaches to PBL. In order to address the challenges for PBL implementation for a university, it is quite necessary to investigate how the managers and staff members interpret PBL in practice. Through the exploration of a university which is in the process of transforming its traditional educational paradigm to PBL, we note that there is a lack of unified understanding of what PBL is at the university. Several different PBL interpretations emerge and some of them are quite inconsistent with, or even contradictory to each other, which further pose significant challenges to the university when implementing PBL. It should be acknowledged that the diversification of PBL interpretation is unlikely to avoid at a university. The diversity of PBL interpretation would create large tensions at a university, but it also points out new possibilities for the university

The Interpretation of Problem Based Learning: A Case Study

 Currently, there are a large number of higher education institutions transforming their traditional educational approaches to PBL. In order to address the challenges for PBL implementation for a university, it is quite necessary to investigate how the managers and staff members interpret PBL in practice. Through the exploration of a university which is in the process of transforming its traditional educational paradigm to PBL, we note that there is a lack of unified understanding of what PBL is at the university. Several different PBL interpretations emerge and some of them are quite inconsistent with, or even contradictory to each other, which further pose significant challenges to the university when implementing PBL. It should be acknowledged that the diversification of PBL interpretation is unlikely to avoid at a university. The diversity of PBL interpretation would create large tensions at a university, but it also points out new possibilities for the university

Bilateral Habenula deep brain stimulation for treatment-resistant depression: clinical findings and electrophysiological features.

Deep brain stimulation (DBS) of structures in the brain's reward system is a promising therapeutic option for patients with treatment-resistant depression (TRD). Recently, DBS of the habenula (HB) in the brain's anti-reward system has also been reported to alleviate depressive symptoms in patients with TRD or bipolar disorder (BD). In this pilot open-label prospective study, we explored the safety and clinical effectiveness of HB-DBS treatment in seven patients with TRD or BD. Also, local field potentials (LFPs) were recorded from the patients' left and right HB to explore the power and asymmetry of oscillatory activities as putative biomarkers of the underlying disease state. At 1-month follow-up (FU), depression and anxiety symptoms were both reduced by 49% (n = 7) along with substantial improvements in patients' health status, functional impairment, and quality of life. Although the dropout rate was high and large variability in clinical response existed, clinical improvements were generally maintained throughout the study [56%, 46%, and 64% reduction for depression and 61%, 48%, and 70% reduction for anxiety at 3-month FU (n = 5), 6-month FU (n = 5), and 12-month FU (n = 3), respectively]. After HB-DBS surgery, sustained improvements in mania symptoms were found in two patients who presented with mild hypomania at baseline. Another patient, however, experienced an acute manic episode 2 months after surgery that required hospitalization. Additionally, weaker and more symmetrical HB LFP oscillatory activities were associated with more severe depression and anxiety symptoms at baseline, in keeping with the hypothesis that HB dysfunction contributes to MDD pathophysiology. These preliminary findings indicate that HB-DBS may offer a valuable treatment option for depressive symptoms in patients who suffer from TRD or BD. Larger and well-controlled studies are warranted to examine the safety and efficacy of HB-DBS for treatment-refractory mood disorders in a more rigorous fashion

Intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilisation (IVF) in couples with non-severe male infertility (NSMI-ICSI) : protocol for a multicentre randomised controlled trial

Funding This study was supported by National Key Research and Development Program of China (2016YFC1000201; 2018YFC1002104) and the National Science Foundation of China (81730038). The study funders had no rule in the study design, implementation, analysis, manuscript, preparation or decision to submit this article for publication.Peer reviewedPublisher PD

Association of Psychological Characteristics and Functional Dyspepsia Treatment Outcome: A Case-Control Study

This study was to investigate the association of psychological characteristics and functional dyspepsia treatment outcome. 109 patients who met the criteria for FD were enrolled. Eysenck Personality Questionnaire (EPQ), Symptom Checklist 90 (SCL90), and the Pittsburgh Sleep Quality Index (PSQI) were used to measure personality, psychological symptoms, and sleep quality in our patients. Leeds Dyspepsia Questionnaire (LDQ) was used to assess dyspeptic symptoms at baseline and after eight weeks of treatment. The LDQ scores change after therapy, and the degraded rate of LDQ was used to assess the prognosis of patients. Logistic regression model was used to assess the effect of the personality, psychological symptoms, and sleep quality on the prognosis of patients. Our result revealed that poor sleep quality (OR=7.68, 95% CI 1.83–32.25) and bad marriage status (OR=1.22, 95% CI 1.10–1.36) had the negative effect on the prognosis of FD, while extroversion in personality traits (OR=0.86, 95% CI 0.76–0.96) had positive effect on the prognosis of FD. We should pay attention to the sleep quality, the personality, and the marriage status of FD patients; psychological intervention may have benefit in refractory FD

Oral-Derived Bacterial Flora Defends Its Domain by Recognizing and Killing Intruders—A Molecular Analysis Using Escherichia coli as a Model Intestinal Bacterium

Within the same human gastrointestinal tract, substantial differences in the bacterial species that inhabit oral cavity and intestinal tract have been noted. Previous research primarily attributed the differences to the influences of host environments and nutritional availabilities (“host habitat” effect). Our recent study indicated that, other than the host habitat effect, an existing microbial community could impose a selective pressure on incoming foreign bacterial species independent of host-mediated selection (“community selection” effect). In this study, we employed in vitro microbial floras representing microorganisms that inhabit the oral cavities and intestinal tract of mice in combination with Escherichia coli as a model intestinal bacterium and demonstrated that E. coli displays a striking community preference. It thrived when introduced into the intestinal microbial community and survived poorly in the microbial flora of foreign origin (oral community). A more detailed examination of this phenomenon showed that the oral community produced oxygen-free radicals in the presence of wild-type E. coli while mutants deficient in lipopolysaccharides (LPS) did not trigger significant production of these cell-damaging agents. Furthermore, mutants of E. coli defective in the oxidative stress response experienced a more drastic reduction in viability when cocultivated with the oral flora, while the exogenous addition of the antioxidant vitamin C was able to rescue it. We concluded that the oral-derived microbial community senses the E. coli LPS and kills the bacterium with oxygen-free radicals. This study reveals a new mechanism of community invasion resistance employed by established microflora to defend their domains

Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke

Background and Objectives Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. Methods We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. Results We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008). Discussion The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.Peer reviewe

Whole-Genome Sequencing Uncovers Two Loci for Coronary Artery Calcification and Identifies Arse as a Regulator of Vascular Calcification

Coronary artery calcification (CAC) is a measure of atherosclerosis and a well-established predictor of coronary artery disease (CAD) events. Here we describe a genome-wide association study (GWAS) of CAC in 22,400 participants from multiple ancestral groups. We confirmed associations with four known loci and identified two additional loci associated with CAC (ARSE and MMP16), with evidence of significant associations in replication analyses for both novel loci. Functional assays of ARSE and MMP16 in human vascular smooth muscle cells (VSMCs) demonstrate that ARSE is a promoter of VSMC calcification and VSMC phenotype switching from a contractile to a calcifying or osteogenic phenotype. Furthermore, we show that the association of variants near ARSE with reduced CAC is likely explained by reduced ARSE expression with the G allele of enhancer variant rs5982944. Our study highlights ARSE as an important contributor to atherosclerotic vascular calcification, and a potential drug target for vascular calcific disease