Attosecond electronic timing with rising edges of photocurrent pulses

For edge-sensitive timing applications, the edge jitter of electrical pulses is important. Here, the authors report on very low rising edge jitter extracted from an optical frequency comb and explore the best condition for low jitter by minimizing the amplitude-to-timing conversion in photodiodes

Impact of metformin on cardiovascular and kidney outcome based on kidney function status in type 2 diabetic patients: a multicentric, retrospective cohort study

Abstract Metformin is the primary treatment for type 2 diabetes mellitus (T2DM) due to its effectiveness in improving clinical outcomes in patients with preserved renal function, however, the evidence on the effectiveness of metformin in various renal functions is lacking. We performed a retrospective, multicenter, observational study used data of patients with T2DM obtained from three tertiary hospitals’ databases. Patients given metformin within run-in periods and with at least one additional prescription formed the metformin cohort. A control cohort comprised those prescribed oral hypoglycemic agents other than metformin and never subsequently received a metformin prescription within observation period. For patients without diabetic nephropathy (DN), the outcomes included events of DN, major adverse cardiovascular events (MACE), and major adverse kidney events (MAKE). After 1:1 propensity matching, 1994 individuals each were selected for the metformin and control cohorts among T2DM patients without baseline DN. The incidence rate ratios (IRR) for DN, MACEs, and MAKEs between cohorts were 1.06 (95% CI 0.96–1.17), 0.76 (0.64–0.92), and 0.45 (0.33–0.62), respectively. In cohorts with renal function of CKD 3A, 3B, and 4, summarized IRRs of MACEs and MAKEs were 0.70 (0.57–0.87) and 0.39 (0.35–0.43) in CKD 3A, 0.83 (0.74–0.93) and 0.44 (0.40–0.48) in CKD 3B, and 0.71 (0.60–0.85) and 0.45 (0.39–0.51) in CKD 4. Our research indicates that metformin use in T2DM patients across various renal functions consistently correlates with a decreased risk of overt DN, MACE, and MAKE

Midterm Blood Pressure Variability Is Associated with Poststroke Cognitive Impairment: A Prospective Cohort Study

ObjectiveThe aim of this study was to investigate the relationship between blood pressure variability (BPV) and poststroke cognitive impairment (PSCI).MethodsSeven-hundred ninety-six patients with acute ischemic stroke were included in this study. Midterm BPV was evaluated by calculating the SD and coefficient of variation (CV, 100 × SD/mean) of systolic blood pressure (SBP) and diastolic blood pressure during the 7 days after stroke onset. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) at admission and at all follow-up visits. Patients with MoCA scores <26 were considered to have PSCI.ResultsThe incidence of PSCI reached its peak (72%) 3 months after stroke onset and decreased to 30.3% at 12 months poststroke. After adjusting for covariables, the increase in the prevalence of PSCI at 3 months was independently associated with increases in the CV of blood pressure during the 7 days after stroke [odds ratios and 95% CI for patients in the second to fifth quintiles of SBP CV were 2.28 (1.18, 4.39), 2.33 (1.18, 4.62), 2.69 (1.31, 5.53), and 4.76 (1.95, 11.67), respectively]. Sub-analysis of the MoCA scores revealed that the patients had impairments in visuoperceptual abilities and executive functions, as well as in naming and delayed recall (p < 0.05).ConclusionMidterm BPV during the early phase of acute ischemic stroke is independently associated with PSCI, especially in the visuoperceptual, executive, and delayed recall domains.Clinical Trial Registrationhttp://www.chictr.org.cn, identifier ChiCTR-TRC-14004804

Metabolic resilience is encoded in genome plasticity

Metabolism plays a central role in evolution, as resource conservation is a selective pressure for fitness and survival.Resource-driven adaptations offer a good model to study evolutionary innovation more broadly. It remains unknown howresource-driven optimization of genome function integrates chromatin architecture with transcriptional phase transitions.Here we show that tuning of genome architecture and heterotypic transcriptional condensates mediate resilience tonutrient limitation. Network genomic integration of phenotypic, structural, and functional relationships reveals that fattissue promotes organismal adaptations through metabolic acceleration chromatin domains and heterotypic PGC1Acondensates. We find evolutionary adaptations in several dimensions; low conservation of amino acid residues withinprotein disorder regions, nonrandom chromatin location of metabolic acceleration domains, condensate-chromatin stabilitythrough cis-regulatory anchoring and encoding of genome plasticity in radial chromatin organization. We show thatenvironmental tuning of these adaptations leads to fasting endurance, through efficient nuclear compartmentalization oflipid metabolic regions, and, locally, human-specific burst kinetics of lipid cycling genes. This process reduces oxidativestress, and fatty-acid mediated cellular acidification, enabling endurance of condensate chromatin conformations.Comparative genomics of genetic and diet perturbations reveal mammalian convergence of phenotype and structuralrelationships, along with loss of transcriptional control by diet-induced obesity. Further, we find that radial transcriptionalorganization is encoded in functional divergence of metabolic disease variant-hubs, heterotypic condensate composition,and protein residues sensing metabolic variation. During fuel restriction, these features license the formation of largeheterotypic condensates that buffer proton excess, and shift viscoelasticity for condensate endurance. This mechanismmaintains physiological pH, reduces pH-resilient inflammatory gene programs, and enables genome plasticity throughtranscriptionally driven cell-specific chromatin contacts. In vivo manipulation of this circuit promotes fasting-likeadaptations with heterotypic nuclear compartments, metabolic and cell-specific homeostasis. In sum, we uncover here ageneral principle by which transcription uses environmental fluctuations for genome function, and demonstrate howresource conservation optimizes transcriptional self-organization through robust feedback integrators, highlighting obesityas an inhibitor of genome plasticity relevant for many diseases

The role of an active surveillance strategy of targeting household and neighborhood contacts related to leprosy cases released from treatment in a low-endemic area of China.

OBJECTIVE:Early diagnosis remains the primary goal for leprosy management programs. This study aims to determine whether active surveillance of patients with leprosy and their contact individuals increased identification of latent leprosy cases in the low-endemic areas. METHODS:This cross-sectional survey was carried out between October 2014 and August 2016 in 21 counties throughout Shandong Province. The survey was conducted among patients with leprosy released from treatment (RFT) and their contacts from both household and neighbors. RESULTS:A total of 2,210 RFT patients and 9,742 contacts comprising 7877 household contacts (HHCs), including 5,844 genetic related family members (GRFMs) and 2033 non-genetic related family members and 1,865 contacts living in neighboring houses (neighbor contacts, NCs), were recruited. Among identified individuals, one relapsed and 13 were newly diagnosed, giving a detection rate of 0.12%, corresponding to 120 times the passive case detection rate. Detection rates were similar for HHCs and NCs (0.114% vs. 0.214%, P = 0.287). Analysis of the family history of leprosy patients revealed clustering of newly diagnosed cases and association with residential coordinates of previously-diagnosed multibacillary leprosy cases. CONCLUSION:Active case-finding programs are feasible and contributes to early case detection by tracking HHCs and NCs in low-endemic areas