Power of linkage analysis using traits generated from simulated longitudinal data of the Framingham Heart Study

The Framingham Heart Study is a very successful longitudinal research for cardiovascular diseases. The completion of a 10-cM genome scan in Framingham families provided an opportunity to evaluate linkage using longitudinal data. Several descriptive traits based on simulated longitudinal data from the Genetic Analysis Workshop 13 (GAW13) were generated, and linkage analyses were performed for these traits. We compared the power of detecting linkage for baseline and slope genes in the simulated data of GAW13 using these traits. We found that using longitudinal traits based on multiple follow-ups may not be more powerful than using cross-sectional traits for genetic linkage analysis

Genome-wide linkage analysis using cross-sectional and longitudinal traits for body mass index in a subsample of the Framingham Heart Study

To evaluate linkage evidence for body mass index (BMI) using both cross-sectional and longitudinal data, we performed genome-wide multipoint linkage analyses on subjects who had complete data at four selected time points (initial, 8(th), 12(th), and 16(th )year following the initial visit) from the Framingham Heart Study. The cross-sectional measures included BMI at each of the four selected time points and the longitudinal measure was the within-subject mean of BMI at the above four time points. Using the variance components method, we consistently observed the maximum LOD score out of the genome scan using BMI at each time point and the mean of BMI between 049xd2 and GATA71H05 on chromosome 16. The highest LOD score (3.0) was at time point 1, while the lowest (1.9) was at time point 4. We also observed other suggestive linkages on chromosome 6, 10, and 18 at time point 1 only. The longitudinal measure we studied (mean of BMI) did not provide greater power to identify a positive linkage than some of the cross-sectional measures (e.g., time point 1). The changing of linkage evidence over time provided some insights on the variation of genetic effect on BMI with aging. There may be a QTL on chromosome 16 that contributes to BMI and this locus, and maybe others, is more likely to affect BMI during early adulthood

Observation of Fungi, Bacteria, and Parasites in Clinical Skin Samples Using Scanning Electron Microscopy

This chapter highlights the description of the clinical manifestation and its pathogen and the host tissue damage observed under the Scanning Electron Microscope, which helps the clinician to understand the pathogen’s superstructure, the change of host subcell structure, and the laboratory workers to understand the clinical characteristics of pathogen-induced human skin lesions, to establish a two-way learning exchange database with vivid image

A Novel ESAT-6 Secretion System-Secreted Protein EsxX of Community-Associated Staphylococcus aureus Lineage ST398 Contributes to Immune Evasion and Virulence

The ESAT-6 secretion system (ESS) has been reported to contribute to the virulence and pathogenicity of several Staphylococcus aureus strains such as USA300 and Newman. However, the role of the ESS in community-associated S. aureus (CA-SA) lineage ST398 in China is not well understood. By comparing the ess locus of ST398 with the published S. aureus sequence in the NCBI database, we found one gene in the ess locus encoding a novel WXG superfamily protein that is highly conserved only in ST398. LC-MS/MS and Western blot analysis revealed that this protein is a novel secreted protein controlled by the ST398 ESS, and we named the protein EsxX. Although EsxX was not under the control of the accessory gene regulator like many other virulence factors and had no influence on several phenotypes of ST398, such as growth, hemolysis, and biofilm formation, it showed important impacts on immune evasion and virulence in ST398. An esxX deletion mutant led to significantly reduced resistance to neutrophil killing and decreased virulence in murine skin and blood infection models, indicating its essential contribution to the evasion of innate host defense and virulence to support the pathogenesis of ST398 infections. The function of this novel secreted protein EsxX might help us better understand the role of the ESS in the virulence and epidemic success of the CA-SA lineage ST398

Association between serum nickel and oral cancer incidence using propensity score matching and inverse probability of treatment weighting

BackgroundThe association between serum nickel (Ni) and oral cancer incidence is unclear and most of the previous studies were observational studies that did not control for confounding factors between groups.ObjectiveTo assess the correlation of serum Ni with oral cancer incidence based on propensity score matching (PSM) and inverse probability of treatment weighting (IPTW).MethodsA cohort of 456 newly diagnosed oral cancer patients was recruited from the First Hospital of Fujian Medical University during November 2011 to May 2019, and residents ordered their health check-up in hospitals or local community health centers over the same period were selected as a control group, which included a total of 1410 participants. Serum Ni was evaluated by inductively coupled plasma mass spectrometry. Case-control pairs were selected using a 1:1 PSM (caliper value of 0.02), and the study subjects in the case group and control group were weighted for subsequent analysis by IPTW. The general characteristics of the study subjects were tested for equilibrium before and after matching by chi-square test and standardized mean difference (SMD). This was followed by exploring the potential nonlinear dose-response relationship between serum Ni and oral cancer using restricted cubic splines as well as analyzing the association between serum Ni and oral cancer incidence by conditional logistic regression and weighted logistic regression.ResultsAfter controlling for between-group covariates by PSM and IPTW, the dose-response curves demonstrated that the risk of developing oral cancer tended to decline and then increase with the increasing serum Ni level. The outcome of the analysis using PSM demonstrated that as compared to the control group, the risk of developing oral cancer in the 0.09-16.80 μg·L−1 serum Ni group was negatively correlated with serum Ni level (OR=0.36, 95%CI: 0.24-0.54), whereas the risk of developing oral cancer in the >16.80 μg·L−1 serum Ni group was positively correlated with serum Ni level (OR=5.43, 95%CI: 2.76-10.68). After applying IPTW, a negative association was found between the risk of oral cancer and serum Ni concentration within a serum Ni window ranging from 0.09 to 20.55 μg·L−1 (OR=0.39, 95%CI: 0.29-0.52), while a positive association with an OR and 95%CI of 5.54 (3.62-8.49) for the Ni concentration > 20.55 μg·L−1.ConclusionIn this study, a J-shaped relationship between serum Ni concentration and the risk of developing oral cancer is found, which shows that high serum Ni concentration (>20.55 μg·L−1) may be a risk factor for oral cancer

Application of nanopore adaptive sequencing in pathogen detection of a patient with Chlamydia psittaci infection

IntroductionNanopore sequencing has been widely used in clinical metagenomic sequencing for pathogen detection with high portability and real-time sequencing. Oxford Nanopore Technologies has recently launched an adaptive sequencing function, which can enrich on-target reads through real-time alignment and eject uninteresting reads by reversing the voltage across the nanopore. Here we evaluated the utility of adaptive sequencing in clinical pathogen detection.MethodsNanopore adaptive sequencing and standard sequencing was performed on a same flow cell with a bronchoalveolar lavage fluid sample from a patient with Chlamydia psittacosis infection, and was compared with the previous mNGS results.ResultsNanopore adaptive sequencing identified 648 on-target stop receiving reads with the longest median read length(688bp), which account for 72.4% of all Chlamydia psittaci reads and 0.03% of total reads in enriched group. The read proportion matched to C. psittaci in the stop receiving group was 99.85%, which was much higher than that of the unblock (<0.01%) and fail to adapt (0.02%) groups. Nanopore adaptive sequencing generated similar data yield of C. psittaci compared with standard nanopore sequencing. The proportion of C. psittaci reads in adaptive sequencing is close to that of standard nanopore sequencing and mNGS, but generated lower genome coverage than mNGS.DiscussionNanopore adaptive sequencing can effectively identify target C. psittaci reads in real-time, but how to increase the targeted data of pathogens still needs to be further evaluated

Strain-activated light-induced halide segregation in mixed-halide perovskite solids

Abstract Light-induced halide segregation limits the bandgap tunability of mixed-halide perovskites for tandem photovoltaics. Here we report that light-induced halide segregation is strain-activated in MAPb(I1−xBrx)3 with Br concentration below approximately 50%, while it is intrinsic for Br concentration over approximately 50%. Free-standing single crystals of CH3NH3Pb(I0.65Br0.35)3 (35%Br) do not show halide segregation until uniaxial pressure is applied. Besides, 35%Br single crystals grown on lattice-mismatched substrates (e.g. single-crystal CaF2) show inhomogeneous segregation due to heterogenous strain distribution. Through scanning probe microscopy, the above findings are successfully translated to polycrystalline thin films. For 35%Br thin films, halide segregation selectively occurs at grain boundaries due to localized strain at the boundaries; yet for 65%Br films, halide segregation occurs in the whole layer. We close by demonstrating that only the strain-activated halide segregation (35%Br/45%Br thin films) could be suppressed if the strain is properly released via additives (e.g. KI) or ideal substrates (e.g. SiO2)

Multi-Layer Kernel Machines: Fast and Optimal Nonparametric Regression with Uncertainty Quantification

Kernel ridge regression (KRR) is widely used for nonparametric regression over reproducing kernel Hilbert spaces. It offers powerful modeling capabilities at the cost of significant computational costs, which typically require $O(n^3)$ computational time and $O(n^2)$ storage space, with the sample size n. We introduce a novel framework of multi-layer kernel machines that approximate KRR by employing a multi-layer structure and random features, and study how the optimal number of random features and layer sizes can be chosen while still preserving the minimax optimality of the approximate KRR estimate. For various classes of random features, including those corresponding to Gaussian and Matern kernels, we prove that multi-layer kernel machines can achieve $O(n^2\log^2n)$ computational time and $O(n\log^2n)$ storage space, and yield fast and minimax optimal approximations to the KRR estimate for nonparametric regression. Moreover, we construct uncertainty quantification for multi-layer kernel machines by using conformal prediction techniques with robust coverage properties. The analysis and theoretical predictions are supported by simulations and real data examples

Effect of Compactness of Urban Growth on Regional Landscape Ecological Security

With rapid urbanization destroying the ecological environment, scholars have focused on ways to coordinate harmonious development using urban spatial layouts and landscape ecological security. To explore landscape ecological security (the landscape elements, spatial positions and connections that are of key significance to the health and safety of ecological processes) from the perspective of urban form evolution pattern will help to open a new perspective of urban management research, and become the basic work of urban space policy and the implementation of the beautiful China strategy. Based on urban growth and land use data from 356 cities in China, this study applied a geographically weighted regression (GWR) model to quantify the impact of China’s urban growth pattern on landscape ecological security at the spatial level. The research results show that: (1) To some extent, the infilling growth pattern has a certain effect on the enhancement of regional landscape ecological security; (2) In the three control variables (DEM, Population density and GDP), the following conclusions are drawn: regional landscape planning should reasonably allocate landscape resources according to the local topographic features to obtain a higher landscape ecological security; The increase of population density leads to the fragmentation and diversity of the landscape in some regions, which makes the landscape ecological security weak; more economically developed areas have stronger landscape ecological security. This paper highlights the importance of urban growth patterns to landscape ecological security. In addition, considering the different urban evolution trajectories in developed and developing countries, this study proposes targeted development recommendations, providing a reference for urban managers to formulate reasonable development policies and to realize sustainable development with the goal of landscape safety management and control