Latent variables and route choice behavior

In the last decade, a broad array of disciplines has shown a general interest in enhancing discrete choice models by considering the incorporation of psychological factors affecting decision making. This paper provides insight into the comprehension of the determinants of route choice behavior by proposing and estimating a hybrid model that integrates latent variable and route choice models. Data contain information about latent variable indicators and chosen routes of travelers driving regularly from home to work in an urban network. Choice sets include alternative routes generated with a branch and bound algorithm. A hybrid model consists of measurement equations, which relate latent variables to measurement indicators and utilities to choice indicators, and structural equations, which link travelers' observable characteristics to latent variables and explanatory variables to utilities. Estimation results illustrate that considering latent variables (i.e., memory, habit, familiarity, spatial ability, time saving skills) alongside traditional variables (e.g., travel time, distance, congestion level) enriches the comprehension of route choice behavior

Amplified B Lymphocyte CD40 Signaling Drives Regulatory B10 Cell Expansion in Mice

Aberrant CD40 ligand (CD154) expression occurs on both T cells and B cells in human lupus patients, which is suggested to enhance B cell CD40 signaling and play a role in disease pathogenesis. Transgenic mice expressing CD154 by their B cells (CD154(TG)) have an expanded spleen B cell pool and produce autoantibodies (autoAbs). CD22 deficient (CD22(-/-)) mice also produce autoAbs, and importantly, their B cells are hyper-proliferative following CD40 stimulation ex vivo. Combining these 2 genetic alterations in CD154(TG)CD22(-/-) mice was thereby predicted to intensify CD40 signaling and autoimmune disease due to autoreactive B cell expansion and/or activation.CD154(TG)CD22(-/-) mice were assessed for their humoral immune responses and for changes in their endogenous lymphocyte subsets. Remarkably, CD154(TG)CD22(-/-) mice were not autoimmune, but instead generated minimal IgG responses against both self and foreign antigens. This paucity in IgG isotype switching occurred despite an expanded spleen B cell pool, higher serum IgM levels, and augmented ex vivo B cell proliferation. Impaired IgG responses in CD154(TG)CD22(-/-) mice were explained by a 16-fold expansion of functional, mature IL-10-competent regulatory spleen B cells (B10 cells: 26.7×10(6)±6 in CD154(TG)CD22(-/-) mice; 1.7×10(6)±0.4 in wild type mice, p<0.01), and an 11-fold expansion of B10 cells combined with their ex vivo-matured progenitors (B10+B10pro cells: 66×10(6)±3 in CD154(TG)CD22(-/-) mice; 6.1×10(6)±2 in wild type mice, p<0.01) that represented 39% of all spleen B cells.These results demonstrate for the first time that the IL-10-producing B10 B cell subset has the capacity to suppress IgG humoral immune responses against both foreign and self antigens. Thereby, therapeutic agents that drive regulatory B10 cell expansion in vivo may inhibit pathogenic IgG autoAb production in humans

Common and Distinct Genetic Properties of ESCRT-II Components in Drosophila

BACKGROUND: Genetic studies in yeast have identified class E vps genes that form the ESCRT complexes required for protein sorting at the early endosome. In Drosophila, mutations of the ESCRT-II component vps25 cause endosomal defects leading to accumulation of Notch protein and increased Notch pathway activity. These endosomal and signaling defects are thought to account for several phenotypes. Depending on the developmental context, two different types of overgrowth can be detected. Tissue predominantly mutant for vps25 displays neoplastic tumor characteristics. In contrast, vps25 mutant clones in a wild-type background trigger hyperplastic overgrowth in a non-autonomous manner. In addition, vps25 mutant clones also promote apoptotic resistance in a non-autonomous manner. PRINCIPAL FINDINGS: Here, we genetically characterize the remaining ESCRT-II components vps22 and vps36. Like vps25, mutants of vps22 and vps36 display endosomal defects, accumulate Notch protein and--when the tissue is predominantly mutant--show neoplastic tumor characteristics. However, despite these common phenotypes, they have distinct non-autonomous phenotypes. While vps22 mutations cause strong non-autonomous overgrowth, they do not affect apoptotic resistance. In contrast, vps36 mutations increase apoptotic resistance, but have little effect on non-autonomous proliferation. Further characterization reveals that although all ESCRT-II mutants accumulate Notch protein, only vps22 and vps25 mutations trigger Notch activity. CONCLUSIONS/SIGNIFICANCE: The ESCRT-II components vps22, vps25 and vps36 display common and distinct genetic properties. Our data redefine the role of Notch for hyperplastic and neoplastic overgrowth in these mutants. While Notch is required for hyperplastic growth, it appears to be dispensable for neoplastic transformation

Biology of human hair: Know your hair to control it

Hair can be engineered at different levels—its structure and surface—through modification of its constituent molecules, in particular proteins, but also the hair follicle (HF) can be genetically altered, in particular with the advent of siRNA-based applications. General aspects of hair biology are reviewed, as well as the most recent contributions to understanding hair pigmentation and the regulation of hair development. Focus will also be placed on the techniques developed specifically for delivering compounds of varying chemical nature to the HF, indicating methods for genetic/biochemical modulation of HF components for the treatment of hair diseases. Finally, hair fiber structure and chemical characteristics will be discussed as targets for keratin surface functionalization

Functional outcome of debridement, antibiotics and implant retention in periprosthetic joint infection involving the hip: a case-control study.

Introduction Advocates of Debridement-Antibiotics-and-Implant-Retention (DAIR) in hip peri-prosthetic joint infection (PJI) argue that a procedure not disturbing a sound prosthesis-bone interface is likely to lead to better survival and functional outcome compared to revision. However, no evidence supports this. This case-control study’s aims were to compare outcome of DAIRs for infected 1° total hip arthroplasty (THA) with outcomes following 1° THA and 2-stage revisions of infected 1° THAs. Methods We retrospectively reviewed all DAIRs, performed for confirmed infected 1° THR (DAIR-Group, n=80), in our unit between 1997-2013. Data recorded included patient demographics, medical history, type of surgery and organism identified. Outcome measures included complications, mortality, implant survivorship and functional outcome using the Oxford Hip Score (OHS). Outcome was compared with 2 control groups matched for gender and age; a cohort of 1° THA (1°-THA-Group, n=120) and a cohort of 2-stage revisions for infection (2-Stage-Revision-Group, n=66). Results The mean age at DAIR was 69 years and mean follow-up was 8 years (SD:5). 60% of DAIRs were for early PJI (&lt; six weeks). Greater infection eradication with DAIR was detected with early-PJI, interval less than a week between onset of symptoms and exchange of modular components with the DAIR procedure. Infection eradication, complications and re-operation rates were similar in the DAIR- and 2-stage-revision Groups (p&gt;0.05). For hips with successful infection eradication with DAIR, the 5-yr survival (98%) was similar to the 1°THA-Group (98%) (p=0.3). The DAIR-Group had inferior OHS (38) compared to the 1°THA-Group (42) (p=0.02) but significantly better OHS compared to the 2-stage-revision-Group (31) (p=0.008). Patients that required only one DAIR for infection eradication had similar OHS (41) to the 1° THA-Group (p=0.2). Discussion The mean age at DAIR was 69 years and mean follow-up was 8 years (SD:5). 60% of DAIRs were for early PJI (&lt; six weeks). Greater infection eradication with DAIR was detected with early-PJI, interval less than a week between onset of symptoms and exchange of modular components with the DAIR procedure. Infection eradication, complications and re-operation rates were similar in the DAIR- and 2-stage-revision Groups (p&gt;0.05). For hips with successful infection eradication with DAIR, the 5-yr survival (98%) was similar to the 1°THA-Group (98%) (p=0.3). The DAIR-Group had inferior OHS (38) compared to the 1°THA-Group (42) (p=0.02) but significantly better OHS compared to the 2-stage-revision-Group (31) (p=0.008). Patients that required only one DAIR for infection eradication had similar OHS (41) to the 1° THA-Group (p=0.2).</p

Discrete Choice Methods And Their Applications To Short Term Travel Decisions

Introduction Modeling travel behavior is a key aspect of demand analysis, where aggregate demand is the accumulation of individuals&apos; decisions. In this chapter, we focus on &quot;short-term&quot; travel decisions. The most important short-term travel decisions include choice of destination for a non-work trip, choice of travel mode, choice of departure time and choice of route. It is important to note that short-term decisions are conditional on long-term travel and mobility decisions such as car ownership and residential and work locations. The analysis of travel behavior is typically disaggregate, meaning that the models represent the choice behavior of individual travelers. Discrete choice analysis is the methodology used to analyze and predict travel decisions. Therefore, we begin this chapter with a review of the theoretical and practical aspects of discrete choice models. After a brief discussion of general assumptions, we introduce the random utility model, which is the most

Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus

YCT is an Australian National Health and Medical Research Council Career Development Fellow (1065736). DAR was supported in part by National Institutes of Health grant GM080602. SRH, PC, MTGH, JP and SDB were supported by Wellcome Trust grant 098051.Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-associated infection, but there is growing awareness of the emergence of multidrug-resistant lineages in community settings around the world. One such lineage is ST772-MRSA-V, which has disseminated globally and is increasingly prevalent in India. Here, we present the complete genome sequence of DAR4145, a strain of the ST772-MRSA-V lineage from India, and investigate its genomic characteristics in regards to antibiotic resistance and virulence factors.Publisher PDFPeer reviewe