Estimating spatial accessibility to facilities on the regional scale: an extended commuting-based interaction potential model

<p>Abstract</p> <p>Background</p> <p>There is growing interest in the study of the relationships between individual health-related behaviours (e.g. food intake and physical activity) and measurements of spatial accessibility to the associated facilities (e.g. food outlets and sport facilities). The aim of this study is to propose measurements of spatial accessibility to facilities on the regional scale, using aggregated data. We first used a potential accessibility model that partly makes it possible to overcome the limitations of the most frequently used indices such as the count of opportunities within a given neighbourhood. We then propose an extended model in order to take into account both home and work-based accessibility for a commuting population.</p> <p>Results</p> <p>Potential accessibility estimation provides a very different picture of the accessibility levels experienced by the population than the more classical "number of opportunities per census tract" index. The extended model for commuters increases the overall accessibility levels but this increase differs according to the urbanisation level. Strongest increases are observed in some rural municipalities with initial low accessibility levels. Distance to major urban poles seems to play an essential role.</p> <p>Conclusions</p> <p>Accessibility is a multi-dimensional concept that should integrate some aspects of travel behaviour. Our work supports the evidence that the choice of appropriate accessibility indices including both residential and non-residential environmental features is necessary. Such models have potential implications for providing relevant information to policy-makers in the field of public health.</p

Assessment of sedentary behaviors and transport-related activities by questionnaire: a validation study

ACTI-Cités consortiumInternational audienceBackground: Comprehensive assessment of sedentary behavior (SB) and physical activity (PA), including transport-related activities (TRA), is required to design innovative PA promotion strategies. There are few validated instruments that simultaneously assess the different components of human movement according to their context of practice (e.g. work, transport, leisure). We examined test-retest reliability and validity of the Sedentary, Transportation and Activity Questionnaire (STAQ), a newly developed questionnaire dedicated to assessing context-specific SB, TRA and PA. Methods: Ninety six subjects (51 women) kept a contextualized activity-logbook and wore a hip accelerometer (Actigraph GT3X + TM) for a 7-day or 14-day period, at the end of which they completed the STAQ. Activity-energy expenditure was measured in a subgroup of 45 subjects using the double labeled water (DLW) method. Test-retest reliability was assessed using intra-class-coefficients (ICC) in a subgroup of 32 subjects who filled the questionnaire twice one month apart. Accelerometry was annotated using the logbook to obtain total and context-specific objective estimates of SB. Spearman correlations, Bland-Altman plots and ICC were used to analyze validity with logbook, accelerometry and DLW data validity criteria. Results: Test-retest reliability was fair for total sitting time (ICC = 0.52), good to excellent for work sitting time (ICC = 0.71), transport-related walking (ICC = 0.61) and car use (ICC = 0.67), and leisure screen-related SB (ICC = 0.64-0.79), but poor for total sitting time during leisure and transport-related contexts. For validity, compared to accelerometry, significant correlations were found for STAQ estimates of total (r = 0.54) and context-specific sitting times with stronger correlations for work sitting time (r = 0.88), and screen times (TV/DVD viewing: r = 0.46; other screens: r = 0.42) than for transport (r = 0.35) or leisure-related sitting-times (r = 0.19). Compared to contextualized logbook, STAQ estimates of TRA was higher for car (r = 0.65) than for active transport (r = 0.41). The questionnaire generally overestimated work-and leisure-related SB and sitting times, while it underestimated total and transport-related sitting times.Conclusions : The STAQ showed acceptable reliability and a good ranking validity for assessment of context-specific SB and TRA. This instrument appears as a useful tool to study SB, TRA and PA in context in adults

Intracerebral Transplantation and In Vivo Bioluminescence Tracking of Human Neural Progenitor Cells in the Mouse Brain

Cell therapy has long been an emerging treatment paradigm in experimental neurobiology. However, cell transplantation studies often rely on end-point measurements and can therefore only evaluate longitudinal changes of cell migration and survival to a limited extent. This paper provides a reliable, minimally invasive protocol to transplant and longitudinally track neural progenitor cells (NPCs) in the adult mouse brain. Before transplantation, cells are transduced with a lentiviral vector comprising a bioluminescent (firefly-luciferase) and fluorescent (green fluorescent protein [GFP]) reporter. The NPCs are transplanted into the right cortical hemisphere using stereotaxic injections in the sensorimotor cortex. Following transplantation, grafted cells were detected through the intact skull for up to five weeks (at days 0, 3, 14, 21, 35) with a resolution limit of 6,000 cells using in vivo bioluminescence imaging. Subsequently, the transplanted cells are identified in histological brain sections and further characterized with immunofluorescence. Thus, this protocol provides a valuable tool to transplant, track, quantify, and characterize cells in the mouse brain

Descriptive study of sedentary behaviours in 35,444 French working adults: cross-sectional findings from the ACTI-Cités study

International audienceBackground : Given the unfavourable health outcomes associated with sedentary behaviours, there is a need to better understand the context in which these behaviours take place to better address this public health concern. We explored self-reported sedentary behaviours by type of day (work/non-work), occupation, and perceptions towards physical activity, in a large sample of adults.Methods : We assessed sedentary behaviours cross-sectionally in 35,444 working adults (mean ± SD age: 44.5 ± 13.0 y) from the French NutriNet-Santé web-based cohort. Participants self-reported sedentary behaviours, assessed as domain-specific sitting time (work, transport, leisure) and time spent in sedentary entertainment (TV/DVD, computer and other screen-based activities, non-screen-based activities) on workdays and non-workdays, along with occupation type (ranging from mainly sitting to heavy manual work) and perceptions towards physical activity. Associations of each type of sedentary behaviour with occupation type and perceptions towards physical activity were analysed by day type in multiple linear regression analyses.Results : On workdays, adults spent a mean (SD) of 4.17 (3.07) h/day in work sitting, 1.10 (1.69) h/day in transport sitting, 2.19 (1.62) h/day in leisure-time sitting, 1.53 (1.24) h/day viewing TV/DVDs, 2.19 (2.62) h/day on other screen time, and 0.97 (1.49) on non-screen time. On non-workdays, this was 0.85 (1.53) h/day in transport sitting, 3.19 (2.05) h/day in leisure-time sitting, 2.24 (1.76) h/day viewing TV/DVDs, 1.85 (1.74) h/day on other screen time, and 1.30 (1.35) on non-screen time. Time spent in sedentary behaviours differed by occupation type, with more sedentary behaviour outside of work (both sitting and entertainment time), in those with sedentary occupations, especially on workdays. Negative perceptions towards physical activity were associated with more sedentary behaviour outside of work (both sitting and entertainment time), irrespective of day type.Conclusions : A substantial amount of waking hours was spent in different types of sedentary behaviours on workdays and non-workdays. Being sedentary at work was associated with more sedentary behaviour outside of work. Negative perceptions towards physical activity may influence the amount of time spent in sedentary behaviours. These data should help to better identify target groups in public health interventions to reduce sedentary behaviours in working adults

Economic Burden of Surgical Site Infections at a European University Hospital

Objective. To quantify the economic burden of in-hospital surgical site infections (SSIs) at a European university hospital. Design. Matched case-control study nested in a prospective observational cohort study. Setting. Basel University Hospital in Switzerland, where an average of 28,000 surgical procedures are performed per year. Methods. All in-hospital occurrences of SSI associated with surgeries performed between January 1, 2000, and December 31, 2001, by the visceral, vascular, and traumatology divisions at Basel University Hospital were prospectively recorded. Each case patient was matched to a control patient by age, procedure code, and National Nosocomial Infection Surveillance System risk index. The case-control pairs were analyzed for differences in cost of hospital care and in provision of specialized care. Results. A total of 6,283 procedures were performed:187 SSIs were detected in inpatients, 168 of whom were successfully matched with a control patient. For case patients, the mean additional hospital cost was SwF19,638 (95% confidence interval [CI], SwF8,492-SwF30,784); the mean additional postoperative length of hospital stay was 16.8 days (95% CI, 13-20.6 days); and the mean additional in-hospital duration of antibiotic therapy was 7.4 days (95% CI, 5.1-9.6 days). Differences were primarily attributable to organ space SSIs (n = 76). Conclusions. Ina European university hospital setting, SSIs are costly and constitute a heavy and potentially preventable burden on both patients and healthcare provider

Mcl-1 deficiency in murine livers leads to nuclear polyploidisation and mitotic errors: Implications for hepatocellular carcinoma

BACKGROUND & AIMS Mcl-1, an antiapoptotic protein overexpressed in many tumours, including hepatocellular carcinoma (HCC), represents a promising target for cancer treatment. Although Mcl-1 non-apoptotic roles might critically influence the therapeutic potential of Mcl-1 inhibitors, these functions remain poorly understood. We aimed to investigate the effects of hepatic Mcl-1 deficiency (Mcl-1$^{Δhep}$) on hepatocyte ploidy and cell cycle in murine liver in vivo and the possible implications on HCC. METHODS Livers of young Mcl-1$^{Δhep}$ and wild-type (WT) mice were analysed for ploidy profile, mitotic figures, in situ chromosome segregation, gene set enrichment analysis and were subjected to two-thirds partial hepatectomy to assess Mcl-1 deficiency effect on cell cycle progression in vivo. Mcl-1$^{Δhep}$ tumours in older mice were analysed for ploidy profile, chromosomal instability, and mutational signatures via whole exome sequencing. RESULTS In young mice, Mcl-1 deficiency leads to nuclear polyploidy and to high rates of mitotic errors with abnormal spindle figures and chromosome mis-segregation along with a prolonged spindle assembly checkpoint activation signature. Chromosomal instability and altered ploidy profile are observed in Mcl-1$^{Δhep}$ tumours of old mice as well as a characteristic mutational signature of currently unknown aetiology. CONCLUSIONS Our study suggests novel non-apoptotic effects of Mcl-1 deficiency on nuclear ploidy, mitotic regulation, and chromosomal segregation in hepatocytes in vivo. In addition, the Mcl-1 deficiency characteristic mutational signature might reflect mitotic issues. These results are of importance to consider when developing anti-Mcl-1 therapies to treat cancer. IMPACT AND IMPLICATIONS Although Mcl-1 inhibitors represent promising hepatocellular carcinoma treatment, the still poorly understood non-apoptotic roles of Mcl-1 might compromise their successful clinical application. Our study shows that Mcl-1 deficiency leads to nuclear polyploidy, mitotic errors, and aberrant chromosomal segregation in hepatocytes in vivo, whereas hepatocellular tumours spontaneously induced by Mcl-1 deficiency exhibit chromosomal instability and a mutational signature potentially reflecting mitotic issues. These results have potential implications for the development of anti-Mcl-1 therapies to treat hepatocellular carcinoma, especially as hyperproliferative liver is a clinically relevant situation

Xeno-free induced pluripotent stem cell-derived neural progenitor cells for in vivo applications

BACKGROUND: Currently, there is no regenerative therapy for patients with neurological and neurodegenerative disorders. Cell-therapies have emerged as a potential treatment for numerous brain diseases. Despite recent advances in stem cell technology, major concerns have been raised regarding the feasibility and safety of cell therapies for clinical applications. METHODS: We generated good manufacturing practice (GMP)-compatible neural progenitor cells (NPCs) from transgene- and xeno-free induced pluripotent stem cells (iPSCs) that can be smoothly adapted for clinical applications. NPCs were characterized in vitro for their differentiation potential and in vivo after transplantation into wild type as well as genetically immunosuppressed mice. RESULTS: Generated NPCs had a stable gene-expression over at least 15 passages and could be scaled for up to 10$^{18}$ cells per initially seeded 10$^{6}$ cells. After withdrawal of growth factors in vitro, cells adapted a neural fate and mainly differentiated into active neurons. To ensure a pure NPC population for in vivo applications, we reduced the risk of iPSC contamination by applying micro RNA-switch technology as a safety checkpoint. Using lentiviral transduction with a fluorescent and bioluminescent dual-reporter construct, combined with non-invasive in vivo bioluminescent imaging, we longitudinally tracked the grafted cells in healthy wild-type and genetically immunosuppressed mice as well as in a mouse model of ischemic stroke. Long term in-depth characterization revealed that transplanted NPCs have the capability to survive and spontaneously differentiate into functional and mature neurons throughout a time course of a month, while no residual pluripotent cells were detectable. CONCLUSION: We describe the generation of transgene- and xeno-free NPCs. This simple differentiation protocol combined with the ability of in vivo cell tracking presents a valuable tool to develop safe and effective cell therapies for various brain injuries