Mesoscopic structure and social aspects of human mobility

The individual movements of large numbers of people are important in many contexts, from urban planning to disease spreading. Datasets that capture human mobility are now available and many interesting features have been discovered, including the ultra-slow spatial growth of individual mobility. However, the detailed substructures and spatiotemporal flows of mobility - the sets and sequences of visited locations - have not been well studied. We show that individual mobility is dominated by small groups of frequently visited, dynamically close locations, forming primary "habitats" capturing typical daily activity, along with subsidiary habitats representing additional travel. These habitats do not correspond to typical contexts such as home or work. The temporal evolution of mobility within habitats, which constitutes most motion, is universal across habitats and exhibits scaling patterns both distinct from all previous observations and unpredicted by current models. The delay to enter subsidiary habitats is a primary factor in the spatiotemporal growth of human travel. Interestingly, habitats correlate with non-mobility dynamics such as communication activity, implying that habitats may influence processes such as information spreading and revealing new connections between human mobility and social networks.Comment: 7 pages, 5 figures (main text); 11 pages, 9 figures, 1 table (supporting information

Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs

A systematic review of randomised controlled trials on the effectiveness of exercise programs on lumbo pelvic pain among postnatal women

Background: A substantial number of women tend to be affected by Lumbo Pelvic Pain (LPP) following child birth. Physical exercise is indicated as a beneficial method to relieve LPP, but individual studies appear to suggest mixed findings about its effectiveness. This systematic review aimed to synthesise evidence from randomised controlled trials on the effectiveness of exercise on LPP among postnatal women to inform policy, practice and future research. Methods: A systematic review was conducted of all randomised controlled trials published between January 1990 and July 2014, identified through a comprehensive search of following databases: PubMed, PEDro, Embase, Cinahl, Medline, SPORTDiscus, Cochrane Pregnancy and Childbirth Group’s Trials Register, and electronic libraries of authors’institutions. Randomised controlled trials were eligible for inclusion if the intervention comprised of postnatal exercise for women with LPP onset during pregnancy or within 3 months after delivery and the outcome measures included changes in LPP. Selected articles were assessed using the PEDro Scale for methodological quality and findings were synthesised narratively as meta-analysis was found to be inappropriate due to heterogeneity among included studies. Results: Four randomised controlled trials were included, involving 251 postnatal women. Three trials were rated as of ‘good’ methodological quality. All trials, except one, were at low risk of bias. The trials included physical exercise programs with varying components, differing modes of delivery, follow up times and outcome measures. Intervention in one trial, involving physical therapy with specific stabilising exercises, proved to be effective in reducing LPP intensity. An improvement in gluteal pain on the right side was reported in another trial and a significant difference in pain frequency in another. Conclusion: Our review indicates that only few randomised controlled trials have evaluated the effectiveness of exercise on LPP among postnatal women. There is also a great amount of variability across existing trials in the components of exercise programs, modes of delivery, follow up times and outcome measures. While there is some evidence to indicate the effectiveness of exercise for relieving LPP, further good quality trials are needed to ascertain the most effective elements of postnatal exercise programs suited for LPP treatment

Forecasting daily attendances at an emergency department to aid resource planning

<p>Abstract</p> <p>Background</p> <p>Accurate forecasting of emergency department (ED) attendances can be a valuable tool for micro and macro level planning.</p> <p>Methods</p> <p>Data for analysis was the counts of daily patient attendances at the ED of an acute care regional general hospital from July 2005 to Mar 2008. Patients were stratified into three acuity categories; i.e. P1, P2 and P3, with P1 being the most acute and P3 being the least acute. The autoregressive integrated moving average (ARIMA) method was separately applied to each of the three acuity categories and total patient attendances. Independent variables included in the model were public holiday (yes or no), ambient air quality measured by pollution standard index (PSI), daily ambient average temperature and daily relative humidity. The seasonal components of weekly and yearly periodicities in the time series of daily attendances were also studied. Univariate analysis by t-tests and multivariate time series analysis were carried out in SPSS version 15.</p> <p>Results</p> <p>By time series analyses, P1 attendances did not show any weekly or yearly periodicity and was only predicted by ambient air quality of PSI > 50. P2 and total attendances showed weekly periodicities, and were also significantly predicted by public holiday. P3 attendances were significantly correlated with day of the week, month of the year, public holiday, and ambient air quality of PSI > 50.</p> <p>After applying the developed models to validate the forecast, the MAPE of prediction by the models were 16.8%, 6.7%, 8.6% and 4.8% for P1, P2, P3 and total attendances, respectively. The models were able to account for most of the significant autocorrelations present in the data.</p> <p>Conclusion</p> <p>Time series analysis has been shown to provide a useful, readily available tool for predicting emergency department workload that can be used to plan staff roster and resource planning.</p

Climate impacts of energy technologies depend on emissions timing

Energy technologies emit greenhouse gases with differing radiative efficiencies and atmospheric lifetimes. Standard practice for evaluating technologies, which uses the global warming potential (GWP) to compare the integrated radiative forcing of emitted gases over a fixed time horizon, does not acknowledge the importance of a changing background climate relative to climate change mitigation targets. Here we demonstrate that the GWP misvalues the impact of CH[subscript 4]-emitting technologies as mid-century approaches, and we propose a new class of metrics to evaluate technologies based on their time of use. The instantaneous climate impact (ICI) compares gases in an expected radiative forcing stabilization year, and the cumulative climate impact (CCI) compares their time-integrated radiative forcing up to a stabilization year. Using these dynamic metrics, we quantify the climate impacts of technologies and show that high-CH[subscript 4]-emitting energy sources become less advantageous over time. The impact of natural gas for transportation, with CH[subscript 4] leakage, exceeds that of gasoline within 1–2 decades for a commonly cited 3 W m[superscript −2] stabilization target. The impact of algae biodiesel overtakes that of corn ethanol within 2–3 decades, where algae co-products are used to produce biogas and corn co-products are used for animal feed. The proposed metrics capture the changing importance of CH[subscript 4] emissions as a climate threshold is approached, thereby addressing a major shortcoming of the GWP for technology evaluation.New England University Transportation Center (DOT Grant DTRT07-G-0001

Functional assessment of older patients in the emergency department: comparison between standard instruments, medical records and physicians' perceptions

BACKGROUND: We evaluated the accuracy of physician recognition of functional status impairment in older emergency departments (ED) patients. In particular, we evaluated the accuracy of medical records (a comparison of the information in the medical record with the functional status based on proxy interviews), and the accuracy of physician knowledge (a comparison of the information obtained from the responsible physician with the functional status based on proxy interviews). METHODS: Cross-sectional study on 101 frail older patients selected at random from among those attending ED, their ED physicians, and respondents. The study was conducted at ED in four general university teaching hospitals in a city, from July through November 2003. Functional data shown on patients' medical records were compared against functional data obtained from respondents (family members), using Kendall's Tau-b statistic. In addition patients' Katz Indices (which assesses six basic activities of daily living – basic ADL) based on interviews with ED physicians were compared against those obtained from respondents, using the coefficient of concordance weighted kappa (κ). Each patient and his respondent were paired with a single physician. RESULTS: The correlation between information on dependence for basic ADL obtained from medical records and that furnished by respondents, was 0.41 (95% CI 0.27–0.55). Concordance between the respective Katz Indices obtained from physicians and respondents was 0.47 (95% CI 0.38–0.57). CONCLUSION: Older subjects' functional status is not properly assessed by emergency department physicians

Glucocorticoids, master modulators of the thymic catecholaminergic system?

There is evidence that the major mediators of stress, i.e., catecholamines and glucocorticoids, play an important role in modulating thymopoiesis and consequently immune responses. Furthermore, there are data suggesting that glucocorticoids influence catecholamine action. Therefore, to assess the putative relevance of glucocorticoid-catecholamine interplay in the modulation of thymopoiesis we analyzed thymocyte differentiation/maturation in non-adrenalectomized and andrenalectomized rats subjected to treatment with propranolol (0.4 mg.100 g body weight(-1).day(-1)) for 4 days. The effects of beta-adrenoceptor blockade on thymopoiesis in non-adrenalectomized rats differed not only quantitatively but also qualitatively from those in adrenalectomized rats. In adrenalectomized rats, besides a more efficient thymopoiesis [judged by a more pronounced increase in the relative proportion of the most mature single-positive TCR alpha beta(high) thymocytes as revealed by two-way ANOVA; for CD4(+)CD8(-)F (1,20) = 10.92, P lt 0.01; for CD4(-)CD8(+)F (1,20) = 7.47, P lt 0.05], a skewed thymocyte maturation towards the CD4(-)CD8(+) phenotype, and consequently a diminished CD4(+)CD8(-)/CD4(-)CD8(+) mature TCR alpha beta(high) thymocyte ratio (3.41 +/- 0.21 in non-adrenalectomized rats vs 2.90 +/- 0.31 in adrenalectomized rats, P lt 0.05) were found. Therefore, we assumed that catecholaminergic modulation of thymopoiesis exhibits a substantial degree of glucocorticoid-dependent plasticity. Given that glucocorticoids, apart from catecholamine synthesis, influence adrenoceptor expression, we also hypothesized that the lack of adrenal glucocorticoids affected not only beta-adrenoceptor- but also alpha-adrenoceptor-mediated modulation of thymopoiesis

Resolving the fibrotic niche of human liver cirrhosis at single-cell level.

Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, here we profile the transcriptomes of more than 100,000 single human cells, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver. We identify a scar-associated TREM2+CD9+ subpopulation of macrophages, which expands in liver fibrosis, differentiates from circulating monocytes and is pro-fibrogenic. We also define ACKR1+ and PLVAP+ endothelial cells that expand in cirrhosis, are topographically restricted to the fibrotic niche and enhance the transmigration of leucocytes. Multi-lineage modelling of ligand and receptor interactions between the scar-associated macrophages, endothelial cells and PDGFRα+ collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in liver cirrhosis.Includes Wellcome, BHF, MRC, BBSRC and NIHR