Skin and soft tissue infections (SSTIs) due to Staphylococcus aureus have become increasingly common in the outpatient setting; however, risk factors for differentiating methicillin-resistant S. ...aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) SSTIs are needed to better inform antibiotic treatment decisions. We performed a case-case-control study within 14 primary-care clinics in South Texas from 2007 to 2015. Overall, 325 patients S. aureus SSTI cases (case group 1, n = 175); MRSA SSTI cases (case group 2, n = 115); MSSA SSTI cases (case group 3, n = 60); uninfected control group (control, n = 150) were evaluated. Each case group was compared to the control group, and then qualitatively contrasted to identify unique risk factors associated with S. aureus, MRSA, and MSSA SSTIs. Overall, prior SSTIs adjusted odds ratio (aOR) 7·60, 95% confidence interval (CI) 3·31–17·45, male gender (aOR 1·74, 95% CI 1·06–2·85), and absence of healthcare occupation status (aOR 0·14, 95% CI 0·03–0·68) were independently associated with S. aureus SSTIs. The only unique risk factor for community-associated (CA)-MRSA SSTIs was a high body weight (⩾110 kg) (aOR 2·03, 95% CI 1·01–4·09).
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Background
International guidelines on the prevention and treatment of parastomal hernias are lacking. The European Hernia Society therefore implemented a Clinical Practice Guideline development ...project.
Methods
The guidelines development group consisted of general, hernia and colorectal surgeons, a biostatistician and a biologist, from 14 European countries. These guidelines conformed to the AGREE II standards and the GRADE methodology. The databases of MEDLINE, CINAHL, CENTRAL and the gray literature through OpenGrey were searched. Quality assessment was performed using Scottish Intercollegiate Guidelines Network checklists. The guidelines were presented at the 38th European Hernia Society Congress and each key question was evaluated in a consensus voting of congress participants.
Results
End colostomy is associated with a higher incidence of parastomal hernia, compared to other types of stomas. Clinical examination is necessary for the diagnosis of parastomal hernia, whereas computed tomography scan or ultrasonography may be performed in cases of diagnostic uncertainty. Currently available classifications are not validated; however, we suggest the use of the European Hernia Society classification for uniform research reporting. There is insufficient evidence on the policy of watchful waiting, the route and location of stoma construction, and the size of the aperture. The use of a prophylactic synthetic non-absorbable mesh upon construction of an end colostomy is strongly recommended. No such recommendation can be made for other types of stomas at present. It is strongly recommended to avoid performing a suture repair for elective parastomal hernia. So far, there is no sufficient comparative evidence on specific techniques, open or laparoscopic surgery and specific mesh types. However, a mesh without a hole is suggested in preference to a keyhole mesh when laparoscopic repair is performed.
Conclusion
An evidence-based approach to the diagnosis and management of parastomal hernias reveals the lack of evidence on several topics, which need to be addressed by multicenter trials. Parastomal hernia prevention using a prophylactic mesh for end colostomies reduces parastomal herniation. Clinical outcomes should be audited and adverse events must be reported.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The coarse spacing of automatic rain gauges complicates near‐real‐time spatial analyses of precipitation. We test the possibility of improving such analyses by considering, in addition to the in situ ...measurements, the spatial covariance structure inferred from past observations with a denser network. To this end, a statistical reconstruction technique, reduced space optimal interpolation (RSOI), is applied over Switzerland, a region of complex topography. RSOI consists of two main parts. First, principal component analysis (PCA) is applied to obtain a reduced space representation of gridded high‐resolution precipitation fields available for a multiyear calibration period in the past. Second, sparse real‐time rain gauge observations are used to estimate the principal component scores and to reconstruct the precipitation field. In this way, climatological information at higher resolution than the near‐real‐time measurements is incorporated into the spatial analysis. PCA is found to efficiently reduce the dimensionality of the calibration fields, and RSOI is successful despite the difficulties associated with the statistical distribution of daily precipitation (skewness, dry days). Examples and a systematic evaluation show substantial added value over a simple interpolation technique that uses near‐real‐time observations only. The benefit is particularly strong for larger‐scale precipitation and prominent topographic effects. Small‐scale precipitation features are reconstructed at a skill comparable to that of the simple technique. Stratifying the reconstruction method by the types of weather type classifications yields little added skill. Apart from application in near real time, RSOI may also be valuable for enhancing instrumental precipitation analyses for the historic past when direct observations were sparse.
Summary
What is known and objective
Few studies have evaluated the effect of vancomycin dosing on the health outcomes in geriatric patients. Data are needed to determine whether higher vancomycin ...dosing strategies are more effective in geriatric patients and/or lead to excessive rates of adverse events.
Methods
This study used a subset of patients aged ≥65 years from a multicentre, retrospective, cohort study of methicillin‐resistant Staphylococcus aureus (MRSA) bacteraemia. Patients received ≥ 48 h of empiric vancomycin between 1 July 2002 and 30 June 2008. We compared the incidence of nephrotoxicity and in‐hospital mortality in patients who received guideline‐recommended dosing (at least 15 mg/kg/dose) to patients who received lower dosing. Multivariable generalized mixed‐effect models were constructed to determine independent risk factors for nephrotoxicity and in‐hospital mortality.
Results and discussion
Half of the cohort (46% of 92 patients) received guideline‐recommended dosing. Empiric use of weight‐based dosing did increase the percentage of patients achieving a vancomycin trough ≥ 15 mg/L (57% vs. 42%). Nephrotoxicity occurred in 32% of patients and 26% died during their hospitalization. Guideline‐recommended dosing was not associated with significant changes in nephrotoxicity (OR 1·13; 95% CI 0·40–3·19) or in‐hospital mortality (OR 1·14; 95% CI 0·41–3·18) in the multivariable analysis.
What is new and conclusion
In this study of geriatric patients, guideline‐recommended dosing was not associated with significant changes in nephrotoxicity or mortality. As 40% of the patients who received guideline‐recommended dosing failed to achieve a target vancomycin trough of ≥ 15 mg/L, future studies should focus on dosing strategies to increase target attainment rate.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
•Flexible, demand-adaptive transit services are intended for low-density areas.•These services provide both local circulation and access to mileposts such as regional rail stations.•Current mode ...usage has strong influence on likelihood of using flexible transit service.•Waiting at one’s origin is considerably less onerous than waiting at transit stop.•Results inform the service design process for flexible transit and mobility services.
This paper assesses the demand for a flexible, demand-adaptive transit service, using the Chicago region as an example. We designed and implemented a stated-preference survey in order to (1) identify potential users of flexible transit, and (2) inform the service design of the flexible transit mode. Multinomial logit, mixed-logit, and panel mixed-logit choice models were estimated using the data obtained from the survey. The survey instrument employed a dp-efficient design and the Google Maps API to capture precise origins and destinations in order to create realistic choice scenarios. The stated-preference experiments offered respondents a choice between traditional transit, car, and a hypothetical flexible transit mode. Wait time, access time, travel time, service frequency, cost, and number of transfers varied across the choice scenarios. The choice model results indicate mode-specific values of in-vehicle travel time ranging between $16.3 per hour (car) and $21.1 per hour (flexible transit). The estimated value of walking time to transit is $25.9 per hour. The estimated value of waiting time at one’s point of origin for a flexible transit vehicle is $11.3 per hour; this value is significantly lower than the disutility typically associated with waiting at a transit stop/station indicating that the ‘at-home’ pick-up option of flexible transit is a highly desirable feature. The choice model results also indicate that respondents who use active-transport modes or public transit for their current commute trip, or are bikeshare members, were significantly more likely to choose flexible and traditional transit than car commuters in the choice experiments. The implications of these and other relevant model results for the design and delivery of flexible, technology-enabled services are discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Hemolysis can saturate the hemoglobin (Hb)/heme scavenging system, resulting in increased circulating cell-free Hb (CF-Hb) in hereditary and acquired hemolytic disease. While recent studies have ...suggested a central role for intravascular hemolysis and CF-Hb in the development of vascular dysfunction, this concept has stimulated considerable debate. This highlights the importance of determining the contribution of CF-Hb to vascular complications associated with hemolysis. Therefore, a novel Hb-binding peptide was synthesized and linked to a small fragment of apolipoprotein E (amino acids 141-150) to facilitate endocytic clearance. Plasma clearance of hE-Hb-b10 displayed a rapid phase t(1/2) of 16 min and slow phase t(1/2) of 10 h, trafficking primarily through the liver. Peptide hE-Hb-B10 decreased CF-Hb in mice treated with phenylhydrazine, a model of acute hemolysis. Administration of hE-Hb-B10 also attenuated CF-Hb in two models of chronic hemolysis: Berkeley sickle cell disease (SS) mice and mice with severe hereditary spherocytosis (HS). The hemolytic rate was unaltered in either chronic hemolysis model, supporting the conclusion that hE-Hb-B10 promotes CF-Hb clearance without affecting erythrocyte lysis. Interestingly, hE-Hb-B10 also decreased plasma ALT activity in SS and HS mice. Although acetylcholine-mediated facialis artery vasodilation was not improved by hE-Hb-B10 treatment, the peptide shifted vascular response in favor of NO-dependent vasodilation in SS mice. Taken together, these data demonstrate that hE-Hb-B10 decreases CF-Hb with a concomitant reduction in liver injury and changes in vascular response. Therefore, hE-Hb-B10 can be used to investigate the different roles of CF-Hb in hemolytic pathology and may have therapeutic benefit in the treatment of CF-Hb-mediated tissue damage.
•Subjective value of travel time depends on activities conducted on board transit.•Certain segments of the population are more likely to recognize this value.•Agencies could focus on attracting and ...retaining these segments.•Traveler information & ICT device use contribute to reducing wait time disutility.
In practice, travel time is assigned a cost and treated as a disutility to be minimized. There is a growing body of research supporting the hypothesis that travel time has some value of its own, and the proliferation of information and communication technology (ICT) may be contributing to that value. Travelers’ attitudes are confounded with their mode choice, and as telecommunications mediate travel behavior, analysts must recognize the interaction between time use and customer satisfaction for appropriate travel demand management. To that end, this paper presents results from jointly estimated models of travelers’ latent satisfaction and on-board activity engagement using Chicago transit rider data gathered in April 2010. The simple questionnaire and small sample corroborate the findings of past research indicating travel attitudes and activity engagement have potential to influence travelers’ value of time, and many transit riders consider transit a better use of time and/or money than driving. The findings affirm the need for a more holistic understanding of value of time for travel demand management and infrastructure valuation. As time use has an influence on users’ valuation of the transit mode, offering opportunities to conduct certain leisure activities could improve the perceived value of travel time.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The TORCH time-of-flight (TOF) detector is being developed to provide particle identification up to a momentum of 10GeV/c over a flight distance of 10m. It has a DIRC-like construction with 10mm ...thick synthetic amorphous fused-silica plates as a Cherenkov radiator. Photons propagate by total internal reflection to the plate periphery where they are focused onto an array of customised position-sensitive micro-channel plate (MCP) detectors. The goal is to achieve a 15ps time-of-flight resolution per incident particle by combining arrival times from multiple photons. The MCPs have pixels of effective size 0.4mm×6.6mm2 in the vertical and horizontal directions, respectively, by incorporating a novel charge-sharing technique to improve the spatial resolution to better than the pitch of the readout anodes. Prototype photon detectors and readout electronics have been tested and calibrated in the laboratory. Preliminary results from testbeam measurements of a prototype TORCH detector are also presented.
•A prototype for a time-of-flight detector for particle identification has been tested.•MCP-PMT detectors, implementing a novel charge sharing technique, were tested.•Laboratory tests show charge sharing results in high quality spatial resolution.•Test-beam measurements with the full prototype were completed.•It was shown that contributions from several reflections can be distinguished.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Here we investigated the binding of Dengue virus envelope glycoprotein domain III (DIII) by two broadly neutralizing antibodies (bNAbs), 4E11 and 4E5A. There are four serotypes of Dengue ...virus (DENV-1 to -4), whose DIII sequences vary by up to 49%. We used combinatorial alanine scanning mutagenesis, a phage display approach, to map functional epitopes (those residues that contribute most significantly to the energetics of antibody–antigen interaction) on these four serotypes. Our results showed that 4E11, which binds strongly to DENV-1, -2, and -3, and moderately to DENV-4, recognized a common conserved core functional epitope involving DIII residues K310, L/I387, L389, and W391. There were also unique recognition features for each serotype, suggesting that 4E11 has flexible recognition requirements. Similar scanning studies for the related bNAb 4E5A, which binds more tightly to DENV-4, identified broader functional epitopes on DENV-1. These results provide useful information for immunogen and therapeutic antibody design.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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