1,904 research outputs found

    Measuring the Impact of Complete Streets Projects on Bicyclist and Pedestrian Safety in Sacramento County, CA

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    This paper aims to quantify the impact of complete streets projects on pedestrian and bicyclist safety. By examining crashes before and after complete streets projects, this study will lead to a better understanding of the cumulative effect of complete streets projects on pedestrian and bicyclist safety. Using data provided by the Sacramento Department of Transportation, a subset of projects completed between 2011 and 2014 were selected and analyzed to determine the number of pedestrian and bicyclist crashes in the 24 months before and after these complete streets projects were constructed and calculate rates of crashes for bicyclists and pedestrians

    Gribov pendulum in the Coulomb gauge on curved spaces

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    In this paper the generalization of the Gribov pendulum equation in the Coulomb gauge for curved spacetimes is analyzed on static spherically symmetric backgrounds. A rigorous argument for the existence and uniqueness of solution is provided in the asymptotically AdS case. The analysis of the strong and weak boundary conditions is equivalent to analyzing an effective one-dimensional Schrodinger equation. Necessary conditions in order for spherically symmetric backgrounds to admit solutions of the Gribov pendulum equation representing copies of the vacuum satisfying the strong boundary conditions are given. It is shown that asymptotically flat backgrounds do not support solutions of the Gribov pendulum equation of this type, while on asymptotically AdS backgrounds such ambiguities can appear. Some physical consequences are discussed.Comment: 22 pages, no figures. V2: The discussion of the physical consequences has been extended. To appear on Physical Review

    Extensive Gene Amplification as a Mechanism for Piperacillin-Tazobactam Resistance in Escherichia coli.

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    Although the TEM-1 β-lactamase (BlaTEM-1) hydrolyzes penicillins and narrow-spectrum cephalosporins, organisms expressing this enzyme are typically susceptible to β-lactam/β-lactamase inhibitor combinations such as piperacillin-tazobactam (TZP). However, our previous work led to the discovery of 28 clinical isolates of Escherichia coli resistant to TZP that contained only blaTEM-1 One of these isolates, E. coli 907355, was investigated further in this study. E. coli 907355 exhibited significantly higher β-lactamase activity and BlaTEM-1 protein levels when grown in the presence of subinhibitory concentrations of TZP. A corresponding TZP-dependent increase in blaTEM-1 copy number was also observed, with as many as 113 copies of the gene detected per cell. These results suggest that TZP treatment promotes an increase in blaTEM-1 gene dosage, allowing BlaTEM-1 to reach high enough levels to overcome inactivation by the available tazobactam in the culture. To better understand the nature of the blaTEM-1 copy number proliferation, whole-genome sequence (WGS) analysis was performed on E. coli 907355 in the absence and presence of TZP. The WGS data revealed that the blaTEM-1 gene is located in a 10-kb genomic resistance module (GRM) that contains multiple resistance genes and mobile genetic elements. The GRM was found to be tandemly repeated at least 5 times within a p1ESCUM/p1ECUMN-like plasmid when bacteria were grown in the presence of TZP.IMPORTANCE Understanding how bacteria acquire resistance to antibiotics is essential for treating infected patients effectively, as well as preventing the spread of resistant organisms. In this study, a clinical isolate of E. coli was identified that dedicated more than 15% of its genome toward tandem amplification of a ~10-kb resistance module, allowing it to escape antibiotic-mediated killing. Our research is significant in that it provides one possible explanation for clinical isolates that exhibit discordant behavior when tested for antibiotic resistance by different phenotypic methods. Our research also shows that GRM amplification is difficult to detect by short-read WGS technologies. Analysis of raw long-read sequence data was required to confirm GRM amplification as a mechanism of antibiotic resistance. MBio 2018 Apr 24; 9(2):e00583-18

    Analysing and Recommending Options for Maintaining Universal Coverage with Long-Lasting Insecticidal Nets: The Case of Tanzania in 2011.

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    Tanzania achieved universal coverage with long-lasting insecticidal nets (LLINs) in October 2011, after three years of free mass net distribution campaigns and is now faced with the challenge of maintaining high coverage as nets wear out and the population grows. A process of exploring options for a continuous or "Keep-Up" distribution system was initiated in early 2011. This paper presents for the first time a comprehensive national process to review the major considerations, findings and recommendations for the implementation of a new strategy. Stakeholder meetings and site visits were conducted in five locations in Tanzania to garner stakeholder input on the proposed distribution systems. Coverage levels for LLINs and their decline over time were modelled using NetCALC software, taking realistic net decay rates, current demographic profiles and other relevant parameters into consideration. Costs of the different distribution systems were estimated using local data. LLIN delivery was considered via mass campaigns, Antenatal Care-Expanded Programme on Immunization (ANC/EPI), community-based distribution, schools, the commercial sector and different combinations of the above. Most approaches appeared unlikely to maintain universal coverage when used alone. Mass campaigns, even when combined with a continuation of the Tanzania National Voucher Scheme (TNVS), would produce large temporal fluctuations in coverage levels; over 10 years this strategy would require 63.3 million LLINs and a total cost of 444millionUSD.Communitymechanisms,whileabletodelivertherequirednumbersofLLINs,wouldrequireamassivescaleupinmonitoring,evaluationandsupervisionsystemstoensureaccurateapplicationofidentificationcriteriaatthecommunitylevel.SchoolbasedapproachescombinedwiththeexistingTNVSwouldreachmostTanzanianhouseholdsanddeliver65.4millionLLINsover10yearsatatotalcostof444 million USD. Community mechanisms, while able to deliver the required numbers of LLINs, would require a massive scale-up in monitoring, evaluation and supervision systems to ensure accurate application of identification criteria at the community level. School-based approaches combined with the existing TNVS would reach most Tanzanian households and deliver 65.4 million LLINs over 10 years at a total cost of 449 million USD and ensure continuous coverage. The cost of each strategy was largely driven by the number of LLINs delivered. The most cost-efficient strategy to maintain universal coverage is one that best optimizes the numbers of LLINs needed over time. A school-based approach using vouchers targeting all students in Standards 1, 3, 5, 7 and Forms 1 and 2 in combination with the TNVS appears to meet best the criteria of effectiveness, equity and efficiency

    Design, implementation and evaluation of a national campaign to distribute nine million free LLINs to children under five years of age in Tanzania.

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    BACKGROUND\ud \ud After a national voucher scheme in 2004 provided pregnant women and infants with highly subsidized insecticide-treated nets (ITNs), use among children under five years (U5s) in mainland Tanzania increased from 16% in 2004 to 26.2% in 2007. In 2008, the Ministry of Health and Social Welfare planned a catch-up campaign to rapidly and equitably deliver a free long-lasting insecticidal net (LLIN) to every child under five years in Tanzania.\ud \ud METHODS\ud \ud The ITN Cell, a unit within the National Malaria Control Programme (NMCP), coordinated the campaign on behalf of the Ministry of Health and Social Welfare. Government contractors trained and facilitated local government officials to supervise village-level volunteers on a registration of all U5s and the distribution and issuing of LLINs. The registration results formed the basis for the LLIN order and delivery to village level. Caregivers brought their registration coupons to village issuing posts during a three-day period where they received LLINs for their U5s. Household surveys in five districts assessed ITN ownership and use immediately after the campaign.\ud \ud RESULTS\ud \ud Nine donors contributed to the national campaign that purchased and distributed 9.0 million LLINs at an average cost of $7.07 per LLIN, including all campaign-associated activities. The campaign covered all eight zones of mainland Tanzania, the first region being covered separately during an integrated measles immunization/malaria LLIN distribution in August 2008, and was implemented one zone at a time from March 2009 until May 2010. ITN ownership at household level increased from Tanzania's 2008 national average of 45.7% to 63.4%, with significant regional variations. ITN use among U5s increased from 28.8% to 64.1%, a 2.2-fold increase, with increases ranging from 22.1-38.3% percentage points in different regions.\ud \ud CONCLUSION\ud \ud A national-level LLIN distribution strategy that fully engaged local government authorities helped avoid additional burden on the healthcare system. Distribution costs per net were comparable to other public health interventions. Particularly among rural residents, ITN ownership and use increased significantly for the intended beneficiaries. The upcoming universal LLIN distribution and further behaviour change communication will further improve ITN ownership and use in 2010-2011

    Towards Solving QCD - The Transverse Zero Modes in Light-Cone Quantization

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    We formulate QCD in (d+1) dimensions using Dirac's front form with periodic boundary conditions, that is, within Discretized Light-Cone Quantization. The formalism is worked out in detail for SU(2) pure glue theory in (2+1) dimensions which is approximated by restriction to the lowest {\it transverse} momentum gluons. The dimensionally-reduced theory turns out to be SU(2) gauge theory coupled to adjoint scalar matter in (1+1) dimensions. The scalar field is the remnant of the transverse gluon. This field has modes of both non-zero and zero {\it longitudinal} momentum. We categorize the types of zero modes that occur into three classes, dynamical, topological, and constrained, each well known in separate contexts. The equation for the constrained mode is explicitly worked out. The Gauss law is rather simply resolved to extract physical, namely color singlet states. The topological gauge mode is treated according to two alternative scenarios related to the In the one, a spectrum is found consistent with pure SU(2) gluons in (1+1) dimensions. In the other, the gauge mode excitations are estimated and their role in the spectrum with genuine Fock excitations is explored. A color singlet state is given which satisfies Gauss' law. Its invariant mass is estimated and discussed in the physical limit.Comment: LaTex document, 26 pages, one figure (obtainable by contacting authors). To appear in Physical. Review

    Complex consequences of Cantu syndrome SUR2 variant R1154Q in genetically modified mice

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    Cantu syndrome (CS) is caused by gain-of-function (GOF) mutations in pore-forming (Kir6.1, KCNJ8) and accessory (SUR2, ABCC9) ATP-sensitive potassium (KATP) channel subunits, the most common mutations being SUR2[R1154Q] and SUR2[R1154W], carried by approximately 30% of patients. We used CRISPR/Cas9 genome engineering to introduce the equivalent of the human SUR2[R1154Q] mutation into the mouse ABCC9 gene. Along with minimal CS disease features, R1154Q cardiomyocytes and vascular smooth muscle showed much lower KATP current density and pinacidil activation than WT cells. Almost complete loss of SUR2-dependent protein and KATP in homozygous R1154Q ventricles revealed underlying diazoxide-sensitive SUR1-dependent KATP channel activity. Surprisingly, sequencing of SUR2 cDNA revealed 2 distinct transcripts, one encoding full-length SUR2 protein; and the other with an in-frame deletion of 93 bases (corresponding to 31 amino acids encoded by exon 28) that was present in approximately 40% and approximately 90% of transcripts from hetero- and homozygous R1154Q tissues, respectively. Recombinant expression of SUR2A protein lacking exon 28 resulted in nonfunctional channels. CS tissue from SUR2[R1154Q] mice and human induced pluripotent stem cell-derived (hiPSC-derived) cardiomyocytes showed only full-length SUR2 transcripts, although further studies will be required in order to fully test whether SUR2[R1154Q] or other CS mutations might result in aberrant splicing and variable expressivity of disease features in human CS

    Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis

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    <b>Background</b><p></p> It is assumed within the accumulated literature that children born of pregnant opioid dependent mothers have impaired neurobehavioral function as a consequence of chronic intrauterine opioid use.<p></p> <b>Methods</b><p></p> Quantitative and systematic review of the literature on the consequences of chronic maternal opioid use during pregnancy on neurobehavioral function of children was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched Cinahl, EMBASE, PsychINFO and MEDLINE between the periods of January 1995 to January 2012.<p></p> <b>Results</b><p></p> There were only 5 studies out of the 200 identified that quantitatively reported on neurobehavioral function of children after maternal opioid use during pregnancy. All 5 were case control studies with the number of exposed subjects within the studies ranging from 33–143 and 45–85 for the controls. This meta-analysis showed no significant impairments, at a non-conservative significance level of p < 0.05, for cognitive, psychomotor or observed behavioural outcomes for chronic intra-uterine exposed infants and pre-school children compared to non-exposed infants and children. However, all domains suggested a trend to poor outcomes in infants/children of opioid using mothers. The magnitude of all possible effects was small according to Cohen’s benchmark criteria.<p></p> <b>Conclusions</b><p></p> Chronic intra-uterine opioid exposed infants and pre-school children experienced no significant impairment in neurobehavioral outcomes when compared to non-exposed peers, although in all domains there was a trend to poorer outcomes. The findings of this review are limited by the small number of studies analysed, the heterogenous populations and small numbers within the individual studies. Longitudinal studies are needed to determine if any neuropsychological impairments appear after the age of 5 years and to help investigate further the role of environmental risk factors on the effect of ‘core’ phenotypes

    Justice Beyond Borders? Australia and the International Criminal Court

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    The International Criminal Court (ICC) came into being on 1 July 2002. A four-person team opened an office in The Hague and will collect reports and allegations of genocide, war crimes and crimes against humanity until judges and a prosecutor are appointed towards the end of 2003. Although the court was heralded by many states and international lawyers as the most important positive development in international law since the formation of the United Nations, it did not get off to an auspicious start. The Bush administration was concerned that US military forces operating overseas would be particularly vulnerable to what it described as 'politicised' prosecutions. It therefore insisted that not only would it not be a part of the ICC, but also that it would not sanction the continuation of UN peacekeeping operations. Closer to home, the Australian Senate only ratified the ICC's founding treaty, the Rome Statute, after a bitter debate that split both the Liberal and National parties. This was the case even though the Howard government-and Foreign Minister Alexander Downer in particular-had been a leading advocate of the court and ratification of the Rome Statute had been a Liberal Party election promise in 2001. The cost that Downer, and pro-ICC Attorney-General Daryl Williams had to pay in order to appease restive conservative backbenchers, the National Party, and an increasingly reluctant (and pro-US) Prime Minister and secure the ratification was a declaration that reaffirmed the primacy of the Australian judicial system over the ICC. The declaration insisted that no Australian would be prosecuted by the court without the consent of the Attomey-General, and asserted Australia's right to define what is meant by the crimes of genocide, war crimes, and crimes against humanity. We argue that although Downer and Williams should be commended for their commitment to international justice, the declaration attached to Australia's ratification was unnecessary and unhelpful. The first and third aspects of the declaration were unnecessary: the principle of complementarity enshrined in the Rome Statute means that the ICC already recognises the primacy of domestic jurisdiction, and the crimes covered are already considered to fall under universal jurisdiction, as the Nuremberg, Tokyo and more recent Pinochet trials showed (see Weller 1999). The second is unhelpful because it contravenes both the letter and the spirit of the Rome Statute. We will begin, then, by tracing the development of the ICC debate in Australian politics. In 1998, the government was an enthusiastic advocate of the court but by 2002 an alliance of an ardently pro-US Prime Minister, vocal right-wing parliamentarians and their supporters, and The Australian (and its foreign affairs editor Greg Sheridan in particular) combined to put ratification in doubt. Contrary to Prime Minister John Howard's claims, this debate was not well informed. Instead, it was characterised by hearsay, inaccuracy and scare-mongering. The subsequent section of the article demonstrates this by focusing on the background to, and creation of, the Rome Statute

    Expanded Quality Management Using Information Power (EQUIP): Protocol for a Quasi-experimental Study to Improve Maternal and Newborn Health in Tanzania and Uganda.

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    Maternal and newborn mortality remain unacceptably high in sub-Saharan Africa. Tanzania and Uganda are committed to reduce maternal and newborn mortality, but progress has been limited and many essential interventions are unavailable in primary and referral facilities. Quality management has the potential to overcome low implementation levels by assisting teams of health workers and others finding local solutions to problems in delivering quality care and the underutilization of health services by the community. Existing evidence of the effect of quality management on health worker performance in these contexts has important limitations, and the feasibility of expanding quality management to the community level is unknown. We aim to assess quality management at the district, facility, and community levels, supported by information from high-quality, continuous surveys, and report effects of the quality management intervention on the utilization and quality of services in Tanzania and Uganda. In Uganda and Tanzania, the Expanded Quality Management Using Information Power (EQUIP) intervention is implemented in one intervention district and evaluated using a plausibility design with one non-randomly selected comparison district. The quality management approach is based on the collaborative model for improvement, in which groups of quality improvement teams test new implementation strategies (change ideas) and periodically meet to share results and identify the best strategies. The teams use locally-generated community and health facility data to monitor improvements. In addition, data from continuous health facility and household surveys are used to guide prioritization and decision making by quality improvement teams as well as for evaluation of the intervention. These data include input, process, output, coverage, implementation practice, and client satisfaction indicators in both intervention and comparison districts. Thus, intervention districts receive quality management and continuous surveys, and comparison districts-only continuous surveys. EQUIP is a district-scale, proof-of-concept study that evaluates a quality management approach for maternal and newborn health including communities, health facilities, and district health managers, supported by high-quality data from independent continuous household and health facility surveys. The study will generate robust evidence about the effectiveness of quality management and will inform future nationwide implementation approaches for health system strengthening in low-resource settings
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