Construction productivity analysis for asphalt concrete pavement rehabilitation in urban corridors

The results of a constructibility and productivity analysis for the California Department of Transportation Long Life Asphalt Concrete Pavement Rehabilitation Strategies program are presented. With the assistance of California asphalt concrete (AC) paving contractors, the analysis explored the effects on construction productivity of rehabilitation materials, design strategy (crack seat and overlay, full-depth replacement), layer profiles, AC cooling time, resource constraints, and alternative lane closure tactics. Deterministic and stochastic analysis programs were developed. A sensitivity study that examined the construction production capability within a 55-h weekend closure was performed. Weekend closures were also compared with continuous closures. Demolition and AC delivery truck flows were the major constraints limiting the AC rehabilitation production capability. It was concluded from the study that efficient lane closure tactics designed to work with the pavement profile (an minimize the nonworking time to increase the construction product! on efficiency. The results of the study will help road agencies evaluate rehabilitation strategies and tactics with the goal of balancing the maximization of production capability and minimization of traffic delay during urban pavement rehabilitation.open114sciescopu

Environmental Racism in St. Louis

This report calls out environmental racism- the disproportionate impact of environmental hazards on people of color 1-in St. Louis. While these disparities have been part of the long-standing discriminatory and profit-driven policies and practices known too well by black St. Louisans, the issue of environmental racism has rarely been addressed in the City. At least three recent reports- For the Sake of All,2 Segregation in St. Louis: Dismantling the Divide,3 and Equity lndicators4-document the heavy health, economic, and quality of life burdens that the St. Louis region imposes on its black residents. This report complements those by focusing on the burdens related to environmental factors. It should come as no surprise that black St. Louisans are disproportionately harmed by lead poisoning, asthma, mold, and high energy costs- all of which are associated with factors such as substandard housing conditions and air pollution- due to living near industrial facilities, highways, and building demolitions. In addition, the City\u27s focus on enhancing majority-white areas has left majority-black areas without adequate access to public transit or healthy food, and with high concentrations of vacant properties and illegal trash dumping

Modelling-based evaluation of the costs, benefits and cost-effectiveness of multipathogen point-of-care tests for sexually transmitted infections in symptomatic genitourinary medicine clinic attendees

Objectives To quantify the costs, benefits and cost-effectiveness of three multipathogen point-of-care (POC) testing strategies for detecting common sexually transmitted infections (STIs) compared with standard laboratory testing. Design Modelling study. Setting Genitourinary medicine (GUM) services in England. Population A hypothetical cohort of 965 988 people, representing the annual number attending GUM services symptomatic of lower genitourinary tract infection. Interventions The decision tree model considered costs and reimbursement to GUM services associated with diagnosing and managing STIs. Three strategies using hypothetical point-of-care tests (POCTs) were compared with standard care (SC) using laboratory-based testing. The strategies were: A) dual POCT for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); B) triplex POCT for CT-NG and Mycoplasma genitalium (MG); C) quadruplex POCT for CT-NG-MG and Trichomonas vaginalis (TV). Data came from published literature and unpublished estimates. Primary and secondary outcome measures Primary outcomes were total costs and benefits (quality-adjusted life years (QALYs)) for each strategy (2016 GB, £) and associated incremental cost-effectiveness ratios (ICERs) between each of the POC strategies and SC. Secondary outcomes were inappropriate treatment of STIs, onward STI transmission, pelvic inflammatory disease in women, time to cure and total attendances. Results In the base-case analysis, POC strategy C, a quadruplex POCT, was the most cost-effective relative to the other strategies, with an ICER of £36 585 per QALY gained compared with SC when using microcosting, and cost-savings of £26 451 382 when using tariff costing. POC strategy C also generated the most benefits, with 240 467 fewer clinic attendances, 808 fewer onward STI transmissions and 235 135 averted inappropriate treatments compared with SC. Conclusions Many benefits can be achieved by using multipathogen POCTs to improve STI diagnosis and management. Further evidence is needed on the underlying prevalence of STIs and SC delivery in the UK to reduce uncertainty in economic analyses

Evaluation of the anti-ischemic effects of D-ribose during dobutamine stress echocardiography: a pilot study

D-Ribose, a pentose sugar, has shown to improve myocardial high-energy phosphate stores depleted by ischemia. This study investigated the ability of D-Ribose with low dose dobutamine to improve the contractile response of viable myocardium to dobutamine and to assess the efficacy of D-ribose in reducing stress-induced ischemia. Twenty-six patients with ischemic cardiomyopathy completed a two-day, randomized, double blind crossover trial comparing the effects of D-Ribose and placebo on regional wall motion. On the first study day, either D-Ribose or placebo was infused for 4.5 hours. Low (5 and 10 μ/kg/min) and subsequently, high (up to 50 μ/kg/min) dose dobutamine echocardiography was then performed. On the second study day, patients crossed over to the alternative article for a similar 4.5 hours infusion time period and underwent a similar evaluation. The wall motion response during low dose dobutamine was the same with D-Ribose and placebo in 77% of segments (203/263, Kappa = 0.37). In segments with discordant responses, more segments improved with D-Ribose than with placebo (41 vs. 19 segments, p = 0.006). With high dose dobutamine infusion, the wall motion response (ischemia vs. no ischemia) was the same with D-Ribose and placebo in 83% of interpretable segments (301/363, kappa = 0.244). In segments with discordant responses, there were more ischemic segments with placebo compared to D-Ribose (36 vs. 26, p = 0.253). Nineteen patients developed ischemia during the dobutamine and placebo infusion and 13 patients had ischemia during dobutamine and D-ribose infusion (p = 0.109). D-Ribose improved contractile responses to dobutamine in viable myocardium with resting dysfunction but had no significant effect in reducing the frequency of stress-induced wall motion abnormalities

Close the Workhouse: A Plan to Close the Workhouse & Promote A New Vision for St. Louis

The City of St. Louis condemns hundreds of mostly poor and Black people to suffer in unspeakably hellish and inhumane conditions at the Workhouse, officially known as the Medium Security Institution. Over 95% of people at the Workhouse are awaiting trial and remain incarcerated due to their inability to afford unusually high and unconstitutional cash bonds. They face horrific conditions in the jail, including extreme heat and cold, abysmal medical care, rats and cockroach infestations, and mold. The City of St. Louis spends over $16 million every year operating this facility with little public benefit. The arrest-and-incarcerate approach to public safety targeting the poor and Black communities in St. Louis not only ruins lives, but also does not make the city safer. The Workhouse represents one facet of a broader system of criminalization and marginalization in St. Louis

Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model.

BACKGROUND: Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. UC can have a considerable impact on patients' quality of life. The burden for the NHS is substantial. OBJECTIVES: To evaluate the clinical effectiveness and safety of interventions, to evaluate the incremental cost-effectiveness of all interventions and comparators (including medical and surgical options), to estimate the expected net budget impact of each intervention, and to identify key research priorities. DATA SOURCES: Peer-reviewed publications, European Public Assessment Reports and manufacturers' submissions. The following databases were searched from inception to December 2013 for clinical effectiveness searches and from inception to January 2014 for cost-effectiveness searches for published and unpublished research evidence: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and NHS Economic Evaluation Database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science and Bioscience Information Service Previews. The US Food and Drug Administration website and the European Medicines Agency website were also searched, as were research registers, conference proceedings and key journals. REVIEW METHODS: A systematic review [including network meta-analysis (NMA)] was conducted to evaluate the clinical effectiveness and safety of named interventions. The health economic analysis included a review of published economic evaluations and the development of a de novo model. RESULTS: Ten randomised controlled trials were included in the systematic review. The trials suggest that adult patients receiving infliximab (IFX) [Remicade(®), Merck Sharp & Dohme Ltd (MSD)], adalimumab (ADA) (Humira(®), AbbVie) or golimumab (GOL) (Simponi(®), MSD) were more likely to achieve clinical response and remission than those receiving placebo (PBO). Hospitalisation data were limited, but suggested more favourable outcomes for ADA- and IFX-treated patients. Data on the use of surgical intervention were sparse, with a potential benefit for intervention-treated patients. Data were available from one trial to support the use of IFX in paediatric patients. Safety issues identified included serious infections, malignancies and administration site reactions. Based on the NMA, in the induction phase, all biological treatments were associated with statistically significant beneficial effects relative to PBO, with the greatest effect associated with IFX. For patients in response following induction, all treatments except ADA and GOL 100 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although these were not significant. The greatest effects at 8-32 and 32-52 weeks were associated with 100 mg of GOL and 5 mg/kg of IFX, respectively. For patients in remission following induction, all treatments except ADA at 8-32 weeks and GOL 50 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although only the effect of ADA at 32-52 weeks was significant. The greatest effects were associated with GOL (at 8-32 weeks) and ADA (at 32-52 weeks). The economic analysis suggests that colectomy is expected to dominate drug therapies, but for some patients, colectomy may not be considered acceptable. In circumstances in which only drug options are considered, IFX and GOL are expected to be ruled out because of dominance, while the incremental cost-effectiveness ratio for ADA versus conventional treatment is approximately £50,300 per QALY gained. LIMITATIONS: The health economic model is subject to several limitations: uncertainty associated with extrapolating trial data over a lifetime horizon, the model does not consider explicit sequential pathways of non-biological treatments, and evidence relating to complications of colectomy was identified through consideration of approaches used within previous models rather than a full systematic review. CONCLUSIONS: Adult patients receiving IFX, ADA or GOL were more likely to achieve clinical response and remission than those receiving PBO. Further data are required to conclusively demonstrate the effect of interventions on hospitalisation and surgical outcomes. The economic analysis indicates that colectomy is expected to dominate medical treatments for moderate to severe UC. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013006883. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Segregation in St. Louis: Dismantling the Divide

Place matters. Where people live in St. Louis has been shaped by an extensive history of segregation that was driven by policies at multiple levels of government and practices across multiple sectors of society. The effect of segregation has been to systematically exclude African American families from areas opportunity that support economic, educational, and health outcomes

Diel turbidity cycles in a headwater stream: evidence of nocturnal bioturbation?

Purpose: A small number of recent studies have linked daily cycles in stream turbidity to nocturnal bioturbation by aquatic fauna, principally crayfish, and demonstrated this process can significantly impact upon water quality under baseflow conditions. Adding to this limited body of research, we use high-resolution water quality monitoring data to investigate evidence of diel turbidity cycles in a lowland, headwater stream with a known signal crayfish (Pacifastacus leniusculus) population and explore a range of potential causal mechanisms. Materials and methods: Automatic bankside monitoring stations measured turbidity and other water quality parameters at 30-min resolution at three locations on the River Blackwater, Norfolk, UK during 2013. Specifically, we focused on two 20-day periods of baseflow conditions during January and April 2013 which displayed turbidity trends typical of winter and spring seasons, respectively. The turbidity time-series, which were smoothed with 6.5 hour Savitzky-Golay filters to highlight diel trends, were correlated against temperature, stage, dissolved oxygen and pH to assess the importance of abiotic influences on turbidity. Turbidity was also calibrated against suspended particulate matter (SPM) over a wide range of values via linear regression. Results and discussion: Pronounced diel turbidity cycles were found at two of the three sites under baseflow conditions during April. Spring night-time turbidity values consistently peaked between 21:00 and 04:00 with values increasing by ~10 nephelometric turbidity units (NTU) compared with the lowest recorded daytime values which occurred between 10:00 and 14:00. This translated into statistically significant increases in median midnight SPM concentration of up to 76% compared with midday, with night-time (18:00 – 05:30) SPM loads also up to 30% higher than that recorded during the daytime (06:00 – 17:30). Relating turbidity to other water quality parameters exhibiting diel cycles revealed there to be neither any correlation that might indicate a causal link, nor any obvious mechanistic connections to explain the temporal turbidity trends. Diel turbidity cycles were less prominent at all sites during the winter. Conclusions: Considering the seasonality and timing of elevated turbidity, visual observations of crayfish activity, and an absence of mechanistic connections with other water quality parameters, the results presented here are consistent with the hypothesis that nocturnal bioturbation is responsible for generating diel turbidity cycles under baseflow conditions in headwater streams. However, further research in a variety of fluvial environments is required to better assess the spatial extent, importance and causal mechanisms of this phenomenon

Histone Acetylation-Mediated Regulation of the Hippo Pathway

The Hippo pathway is a signaling cascade recently found to play a key role in tumorigenesis therefore understanding the mechanisms that regulate it should open new opportunities for cancer treatment. Available data indicate that this pathway is controlled by signals from cell-cell junctions however the potential role of nuclear regulation has not yet been described. Here we set out to verify this possibility and define putative mechanism(s) by which it might occur. By using a luciferase reporter of the Hippo pathway, we measured the effects of different nuclear targeting drugs and found that chromatin-modifying agents, and to a lesser extent certain DNA damaging drugs, strongly induced activity of the reporter. This effect was not mediated by upstream core components (i.e. Mst, Lats) of the Hippo pathway, but through enhanced levels of the Hippo transducer TAZ. Investigation of the underlying mechanism led to the finding that cancer cell exposure to histone deacetylase inhibitors induced secretion of growth factors and cytokines, which in turn activate Akt and inhibit the GSK3 beta associated protein degradation complex in drug-affected as well as in their neighboring cells. Consequently, expression of EMT genes, cell migration and resistance to therapy were induced. These processes were suppressed by using pyrvinium, a recently described small molecule activator of the GSK 3 beta associated degradation complex. Overall, these findings shed light on a previously unrecognized phenomenon by which certain anti-cancer agents may paradoxically promote tumor progression by facilitating stabilization of the Hippo transducer TAZ and inducing cancer cell migration and resistance to therapy. Pharmacological targeting of the GSK3 beta associated degradation complex may thus represent a unique approach to treat cancer. © 2013 Basu et al

A Cyproheptadine-Reversible Defect in ACTH Control Persisting after Removal of the Pituitary Tumor in Cushing\u27s Disease

Abstract We studied two phases of cortisol feedback suppression of ACTH in nine patients who had had adrenalectomy for Cushing\u27s disease. Four had been treated by adrenalectomy alone and presumably had ACTH-secreting pituitary tumors. Five others were studied two or more years after transsphenoidal removal of an ACTH-secreting microadenoma. In both groups, cortisol-ACTH feedback during the first 30 minutes of cortisol infusion was abnormal; plasma ACTH fell only 2.7±2.6 per cent (mean ±S.E.), as compared with 28.0±10.1 per cent in five hypoadrenal controls (P\u3c0.01). The fall in ACTH during the second phase of cortisol infusion was similar in the patients and the controls. Cyproheptadine corrected the feedback abnormality occurring during the first phase in both groups of patients with Cushing\u27s disease; ACTH fell by 24.4±4.8 per cent (P\u3c0.005). Persistence of a cortisol-ACTH feedback abnormality after removal of the pituitary tumor in Cushing\u27s disease, as well as the correction by cyproheptadine, suggests that higher centers have a role in the pathophysiology of Cushing\u27s disease. (N Engl J Med. 1981; 305:1244–8.