A cohort study of the recovery of health and wellbeing following colorectal cancer (CREW study): protocol paper

Background: the number of people surviving colorectal cancer has doubled in recent years. While much of the literature suggests that most people return to near pre-diagnosis status following surgery for colorectal cancer, this literature has largely focused on physical side effects. Longitudinal studies in colorectal cancer have either been small scale or taken a narrow focus on recovery after surgery. There is a need for a comprehensive, long-term study exploring all aspects of health and wellbeing in colorectal cancer patients. The aim of this study is to establish the natural history of health and wellbeing in people who have been treated for colorectal cancer. People have different dispositions, supports and resources, likely resulting in individual differences in restoration of health and wellbeing. The protocol described in this paper is of a study which will identify who is most at risk of problems, assess how quickly people return to a state of subjective health and wellbeing, and will measure factors which influence the course of recovery. Methods: this is a prospective, longitudinal cohort study following 1000 people with colorectal cancer over a period of two years, recruiting from 30 NHS cancer treatment centres across the UK. Questionnaires will be administered prior to surgery, and 3, 9, 15 and 24 months after surgery, with the potential to return to this cohort to explore on-going issues related to recovery after cancer. Discussion: outcomes will help inform health care providers about what helps or hinders rapid and effective recovery from cancer, and identify areas for intervention development to aid this process. Once established the cohort can be followed up for longer periods and be approached to participate in related projects as appropriate and subject to funding<br/

Design and Testing of a Low-Cost and Low-Maintenance Drip Irrigation Filtration System for Micro-Irrigation in Developing Countries

The cylindrical filters presently used in <1000 m2 drip irrigation systems are frequently clogged, increasing pressure loss and lowering the flow rate through the filters. This work investigates the mechanisms for this clogging and proposes an alternative filtration design that would enable both more reliable and lower maintenance filtering. This proposed system is compatible with existing drip irrigation systems and could be made inexpensively with plastic bottle manufacturing equipment. To compare the proposed design to off-the-shelf options, a drip irrigation test setup was built to measure the pressure loss across different filters as particles accumulated. These experiments confirmed that pleated cartridge filters, with high effective surface area, incurred lower pressure losses than cylindrical filters. These tests revealed that the greatest reason for clogged performance was that filtered particles (not the cartridge filter itself) eventually restricted the flow of water through the system. This inspired the redesign of the filter housing such that the housing extended far below the filter, providing a catch basin away from the filter for the particles to settle. Fixing the filter independently of the bottom casing significantly improved the overall performance of the filtration system, reduced the maintenance requirement necessary from the user, and would enable inexpensive manufacturing via blow molding. This paper experimentally demonstrates that the cartridge filter inside the redesigned housing can filter out over 2 kg of sand while maintaining less than a .03 bar pressure drop across the filter at a flow rate of 25 l/s.Massachusetts Institute of Technology. Tata Center for Technology and DesignMassachusetts Institute of Technology. Department of Mechanical Engineerin

Increased expression of a microRNA correlates with anthelmintic resistance in parasitic nematodes

Resistance to anthelmintic drugs is a major problem in the global fight against parasitic nematodes infecting humans and animals. While previous studies have identified mutations in drug target genes in resistant parasites, changes in the expression levels of both targets and transporters have also been reported. The mechanisms underlying these changes in gene expression are unresolved. Here, we take a novel approach to this problem by investigating the role of small regulatory RNAs in drug resistant strains of the important parasite Haemonchus contortus. microRNAs (miRNAs) are small (22 nt) non-coding RNAs that regulate gene expression by binding predominantly to the 3′ UTR of mRNAs. Changes in miRNA expression have been implicated in drug resistance in a variety of tumor cells. In this study, we focused on two geographically distinct ivermectin resistant strains of H. contortus and two lines generated by multiple rounds of backcrossing between susceptible and resistant parents, with ivermectin selection. All four resistant strains showed significantly increased expression of a single miRNA, hco-miR-9551, compared to the susceptible strain. This same miRNA is also upregulated in a multi-drug-resistant strain of the related nematode Teladorsagia circumcincta. hco-miR-9551 is enriched in female worms, is likely to be located on the X chromosome and is restricted to clade V parasitic nematodes. Genes containing predicted binding sites for hco-miR-9551 were identified computationally and refined based on differential expression in a transcriptomic dataset prepared from the same drug resistant and susceptible strains. This analysis identified three putative target mRNAs, one of which, a CHAC domain containing protein, is located in a region of the H. contortus genome introgressed from the resistant parent. hco-miR-9551 was shown to interact with the 3′ UTR of this gene by dual luciferase assay. This study is the first to suggest a role for miRNAs and the genes they regulate in drug resistant parasitic nematodes. miR-9551 also has potential as a biomarker of resistance in different nematode species

Delivering a low-cost, reliable drip irrigation filtration system for micro-irrigation in developing countries

The cylindrical filters presently used in drip irrigation systems frequently clog, increasing pressure loss and lowering the flow rate through the filters. This work investigates alternative filtration strategies that increase the reliability of, and are compatible with, existing systems. To test different filtration strategies, a drip irrigation test setup was built to measure the pressure loss across different filters as particles accumulated. These experiments found that pleated cartridge filters, with high effective surface area, incurred the lowest pressure losses. More significantly, it was observed during these tests that the filtered out particles settled to the bottom of the filter housing when flow through the filter ceased. This inspired the redesign of the filter housing such that the housing extended far below the filter, providing a catch basin away from the filter for the particles to settle. Fixing the filter independently of the bottom casing significantly improves the overall performance of the filtration system and can be inexpensively manufactured via blow molding. This paper experimentally demonstrates that the cartridge filter inside the redesigned housing can filter out over 2 kg of sand while maintaining less than a .03 bar pressure drop across the filter at a flow rate of 25 l/s.MIT Tata Center for Technology and DesignMassachusetts Institute of Technology. Department of Mechanical EngineeringInternational Development Enterprise

How the structure of the large subunit controls function in an oxygen-tolerant [NiFe]-hydrogenase

Salmonella enterica is an opportunistic pathogen that produces a [NiFe]-hydrogenase under aerobic conditions. In the present study, genetic engineering approaches were used to facilitate isolation of this enzyme, termed Hyd-5. The crystal structure was determined to a resolution of 3.2 Å and the hydro-genase was observed to comprise associated large and small subunits. The structure indicated that His(229) from the large subunit was close to the proximal [4Fe–3S] cluster in the small subunit. In addition, His(229) was observed to lie close to a buried glutamic acid (Glu(73)), which is conserved in oxygen-tolerant hydrogenases. His(229) and Glu(73) of the Hyd-5 large subunit were found to be important in both hydrogen oxidation activity and the oxygen-tolerance mechanism. Substitution of His(229) or Glu(73) with alanine led to a loss in the ability of Hyd-5 to oxidize hydrogen in air. Furthermore, the H229A variant was found to have lost the overpotential requirement for activity that is always observed with oxygen-tolerant [NiFe]-hydrogenases. It is possible that His(229) has a role in stabilizing the super-oxidized form of the proximal cluster in the presence of oxygen, and it is proposed that Glu(73)could play a supporting role in fine-tuning the chemistry of His(229) to enable this function

Effect of hands-on interprofessional simulation training for local emergencies in Scotland:the THISTLE stepped-wedge design randomised controlled trial

OBJECTIVE: To assess whether the implementation of an intrapartum training package (PROMPT (PRactical Obstetric Multi-Professional Training)) across a health service reduced the proportion of term babies born with Apgar score <7 at 5 min (<75mins). // DESIGN: Stepped-wedge cluster randomised controlled trial. SETTING: Twelve randomised maternity units with ≥900 births/year in Scotland. Three additional units were included in a supplementary analysis to assess the effect across Scotland. The intervention commenced in March 2014 with follow-up until September 2016. // INTERVENTION: The PROMPT training package (Second edition), with subsequent unit-level implementation of PROMPT courses for all maternity staff. // MAIN OUTCOME MEASURES: The primary outcome was the proportion of term babies with Apgar<75mins. // RESULTS: 87 204 eligible births (99.2% with an Apgar score), of which 1291 infants had an Apgar<75mins were delivered in the 12 randomised maternity units. Two units did not implement the intervention. The overall Apgar<75mins rate observed in the 12 randomised units was 1.49%, increasing from 1.32% preintervention to 1.59% postintervention. Once adjusted for a secular time trend, the 'intention-to-treat' analysis indicated a moderate but non-significant reduction in the rate of term babies with an Apgar scores <75mins following PROMPT training (OR=0.79 95%CI(0.63 to 1.01)). However, some units implemented the intervention earlier than their allocated step, whereas others delayed the intervention. The content and authenticity of the implemented intervention varied widely at unit level. When the actual date of implementation of the intervention in each unit was considered in the analysis, there was no evidence of improvement (OR=1.01 (0.84 to 1.22)). No intervention effect was detected by broadening the analysis to include all 15 large Scottish maternity units. Units with a history of higher rates of Apgar<75mins maintained higher Apgar rates during the study (OR=2.09 (1.28 to 3.41)) compared with units with pre-study rates aligned to the national rate. // CONCLUSIONS: PROMPT training, as implemented, had no effect on the rate of Apgar <75mins in Scotland during the study period. Local implementation at scale was found to be more difficult than anticipated. Further research is required to understand why the positive effects observed in other single-unit studies have not been replicated in Scottish maternity units, and how units can be best supported to locally implement the intervention authentically and effectively

Best practices for virtual participation in meetings : experiences from synthesis centers

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Pre-Surgery Depression and Confidence to Manage Problems Predict Recovery Trajectories of Health and Wellbeing in the First Two Years following Colorectal Cancer: Results from the CREW Cohort Study

Purpose This paper identifies predictors of recovery trajectories of quality of life (QoL), health status and personal wellbeing in the two years following colorectal cancer surgery. Methods 872 adults receiving curative intent surgery during November 2010 to March 2012. Questionnaires at baseline, 3, 9, 15, 24 months post-surgery assessed QoL, health status, wellbeing, confidence to manage illness-related problems (self-efficacy), social support, co-morbidities, socio-demographic, clinical and treatment characteristics. Group-based trajectory analyses identified distinct trajectories and predictors for QoL, health status and wellbeing. Results Four recovery trajectories were identified for each outcome. Groups 1 and 2 fared consistently well (scores above/within normal range); 70.5% of participants for QoL, 33.3% health status, 77.6% wellbeing. Group 3 had some problems (24.2% QoL, 59.3% health, 18.2% wellbeing); Group 4 fared consistently poorly (5.3% QoL, 7.4% health, 4.2% wellbeing). Higher pre-surgery depression and lower self-efficacy were significantly associated with poorer trajectories for all three outcomes after adjusting for other important predictors including disease characteristics, stoma, anxiety and social support. Conclusions Psychosocial factors including self-efficacy and depression before surgery predict recovery trajectories in QoL, health status and wellbeing following colorectal cancer treatment independent of treatment or disease characteristics. This has significant implications for colorectal cancer management as appropriate support may be improved by early intervention resulting in more positive recovery experiences

Effects of Video Enhancement in a Stated-Choice Experiment on Medical Decision Making

Background. The internet can be useful in administering stated-choice experiments to understand medical decision making and refine the content of patient decision aids. In internet-based stated-choice experiments, video and audio files can be used to provide information to respondents. Quality of data may or may not be affected. Objectives. In a methodological experiment concerned with administration of a stated-choice experiment on the internet concerned with knee-replacement surgery, we compared the data quality obtained with video-enhanced and conventional text formats. Methods. Members of the RAND Corporation’s American Life Panel and 50 years of age or older (n=1616) were randomly assigned to one of two survey modes: video (80%) or text (20%). Quality of data was measured by both the frequency of respondent speeding and plausibility of respondent choices. Results. Typical respondents completed the research task much more rapidly in the text condition than the video condition (10.6 versus 16.4 minutes). The choices were 5 to 10% more likely to be plausible for those in the video-enhanced condition than for those in the text version. The mode of administration did not affect respondents in the extent of their reported interest in the survey or in the degree to which they reported identifying with patients in vignettes. Conclusions. The advantages of the video enhancement in engaging respondents appeared to be offset by the greater time demands on respondents. Video-enhancements in stated-choice experiments may be most useful when used selectively to deliver information that cannot be delivered adequately by text

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using √s=8 TeV proton-proton collision data

A search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in s√=8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A 0 = −2m 0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector