The association between baseline persistent pain and weight change in patients attending a specialist weight management service

To quantify the influence of baseline pain levels on weight change at one-year follow-up in patients attending a National Health Service specialist weight management programme.We compared one-year follow-up weight (body mass) change between patient sub-groups of none-to-mild, moderate, and severe pain at baseline. A mean sub-group difference in weight change of ≥5kg was considered clinically relevant.Of the 141 complete cases, n = 43 (30.5%) reported none-to-mild pain, n = 44 (31.2%) reported moderate pain, and n = 54 (38.3%) reported severe pain. Covariate-adjusted mean weight loss (95%CI) was similar for those with none-to-mild (8.1kg (4.2 to 12.0kg)) and moderate pain (8.3kg (4.9 to 11.7kg). The mean weight loss of 3.0kg (-0.4 to 6.4kg) for the severe pain group was 5.1kg (-0.6 to 10.7, p = 0.08) lower than the none-to-mild pain group and 5.3kg (0.4 to 10.2kg, p = 0.03) lower than the moderate pain group.Patients with severe pain upon entry to a specialist weight management service in England achieve a smaller mean weight loss at one-year follow-up than those with none-to-moderate pain. The magnitude of the difference in mean weight loss was clinically relevant, highlighting the importance of addressing severe persistent pain in obese patients undertaking weight management programmes

The fundamental left-right asymmetry in the Germanic verb cluster

Cinque (2005, 2009, 2014a) observes that there is an asymmetry in the possible ordering of dependents of a lexical head before versus after the head. A reflection on some of the concepts needed to develop Cinque’s ideas into a theory of neutral word order reveals that dependents need to be treated separately by class. The resulting system is applied to the problem of word order in the Germanic verb cluster. It is shown that there is an extremely close match between theoretically derived expectations for clusters made up of auxiliaries, modals, causative ‘let’, a main verb, and verbal particles. The facts point to the action of Cinque’s fundamental left-right asymmetry in language in the realm of the verb cluster. At the same time, not all verb clusters fall under Cinque’s generalization, which, therefore, argues against treating all cases of restructuring uniformly

Integrity of SRP RNA is ensured by La and the nuclear RNA quality control machinery

The RNA component of signal recognition particle (SRP) is transcribed by RNA polymerase III, and most steps in SRP biogenesis occur in the nucleolus. Here, we examine processing and quality control of the yeast SRP RNA (scR1). In common with other pol III transcripts, scR1 terminates in a U-tract, and ma-ture scR1 retains a U4–5 sequence at its 3 ′ end. In cells lacking the exonuclease Rex1, scR1 terminates in a longer U5–6 tail that presumably represents the primary transcript. The 3 ′ U-tract of scR1 is protected from aberrant processing by the La homologue, Lhp1 and overexpressed Lhp1 apparently competes with both the RNA surveillance system and SRP assem-bly factors. Unexpectedly, the TRAMP and exosome nuclear RNA surveillance complexes are also impli-cated in protecting the 3 ′ end of scR1, which accu-mulates in the nucleolus of cells lacking the activities of these complexes. Misassembled scR1 has a pri-mary degradation pathway in which Rrp6 acts early, followed by TRAMP-stimulated exonuclease degra-dation by the exosome. We conclude that the RNA surveillance machinery has key roles in both SRP biogenesis and quality control of the RNA, poten-tially facilitating the decision between these alterna-tive fates

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Alternative Approaches to On-Farm Research and Technology Exchange

Decision Case Studies are Ideal for On-Farm Research R. Kent Crookston, University of Minnesota . . . . . . . . . . . . . . . . . . . . . . . . .. I Use of On-Farm Research by Farmers for Technology Development and Transfer Stewart Wuest, Baird Miller, Stephen Guy, Russ Karow, Rojer Veseth, and Donald Wysocki, Washington State U., U. of Idaho, Oregon State U. . ...... 7 Best Information for Choosing Crop Varieties Dale Hicks and Robert Stucker, University of Minnesota . . . .. …….. 13 Adaptability Analysis for Diverse Environments Peter Hildebrand and John Russell, University of Florida ………… 19 Washington State University, .................................. 29 Complementary Abilities and Objectives in On-Farm Research Derrick Exner, Iowa State University ............................. 33 Credibility of On-Farm Research in Future Information Networks Charles Francis, University of Nebraska-Lincoln ...................... 37 Recent Papers Related to On-Fann Research Participatory Research and Other Sharing of Experience Committee Report Summarized by Charles Francis, U. Nebraska - Lincoln; from W.K. Kellogg Foundation Cluster Workshop, Integrated Farming Systems, Santa Cruz, California; February 23, 1995 . . . . . . . . . . . . . . . . . . . . . . . . .. 51 On-Farm Research Emerson Nafziger, University of Illinois (Chapter 19 from 1994 book from Department of Agronomy, U. Illinois. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 55 Responsive Constructivist Requirements Engineering: a Paradigm Michael Mayhew and Samuel Alessi, Iowa State Univ. and USDA/ARS, Morris, Minnesota (In Systems Engineering: A Competitive Edge in a Changing World, J. T. Whalen, D. J. Sifferman, and R. Olson, eds. Proc. 4th Ann. Int. Sym. Natl. Council on Systems Engin., Aug. 10-12, 1994. San Jose, CA) . . . . . . . . . . . . .. 61 On-Farm Research in Kansas, 1993: Summarized Results of a Farmer Opinion Survey Stay Freyenberger, Kansas St.ate University (unpublished) . . . . . . . . . . . . . . . .. 69 On-Farm Experiment Designs and Implications for Locating Research Sites Phil Rzewnicki, Richard Thompson, Gary Lesoing, Roger Elmore, Charles Francis, Anne Parkhurst, and Russell Moomaw, U. Nebraska and Practical Farmers of Iowa (Amer. J. Altern. Agric. 3:168-173. 1988) . . . . . . . . . . . . . . . . . . . . . . . . .. 81 Establishing the Proper Role for On-Farm Research William Lockeretz, Tufts University (Amer. J. Altern. Agric. 2:132-136. 1987) 87 Farmer Participation in Research and Extension: N Fertilizer Response in Crop Rotation Alan Franzleubbers and Charles Francis, University of Nebraska (J. Sustain. Agric. 2:9-30. 1991) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 93 Modified Stability Analysis of Farmer Managed, On-Farm Trials Peter Hildebrand, Univ. of Florida (Agron. J. 76:271-274. 1984) ............ 105 Farmer Initiated On-Farm Research Ron Rosmann, Practical Farmers of Iowa (Amer. J. Altern. Agric. 9:34-37. 1994) . 109 Participatory Strategies for Information Exchange Charles Francis, James King, Jerry DeWitt, James Bushnell, and Leo Lucas, Univ. of Nebraska and Iowa State Univ. (Amer. J. Altern. Agric. 5:153-160.1990) 113 Farmer Participation in Research: A Model for Adaptive Research and Education John Gerber, Univ. of Massachusetts (Amer. 1. Altern. Agric. 7:118-121. 1992) ... 121 Communicating between Farmers and Scientists: A Story about Stories Connie and Doc Hatfield, Preston and Wanda Boop, and Ray William, Oregon and Pennsylvania Farmers, and Oregon State Univ. (Amer. J. Altern. Agric. 9: 186-187. 1994). . ........................ 125 On-Farm Sustainable Agriculture Reseach: Lessons from the Past, Directions for the Future Donald Taylor, South Dakota State Univ. (J. Sustain. Agric. 1:43-86. 1990) ..... 127 Farmers\u27 Use of Validity Cues to Evaluate Reports of Field-Scale Agricultural Research Gerry Walter, Univ. of Illinois (Amer. J. Altern. Agric. 8:107-117.1993) ...... 15

Communities in Control: A mixed method evaluation of the Big Local community empowerment initiative in England - First Look Summary

BACKGROUND: Most research on community empowerment provides evidence on engaging communities for health promotion purposes rather than attempts to create empowering conditions. This study addresses this gap. INTERVENTION: Big Local started in 2010 with £271M from the National Lottery. Ending in 2026, it gives 150 relatively disadvantaged communities in England control over £1M to improve their neighbourhoods. OBJECTIVE: To investigate health and social outcomes, at the population level and among engaged residents, of the community engagement approach adopted in a place-based empowerment initiative. STUDY DESIGN, DATA SOURCES AND OUTCOME VARIABLES: This study reports on the third wave of a longitudinal mixed-methods evaluation. Work package 1 used a difference-in-differences design to investigate the impact of Big Local on population outcomes in all 150 Big Local areas compared to matched comparator areas using secondary data. The primary outcome was anxiety; secondary outcomes included a population mental health measure and crime in the neighbourhood. Work package 2 assessed active engagement in Big Local using cross-sectional data and nested cohort data from a biannual survey of Big Local partnership members. The primary outcome was mental well-being and the secondary outcome was self-rated health. Work package 3 conducted qualitative research in 14 Big Local neighbourhoods and nationally to understand pathways to impact. Work package 4 undertook a cost-benefit analysis using the life satisfaction approach to value the benefits of Big Local, which used the work package 1 estimate of Big Local impact on life satisfaction. RESULTS: At a population level, the impacts on 'reporting high anxiety' (-0.8 percentage points, 95% confidence interval -2.4 to 0.7) and secondary outcomes were not statistically significant, except burglary (-0.054 change in z-score, 95% confidence interval -0.100 to -0.009). There was some effect on reduced anxiety after 2017. Areas progressing fastest had a statistically significant reduction in population mental health measure (-0.053 change in z-score, 95% confidence interval -0.103 to -0.002). Mixed results were found among engaged residents, including a significant increase in mental well-being in Big Local residents in the nested cohort in 2018, but not by 2020; this is likely to be COVID-19. More highly educated residents, and males, were more likely to report a significant improvement in mental well-being. Qualitative accounts of positive impacts on mental well-being are often related to improved social connectivity and physical/material environments. Qualitative data revealed increasing capabilities for residents' collective control. Some negative impacts were reported, with local factors sometimes undermining residents' ability to exercise collective control. Finally, on the most conservative estimate, the cost-benefit calculations generate a net benefit estimate of £64M. MAIN LIMITATIONS: COVID-19 impacted fieldwork and interpretation of survey data. There was a short 4-year follow-up (2016/20), no comparators in work package 2 and a lack of power to look at variations across areas. CONCLUSIONS: Our findings suggest the need for investment to support community organisations to emerge from and work with communities. Residents should lead the prioritisation of issues and design of solutions but not necessarily lead action; rather, agencies should work as equal partners with communities to deliver change. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research Programme (16/09/13) and will be published in full in Public Health Research; Vol. 11, No. 9. See the NIHR Journals Library website for further project information

Investigating health and social outcomes of the Big Local community empowerment initiative in England: a mixed method evaluation.

BackgroundMost research on community empowerment provides evidence on engaging communities for health promotion purposes rather than attempts to create empowering conditions. This study addresses this gap.InterventionBig Local started in 2010 with £271M from the National Lottery. Ending in 2026, it gives 150 relatively disadvantaged communities in England control over £1M to improve their neighbourhoods.ObjectiveTo investigate health and social outcomes, at the population level and among engaged residents, of the community engagement approach adopted in a place-based empowerment initiative.Study design, data sources and outcome variablesThis study reports on the third wave of a longitudinal mixed-methods evaluation. Work package 1 used a difference-in-differences design to investigate the impact of Big Local on population outcomes in all 150 Big Local areas compared to matched comparator areas using secondary data. The primary outcome was anxiety; secondary outcomes included a population mental health measure and crime in the neighbourhood. Work package 2 assessed active engagement in Big Local using cross-sectional data and nested cohort data from a biannual survey of Big Local partnership members. The primary outcome was mental well-being and the secondary outcome was self-rated health. Work package 3 conducted qualitative research in 14 Big Local neighbourhoods and nationally to understand pathways to impact. Work package 4 undertook a cost-benefit analysis using the life satisfaction approach to value the benefits of Big Local, which used the work package 1 estimate of Big Local impact on life satisfaction.ResultsAt a population level, the impacts on 'reporting high anxiety' (-0.8 percentage points, 95% confidence interval -2.4 to 0.7) and secondary outcomes were not statistically significant, except burglary (-0.054 change in z-score, 95% confidence interval -0.100 to -0.009). There was some effect on reduced anxiety after 2017. Areas progressing fastest had a statistically significant reduction in population mental health measure (-0.053 change in z-score, 95% confidence interval -0.103 to -0.002). Mixed results were found among engaged residents, including a significant increase in mental well-being in Big Local residents in the nested cohort in 2018, but not by 2020; this is likely to be COVID-19. More highly educated residents, and males, were more likely to report a significant improvement in mental well-being. Qualitative accounts of positive impacts on mental well-being are often related to improved social connectivity and physical/material environments. Qualitative data revealed increasing capabilities for residents' collective control. Some negative impacts were reported, with local factors sometimes undermining residents' ability to exercise collective control. Finally, on the most conservative estimate, the cost-benefit calculations generate a net benefit estimate of £64M.Main limitationsCOVID-19 impacted fieldwork and interpretation of survey data. There was a short 4-year follow-up (2016/20), no comparators in work package 2 and a lack of power to look at variations across areas.ConclusionsOur findings suggest the need for investment to support community organisations to emerge from and work with communities. Residents should lead the prioritisation of issues and design of solutions but not necessarily lead action; rather, agencies should work as equal partners with communities to deliver change.FundingThis project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research Programme (16/09/13) and will be published in full in Public Health Research; Vol. 11, No. 9. See the NIHR Journals Library website for further project information