Background: Health-related quality of life (HRQoL) among patients with localized prostate cancer (PC) on active surveillance (AS) and whether it may be improved through lifestyle-focused interventions remain underdefined. Objective: To assess longitudinal changes in HRQoL in patients who received and those who did not receive a behavioral intervention that increased vegetable intake. Design, setting, and participants: A secondary analysis of participants in the Men's Eating and Living (MEAL) study (Cancer and Leukemia Group 70807 [Alliance]), a randomized trial of vegetable consumption in patients on AS, was conducted. Outcome measurements and statistical analysis: Patient-reported outcomes (PROs) included the Memorial Anxiety Scale for Prostate Cancer (MAX-PC), the Expanded Prostate Cancer Index Composite 26 (EPIC-26), and the Functional Assessment of Cancer Therapy Scale-Prostate (FACT-P). Areas under the curves (AUCs) were used to summarize serial HRQoL. Results and limitations: PROs were completed in 87% (n = 387) of the intention-tocollect population. Baseline characteristics of patients completing HRQoL measures did not differ significantly from the entire study population or between groups. Baseline scores were high for all PROs and remained stable over 24 mo, with no significant differences from baseline at any time point. In adjusted analyses, there were no significant differences in summary AUC measures comparing control with intervention for the total MAX-PC score (p = 0.173); EPIC-26 domains of urinary incontinence (p = 0.210), urinary obstruction (p = 0.062), bowel health (p = 0.607), sexual health (p = 0.398), and vitality (p = 0.363); and total FACT-P scores (p = 0.471). Conclusions: Among men with localized PC on AS enrolled in a randomized trial, HRQoL was high across multiple domains at baseline, remained high during follow-up, and did not change in response to a behavioral intervention that increased vegetable intake. Patient summary: Patients with localized prostate cancer enrolled on active surveillance experience minimal cancer-associated anxiety, suffer low levels of cancer-associated symptoms, and perceive high physical and emotional well-being. (C) 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Background Lymphedema is an adverse effect of breast cancer treatment that causes swelling and pain in the arm and hand. We tested 2 lymphedema prevention interventions and their impact on health-related quality of life (HRQOL) in a group-randomized trial at 38 cooperative group sites within the United States. Methods Patients were recruited before breast surgery. Sites were randomly assigned to education-only (EO) lymphedema prevention or education plus exercise and physical therapy (LEAP). Lymphedema was defined as a >= 10% difference in arm volume at any time from baseline to 18 months postsurgery. HRQOL was assessed using the Functional Assessment of Cancer Therapy-Breast plus 4 lymphedema items (FACT-B+4). Longitudinal mixed model regression analysis, adjusting for key demographic and clinical variables, examined participants' HRQOL by intervention group and lymphedema status. Results A total of 547 patients (56% LEAP) were enrolled and completed HRQOL assessments. The results revealed no differences between the interventions in preventing lymphedema (P= .37) or HRQOL (FACT-B+4 total score;P= .8777). At 18 months, the presence of lymphedema was associated with HRQOL at borderline significance (P= .0825). However, African American patients reported greater lymphedema symptoms (P= .0002) and better emotional functioning (P= .0335) than patients of other races or ethnicities. Lower HRQOL during the intervention was associated with younger age (P <= .0001), Eastern Cooperative Oncology Group performance status >0 (P= .0002), >= 1 positive lymph nodes (P= .0009), having no education beyond high school (P< .0001), having undergone chemotherapy (P= .0242), and having had only axillary node dissection or sentinel node biopsy versus both (P= .0007). Conclusion The tested interventions did not differ in preventing lymphedema or in HRQOL outcomes. African American women reported greater HRQOL impacts due to lymphedema symptoms than women of other races or ethnicities.

ImportanceGuidelines endorsing vegetable-enriched diets to improve outcomes for prostate cancer survivors are based on expert opinion, preclinical studies, and observational data.ObjectiveTo determine the effect of a behavioral intervention that increased vegetable intake on cancer progression in men with early-stage prostate cancer.Design, Setting, and ParticipantsThe Men's Eating and Living (MEAL) Study (CALGB 70807 [Alliance]) was a randomized clinical trial conducted at 91 US urology and medical oncology clinics that enrolled 478 men aged 50 to 80 years with biopsy-proven prostate adenocarcinoma (International Society of Urological Pathology grade group = 1 in those <70 years and ≤2 in those ≥70 years), stage cT2a or less, and serum prostate-specific antigen (PSA) level less than 10 ng/mL. Enrollment occurred from January 2011 to August 2015; 24-month follow-up occurred from January 2013 to August 2017.InterventionsPatients were randomized to a counseling behavioral intervention by telephone promoting consumption of 7 or more daily vegetable servings (MEAL intervention; n = 237) or a control group, which received written information about diet and prostate cancer (n = 241).Main Outcomes and MeasuresThe primary outcome was time to progression; progression was defined as PSA level of 10 ng/mL or greater, PSA doubling time of less than 3 years, or upgrading (defined as increase in tumor volume or grade) on follow-up prostate biopsy.ResultsAmong 478 patients randomized (mean [SD] age, 64 [7] years; mean [SD] PSA level, 4.9 [2.1] ng/mL), 443 eligible patients (93%) were included in the primary analysis. There were 245 progression events (intervention: 124; control: 121). There were no significant differences in time to progression (unadjusted hazards ratio, 0.96 [95% CI, 0.75 to 1.24]; adjusted hazard ratio, 0.97 [95% CI, 0.76 to 1.25]). The 24-month Kaplan-Meier progression-free percentages were 43.5% [95% CI, 36.5% to 50.6%] and 41.4% [95% CI, 34.3% to 48.7%] for the intervention and control groups, respectively (difference, 2.1% [95% CI, -8.1% to 12.2%]).Conclusions and RelevanceAmong men with early-stage prostate cancer managed with active surveillance, a behavioral intervention that increased vegetable consumption did not significantly reduce the risk of prostate cancer progression. The findings do not support use of this intervention to decrease prostate cancer progression in this population, although the study may have been underpowered to identify a clinically important difference.Trial RegistrationClinicalTrials.gov Identifier: NCT01238172.

Background Lymphedema affects many women who are treated for breast cancer. We examined the effectiveness of an education-only (EO) versus education plus sleeve compression/exercise intervention (lymphedema education and prevention [LEAP]) on lymphedema incidence and range of motion (ROM) in a group-randomized trial across 38 cooperative group sites. Methods The treating institution was randomly assigned to either EO or LEAP by a study statistician. All patients at a treating institution participated in the same intervention (EO or LEAP) to minimize contamination bias. Participants completed surveys, arm volume measurements, and self-reported ROM assessments before surgery and at 12 and 18 months after surgery. Lymphedema was defined as a >= 10% difference in limb volume at any time post-surgery up to 18 months after surgery or diagnosis by a health provider. Cochran-Mantel-Haenszel tests were used to compare lymphedema-free rates between groups, stratified by lymph node surgery type. Self-reported ROM differences were compared between groups. Results A total of 554 participants (56% LEAP) were included in the analyses. At 18 months, lymphedema-free rates were 58% (EO) versus 55% (LEAP) (P= .37). ROM for both arms was greater in LEAP versus EO at 12 months; by 18 months, most women reported full ROM, regardless of group. In LEAP, only one-third wore a sleeve >= 75% of the time; 50% performed lymphedema exercises at least weekly. Conclusion Lymphedema incidence did not differ by intervention group at 18 months. Poor adherence in the LEAP group may have contributed. However, physical therapy may speed recovery of ROM. Further research is needed to effectively reduce the incidence and severity of lymphedema in patients who have breast cancer.

You have accessJournal of UrologyPlenary: Next Frontier1 Apr 2018LBA19 THE MEN’S EATING AND LIVING (MEAL) STUDY (CALGB 70807 [ALLIANCE]): A RANDOMIZED CLINICAL TRIAL OF A DIET INTERVENTION IN MEN ON ACTIVE SURVEILLANCE FOR PROSTATE CANCER J Parsons, David Zarieh, John Pierce, James Mohler, Electra Paskett, Donna Hansel, Adam Kibel, Olwen Hahn, John Taylor, Robert Grubb, Sean Stroup, Eric Small, Peter Van Veldhuizen, Michael Morris, and James Marshall J ParsonsJ Parsons More articles by this author , David ZariehDavid Zarieh More articles by this author , John PierceJohn Pierce More articles by this author , James MohlerJames Mohler More articles by this author , Electra PaskettElectra Paskett More articles by this author , Donna HanselDonna Hansel More articles by this author , Adam KibelAdam Kibel More articles by this author , Olwen HahnOlwen Hahn More articles by this author , John TaylorJohn Taylor More articles by this author , Robert GrubbRobert Grubb More articles by this author , Sean StroupSean Stroup More articles by this author , Eric SmallEric Small More articles by this author , Peter Van VeldhuizenPeter Van Veldhuizen More articles by this author , Michael MorrisMichael Morris More articles by this author , and James MarshallJames Marshall More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.03.090AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Diet modifies the risks of prostate cancer incidence and progression. We tested the efficacy of a high-vegetable diet to prevent clinical progression in prostate cancer patients on active surveillance METHODS In the Men′s Eating and Living (MEAL) Study (CALGB 70807 [Alliance]), we randomized (1:1) eligible participants to a telephone-based, validated diet counseling intervention promoting vegetable intake or to a control condition for 2 years. Eligibility criteria included age 50 to 80 years; biopsy-proven adenocarcinoma of the prostate; diagnosis ≤ 24 months prior to presentation with ≥ 10-core prostate biopsy in which < 25% of the total number of cores and ≤ 50% of any single core contained cancer; Gleason sum ≤ 6 for men ≤ 70 years and Gleason sum ≤ (3 + 4) = 7 for men > 70 years; clinical stage ≤ T2a; and serum PSA < 10 ng/mL. Randomization was stratified by age (> 70 years vs. ≥ 70 years), race (African American vs. Other) and time since diagnostic biopsy (0-12 months vs. > 12 and ≤ 24 months). The primary outcome was clinical progression defined as serum prostate-specific antigen (PSA) ≥ 10 ng/mL, PSA doubling time (PSADT) < 3 years, or pathological progression on follow-up biopsy. The primary endpoint was time to progression (TTP), defined as the length of time from the date of random assignment to clinical progression; patients who died from any cause without experiencing progression were censored at the time of death and patients who elected to pursue treatment despite not meeting the criteria for progression were censored at the time of withdrawal. The primary analysis will be based on all randomized patients, but exclude those patients who later became ineligible by centralized pathology review of their baseline tissue specimens. Secondary outcomes included the incidence of definitive treatment for prostate cancer. RESULTS From 2011 to 2015, 478 (103%) of a targeted 464 patients were randomized at 91 study sites. Final results for the primary and secondary outcomes comparing intervention to control will be presented. CONCLUSIONS The MEAL Study is the first national, multi-institutional phase III clinical trial of a diet intervention for prostate cancer. These results may substantially inform clinical care of prostate cancer patients. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1077 Advertisement Copyright & Permissions© 2018MetricsAuthor Information J Parsons More articles by this author David Zarieh More articles by this author John Pierce More articles by this author James Mohler More articles by this author Electra Paskett More articles by this author Donna Hansel More articles by this author Adam Kibel More articles by this author Olwen Hahn More articles by this author John Taylor More articles by this author Robert Grubb More articles by this author Sean Stroup More articles by this author Eric Small More articles by this author Peter Van Veldhuizen More articles by this author Michael Morris More articles by this author James Marshall More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

BACKGROUND:Treatments for localized prostate cancer present challenging tradeoffs in the face of uncertain treatment benefits. These options are best weighed in a process of shared decision-making with the patient's healthcare team. Minority men experience disparities in prostate cancer outcomes, possibly due in part to a lack of optimal communication during treatment selection. Decision aids facilitate shared decision-making, improve knowledge of treatment options, may increase satisfaction with treatment choice, and likely facilitate long-term quality of life. METHODS/DESIGN:This study will compare the effect of two evidence-based decision aids on patient knowledge and on quality of life measured one year after treatment, oversampling minority men. One decision aid will be administered prior to specialist consultation, preparing patients for a treatment discussion. The other decision aid will be administered within the consultation to facilitate transparent, preference-sensitive, and evidence-informed deliberations. The study will utilize a four-arm, block-randomized design to test whether each decision aid alone (Arms 1 and 2) or in combination (Arm 3) can improve patient knowledge and quality of life compared to usual care (Arm 4). The study, funded by the National Cancer Institute's Community Oncology Research Program (NCORP), will be deployed within select institutions that have demonstrated capacity to recruit minority populations into urologic oncology trials. DISCUSSION:Upon completion of the trial, we will have 1) tested the effectiveness of two evidence-based decision aids in enhancing patients' knowledge of options for prostate cancer therapy and 2) estimated whether decision aids may improve patient quality of life one year after initial treatment choice. TRIAL REGISTRATION:Clinicaltrials.gov: NCT03103321 . The trial registration date (on ClinicalTrials.gov) was April 6, 2017.

OBJECTIVE:To assess the feasibility of performing national, randomized trials of dietary interventions for localized prostate cancer.METHODS:The Men's Eating and Living (MEAL) study (CALGB 70807 [Alliance]) is a phase III clinical trial testing the efficacy of a high-vegetable diet to prevent progression in patients with prostate cancer on active surveillance (AS). Participants were randomized to a validated diet counselling intervention or to a control condition. Chi-squared and Kruskal-Wallis analyses were used to assess between-group differences at baseline.RESULTS:Between 2011 and 2015, 478 (103%) of a targeted 464 patients were randomized at 91 study sites. At baseline, the mean (sd) age was 64 (6) years and mean (sd) PSA concentration was 4.9 (2.1) ng/mL. Fifty-six (12%) participants were African-American, 17 (4%) were Hispanic/Latino, and 16 (3%) were Asian-American. There were no significant between-group differences for age (P = 0.98), race/ethnicity (P = 0.52), geographic region (P = 0.60), time since prostate cancer diagnosis (P = 0.85), PSA concentration (P = 0.96), clinical stage (T1c or T2a; P = 0.27), or Gleason sum (Gleason 6 or 3+4 = 7; P = 0.76). In a pre-planned analysis, the baseline prostate biopsy samples of the first 50 participants underwent central pathology review to confirm eligibility, with an expectation that <10% would become ineligible. One of 50 participants (2%) became ineligible.CONCLUSION:The MEAL study shows the feasibility of implementing national, multi-institutional phase III clinical trials of diet for prostate cancer and of testing interventions to prevent disease progression in AS.

We examine the renormalization of the first order formulation of the Yang–Mills theory, by using the BRST identities. These preserve the gauge invariance of the theory and enable a recursive proof of renormalizability to higher orders in perturbation theory. The renormalization involves non-linear mixings as well as re-scalings of the fields and sources, which lead to a renormalized action at all orders.

BACKGROUND:Diet may substantially alter prostate cancer initiation and progression. However, large-scale clinical trials of diet modification have yet to be performed for prostate cancer. The Men's Eating and Living (MEAL) Study (CALGB 70807 [Alliance]) is investigating the effect of increased vegetable consumption on clinical progression in men with localized prostate cancer. STUDY DESIGN:MEAL is a randomized, phase III clinical trial designed to test whether an intervention that increases vegetable intake will decrease the incidence of clinical progression in men with clinically localized prostate cancer on active surveillance. We are randomizing 464 patients to either a validated telephone-based diet counseling intervention or a control condition in which patients receive a published diet guideline. The intervention will continue for two years. The primary outcome variable is clinical progression defined by serum prostate-specific antigen (PSA) and pathological findings on follow-up prostate biopsy. Secondary outcome variables include incidence of surgical and non-surgical treatments for prostate cancer, prostate-cancer related patient anxiety and health-related quality of life. CONCLUSION:The MEAL Study is assessing the effectiveness of a high-vegetable diet intervention for preventing clinical progression in men with localized prostate cancer on active surveillance.

The methionine adenosyltransferase from the thermophile Methanococcus jannaschii is fully and irreversibly unfolded in the presence of guanidinium chloride. Unfolding of this dimeric protein is a three-state process in which a dimeric intermediate could be identified. The less stable secondary structural elements of the protein are the C-terminal ends of β-strands E2 and E6, as deduced from the behavior of tyrosine to tryptophan mutants at residues 72 and 170, which are located in the subunit interface. Unraveling of these elements at the monomer interface may soften intersubunit interactions, leading to the observed 85% activity loss. Accumulation of the intermediate was associated with maintenance of residual activity, an increase in the elution volume of the protein upon gel filtration and a decrease in the sedimentation coefficient. Elimination of the remaining enzymatic activity occurred in conjunction with a 50% reduction in helicity and fluorescence alterations illustrating a transient burial of tryptophans at β-strands E2, E3 and E9. The available 3D-model predicted that these β-strands are involved in the central and N-terminal domains of the monomer structure. Severe perturbation of this area of the monomer–monomer interface may destroy the remaining intermolecular interactions, thus leading to dissociation and aggregation. Finally, transition to the denatured state includes completion of the changes detected in the microenvironments around tryptophans included at α-helixes H5 and H6, the loops connecting H5–E8 and E9, β-strands E3 and E12.

In the Coulomb gauge of QCD. the Hamiltonian contains a nonlinear Christ-Lee term, which may alternatively be derived from a careful treatment of ambiguous Feynman integrals at 2-loop order. We investigate how and if UV divergences from higher order graphs can be consistently absorbed by renormalization of the Christ-Lee term. We find that they cannot. (C) 2010 Elsevier Inc. All rights reserved.

We investigate the dynamics of a resistively shunted Josephson junction. We compute the Josephson frequency and the generalized impedances for a variety of the parameters, particularly with relevance to predicting the measurable effects of zero-temperature current noise in the resistor.

Archaea contain a class of methionine adenosyltransferases (MATs) that exhibit substantially higher stability than their mesophilic counterparts. Their sequences are highly divergent, but preserve the essential active site motifs of the family. We have investigated the origin of this increased stability using chemical denaturation experiments on Methanococcus jannaschii MAT (Mj-MAT) and mutants containing single tryptophans in place of tyrosine residues. The results from fluorescence, circular dichroism, hydrodynamic, and enzyme activity measurements showed that the higher stability of Mj-MAT derives largely from a tighter association of its subunits in the dimer. Local fluorescence changes, interpreted using secondary structure predictions, further identify the least stable structural elements as the C-terminal ends of β-strands E2 and E6, and the N-terminus of E3. Dimer dissociation however requires a wider perturbation of the molecule. Additional analysis was initially hindered by the lack of crystal structures for archaeal MATs, a limitation that we overcame by construction of a 3D-homology model of Mj-MAT. This model predicts preservation of the chain topology and three-domain organization typical of this family, locates the least stable structural elements at the flat contact surface between monomers, and shows that alterations in all three domains are required for dimer dissociation.

We study to one-loop order the renormalization of QCD in the Coulomb gauge using the Hamiltonian formalism. Divergences occur which might require counter-terms outside the Hamiltonian formalism, but they can be cancelled by a redefinition of the Yang–Mills electric field.

S-adenosylmethionine (AdoMet) lies at an intersection of nucleotide and amino acid metabolism and performs a multitude of metabolic functions. AdoMet formation is catalyzed by S-adenosylmethionine synthetase (ATP: L-methionine S-adenosyltransferase (MAT)), which is a target for development of anticancer and antimicrobial agents. High affinity MAT inhibitors have been found through computational docking of more than 200000 compounds for predicted binding to the crystallographically defined nucleotide binding region of the enzyme's active site. Two of the top scoring candidate compounds had IC(50) values less than 10 nM, more than 10000-fold lower than the substrates' K(M) values. The compounds are structurally unrelated to the natural ligands of the enzyme. The enzyme is protected from inhibition by ATP, but not by methionine, consistent with binding at the adenosyl region of the active site. These results validate in silico screening as a robust approach to the discovery of inhibitors of this chemotherapeutically relevant enzyme.

In recent decades, applied demography has emerged as a sub-field of demography partly in response to a growing demand from governments and private sector interests to better understand the implications of population trends for public policy and business strategy (Murdock and Ellis 1991; Siegel 2002). While in essence, this involves the practical application of demographic materials and methods (Siegel 2002: 2), the emphasis is on gaining knowledge of the consequences and concomitants of change in the size of populations, their distribution, composition and characteristics, so as to guide decision-making related to planning and the distribution of public or private sector goods and services for current and future use (Murdock and Ellis 1991: 6). This is precisely the empirical input that industry, government and Indigenous stakeholders have begun to identify as contributing to meaningful discussions about options for integrating the activities of mining operations with broader social and economic development goals in mine hinterlands. Accordingly, a push for profiling regional social and economic conditions has emerged from a coalition of these interests (Harvey and Brereton 2005).

There is growing evidence that some chronic diseases are caused, or promoted, by infectious disease. 'Population mixing' has been used as a proxy for the range and dose of infectious agents circulating in a community. Given the speculation over the role of population mixing in many chronic diseases, we review the various methods used for measuring population mixing, and provide a classification of these. We recommend that authors fulfill two criteria in publications: measures are demonstrably associated with the putative risk factors for which population-mixing is acting as a proxy and fundamental characteristics of the chosen measures are clearly defined.

I examine the arguments which have been given for quantum fluctuation–dissipation theorems. I distinguish between a weak form of the theorem, which is true under rather general conditions, and a strong form which requires a Langevin equation for its statement. I argue that the latter has not been reliably derived in general.