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Patients taking adjuvant endocrine therapy (AET) after breast cancer face adherence challenges and symptom-related distress. We conducted a randomized trial to evaluate the feasibility, acceptability, and preliminary efficacy of a telehealth intervention (Symptom-Targeted Randomized Intervention for Distress and Adherence to Adjuvant Endocrine Therapy [STRIDE]) for patients taking AET.From October 2019 to June 2021, 100 patients reporting difficulty with AET were randomly assigned to either STRIDE or a medication monitoring (MedMon) control group. STRIDE included six weekly small-group videoconferencing sessions and two individual calls. We defined feasibility as having50% of eligible patients enroll,70% complete the 12-week assessment, and 70% of STRIDE patients complete ≥4/6 sessions. We monitored adherence with the Medication Event Monitoring System Caps (MEMS Caps). At baseline and 12- and 24-weeks after baseline, patients self-reported adherence (Medication Adherence Report Scale), AET satisfaction (Cancer Therapy Satisfaction Questionnaire), symptom distress (Breast Cancer Prevention Trial-Symptom Checklist), self-management of symptoms (Self-efficacy for Symptom Management-AET), coping (Measure of Current Status), quality of life (QOL; Functional Assessment of Cancer Therapy-Breast), and mood (Hospital Anxiety and Depression Scale). We used linear mixed effects models to assess the effect of STRIDE on longitudinal outcomes.We enrolled 70.9% (100/141) of eligible patients; 92% completed the 12-week assessment, and 86% completed ≥4/6 STRIDE sessions. Compared with MedMon, STRIDE patients reported less symptom distress (B[difference] = -1.91; 95% CI, -3.29 to -0.52; p = .007) and better self-management of AET symptoms, coping, QOL, and mood. We did not observe significant differences in AET satisfaction or adherence.STRIDE is feasible and acceptable, showing promise for improving outcomes in patients taking AET after breast cancer.Patients taking adjuvant endocrine therapy (AET) after breast cancer may face challenges while following their treatment regimen. In this randomized controlled trial of 100 patients taking AET, a brief, small-group virtual intervention (STRIDE) was well-received by patients and led to improvements in how upset patients were due to symptoms, how confident they were in managing symptoms, and how well they could cope with stress. Thus, STRIDE is a promising intervention and should be tested in future multi-site trials.

Purpose: Identifying clinically relevant comorbidities and their effect on health-related quality of life (HRQoL) outcomes among men with advanced prostate cancer (APC) can inform patient care and improve outcomes; however, this is poorly understood. The aim of this observational study was to examine the prevalence of comorbidities, and the relationship of comorbidity burden to HRQoL and other patient-reported outcomes (PROs) among men with APC. Methods: Participants were 192 men (average age 68.8) with APC (stage III or IV) who completed a psychosocial battery including measures of sociodemographic factors, HRQoL and other PROs, and the Charlson Comorbidity Index (CCI). Hierarchical multiple regression analysis was used to examine the relationships between CCI, HRQOL, and PROs. Results: The vast majority (82%) of participants had at least one comorbidity, with the most common being: hypertension (59%), connective tissue disease or arthritis (31%), diabetes (24%), and problems with kidneys, vision, or another organ (24%). After controlling for covariates, regressions showed that a higher CCI score was significantly associated with worse HRQoL (p < 0.001), lower levels of positive affect (p < 0.05), and higher levels of depression (p < 0.05), fatigue (p < 0.001), pain (p < 0.01), stress (p < 0.01), and cancer-specific distress (p < 0.05). Conclusions: Comorbidities were common among men with APC, and a greater CCI score was associated with detriments in several domains of HRQoL and other PROs. Our findings show the need to address comorbidities in the presence of a cancer diagnosis and subsequent treatment.

Men with advanced prostate cancer (APC) experience high levels of pain, which contribute to poor psychosocial and functional outcomes. Cancer-related distress explains the relationship between pain severity and interference, yet specificity of distress characteristics (e.g., hyperarousal, intrusive, or avoidant symptoms) in explaining associations between pain experiences and well-being has not been explored within APC. This study examined men with APC entering a clinical trial and tested associations of baseline pain, cancer-related distress, and physical and functional well-being.One hundred ninety men with APC enrolled in a randomized-controlled trial and were assessed prior to randomization. The McGill Pain Questionnaire assessed pain severity, and the Functional Assessment of Cancer Therapy-General captures physical and functional well-being. The Impact of Events Scale-Revised measured cancer-specific distress symptoms, including hyperarousal, avoidance, and intrusion symptoms. Controlling for age, cancer stage at diagnosis, income, education, and race/ethnicity, mediation models (SPSS PROCESS, model 4) tested whether cancer-specific distress accounted for the associations between pain severity and physical and functional well-being.Men were on average 68 years of age, White non-Hispanic, with stage IV cancer. Pain severity was related to poorer physical (p .001) and functional well-being (p .001). Associations between pain severity and physical and functional well-being were partially mediated by greater intrusive and hyperarousal symptoms but not avoidant symptoms.For men with APC, intrusive and hyperarousal symptoms may partially explain the relationship between pain severity and decrements in physical and functional well-being. APC pain management should attend to such distress symptoms, which may contribute to interference if left unaddressed.ClinicalTrials.gov Identifier: NCT03149185.

Despite life-saving potential, many women struggle to adhere to adjuvant endocrine therapy (AET) for their breast cancer (BCa). Prior research has demonstrated that emotional distress is a barrier to AET adherence. We followed women from a trial to test the long-term effects of two 5-week post-surgical group-based stress management interventions, cognitive behavioral therapy (CBT), and relaxation training versus an attention-matched health education control, on AET adherence. We conducted a long-term follow-up (median = 8 years) of women randomized to CBT, relaxation training, or health education after surgery for stage 0–3 BCa. We measured adherence with the Endocrine Therapy Medication Usage Questionnaire (ETMUQ). First, we established factors on the ETMUQ via confirmatory factor analysis. We then used Bayesian structural equation modeling to regress these factors on study arm, controlling for age and treatments received. Of those who completed long-term follow-up (n = 59, 44.7%), over half (n = 33; 55.9%) reported problems with adherence generally. Women receiving relaxation training (n = 15) had better adherence than those receiving health education (n = 24) on the Forgetfulness/Inconsistency [B(SE) = 0.25(0.14), p = 0.049] and Intentional Nonadherence [B(SE) = 0.31(0.14), p = 0.018] factors of the ETMUQ. Similar results were observed for those receiving relaxation training compared to CBT (n = 20): Forgetfulness/Inconsistency [B(SE) = − 0.47(0.25), p = 0.031]; Intentional Nonadherence [B(SE) = − 0.31(0.15), p = 0.027]. Women receiving relaxation training were less likely to (1) forget to take their AET and (2) intentionally miss doses of AET in the long term compared to women receiving health education or CBT. This is evidence for the need of randomized trials that aim to improve adherence by incorporating theoretically based behavioral change techniques. Trial 2R01-CA-064710 was registered March 26, 2006.

Most patients report pain while taking adjuvant endocrine therapy (AET) for the treatment of breast cancer. While studies have examined patients' experiences with side effects, none solely capture patients' experiences with AET-related pain, a troubling symptom that reduces quality of life and impairs treatment adherence. This study explored themes of AET-related pain to inform future intervention development.Between November 2017 and November 2018, female patients (n = 30) with early-stage breast cancer enrolled between 3 and 36 months post-initiation of AET. Purposeful sampling was stratified by adherence level, age, distress level and time taking AET. Study staff conducted, transcribed and coded semi-structured interviews via inductive thematic coding to identify pain-related themes and achieved high inter-coded reliability (Kappa = 0.96).Several pain-related themes were observed. Attitudes around pain are generally negative, and management needs are largely unmet. Patients reported preferences for non-pharmacological management strategies and cited AET pain as a reason for medication breaks but not discontinuation. Patients within 19 months of starting AET and low adherers reported more intense and disruptive pain.Patients' experiences varied by patient attributes and revealed modifiable factors that may be targeted through behavioural interventions. AET-related pain is a complex side effect for which psychosocial support may be beneficial.

Targets of intervention in cognitive behavioral stress management (CBSM), such as benefit finding (BF) and perceived stress management skills (PSMS), may counteract stress-related changes that impact the immune system. This study tested whether BF, PSMS, and optimism influence the effects of CBSM on immune status in men with prostate cancer.Men with prostate cancer were randomized to receive CBSM or a psychoeducation (PE) control comparison (NCT05486754). Life Orientation Test-Revised assessed baseline optimism. The Benefit Finding Scale and Measure of Current Status measured BF and PSMS after CBSM. T-cells and T-helper cells captured immune status change at baseline and 6-months post-CBSM. MPlus and SPSS (PROCESS) tested condition effects and moderated mediation, controlling for covariates.256 primarily middle-aged, White Non-Hispanic or Hispanic men enrolled. PSMS mediated CBSM effects on T-cell and T-helper cell percentage, such that T-cell and T-helper cell percentages were reduced in men in CBSM versus PE via PSMS. Optimism moderated this mediation with the mediating effect of PSMS only observed among men with average optimism versus those with low or high optimism.Baseline psychological characteristics, as well as limited specificity of immune measurement, could explain the conditional effects in this sample.NCT05486754.

Cognitive behavioral stress management (CBSM) improves quality of life and mitigates stress biology in patients with early-stage cancer, including men with localized prostate cancer. However, treatments for advanced prostate cancer like androgen deprivation therapy (ADT) can lead to significant symptom burden that may be further exacerbated by stress-induced inflammation and cortisol dysregulation. The aim of this study was to examine the effects of CBSM (versus an active health promotion control) on circulating inflammatory markers and cortisol in men with advanced prostate cancer. Methods: Men with stage III or IV prostate cancer (N = 192) who had undergone ADT within the last year were randomized to CBSM or health promotion. Both interventions were 10 weeks, group-based, and delivered online. Venous blood was drawn at baseline, 6 months, and 12 months to measure circulating levels of CRP, IL-6, IL8, IL-10, and TNF-α. Saliva samples were collected at awakening, 30 minutes after awakening, evening, and night for two consecutive days at baseline, 6-months, and 12-months to measure diurnal cortisol slopes. Results: Mixed modeling analyses demonstrated that changes in inflammatory markers and cortisol did not differ by intervention. Men in both CBSM and health promotion showed decreases in IL-10, IL-8, and TNF-α from baseline to 6 months (β=−3.85–5.04, p’s=.004–

The mechanisms underlying memory loss associated with Alzheimer’s disease and related dementias (ADRD) remain unclear, and no effective treatments exist. Fundamental studies have shown that a set of transcriptional regulatory proteins of the nuclear receptor 4a (Nr4a) family serve as molecular switches for long-term memory. Here, we show that Nr4a proteins regulate the transcription of genes encoding chaperones that localize to the endoplasmic reticulum (ER). These chaperones fold and traffic plasticity-related proteins to the cell surface during long-lasting forms of synaptic plasticity and memory. Dysregulation of Nr4a transcription factors and ER chaperones is linked to ADRD, and overexpressing Nr4a1 or the chaperone Hspa5 ameliorates long-term memory deficits in a tau-based mouse model of ADRD, pointing toward innovative therapeutic approaches for treating memory loss. Our findings establish a unique molecular concept underlying long-term memory and provide insights into the mechanistic basis of cognitive deficits in dementia.

Objective Our goal was to examine potential predictors of a comprehensive operationalization of eating disorder recovery, characterized by physical, behavioral, and cognitive recovery, focusing on constructs related to self-concept, personality, and negative affect. Method Participants were women with a history of an eating disorder who provided data via survey and interview at two time points separated by about 7-8 years and who met criteria for an eating disorder diagnosis at baseline (N = 36). Results Logistic regression models revealed that self-esteem was a significant predictor of recovery status (OR = 1.12, p = .039) such that individuals with higher self-esteem at baseline demonstrated significantly greater odds of being in full recovery at follow-up. However, when self-esteem was considered in a set along with baseline imposter phenomenon and anxiety, no single construct emerged as a significant unique predictor of recovery in logistic regression analyses. Discussion These results highlight the potential importance of self-esteem in relation to recovery, with clinical implications related to bolstering self-esteem as part of eating disorder treatment. Future research should continue to explore predictors using a comprehensive operationalization of eating disorder recovery in larger, more diverse samples to optimally identify factors associated with achieving recovery.

Aged cheese is an increasingly popular dairy product. One approach to reduce Cheddar cheese maturation time is by utilizing elevated temperature, despite potential problems including development of imbalanced or off-flavors and negative changes in texture. Therefore, the objective of this study was to evaluate the influence of elevated ripening temperature on chemical and sensory properties of aged white Cheddar cheese. White Cheddar cheese was aged at 7.2, 10, or 12.8 °C for 12 months, with samples evaluated at 2, 5, 8, 10, 11, and 12 months by a trained sensory panel (n = 10). Two consumer sensory panels (n = 120) assessed 8- and 12-month aged cheese for comparison to a commercially available reference sample of the same cheese, aged for 12 months. An electronic tongue methodology was developed for analysis of nonvolatile compounds. Trained panel results showed that 2-month cheeses were described by milkfat flavor and sweet taste, 5-month cheeses were described by nutty aroma and white color, and 8-, 10-, 11-, and 12-month cheeses developed aged characteristics, such as umami and bitter tastes, brothy aroma, and aged flavor. Consumer panel results showed similar overall liking scores for the reference cheese and cheeses aged at 10 or 12.8 °C for both evaluations. The electronic tongue could classify samples according to aging month with a validity value of 92.59%. In conclusion, the electronic tongue served as a valid method of instrumental analysis for Cheddar cheese samples throughout maturation. This study demonstrated that aging white Cheddar cheese for 8 months at an elevated storage temperature of 10 °C produced cheese similar in consumer acceptance to that aged at 7 °C for 12 months. PRACTICAL APPLICATION: This study showed that aged white Cheddar storage at a higher temperature was perceived similarly by consumers as one stored for 1 year at a slightly lower temperature. This may be useful to those in the dairy industry exploring ways to accelerate aging, reducing devoted resources, while still producing an acceptable product. Also, the electronic tongue was effective at distinguishing among aged white Cheddar cheese samples showing another application for this technology.

BackgroundThere are few if any well-known approaches to reducing avoidable health care utilization and costs in patients with social needs. This study’s objective was to explore the goals, and approaches to organizing and delivering care, of interventions attempting to reduce avoidable resource use by addressing patients’ medical and social needs.MethodsSemi-structured interviews were conducted with study investigators about early interventions in the peer-reviewed literature. A template analysis approach was used to review interview transcripts for common themes and create a final code list. Coder dyads separately coded each interview and resolved any discrepancies.ResultsInterviews were conducted with 15 investigators of interventions that delivered a variety of health services and addressed several individual social needs. Participants frequently described their overall goal as meeting patients’ diverse needs to prevent unnecessary acute care utilization. Reported approaches to addressing medical needs included assistance with receipt of primary care and care coordination across settings. Social needs were described as tightly linked with medical needs; addressing social support and housing were perceived as distinct from addressing other social needs. Participants described their overall approach to meeting patients’ needs in terms of establishing connections, partnership, respect, and being adaptable to patients’ priorities.ConclusionsFindings shed new light on how to simultaneously address medical and social needs. Opportunities for future research include evaluating different approaches to addressing medical needs (primary care versus care coordination), separately evaluating the impacts of housing or social support, and hiring and training procedures to promote trauma-informed, patient-centered care.

BACKGROUND The emotional health of adolescent and young adult (AYA) cancer survivors is compromised both during and after cancer treatment. Targeted programs designed to support AYAs’ ability to cope with stress in the years following treatment completion are lacking. Mind-body programs may ameliorate the negative psychological and emotional effects of stress and assist AYAs with managing the psychosocial challenges of early survivorship. OBJECTIVE Our randomized waitlist-control trial aims to assess the feasibility, acceptability, and preliminary efficacy of a virtual group program (Bounce Back) to promote stress management and resiliency among posttreatment AYAs. METHODS Bounce Back is a stress management and resiliency program delivered via videoconference by a trained mental health clinician. Sessions were adapted from an evidence-based mind-body program (Stress Management and Resiliency Training - Relaxation Response Resiliency Program [SMART-3RP]) grounded in relaxation response elicitation, mindfulness, cognitive behavioral therapy, and positive psychology. Seventy-two AYAs (diagnosed with cancer between ages 14 years and 29 years and had completed cancer treatment within the last 5 years) were randomly assigned to the Bounce Back program or waitlist-control group and completed assessments at baseline, 3 months postbaseline, and 6 months postbaseline. The primary aim of the study is to determine the feasibility and acceptability of the Bounce Back program. Descriptive statistics, including means, frequencies, and ranges supplemented by qualitative exit interview feedback will be used to characterize the sample and to summarize feasibility and acceptability. The exploratory aims are to evaluate the preliminary effects of the program on stress coping and psychosocial outcome measures (ie, anxiety, depression) collected across the 3 time points. RESULTS This study was funded by the National Cancer Institute in July 2017. Study procedures were approved by the Dana-Farber Harvard Cancer Center Institutional Review Board in October 2018 (Protocol 18-428). The randomized trial was conducted from July 2019 to March 2021. Quantitative data collection is complete, and qualitative exit interview data collection is ongoing. Results are expected to be published in peer-reviewed journals and presented at local, national, or international meetings in the coming years. CONCLUSIONS Few evidence-based programs exist that tackle the key transitional issues faced by AYA cancer survivors. Future analyses will help us determine the feasibility and acceptability of the Bounce Back program and its impact on AYA stress coping and psychological well-being. CLINICALTRIAL ClinicalTrials.gov NCT03768336; https://clinicaltrials.gov/ct2/show/NCT03768336 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/34033

Purpose Research on principal supervisors (PSs) is an emerging field, and principal supervision for racial equity has not yet been studied or theorized. Conducted in partnership with practicing district leaders, the purpose of this paper is to examine current PS leadership in three districts at various points of engagement in equitable leadership practices and set forth a framework for conceptualizing systems equitable leadership practice. Design/methodology/approach This collaborative study emerged from an EdD course project in which groups of practitioner–scholars identified and collected qualitative interview, survey and artifact data about problems of practice in their districts. University researchers supported data collection and conducted analyses across settings, building on Ishimaru and Galloway’s (2014) equitable leadership practices framework. Findings Equitable PS leadership practices were variable. No district engaged with “proficiency” across all drivers of equitable leadership practice, but the district that engaged in equitable PS practices most deeply framed the work of schooling as a race-explicit endeavor, suggesting that framing is a fundamental driver. Research limitations/implications This paper builds on PS and equity-focused leadership research by adding a systems-level equity focus. Practical implications Findings suggest that districts should focus on equity framing as the foundation for principal support and development. Originality/value This researcher/practitioner–scholar collaboration shows how practitioner–scholars provide focus and expertise to the field unavailable to traditional researchers.

The field of educational leadership has also come to recognize the central importance of improving the quality of leadership preparation across leaders’ careers, including at the doctoral level, fo...

Objective: To summarize literature assessing the safety and efficacy of budesonide/formoterol, a low dose inhaled corticosteroid (ICS) and long-acting beta agonist (LABA) used as needed for the treatment of adult patients with mild persistent asthma requiring step 2 therapy compared to low dose inhaled corticosteroid (ICS) plus short-acting beta agonist (SABA) and SABA monotherapy. Data Sources: A literature search of PubMed (1966-October 2020), EMBASE (1973-October 2020) and clinicaltrials.gov was conducted using the following search terms: budesonide, formoterol, as needed, and mild asthma. Study selection and data extraction: Randomized, controlled trials with data describing as needed use of budesonide-formoterol in the treatment of mild, persistent asthma were included. Data synthesis: Current trials demonstrate a reduced risk of exacerbation and an improvement in symptom control in patients receiving budesonide/formoterol as needed when compared to as needed SABA alone. However, when compared to scheduled budesonide maintenance, patients receiving budesonide/formoterol as needed experienced worse symptom control and mixed exacerbation results. Relevance to patient care and clinical practice: This review evaluates the efficacy and safety of budesonide/formoterol as needed for patients with mild asthma. The Global Initiative for Asthma (GINA), a global strategy for asthma management and prevention adopted this change in 2019, and the most recent updated Expert Panel Report 4 of the National Asthma Education and Prevention Program (NAEPP) did not address this area. Conclusions: Based on this review of the literature, further study is needed to determine the place in therapy for budesonide/formoterol as needed in the treatment of mild persistent asthma. Low-dose ICS should remain the standard of therapy in patients with mild asthma requiring Step 2 therapy.

OBJECTIVES: To adapt and test the feasibility, acceptability, and preliminary efficacy of an 8-week resiliency group program for posttreatment lymphoma survivors. DESIGN AND OUTCOMES. This is an exploratory mixed methods study. Phase 1: We conducted qualitative interviews to inform program adaptation. Phase 2: Using a single-arm pilot design, we assessed program feasibility, acceptability, and preliminary efficacy (exploratory outcomes: stress coping, uncertainty intolerance, distress). We also examined the feasibility of collecting hair cortisol samples. RESULTS. Phase 1: Survivors reported feeling socially isolated as they grappled with lingering symptoms that interfered with their return to normalcy. Fears about recurrence triggered bodily hypervigilance. Survivors desired wellness programs that 1) target their whole-body experience, 2) promote social connectedness, and 3) manage fear of recurrence. Phase 2: Thirty-seven survivors enrolled. Participants completed a median of 7/8 sessions, and 76.9% completed ≥6/8 sessions; 65% provided a hair sample. Survivors demonstrated improvements in stress coping (d=.67), uncertainty tolerance (d=.71), and anxiety (d=.41) at program completion. CONCLUSIONS. Findings suggest promising feasibility and efficacy of this program in addressing posttreatment survivorship challenges, particularly fears of uncertainty. A cancer care model that adopts early integration of this program posttreatment has the potential to improve survivors’ emotional, social and physical well-being.

Machine harvest of ‘Brown Snout’ specialty cider apple (Malus ×domestica) has been shown to provide yield and juice quality characteristics similar to that of hand harvest. In this 2-year study, the sensory perception (color, aroma, flavor, mouthfeel, taste, and aftertaste) of ciders produced from machine-harvested and hand-harvested fruit that were ambient stored (56 °F) 0–4 weeks postharvest were compared using a trained panel and electronic tongue (e-tongue). For nearly all sensory attributes evaluated, the trained panelists scored the 2014 machine-harvested samples higher than the 2014 hand-harvested samples. Some of the key sensory differences included a darker color, a more astringent and heated mouthfeel, and a more sour taste of the machine-harvested samples than the hand-harvested samples. Trained panelists perceived no differences due to the harvest method among the 2015 samples for any of the sensory attributes evaluated. The e-tongue demonstrated good discrimination (index value = 95) of 2014 samples, but poor discrimination (index value = −0.5) of 2015 samples, mirroring the year-to-year variation experienced by the trained panelists. Overall, the e-tongue demonstrated a response to metallic and sour that was more associated with the machine-harvested samples and a response to sweet and umami that was more associated with the hand-harvested samples. These results demonstrate that cider made from machine-harvested fruit can have a different sensory profile than cider made from hand-harvested fruit. A consumer tasting panel should be conducted next to provide an indication of market response to the differing sensory profiles, qualifying the impact of harvest method. Results also indicate that ambient storage (56 °F) of fruit up to 4 weeks may not impact cider sensory attributes; however, cider apple growers should avoid ambient storage of machine-harvested fruit given the significant yield losses demonstrated in previous studies. Variation in cider quality due to year of harvest was most likely a result of differences in the hand-harvest technique between the 2 years, specifically more fruit bruising in 2014 than in 2015, demonstrating the importance of harvesting fully mature fruit with a standard protocol so as to supply a consistent raw material to cider producers. The e-tongue produced variable results compared with trained panelists and more development is needed before it can be incorporated into cider sensory evaluation protocol.

Rapid review products are intended to synthesize available evidence in a timely fashion while still meeting the needs of healthcare decision makers. Various methods and products have been applied for rapid evidence syntheses, but no single approach has been uniformly adopted. Methods to gain efficiency and compress the review time period include focusing on a narrow clinical topic and key questions; limiting the literature search; performing single (versus dual) screening of abstracts and full-text articles for relevance; and limiting the analysis and synthesis. In order to maintain the scientific integrity, including transparency, of rapid evidence syntheses, it is imperative that procedures used to streamline standard systematic review methods are prespecified, based on sound review principles and empiric evidence when possible, and provide the end user with an accurate and comprehensive synthesis. The collection of clinical preventive service recommendations maintained by the U.S. Preventive Services Task Force, along with its commitment to rigorous methods development, provide a unique opportunity to refine, implement, and evaluate rapid evidence synthesis methods and add to an emerging evidence base on rapid review methods. This paper summarizes the U.S. Preventive Services Task Force's use of rapid review methodology, its criteria for selecting topics for rapid evidence syntheses, and proposed methods to streamline the review process.

7005 Background: Studies suggest that decreased microbial diversity due to chemotherapeutic and antibiotic exposure may be associated with acute graft vs host disease (aGvHD) and mortality in patients undergoing allogeneic HSCT. In addition, disruption of the microbiome by antibiotics may lead to intestinal domination by pro-inflammatory bacteria, resulting in increased risk of aGvHD. This relationship has been described in settings with prophylactic antibiotic use, a standard of care in most transplant centers. Here we assessed how the microbiome and GvHD outcomes differ when prophylactic use of antibiotics is avoided. Methods: We collaborated on an observational study (COLLECT) to evaluate changes in microbial diversity over time in subjects undergoing allogeneic HSCT. According to protocol at the University Hospital of Cologne, antibiotics were administered only as empiric treatment for febrile neutropenia or as targeted treatment. Stool was collected weekly from 65 subjects at baseline (pre-HSCT) to day 28 with additional time points taken at day 56, day 90, day 365, and upon diagnosis of intestinal GvHD (GvHD-day 0 and GvHD-day 7). Patients were monitored for incidence of GvHD, including acute GvHD of the liver, intestine, and skin. Microbiome 16SV4 profiles were generated from 381 stool samples. Linear effects models were developed to evaluate the association between Shannon diversity, intestinal domination, and the incidence of intestinal GvHD and mortality. Results: Of the 65 subjects, 28 subjects (42%) went on to develop intestinal GvHD, and 16 subjects (25%) did not survive to day 365. A decline in Shannon diversity was observed during the neutropenic period following HSCT. Subjects who went on to develop intestinal GvHD had significantly lower Shannon diversity at the time of stem cell engraftment (p < 0.0468). Furthermore, lower diversity was observed throughout the study period in subjects experiencing intestinal GvHD. We developed a linear model evaluating the association between mortality and Shannon diversity and found a significant relationship at days 28 and 90 post HSCT (p < 0.0001 and 0.0121, resp). Intestinal domination by Enterobacteriaceae or Enterococcus was significantly associated with the incidence of intestinal GvHD (p < 0.0082) or mortality (p < 0.001), respectively. Conclusions: Data from this observational study (COLLECT) suggests decreases in microbial diversity over time occur in subjects undergoing allogeneic HSCT despite the lack of prophylactic antibiotics. Investigation of whether administration of microbiome therapeutic drugs prior to transplant and/or at the time of engraftment can reduce morbidity and mortality in this high-risk patient population is warranted. Clinical trial information: NCT03148197.

12061 Background: Despite life-saving potential, many women struggle to adhere to adjuvant endocrine therapy (AET) for their early-stage, hormone receptor-positive breast cancer. Prior research has demonstrated that emotional distress is a barrier to AET adherence. The current study aimed to test the long-term effects of two 5-week post-surgical group-based stress management interventions, cognitive behavioral therapy (CBT) and relaxation training (RT), versus an attention-matched health education (HE) control on AET adherence at long-term follow-up. Methods: We conducted long-term follow-up (median = 8 years, range = 7-11 years) of a cohort of women who enrolled in a randomized controlled trial of CBT vs. RT vs. HE shortly after surgery for stage 0-3 breast cancer.We measuredadherence with the Endocrine Therapy Medication Usage Questionnaire (ETMUQ) given at long-term follow-up. First, we established adherence factors on the ETMUQ via confirmatory factor analysis. We then used structural equation modeling to regress these factors on study arm, controlling for patient age, stage of disease, and treatments received (chemotherapy/radiation). Results: The sample was predominately middle-aged ( M= 54.81, SD= 10.19), White (41.5%) and Hispanic (42.2%), partnered (62.2%) with stage 1 (57.0%) or stage 2 (25.9%) disease. Of the women who completed long-term follow-up (N = 59, 44.7% of original sample); more than half (n = 30; 50.8%) reported having at least some problems with adherence. There was an effect of intervention group on adherence, such that women receiving RT (n = 15) had significantly better adherence than those receiving CBT (n = 20) on the factor measuring Forgetfulness/Inconsistency ( B(SE) =.57 (.34), p=.001), and marginally better adherence than those receiving CBT on the factor measuring Intentional Nonadherence ( B(SE) =.60 (.33), p =.062). There was no such effect when comparing RT or CBT to HE (n = 24). Conclusions: Women receiving RT were less likely to forget to take their AET and marginally less likely to intentionally miss doses of AET in the long-term compared to women receiving CBT. Future research could investigate the mechanism by which RT may improve adherence. For example, RT may reduce somatic symptoms related to AET or improve a patients’ self-efficacy to cope with these symptoms thereby reducing intentional non-adherence. In addition, RT may improve patients’ attention and awareness leading to less forgetfulness. Clinical trial information: NCT02103387.

The complex consequences of current consumption practices, such as climate change and ecosystem degradation, necessitate increased interdisciplinary exploration. In order to raise student awareness of these consumption-related issues, we designed a first-year team-taught seminar on sustainability. This innovative interdisciplinary course links geology and sociology in examining real-world problems through a variety of reflective, experiential, and collaborative activities. Our assessment of this course was based on a qualitative review of 18 students' reflective blog posts as a direct measure of student learning. While we continue to work on deepening the interconnections between geology and sociology and promoting student agency, students were successful in understanding the multifaceted complex nature of sustainability and recognizing the personal and social implications of consumption. Given these positive outcomes, we encourage the development of similar interdisciplinary collaborations.

Age-associated cognitive impairments affect an individual’s quality of life and are a growing problem in society. Therefore, therapeutic strategies to treat age-related cognitive decline are needed to enhance the quality of life among the elderly. Activation of the Nr4a family of transcription factors has been closely linked to memory formation and dysregulation of these transcription factors is thought to be associated with age-related cognitive decline. Previously, we have shown that Nr4A transcription can be activated by synthetic bis-indole derived compounds (C-DIM). C-DIM compounds enhance synaptic plasticity and long-term contextual fear memory in young healthy mice. In this study, we show that activation of Nr4a2 by 1,1-bis(3′-Indolyl)-1-(p-chlorophenyl) methane (C-DIM12), enhances long-term spatial memory in young mice and rescues memory deficits in aged mice. These findings suggest that C-DIM activators of Nr4a transcription may be suitable to prevent memory deficits associated with aging.

Objective Eating disorder recovery research has emphasized the absence of symptoms over the presence of adaptive aspects like positive body image and healthy eating attitudes. The current study examined how body appreciation and intuitive eating related to eating disorder recovery using a comprehensive recovery definition (physical, behavioral, and cognitive recovery). Method Data were collected from 66 women with an eating disorder history and 31 controls with no history of eating pathology. Participants completed an online survey followed by a phone interview. Results The fully recovered group did not differ from controls on body appreciation, with both groups endorsing significantly higher levels of body appreciation than the partially recovered and current eating disorder groups. Similarly, the fully recovered group did not differ from controls on overall intuitive eating, with both groups endorsing significantly higher levels of overall intuitive eating than the partially recovered and current eating disorder groups. Discussion Positive psychological constructs such as body appreciation and intuitive eating relate to eating disorder recovery status. Understanding recovery within a strengths-based framework may inform intervention and relapse prevention.

Patients with cancer are increasingly prescribed oral therapies, bearing greater responsibility for self-management of treatment adherence and adverse events. We conducted a randomized trial to test the use of a smartphone mobile app to improve symptoms and adherence to oral cancer therapy.From February 18, 2015, through December 31, 2016, 181 patients with diverse cancers who were prescribed oral therapy were randomized to receive either the smartphone mobile app or standard care. The mobile app included a medication plan with reminders, a symptom-reporting module, and patient education. Primary outcomes were adherence (per electronic pill caps), symptom burden (per MD Anderson Symptom Inventory), and quality of life (per the Functional Assessment of Cancer Therapy-General). Participants also completed self-report measures of medication adherence, anxiety and depression symptoms, social support, quality of care, and healthcare utilization. Linear regression was used to assess intervention effects on adherence and change in self-report outcomes from baseline to week 12, controlling for baseline scores and social support.Study groups did not differ across any outcome measure, with an overall mean adherence of 78.81% (SD, 26.66%) per electronic pill caps. However, moderation analyses showed that intervention effects on the primary adherence measure varied by baseline self-reported adherence and anxiety symptoms. Specifically, adherence rates per electronic pill caps were higher in patients randomized to the mobile app versus standard care within the subsamples of patients who reported baseline adherence problems (mean difference, -22.30%; 95% CI, -42.82 to -1.78; P=.034) and elevated anxiety (mean difference, -16.08%; 95% CI, -31.74 to -0.41; P=.044).Although the mobile app may not improve outcomes for all patients prescribed oral cancer therapy, the intervention may be beneficial for those with certain risk factors, such as difficulties with adherence or anxiety.

Many studies have examined relationships of microorganisms to geochemical zones in subseafloor sediment. However, responses to selective pressure and patterns of community succession with sediment depth have rarely been examined. Here we use 16S rDNA sequencing to examine the succession of microbial communities at sites in the Indian Ocean and the Bering Sea. The sediment ranges in depth from 0.16 to 332 m below seafloor and in age from 660 to 1,300,000 years. The majority of subseafloor taxonomic diversity is present in the shallowest depth sampled. The best predictor of sequence presence or absence in the oldest sediment is relative abundance in the near-seafloor sediment. This relationship suggests that perseverance of specific taxa into deep, old sediment is primarily controlled by the taxonomic abundance that existed when the sediment was near the seafloor. The operational taxonomic units that dominate at depth comprise a subset of the local seafloor community at each site, rather than a grown-in group of geographically widespread subseafloor specialists. At both sites, most taxa classified as abundant decrease in relative frequency with increasing sediment depth and age. Comparison of community composition to cell counts at the Bering Sea site indicates that the rise of the few dominant taxa in the deep subseafloor community does not require net replication, but might simply result from lower mortality relative to competing taxa on the long timescale of community burial.

As cancer treatment shifts progressively to the outpatient setting, informal caregivers, including family and friends, play an increasingly central role in ensuring optimal ongoing care of these patients. Cancer caregivers may provide a range of emotional, instrumental, and informational support, including handling complex treatment schedules, managing side effects, juggling household chores and transportation, communicating with the healthcare team and friends and family, and coping with the uncertainty of their loved one’s prognosis. Cancer caregivers may become overwhelmed and burdened by these tasks, receiving minimal support and guidance related to managing distress and maintaining their own quality of life while caring for a loved one. Cognitive behavioral therapy is evidence- and skills-based therapy efficacious for patients with cancer in managing anxiety and depression and improving quality of life. This chapter reviews the application of and evidence for cognitive behavioral therapy for addressing psychosocial distress and burden in informal cancer caregivers.

This study reports on the safety and putative probiotic properties of Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA1933. According to the bacterial reverse mutation (Ames) test, cell-free supernatants of B. amyloliquefaciens B-1895 and B. subtilis KATMIRA1933 were not mutagenic. The two strains co-aggregated with Escherichia coli and Pseudomonas aeruginosa, and cell-free supernatants inhibited the growth of Streptococcus intermedius and Porphyromonas gingivalis. Endospores of B. amyloliquefaciens B-1895 and B. subtilis KATMIRA1933 were tolerant to 0.3% (w/v) bile salts and survived incubation for 4 h in MRS broth at pH 2.0 to 3.0. The ability of the two strains to produce antimicrobial compounds potentiates their application in health care formulations, personal care products, food and animal feed.

Background CDI is a 2-hit process requiring C. difficile spores and antibiotic-mediated dysbiosis, a low diversity state of the gut microbiome. Recurrent CDI (rCDI) is common and may be related to inadequate antibiotic concentrations (e.g., metronidazole; MET) or persistent dysbiosis (e.g., vancomycin; VAN). SER-262 is an oral investigational microbiome drug rationally designed to reduce rCDI by restoring colonization resistance. Methods SERES-262-001 was a Phase 1b randomized placebo (PBO)-controlled single and multidose study. Subjects with primary CDI (n = 96) were enrolled in 8 cohorts (SER-262: PBO, 5:1). Subjects were dosed after MET (n = 57) or VAN (n = 39) per investigator discretion. Engraftment of SER-262 strains was evaluated using strain-specific molecular probes in fecal samples; microbial diversity was measured via whole metagenomic shotgun sequencing. Endpoints included safety and rCDI rates up to 8 weeks posttreatment and strain engraftment at 1, 4, 8, 12, and 24 weeks. Results SER-262 safety was comparable to PBO. Although overall rCDI rates were similar in SER-262 (n = 80) and PBO (n = 16) subjects (18.8% vs. 12.5%, respectively), in a post-hoc analysis we observed reduced rates of rCDI in the VAN+SER-262 arm compared with MET+SER-262 (6.3 vs. 27.1%, respectively, P = 0.02, Figure 1). Overall, 8 of 12 SER-262 strains showed significant engraftment relative to PBO. However, greater SER-262 strain engraftment was observed in VAN-treated subjects compared with MET-treated subjects (P < 0.001, Figure 2). To better understand the impact of dysbiosis on engraftment, we evaluated baseline microbial diversity by prior antibiotic received and observed that the diversity of Bacteroidetes and Firmicute species was lower in VAN-treated subjects compared with MET-treated subjects (P < 0.001, Figure 3). Conclusion In this first phase 1b study of a fermented microbiome drug in subjects with primary CDI, SER-262 was safe and well-tolerated. The higher efficacy rates of SER-262 in reducing rCDI among VAN-treated subjects may be due to low baseline microbial diversity, which creates an ecologic niche for greater engraftment of dose species. Treatment of C. difficile with VAN, followed by restoration of colonization resistance with SER-262, is a promising 2-pronged therapeutic paradigm to reduce rCDI. Disclosures All authors: No reported disclosures.

Chemical Geology 409 (2015) 28–41 Contents lists available at ScienceDirect Chemical Geology journal homepage: www.elsevier.com/locate/chemgeo Monazite response to ultrahigh-pressure subduction from U–Pb dating by laser ablation split stream Bradley R. Hacker a, ⁎ , Andrew R.C. Kylander-Clark a , Robert Holder a , Torgeir B. Andersen b , Emily M. Peterman c , Emily O. Walsh d , Jonathan K. Munnikhuis e a Earth Science, University California, Santa Barbara, CA 93106-9630, USA University of Oslo, Physics of Geological Processes, PO Box 1048, Blindern, 0316 Oslo, Norway Earth and Oceanographic Science, Bowdoin College, 6800 College Station, Brunswick, ME 04011, USA d Geology, Cornell College, Mount Vernon, IA 52314, USA e Geological Sciences, University of North Carolina, Chapel Hill, Campus Box #3315 Chapel Hill, NC 27599-3315, USA b c a r t i c l e i n f o Article history: Received 5 February 2015 Received in revised form 6 May 2015 Accepted 11 May 2015 Available online 22 May 2015 Editor: K. Mezger Keywords: Monazite Laser ablation Split stream Petrochronology a b s t r a c t To assess the response of monazite during subduction of continental crust to mantle depths, U–Pb isotopic ratios and elemental abundances were measured simultaneously by laser-ablation split-stream inductively-coupled plasma mass spectrometry (LASS) in rocks from the ultrahigh-pressure Western Gneiss Region of the Scandinavian Caledonides. Nearly seventy different samples of quartzofeldspathic basement and overlying metasedimentary rocks were studied. Pre-subduction monazite (chiefly 1.6 Ga and 1.0 Ga) is preserved locally in the structurally lowest, basement rocks because earlier, Precambrian tectonism produced coarse-grained, high-grade rocks that were resistant to further recrystallization in spite of syn-subduction temperatures and pressures of 650–800 °C and 2–3.5 GPa. A few of the monazite in the metasedimentary rocks atop the basement preserve syn-subduction U–Pb dates, but the majority continued to recrystallize during post-subduction exhumation and record a general westward decrease in age related to westward-progressing exhumation. The absence of Precambrian monazite in the metasedimentary rock atop the basement suggests that sedimentation postdated the 1.0–0.9 Ga high-grade metamorphism and was late Proterozoic to early Paleozoic. © 2015 Elsevier B.V. All rights reserved. 1. Introduction The development of techniques to analyze monazite U/Th–Pb dates in situ by electron probe [Suzuki et al., 1991], SIMS [Harrison et al., 1995], and LA-ICP-MS [Kosler et al., 2001] has spurred renewed interest in the petrogenesis of monazite, including understanding neocrystal- lization [Kingsbury et al., 1993], recrystallization [Finger, 1998], compo- sition [Franz et al., 1996], and thermometry [Gratz and Heinrich, 1997; Pyle et al., 2001]. Advances in these complementary tracks of analytical methods and petrologic interpretation have enabled increasing use of monazite as a petrochronometer—i.e., the interpretation of isotopic dates in the context of elemental or complementary isotopic informa- tion collected from the same mineral. One might infer from recent models [Kelsey, 2008] [Yakymchuk and Brown, 2014] that monazite is routinely recrystallized during high- temperature orogenesis and that its U–Pb age records only the final, cooling stage. Here we apply LASS (laser-ablation split-stream inductively-coupled plasma mass spectrometry) [Kylander-Clark et al., 2013] to monazite from the ultrahigh-pressure (UHP) Western Gneiss ⁎ Corresponding author. Tel.: +1 805 893 7952. E-mail address: hacker@geol.ucsb.edu (B.R. Hacker). http://dx.doi.org/10.1016/j.chemgeo.2015.05.008 0009-2541/© 2015 Elsevier B.V. All rights reserved. Region (WGR). Our objective in using in situ, combined U–Pb and trace-element analysis of monazite is to understand the broad-scale metamorphic response of monazite and its host rocks during subduc- tion to, and exhumation from, UHP conditions. The premise behind collecting trace-element and isotopic data simultaneously is that the trace elements provide insight into the petrological context of the isoto- pic dates: depressed heavy rare earth element concentrations may indi- cate that an interpreted U–Pb date coincides with the stability of garnet [Rubatto, 2002], elevated Eu and Sr may indicate HP recrystallization and plagioclase instability [Finger and Krenn, 2007; Holder et al., 2015], and Th and U help understand fluid availability [Hoskin and Schaltegger, 2003] and its potential role in monazite recrystallization [Seydoux-Guillaume et al., 2002]. We show that some monazite sur- vived amphibolite–granulite-facies metamorphism, partial melting, and subduction with its original age intact. 2. Geologic setting The Western Gneiss Region (WGR) of Norway contains one of Earth's largest ultrahigh-pressure terranes (Fig. 1). Like most well-exposed and extensively investigated UHP terranes, the WGR is dominated by quartzofeldspathic gneiss; eclogite and (U)HP

The efficient generation of meshes is an important component in the numerical solution of problems in physics and engineering. Of interest are situations where global mesh quality and a tight coupling to the solution of the physical partial differential equation (PDE) is important. We consider parabolic PDE mesh generation and present a method for the construction of adaptive meshes in two spatial dimensions using stochastic domain decomposition that is suitable for an implementation in a multi- or many-core environment. Methods for mesh generation on periodic domains are also provided. The mesh generator is coupled to a time dependent physical PDE and the system is evolved using an alternating solution procedure. The method uses the stochastic representation of the exact solution of a parabolic linear mesh generator to find the location of an adaptive mesh along the (artificial) subdomain interfaces. The deterministic evaluation of the mesh over each subdomain can then be obtained completely independently using the probabilistically computed solutions as boundary conditions. The parallel performance of this general stochastic domain decomposition approach has previously been shown. We demonstrate the approach numerically for the mesh generation context and compare the mesh obtained with the corresponding single domain mesh using a representative mesh quality measure., 15 pages, 3 figures

Importance Obesity is common in children and adolescents in the United States, is associated with negative health effects, and increases the likelihood of obesity in adulthood. Objective To systematically review the benefits and harms of screening and treatment for obesity and overweight in children and adolescents to inform the US Preventive Services Task Force. Data Sources MEDLINE, PubMed, PsycINFO, Cochrane Collaboration Registry of Controlled Trials, and the Education Resources Information Center through January 22, 2016; references of relevant publications; government websites. Surveillance continued through December 5, 2016. Study Selection English-language trials of benefits or harms of screening or treatment (behavior-based, orlistat, metformin) for overweight or obesity in children aged 2 through 18 years, conducted in or recruited from health care settings. Data Extraction and Synthesis Two investigators independently reviewed abstracts and full-text articles, then extracted data from fair- and good-quality trials. Random-effects meta-analysis was used to estimate the benefits of lifestyle-based programs and metformin. Main Outcomes and Measures Weight or excess weight (eg, body mass index [BMI]; BMI z score, measuring the number of standard deviations from the median BMI for age and sex), cardiometabolic outcomes, quality of life, other health outcomes, harms. Results There was no direct evidence on the benefits or harms of screening children and adolescents for excess weight. Among 42 trials of lifestyle-based interventions to reduce excess weight (N = 6956), those with an estimated 26 hours or more of contact consistently demonstrated mean reductions in excess weight compared with usual care or other control groups after 6 to 12 months, with no evidence of causing harm. Generally, intervention groups showed absolute reductions in BMI z score of 0.20 or more and maintained their baseline weight within a mean of approximately 5 lb, while control groups showed small increases or no change in BMI z score, typically gaining a mean of 5 to 17 lb. Only 3 of 26 interventions with fewer contact hours showed a benefit in weight reduction. Use of metformin (8 studies, n = 616) and orlistat (3 studies, n = 779) were associated with greater BMI reductions compared with placebo: −0.86 (95% CI, −1.44 to −0.29; 6 studies; I2 = 0%) for metformin and −0.50 to −0.94 for orlistat. Groups receiving lifestyle-based interventions offering 52 or more hours of contact showed greater improvements in blood pressure than control groups: −6.4 mm Hg (95% CI, −8.6 to −4.2; 6 studies; I2 = 51%) for systolic blood pressure and −4.0 mm Hg (95% CI, −5.6 to −2.5; 6 studies; I2 = 17%) for diastolic blood pressure. There were mixed findings for insulin or glucose measures and no benefit for lipids. Medications showed small or no benefit for cardiometabolic outcomes, including fasting glucose level. Nonserious harms were common with medication use, although discontinuation due to adverse effects was usually less than 5%. Conclusions and Relevance Lifestyle-based weight loss interventions with 26 or more hours of intervention contact are likely to help reduce excess weight in children and adolescents. The clinical significance of the small benefit of medication use is unclear.

Cardiovascular disease can alter the mechanical environment of the vascular system, leading to mechano-adaptive growth and remodeling. Predictive models of arterial mechano-adaptation could improve patient treatments and outcomes in cardiovascular disease. Vessel-scale mechano-adaptation includes remodeling of both the cells and extracellular matrix. Here, we aimed to experimentally measure and characterize a phenomenological mechano-adaptation law for vascular smooth muscle cells (VSMCs) within an artery. To do this, we developed a highly controlled and reproducible system for applying a chronic step-change in strain to individual VSMCs with in vivo like architecture and tracked the temporal cellular stress evolution. We found that a simple linear growth law was able to capture the dynamic stress evolution of VSMCs in response to this mechanical perturbation. These results provide an initial framework for development of clinically relevant models of vascular remodeling that include VSMC adaptation.

Background Recommended use of clinical preventive services (CPS) reduces morbidity and mortality from preventable conditions. Disparities in CPS utilization between individuals with and without disabilities have been shown, but a greater understanding of the disability subpopulations with lowest utilization is needed to better inform research, policy, and practice. Objective The objective was to conduct a scoping review of the literature to identify relevant studies on disparities in receipt of CPS among subgroups of individuals with disabilities. Methods In July 2010, electronic and manual literature searches were conducted for years 2000–2009. Review for inclusion/exclusion and data analysis occurred in 2010 and 2011. In 2012, the review was updated to cover abstracts published in 2010 and 2011. Identified abstracts, and then full-text articles of included abstracts, were reviewed according to inclusion/exclusion criteria by multiple reviewers. For articles meeting all criteria, two reviewers performed independent data extraction. A gap analysis was performed to identify areas of concentration and gaps in the literature. Results Twenty-seven articles met inclusion criteria for this review. Studies varied substantially in sample composition and research methods. CPS examined most often were cervical cancer screening (14 studies) and mammography (13 studies). Potential disparity factors studied most often were disability factors (i.e., disabling condition in 12 studies, disability severity in 10 studies). Stratification of CPS by disparity factors revealed substantial gaps in the literature. Conclusions The literature gaps point to a need for high quality research on access disparities among subgroups of individuals with disabilities.

article i nfo Ar/ 39 Ar muscovite thermochronology 40 Ar/ 39 Ar K-feldspar thermochronology Fault-slip analysis New 40 Ar/ 39 Ar muscovite and K-feldspar thermochronology combined with existing data reveal the timing and patterns of late-stage exhumation across the Western Gneiss Region (U)HP terrane. Muscovite age contours show that exhumation into the mid-upper crust progressed westward over a ~20 Myr period (~400-380 Ma). This exhumation was caused by i) E-W stretching and eastward tilting north of Nordfjord, where muscovite ages decrease from the foreland allochthons westward into the UHP domains, and ii) differential exhumation south of Nordfjord, where muscovite ages depict a NE-SW dome-like pattern and the Western Gneiss Region is bounded by overlying units little affected by the Scandian metamorphism. Exhumation of the UHP domains into the mid-upper crust by late folding continued through ~374 Ma. The smooth gradient of fairly flat muscovite age spectra demonstrates minimal influence of excess Ar, which is relatively unusual for a (U)HP terrane. 40 Ar/ 39 Ar spectra and modeled cooling histories from K-feldspar combined with brittle-ductile