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The theory of full correspondence posits that all placebo-induced effects are accompanied by corresponding subjective experiences. It was first put forward as a means of explaining the nature of the placebo effect and of reconciling the leading approaches to the phenomenon in a single overarching theory. In this paper, we examine several points of contact between full correspondence and biofeedback research and consider some of their clinical and experimental implications.

Purpose Financial toxicity is a contributor to the psychosocial burden of cancer care. There is no consensus measure of financial toxicity, however, recent studies have adopted the COmprehensive Score for financial Toxicity (COST). Despite its growing popularity, data on the responsiveness to change of the COST are lacking. To address this gap in the literature, we performed a sequential mixed-methods study of people with multiple myeloma.Methods In the quantitative phase of the study, we collected COST scores at two time points approximately 8 weeks apart from 72 patients. In the qualitative phase, we conducted semi-structured interviews with a subset of 12 patients who reported the largest changes in COST scores. The qualitative data were analyzed using a deductive coding scheme developed using the Framework Method in the context of a commonly cited conceptual model of financial toxicity.Results The median absolute change in COST scores was 4 points (IQR 2–6). Only 13% of the sample had the same COST scores at both assessments; 38% had an improved score and 50% had a worsened score. Only, seven of the twelve patients (58%) interviewed reported changes to one or more of the constructs in the conceptual model of financial toxicity. Most commonly, changes to out-of-pocket costs were reported (5/12). Changes to non-medical expenses (n = 2) and subjective financial distress without changes to objective financial burden (n = 2) were also reported.Conclusion Additional research is needed to explicate changes in COST scores over time.

Purpose Physicians are expected to provide compassionate, error-free care while navigating systemic challenges and organizational demands. Many are burning out. While organizations are scrambling to address the burnout crisis, physicians often resist interventions aimed at enhancing their wellness and building their resilience. The purpose of this research was to empirically study this phenomenon. Method Constructivist grounded theory was used to inform the iterative data collection and analysis process. In spring 2018, 22 faculty physicians working in Canada participated in semistructured interviews to discuss their experiences of wellness and burnout, their perceptions of wellness initiatives, and how their experiences and perceptions influence their uptake of the rapidly proliferating strategies aimed at nurturing their resilience. Themes were identified using constant comparative analysis. Results Participants suggested that the values of compassion espoused by health care organizations do not extend to physicians, and they described feeling dehumanized by professional values steeped in an invincibility myth in which physicians are expected to be "superhuman" and "sacrifice everything" for medicine. Participants described that professional values and organizational norms impeded work-life balance, hindered personal and professional fulfillment, and discouraged disclosure of struggles. In turn, participants seemed to resist wellness and resilience-building interventions focused on fixing individuals rather than broader systemic, organizational, and professional issues. Participants perceived that efforts aimed at building individual resilience are futile without changes in professional values and sustained organizational support. Conclusions Findings suggest that professional and organizational norms and expectations trigger feelings of dehumanization for some physicians. These feelings likely exacerbate burnout and may partly explain physicians' resistance to resilience-building strategies. Mitigating burnout and developing and sustaining a resilient physician workforce will require both individual resistance to problematic professional values and an institutional commitment to creating a culture of compassion for patients and physicians alike.

Elevated concentrations of per- and polyfluoroalkyl substances (PFAS) in drinking-water supplies are a major concern for human health. It is therefore essential to understand factors that affect PFAS concentrations in surface water and groundwater and the transformation of perfluoroalkyl acid (PFAA) precursors that degrade into terminal compounds. Surface-water/groundwater exchange can occur along the flow path downgradient from PFAS point sources and biogeochemical conditions can change rapidly at these exchange boundaries. Here, we investigate the influence of surface-water/groundwater boundaries on PFAS transport and transformation. To do this, we conducted an extensive field-based analysis of PFAS concentrations in water and sediment from a flow-through lake fed by contaminated groundwater and its downgradient surface-water/groundwater boundary (defined as ≤100 cm below the lake bottom). PFAA precursors comprised 45 ± 4.6% of PFAS (PFAA precursors + 18 targeted PFAA) in the predominantly oxic lake impacted by a former fire-training area and historical wastewater discharges. In shallow porewater downgradient from the lake, this percentage decreased significantly to 25 ± 11%. PFAA precursor concentrations decreased by 85% between the lake and 84–100 cm below the lake bottom. PFAA concentrations increased significantly within the surface-water/groundwater boundary and in downgradient groundwater during the winter months despite lower stable concentrations in the lake water source. These results suggest that natural biogeochemical fluctuations associated with surface-water/groundwater boundaries may lead to PFAA precursor loss and seasonal variations in PFAA concentrations. Results of this work highlight the importance of dynamic biogeochemical conditions along the hydrological flow path from PFAS point sources to potentially affected drinking water supplies., Aqueous PFAS concentrations fluctuate seasonally and precursor concentrations rapidly decline within the surface-water/groundwater boundary, indicating that transport through this boundary can affect spatial and temporal PFAS composition.

This study describes the prevalence and persistence of fatigue among a cohort of long-term non-Hodgkin lymphoma (NHL) survivors. Mailed surveys assessed quality-of-life including fatigue (SF-36) at baseline and five years. Logistic regression was used to identify factors associated with prevalence of fatigue at baseline and persistence of fatigue across timepoints. More than one-quarter (27.7%) of the 555 NHL survivors reported clinically meaningful fatigue at baseline and 18.7% reported persistent fatigue at five years. One-third (34.4%) reported clinically meaningful worsening of fatigue over time. Independent associations with persistent fatigue included female gender, less education, past chemotherapy, increased comorbidities, and posttraumatic stress symptoms (P

Burnout is a growing concern, with significant negative consequences for physicians and patient care. Burnout is negatively associated with physician empathy, while resilience may be a protective factor against the development of burnout but few studies have examined all three constructs in the same cohort. Understanding the associations between these constructs could aid in the development of interventions for physicians experiencing burnout and improve the delivery of compassionate care. We conducted a cross-sectional survey to determine levels of burnout, empathy and resilience in a sample of academic physicians and investigate the relationships between these variables. Validated scales were administered online to measure burnout (Maslach Burnout Inventory - Human Services Survey, MBI-HSS), empathy (Jefferson Scale of Empathy - Physicians/Health Professions Version, JSE) and resilience (Connor-Davidson Resilience Scale, CD-RISC). Descriptive statistics, correlation coefficients, and group comparisons were examined. Eighty-three physicians completed the JSE and CD-RISC, while a subset of 49 physicians also completed the MBI-HSS. Response rates were 31.9% and 18.8%, respectively. High burnout was reported by 49% of the sample. Physicians with high burnout reported lower levels of resilience than those who were not burnt-out. No differences in levels of empathy were observed between these two groups. Older physicians (>45 years) reported higher resilience scores than younger physicians. Resilience and empathy were significantly positively correlated. The reported rate of physician burnout in this sample of academic physicians is concerning, with burnout associated with lower levels of resilience. Further research is required to explore the relationship between physician age and resilience, the impact of resilience-building interventions on burnout and empathy in physicians, and how modifying these variables influences the delivery of compassionate care for patients.

In the early 1880s, Joseph Delboeuf proposed a little-known but ingenious solution to the problem the law of the conservation of energy poses for free will. When energy is transferred between two bodies, the law of energy conservation requires that the energy before and after the transfer be the same, but it says nothing of the time it must take. If we could delay this transfer, Delboeuf proposed, we could alter the course of matter without compromising the conservation of energy. This article begins by tracing the early history of the conflict between free will and the first law of thermodynamics and by recounting some initial attempts to resolve it. It next describes Delboeuf’s theory and the arguments that were made against it, before situating it with respect to some recent developments in the philosophy and psychology of free will.

Water supplies for millions of U.S. individuals exceed maximum contaminant levels for per- and polyfluoroalkyl substances (PFAS). Contemporary and legacy use of aqueous film forming foams (AFFF) is a major contamination source. However, diverse PFAS sources are present within watersheds, making it difficult to isolate their predominant origins. Here we examine PFAS source signatures among six adjacent coastal watersheds on Cape Cod, MA, U.S.A. using multivariate clustering techniques. A distinct signature of AFFF contamination enriched in precursors with six perfluorinated carbons (C6) was identified in watersheds with an AFFF source, while others were enriched in C4 precursors. Principal component analysis of PFAS composition in impacted watersheds showed a decline in precursor composition relative to AFFF stocks and a corresponding increase in terminal perfluoroalkyl sulfonates with < C6 but not those with ≥ C6. Prior work shows that in AFFF stocks, all extractable organofluorine (EOF) can be explained by targeted PFAS and precursors inferred using Bayesian inference on the total oxidizable precursor assay. Using the same techniques for the first time in impacted watersheds, we find that only 24%-63% of the EOF can be explained by targeted PFAS and oxidizable precursors. Our work thus indicates the presence of large non-AFFF organofluorine sources in these coastal watersheds.

Background: Anticipating and making health care decisions about appropriate or preferred treatment around end-of-life care are intellectually challenging and emotionally distressing for metastatic ...

Classical MCL (cMCL) constitutes 6-8% of all B cell NHL. Despite recent advances, MCL is incurable except with allogeneic stem cell transplant. Blastic mantle cell lymphoma (bMCL) is a rarer subtype of cMCL associated with an aggressive clinical course and poor treatment response, frequent relapse and poor outcomes. We treated 13 bMCL patients with combined epigenetic and immunotherapy treatment consisting of vorinostat, cladribine and rituximab (SCR). We report an increased OS greater than 40 months with several patients maintaining durable remissions without relapse for longer than 5 years. This is remarkably better then current treatment regimens which in bMCL range from 14.5-24 months with conventional chemotherapy regimens. We demonstrate that the G/A870

BACKGROUND: The purpose of this manuscript is to describe health-related quality of life (HRQoL) outcomes in a United States (US) based sample of multiple myeloma (MM) patients and identify characteristics associated with poor HRQoL. PATIENTS AND METHODS: MM patients identified through the Tumor Registry of a Southeastern US medical center were mailed surveys assessing patient characteristics and HRQoL outcomes. HRQoL outcomes were measured using PROMIS short form instruments which included measures of global health (global physical health and global mental health), physical function, and ability to participate in social roles and activities (social function). HRQoL domain scores were summarized, and best subsets linear regression was used to identify predictors of HRQoL. RESULTS: 690 patients completed and returned surveys for a response rate of 64.7%. Respondents reported global physical health (44.9), global mental health (47.5), and physical function (44.1) significantly worse than the general population mean of 50 (p

BackgroundThe plasma cell disorders (PCDs), multiple myeloma (MM), and light-chain amyloidosis (AL) are disproportionately diseases of older adults, whose care may be complicated by frailty associated with advancing age. We sought to evaluate the prevalence of functional deficits and symptoms in a cohort of persons with PCDs and associations of demographic, disease-related, functional, and psychosocial measures with quality of life (QoL).Patients and MethodsAdults with PCDs were recruited into an observational registry in 2018-2020. Patients completed a functional assessment and European Organization for Research and Treatment of Cancer QoL questionnaire (QLQ-C30). Associations of covariates of interest with QoL were evaluated via univariate linear regression.ResultsAmong 121 adults, the mean age was 68.6. Diagnoses were 74% MM, 14% AL, 7% both MM and AL, and 5% other PCDs. The median time from diagnosis was 34.9 months. Median lines of therapy were 2, with 11% having received ≥4th-line therapy.Patients with functional deficits had lower mean QoL scores: dependence in IADLs (66.3 vs. 79.9, P = .001) and recent falls (56.7 vs. 76.8, P = .001). Patients ≤6 months from diagnosis had lower QoL (66.7) than those ≥2 years from diagnosis (77.3, P = .03). However, patients on later lines of therapy (≥4th-line) had lower QoL (62.2) than those on 1st-line treatment (76.0, P = .04).ConclusionsPatients with physical impairments and more advanced PCDs had lower QoL than those without deficits or earlier in their disease course. Early identification of physical impairments may facilitate interventions that mitigate these deficits and thereby improve QoL for patients with PCDs.

PURPOSE: Patients with relapsed and/or refractory multiple myeloma (RRMM) are living longer due in part to changing treatment patterns. It is important to understand how changing treatment patterns affect patients’ lives beyond extending survival. Research suggests that direct patient report is the best way to capture information on how patients feel and function in response to their disease and its treatment. Therefore, the purpose of this review is to summarize evidence of patients’ experience collected through patient-reported outcomes (PRO) in RRMM patients, and to explore PRO reporting quality. METHODS: We conducted a systematic search to identify manuscripts reporting PROs in RRMM and summarized available evidence. We assessed PRO reporting quality using the Consolidated Standards of Reporting Trials (CONSORT) PRO Extension checklist. RESULTS: Our search resulted in 30 manuscripts. Thirteen unique PRO measures were used to assess 18 distinct PRO domains. Pain, fatigue, and emotional function were commonly assessed domains though reporting formats limited our ability to understand prevalence and severity of PRO challenges in RRMM. Evaluation of PRO reporting quality revealed significant reporting deficiencies. Several reporting criteria were included in less than 25% of manuscripts. CONCLUSIONS: Existing evidence provides a limited window for understanding the patient experience of RRMM and is further limited by suboptimal reporting quality. Observational studies are needed to describe prevalence, severity and patterns of PROs in RRMM overtime. Future studies that incorporate PROs would benefit from following existing guidelines to ensure that study evidence and conclusions can be fully assessed by readers, clinicians and policy makers.

Boxwood blight, a fungal disease of ornamental plants (Buxus spp.), is caused by two sister species, Calonectria pseudonaviculata (Cps) and C. henricotiae (Che). Compared to Cps, Che is documented to display reduced sensitivity to fungicides, including the azole class of antifungals, which block synthesis of a key fungal membrane component, ergosterol. A previous study reported an ergosterol biosynthesis gene in Cps, CYP51A, to be a pseudogene, and RNA-Seq data confirm that a functional CYP51A is expressed only in Che. The lack of additional ergosterol biosynthesis genes showing significant differential expression suggests that the functional CYP51A in Che could contribute to reduced azole sensitivity when compared to Cps. RNA-Seq and bioinformatic analyses found that following azole treatment, 55 genes in Cps, belonging to diverse pathways, displayed a significant decrease in expression. Putative xenobiotic detoxification genes overexpressed in tetraconazole-treated Che encoded predicted monooxygenase and oxidoreductase enzymes. In summary, expression of a functional CYP51A gene and overexpression of predicted xenobiotic detoxification genes appear likely to contribute to differential fungicide sensitivity in these two sister taxa.

BackgroundGait difficulties in Parkinson’s disease have been related to problems shifting center of gravity forward. We previously showed reduced forward stepping latencies for people with Parkinson’s disease after one session of adaptation to upward visual shifts, which produces downward motor after-effects and potentially shifts center of gravity forward. Here we tested if repeated prism adaptation improved gait and postural control in Parkinson’s disease through a parallel, double-blind, randomized, sham-controlled trial.MethodsWe recruited participants with idiopathic Parkinson’s disease aged 40 – 80 and meeting any one of three clinical criteria: 1) Hoehn and Yahr Stage II.5 – IV; 2) Scoring > 0 on the gait, freezing of gait, and/or postural stability items of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale; or 3) Timed Up and Go > 12 seconds. Sealed envelope style randomization allocated participants to two weeks of twice-daily prism adaptation or sham treatment. Participants, care givers, and those assessing the outcomes were blinded to group assignment. Primary outcomes were changes in postural control measured using the Berg Balance Scale; and the Limits of Stability, Sensory Organisation, and Motor Control tests from the Smart EquiTest system. Secondary outcomes included other physiotherapy and questionnaire measures. Outcomes were assessed at the Dartmouth Hitchcock Medical Center immediately before and after the treatment period, with further long-term postal follow-up over two months. Outcomes were analysed using Analyses of Variance with follow-up t-tests. ResultsEighteen participants were allocated to undergo prism adaptation, of which sixteen were analysed. Thirteen participants were allocated to undergo sham treatment, and all were analysed. The prism adaptation group showed increased forward stepping velocity on the Limits of Stability test (Pre: M=2.33, SEM=0.24; post: M=2.88, SEM=0.26; t(15)=3.2, p=.005, d=.819). The sham group showed no such change (Pre: M=2.13, SEM=0.22; 1d post: M=2.24, SEM=0.22; t(13)=.636, p=.537, d=.176). However, there were no group differences for any other outcome measures, and no indications that prism adaptation produced functional improvements in posture, gait, or activities of daily living. ConclusionsPrism adaptation does not improve gait or postural control in Parkinson’s disease. Trial RegistrationRegistered prospectively at ClinicalTrials.gov, 5th March 2015, NCT02380859, https://clinicaltrials.gov/ct2/show/NCT02380859.

PURPOSE: Survival improvements in multiple myeloma (MM) over the past fifteen years have been fueled by the introduction of new therapies and changes in treatment patterns. The purpose of this study was to explore the ways MM impacts a person’s life in the modern treatment era. PARTICIPANTS AND SETTING: Fifteen individuals with MM and ten clinicians were recruited from two academic medical centers in the Southeastern United States. METHODOLOGIC APPROACH: Semi-structured interviews were conducted with people with MM and clinicians to explore the impact of MM diagnosis and treatment on peoples’ lives. Transcribed interviews were analyzed using conventional content analysis. FINDINGS: Four themes emerged from our analysis: (1) Treatment without end (2) Social impacts and isolation (3) Ongoing financial pressure and (4) Relationship impacts. IMPLICATIONS FOR NURSING: The treatment journey for those with MM can be life-long, require frequent visits to the oncologist and potentially many successive lines of therapy. Life impacts are far reaching and long term. Nurses should be aware of the multidisciplinary resources to help meet these needs. With thorough assessment, care planning and education nurses can play a key role in mitigating the negative effects of MM and its treatment

PURPOSE: People living in rural areas experience greater health disparities than their non-rural counterparts, but little is known about the association between rural status and quality of life (QOL) in non-Hodgkin’s lymphoma (NHL) survivors. We compared self-reported quality of life and impact of cancer in rural and non-rural NHL survivors. METHODS: This study is a secondary analysis of 566 NHL cancer survivors recruited from cancer registries at 2 large academic medical centers in 1 state. Standardized measures collected information on demographics and clinical characteristics, quality of life (QOL; SF-36), and the Impact of Cancer (IOCv2). Rural residence was determined by Rural-Urban Commuting Area (RUCA) codes designated as non-metropolitan. Multiple linear regression analysis, adjusted for demographic and clinical covariates, was used to evaluate the relationship between rural residence and QOL and impact of cancer. FINDINGS: Among the 566 participants (83% response rate), rural residence was independently associated with lower SF-36 physical component summary scores and the physical function subscale (all P < .05). Rural residence was also associated with higher IOCv2 positive impact scores and the subscales of altruism/empathy and meaning of cancer scores in the adjusted models (all P < .05). CONCLUSIONS: Given documented rural cancer disparities and the lack of resources in rural communities, study findings support the continued need to provide supportive care to rural cancer survivors to improve their QOL. Consistent with previous research, rural residence status is associated with increased positive impact following cancer diagnosis.

Identifying and quantifying groundwater exchange is critical when considering contaminant fate and transport at the groundwater/surface-water interface. In this paper, areally distributed temperature and point seepage measurements are used to efficiently assess spatial and temporal groundwater discharge patterns through a glacial-kettle lakebed area containing a zero-valent iron permeable reactive barrier (PRB). Concern was that the PRB was becoming less permeable with time owing to biogeochemical processes within the PRB. Patterns of groundwater discharge over an 8-year period were examined using fiber-optic distributed temperature sensing (FO-DTS) and snapshot-in-time point measurements of temperature. The resulting thermal maps show complex and uneven distributions of temperatures across the lakebed and highlight zones of rapid seepage near the shoreline and along the outer boundaries of the PRB. Repeated thermal mapping indicates an increase in lakebed temperatures over time at periods of similar stage and surface-water temperature. Flux rates in six seepage meters permanently installed on the lakebed in the PRB area decreased on average by 0.021 md-1 (or about 4.5 percent) annually between 2004 and 2015. Modeling of diurnal temperature signals from shallow vertical profiles yielded mean flux values ranging from 0.39 to 1.15 md-1, with stronger fluxes generally related to colder lakebed temperatures. The combination of an increase in lakebed temperatures, declines in direct seepage, and observations of increased cementation of the lakebed surface provide in situ evidence that the permeability of the PRB is declining. The presence of temporally persistent rapid seepage zones is also discussed.

Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period.Pediatric-onset IBD (17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification.1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/10In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.

Background/aims Many cancer survivors who received intensive treatment such as hematopoietic stem cell transplantation (HCT) experience posttraumatic stress disorder (PTSD) symptoms. PTSD is associated with lower quality of life and other symptoms that require clinical treatment. The iterative treatment decisions that happen in clinical practice are not adequately represented in traditional randomized controlled trials (RCT) of PTSD treatments. The proposed stepped-care SMART design allows for evaluation of initial response to the Cancer Distress Coach mobile app; adaptive stepped-care interventions; and precision treatment strategies that tailor treatment selection to patient characteristics. Methods/design HCT survivors (N = 400) reporting PTSD symptoms are being recruited at two cancer centers and randomly assigned to: 1) Cancer Distress Coach app or 2) Usual Care. The app includes educational and cognitive behavioral therapy (CBT)-based activities. Four weeks post-randomization, participants re-rate their PTSD symptoms and, based on intervention response, non-responders are re-randomized to receive video-conferenced sessions with a therapist: 3) coaching sessions in using the mobile app; or 4) CBT specific to HCT survivors. Participants complete outcome measures of PTSD, depression, and anxiety after Months 1, 3, and 6. Participant characteristics moderating intervention responses will be examined. Conclusions This novel adaptive trial design will afford evidence that furthers knowledge about optimizing PTSD interventions for HCT survivors. To our knowledge, this study is the first SMART design evaluating PTSD symptom management in cancer survivors. If successful, it could be used to optimize treatment among a range of cancer and other trauma survivors.

This research documented the history of landscape transformation on the island of Barbuda in the Lesser Antilles, Caribbean through cross-disciplinary research approaches. Excavations confirmed a h...