A brief acceptance and commitment intervention for work-related stress and burnout amongst frontline homelessness staff: A single case experimental design series.

PURPOSE: Recent intervention research for burnout amongst those working in health and social care contexts has found acceptance and commitment therapy (ACT) interventions to be of use but has provided less clarity on the role of psychological flexibility (a key ACT construct). This study further evaluated the usefulness of ACT for burnout and work-engagement and assessed the role of psychological flexibility in contributing to therapeutic change. PROCEDURE: A nonconcurrent multiple-baseline across-participants single-case experimental design was used. Four participants were recruited from a homelessness organization in the East Midlands, England. The ACT-intervention was split into three modules to reflect the three aspects of the ACT triflex, and the sequence of delivery was randomized for each participant in order to test the relationship between these aspects. FINDINGS: Support was found for the ACT intervention reducing exhaustion and increasing work-engagement. Psychological Flexibility increased in all participants and was temporally related to increases in other outcome variables in some instances. Delivery of the intervention focussed on any given aspect of the ACT triflex could increase different domains of psychological flexibility. IMPLICATIONS: This study adds to the growing body of research in favour of ACT interventions for burnout and adds to the understanding of psychological flexibility as a mediating variable.

Wildfire loss of forest soil C and N: Do pre-fire treatments make a difference?

Losses of C and N from the forest floor and top 20-cm of soil were estimated following separate severe wildfires at two Long-Term Soil Productivity sites in the Sierra Nevada of California, USA. Experimental treatments applied 20 years prior to the wildfires included factorial combinations of 1) organic matter (OM) removal following clear-cut harvesting (SO, stem only harvest, WTH, whole-tree harvest, and WTH + FF, WTH plus the forest floor removal), 2) soil compaction (three levels of intensity), and 3) with and without understory vegetation control. Wildfires caused complete losses of the forest floor in all treatments and also oxidized varying portions of OM in the topsoil. As such, pre-fire forest floor measures were used as an estimate of forest floor C and N loss, and post-fire soil measures of C and N were compared to pre-fire soil data to estimate of mineral soil losses. Averaged over all treatments, the less-productive site that also had lesser accumulations of detritus (Wallace) lost 35.1 Mg C ha-1, or 25 % of its original C stores, while the more-productive site with greater detritus (Rogers) lost 18.4 Mg C ha-1, or 20 % of its original. The SO treatments that left harvest residue on site ended up with much greater losses of C: 36 % versus 15 and 17 % for WTH and WTH + FF, respectively. The SO also yielded the largest losses (25-30 %) of C in the top 10-cm of soil. The other treatments had smaller or inconsistent effects (understory vegetation control) or no effect (soil compaction). Our results suggest that potential benefits from SO by leaving residue on site to soil C and N accumulation can also be readily eliminated by wildfire which commonly occurs at these fire-prone forest ecosystems.

Multi-level functional genomics reveals molecular and cellular oncogenicity of patient-based 3' untranslated region mutations.

3' untranslated region (3' UTR) somatic mutations represent a largely unexplored avenue of alternative oncogenic gene dysregulation. To determine the significance of 3' UTR mutations in disease, we identify 3' UTR somatic variants across 185 advanced prostate tumors, discovering 14,497 single-nucleotide mutations enriched in oncogenic pathways and 3' UTR regulatory elements. By developing two complementary massively parallel reporter assays, we measure how thousands of patient-based mutations affect mRNA translation and stability and identify hundreds of functional variants that allow us to define determinants of mutation significance. We demonstrate the clinical relevance of these mutations, observing that CRISPR-Cas9 endogenous editing of distinct variants increases cellular stress resistance and that patients harboring oncogenic 3' UTR mutations have a particularly poor prognosis. This work represents an expansive view of the extent to which disease-relevant 3' UTR mutations affect mRNA stability, translation, and cancer progression, uncovering principles of regulatory functionality and potential therapeutic targets in previously unexplored regulatory regions.

Patient perspectives on elexacaftor/tezacaftor/ivacaftor after lung transplant.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, including elexacaftor/tezacaftor/ivacaftor (ETI), significantly improve outcomes and quality of life for people with cystic fibrosis (CF). However, little is known about how lung transplant recipients (LTRs) perceive the use of ETI. We conducted a survey to assess perspectives on ETI among LTRs with CF at our lung transplant program. Of 81 CF LTRs, 46 participants (58 %) responded. The majority of respondents (88 %) were aware of ETI. Over 80 % considered treating non-lung symptoms of CF to be very important. Concerns regarding ETI included potential drug interactions with transplant medications (77 %), side effects (53 %), cost of medication (49 %), and lack of clinical trial data for LTRs (43 %). Half reported they would only consider taking ETI if their CF or transplant doctor recommended it. The findings suggest that CF LTRs seek informational support and shared decision-making about ETI from their clinicians.

Cystic Fibrosis Foundation consensus guidelines for the care of individuals with advanced cystic fibrosis lung disease.

BACKGROUND: Advanced cystic fibrosis lung disease (ACFLD) is common, is associated with reduced quality of life, and remains the most frequent cause of death in individuals with cystic fibrosis (CF). These consensus guidelines provide recommendations to the CF community on management of both common and unique issues that arise when individuals reach a state of ACFLD. METHODS: The CF Foundation assembled a multidisciplinary expert panel consisting of three workgroups: Pulmonary management; Management of comorbid conditions; Symptom management and psychosocial issues. Topics were excluded if the management considerations did not differ in ACFLD from in the overall CF population or if already addressed in other published guidelines. Recommendations were based on a systematic literature review combined with expert opinion when appropriate. RESULTS: The committee formulated twenty-three recommendation statements specific to ACFLD that address the definition of ACFLD, pulmonary and intensive care unit management, management of selected comorbidities, symptom control, and psychosocial issues. CONCLUSIONS: These recommendations are intended to be paired with previously published management guidelines for the overall CF population, with the objective of reducing practice variability and improving overall care, quality of life, and survival in those with ACFLD.

Silencing the myotrophin gene by RNA interference leads to the regression of cardiac hypertrophy.

Myotrophin-induced activation of NF-kappaB has been shown to be associated with cardiac hypertrophy (CH) that progresses to heart failure (HF). In the present study, we examined the cause-and-effect relationship between myotrophin and NF-kappaB activation using small hairpin RNA (shRNA) against myotrophin both in vitro (using neonatal rat myocytes) and in vivo [using myotrophin transgenic (Myo-Tg) mice, which overexpress myotrophin in the heart, develop CH, and gradually progress to HF]. Among several lentiviral vectors expressing myotrophin shRNAs, L-sh-109 showed the best silencing effect at both the mRNA (155.3 +/- 5.9 vs. 32.5 +/- 5.5, P < 0.001) and protein levels associated with a significant reduction of atrial natriuretic factor (ANF) and NF-kappaB. In vivo, when L-sh-109 was delivered directly into the hearts of 10-wk-old Myo-Tg mice, we observed a significant regression of cardiac mass (8.0 vs. 5.7 mg/g, P < 0.001) and myotrophin gene expression (54.5% over untreated Myo-Tg mice, P < 0.001) associated with a reduction in ANF and NF-kappaB signaling components. Our data suggest that using RNA interference to silence the myotrophin gene prevents NF-kappaB activation, associated with an attenuation of CH. This strategy could be an excellent therapeutic means for the treatment of CH and HF.

Adherence to current guidelines for chronic obstructive pulmonary disease (COPD) among patients treated with combination of long-acting bronchodilators or inhaled corticosteroids.

BACKGROUND: To estimate the potential cost savings by following the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline recommendations in patients being treated for chronic obstructive pulmonary disease (COPD) with the combination of long-acting ß(2)-agonist (LABA), long-acting muscarinic antagonist (LAMA) or inhaled corticosteroids (ICS). METHODS: The Geisinger Health System (GHS) database was utilized to identify subjects between January 1, 2004 to March 12, 2007. The index date was based on the first prescription of a LAMA plus LABA, LAMA plus LABA/ICS, or LABA plus ICS. Patients were included in the study if they: had a COPD diagnosis; had data representative of treatment 12 months prior to and 12 months post index date; were 40 years of age or over; had no prior diagnosis for asthma; and had pulmonary function test (PFT) data. We examined the baseline characteristics of these patients along with their healthcare resource utilization. Based on PFT data within 30 days of the index date, a subgroup was classified as adhering or non-adhering to GOLD guidelines. RESULTS: A total of 364 subjects could be classified as adhering or non-adherent to current GOLD guidelines based on their PFT results. The adherent subgroup received COPD medications consistent with current GOLD guidelines. Of the LAMA plus LABA cohort, 25 patients adhered and 39 patients were non-adherent to current GOLD guidelines. In the cohort of LABA plus ICS, 74 patients were adherent and 180 patients non-adherent to current GOLD guidelines. In the cohort of LAMA plus LABA/ICS, 21 patients were adherent and 25 patients non-adherent to current GOLD guidelines. GOLD adherence was associated with mean total cost of all services savings of $5,889 for LAMA plus LABA, $3,330 for LABA + ICS, and $10,217 for LAMA plus LABA/ICS cohorts. CONCLUSION: Staging of COPD with a PFT and adherence to current GOLD guidelines was associated with lower costs in subjects with moderate to severe COPD. Appropriate use of LAMA plus LABA, LABA plus ICS, and LAMA plus LABA/ICS has economic as well as clinical benefits for patients and payers.

Accurate radiometry from space: an essential tool for climate studies.

The Earth's climate is undoubtedly changing; however, the time scale, consequences and causal attribution remain the subject of significant debate and uncertainty. Detection of subtle indicators from a background of natural variability requires measurements over a time base of decades. This places severe demands on the instrumentation used, requiring measurements of sufficient accuracy and sensitivity that can allow reliable judgements to be made decades apart. The International System of Units (SI) and the network of National Metrology Institutes were developed to address such requirements. However, ensuring and maintaining SI traceability of sufficient accuracy in instruments orbiting the Earth presents a significant new challenge to the metrology community. This paper highlights some key measurands and applications driving the uncertainty demand of the climate community in the solar reflective domain, e.g. solar irradiances and reflectances/radiances of the Earth. It discusses how meeting these uncertainties facilitate significant improvement in the forecasting abilities of climate models. After discussing the current state of the art, it describes a new satellite mission, called TRUTHS, which enables, for the first time, high-accuracy SI traceability to be established in orbit. The direct use of a 'primary standard' and replication of the terrestrial traceability chain extends the SI into space, in effect realizing a 'metrology laboratory in space'.