Are processes in acceptance & commitment therapy (Act) related to chronic pain outcomes within individuals over time? : an exploratory study using n-of-1 designs

Acknowledgements The authors would like to thank the European Health Psychology Society for providing a grant that enabled the collaboration of the co-authors for this article. Author contributions HT designed the study, organized the data collection, carried out the statistical analyses and drafted the first version of the manuscript. DJ and MJ supervised the statistical analyses and were actively involved in writing and revising the manuscript. MVH and KS designed the study and were actively involved in writing and revising the manuscript. All authors read and approved the final manuscript.Peer reviewedPublisher PD

Thermally stable perovskite solar cells by all-vacuum deposition

Vacuum deposition is a solvent-free method suitable for growing thin films of metal halide perovskite (MHP) semiconductors. However, most reports of high-efficiency solar cells based on such vacuum-deposited MHP films incorporate solution-processed hole transport layers (HTLs), thereby complicating prospects of industrial upscaling and potentially affecting the overall device stability. In this work, we investigate organometallic copper phthalocyanine (CuPc) and zinc phthalocyanine (ZnPc) as alternative, low-cost, and durable HTLs in all-vacuum-deposited solvent-free formamidinium-cesium lead triodide [CH(NH2)2]0.83Cs0.17PbI3 (FACsPbI3) perovskite solar cells. We elucidate that the CuPc HTL, when employed in an "inverted"p-i-n solar cell configuration, attains a solar-to-electrical power conversion efficiency of up to 13.9%. Importantly, unencapsulated devices as large as 1 cm2 exhibited excellent long-term stability, demonstrating no observable degradation in efficiency after more than 5000 h in storage and 3700 h under 85 °C thermal stressing in N2 atmosphere

The organics revolution: new narratives and how we can achieve them

Organic remains from excavated sites include a wide range of materials, from distinct organisms (‘ecofacts’) to biomolecules. Biomolecules provide a variety of new research avenues, while ecofacts with longer histories of study are now being re-harnessed in unexpected ways. These resources are unlocking research potential, transcending what was previously imagined possible. However, this ‘organics revolution’ comes with a salutary corollary: our approaches to recovering and curating organics, and making accessible research data, are not developing as quickly as we need. In this paper, we review retention guidelines for institutions in Britain and Ireland, setting this against the backdrop of a ‘curation crisis’ that is affecting museums throughout Europe, and beyond. We suggest key themes, including the state of existing documentation and considerations of intrinsic and allied research potential, that should be used to open a discussion about the development of more comprehensive and standardised approaches to archiving in the future. Engaging in this conversation is the only way that we can hope to ensure the long-term retention and preservation of organics, while safeguarding associated research data. These changes are needed to ensure future global research collaborations across the academic, curatorial and professional archaeological sectors

Open-circuit and short-circuit loss management in wide-gap perovskite p-i-n solar cells

In this work, we couple theoretical and experimental approaches to understand and reduce the losses of wide bandgap Br-rich perovskite pin devices at open-circuit voltage (VOC) and short-circuit current (JSC) conditions. A mismatch between the internal quasi-Fermi level splitting (QFLS) and the external VOC is detrimental for these devices. We demonstrate that modifying the perovskite top-surface with guanidinium-Br and imidazolium-Br forms a low-dimensional perovskite phase at the n-interface, suppressing the QFLS-VOC mismatch, and boosting the VOC. Concurrently, the use of an ionic interlayer or a self-assembled monolayer at the p-interface reduces the inferred field screening induced by mobile ions at JSC, promoting charge extraction and raising the JSC. The combination of the n- and p-type optimizations allows us to approach the thermodynamic potential of the perovskite absorber layer, resulting in 1 cm2 devices with performance parameters of VOCs up to 1.29 V, fill factors above 80% and JSCs up to 17 mA/cm2, in addition to a thermal stability T80 lifetime of more than 3500 h at 85 °C

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Dbl3 drives Cdc42 signaling at the apical margin to regulate junction position and apical differentiation

Epithelial cells develop morphologically characteristic apical domains that are bordered by tight junctions, the apical-lateral border. Cdc42 and its effector complex Par6-atypical protein kinase c (aPKC) regulate multiple steps during epithelial differentiation, but the mechanisms that mediate process-specific activation of Cdc42 to drive apical morphogenesis and activate the transition from junction formation to apical differentiation are poorly understood. Using a small interfering RNA screen, we identify Dbl3 as a guanine nucleotide exchange factor that is recruited by ezrin to the apical membrane, that is enriched at a marginal zone apical to tight junctions, and that drives spatially restricted Cdc42 activation, promoting apical differentiation. Dbl3 depletion did not affect junction formation but did affect epithelial morphogenesis and brush border formation. Conversely, expression of active Dbl3 drove process-specific activation of the Par6-aPKC pathway, stimulating the transition from junction formation to apical differentiation and domain expansion, as well as the positioning of tight junctions. Thus, Dbl3 drives Cdc42 signaling at the apical margin to regulate morphogenesis, apical-lateral border positioning, and apical differentiation