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Background Cosmetic treatments that inspire one's appearance to resemble their younger portrait often utilize ingredients that confer acute effects, particularly hydration by creating hydrophobic barriers or transient elevation of barrier water content. But superior therapies successfully promote morphogenesis of the dermal‐epidermal junction, inspiring extracellular matrix (ECM) formation. This can be achieved by agonism of the very well‐known retinoid nuclear receptors using the endogenous ligand all‐trans retinoic acid (tRA), tRA precursors or plant‐based functional analogues, with reduced side effects. Aims, Materials and Methods While there are already many promising cosmetic ingredients available from the world's flora, higher potency is favoured, so increasing known candidates is a worth undertaking. Functional analogues of retinoic acid can be identified by culturing fibroblasts with lipophilic candidates from the plant kingdom and assessing gene‐arrays. Modern approaches to validating these findings include the coculturing of fibroblasts with keratinocytes as a measure to predict the potential effects of crosstalk. Results and Discussion In this regard, the most promising plant‐derived candidates are of terpene or meroterpene origin, including derivatives of squalene and phytol. Surprisingly pimaric or abietic acids and labdane diterpenes are also noteworthy agonists of the retinoic acid receptor, stimulating collagen expression in dermal fibroblasts. Conclusion There are numerous derivatives of these terpenes available from the world's flora and research conducted thus far encourages further screening of these chemical candidates.

Increasing trade in plants and plant products across continents heightens the risk of exotic insect pests expanding geographically into new habitats. This threatens not only the production and economic value of widely traded crops but the survival of species grown or sought by low-income communities. The first European outbreak of Scirtothrips dorsalis was detected in the Palm House collections at Kew in 2007 and triggered a monitoring program. This monitoring along with a robust review of the literature brought together information on new and known hosts for S. dorsalis . Further to this, we used molecular characterization techniques to identify which proposed cryptic species of S. dorsalis was present in this outbreak. The study revealed that 39% of the species of plants among the collections supported the proposed S. dorsalis South Asia 1 cryptic species, with over 50% of those species supporting immature life stages of the thrips confirming that they are suitable breeding hosts. Of particular importance are the newly identified hosts that are crops, and two further hosts reported as endangered/critically endangered. This study demonstrates the role that botanic garden collections can play in generating host relationship data that can feed into the development of robust predictive risk assessments for invasive insects. This can provide plant health authorities with the scientific basis for prioritizing management plans to protect important, vulnerable crop and non-crop plant species.

Graves’ disease (GD) and Hashimoto's thyroiditis (HT) represent the commonest forms of autoimmune thyroid disease (AITD) each presenting with distinct clinical features. Progress has been made in determining association of HLA class II DRB1, DQB1 and DQA1 loci with GD demonstrating a predisposing effect for DR3 (DRB1 * 03-DQB1 * 02-DQA1 * 05) and a protective effect for DR7 (DRB1 * 07-DQB1 * 02-DQA1 * 02). Small data sets have hindered progress in determining HLA class II associations with HT. The aim of this study was to investigate DRB1-DQB1-DQA1 in the largest UK Caucasian HT case control cohort to date comprising 640 HT patients and 621 controls. A strong association between HT and DR4 (DRB1 * 04-DQB1 * 03-DQA1 * 03) was detected ( P =6.79 × 10 −7 , OR=1.98 (95% CI=1.51–2.59)); however, only borderline association of DR3 was found ( P =0.050). Protective effects were also detected for DR13 (DRB1 * 13-DQB1 * 06-DQA1 * 01) ( P =0.001, OR=0.61 (95% CI=0.45–0.83)) and DR7 ( P =0.013, OR=0.70 (95% CI=0.53–0.93)). Analysis of our unique cohort of subjects with well characterized AITD has demonstrated clear differences in association within the HLA class II region between HT and GD. Although HT and GD share a number of common genetic markers this study supports the suggestion that differences in HLA class II genotype may, in part, contribute to the different immunopathological processes and clinical presentation of these related diseases.

Genome-wide association studies provide insight into multigenic diseases through the identification of susceptibility genes and etiological pathways. In addition, the identification of shared variants among autoimmune disorders provides insight into common disease pathways. We previously reported an association of a nonsynonymous single nucleotide polymorphism (SNP) rs763361/Gly307Ser in the immune response gene CD226 on chromosome 18q22 with type 1 diabetes (T1D) susceptibility. Here, we report efforts toward identifying the causal variant by exonic resequencing and tag SNP mapping of the 18q22 region in both T1D and multiple sclerosis (MS). In addition to the analysis of newly available samples in T1D (2088 cases and 3289 controls) and autoimmune thyroid disease (AITD) (821 cases and 1920 controls), resulting in strong support for the Ser 307 association with T1D ( P =3.46 × 10 −9 ) and continued potential evidence for AITD ( P =0.0345), we provide evidence for association of Gly307Ser with MS ( P =4.20 × 10 −4 ) and rheumatoid arthritis (RA) ( P =0.017). The Ser 307 allele of rs763361 in exon 7 of CD226 predisposes to T1D, MS, and possibly AITD and RA, and based on the tag SNP analysis, could be the causal variant.

Single-nucleotide polymorphisms (SNPs) within the tumour necrosis factor alpha (TNF-α) gene on chromosome 6p21.3 have been associated with many autoimmune diseases; however, results have been conflicting and accurate allele frequencies have never been established in a UK Caucasian population. The aim of this study was to assess the frequency of 22 known TNF-α SNPs in a UK Caucasian control population and investigate association of all polymorphisms with >5% minor allele frequency in a large case–control data set of patients with Graves' disease (GD). Eight of the 22 SNPs had minor allele frequencies >5% and were investigated further. The other 14 SNPs were present in the UK population at frequencies ranging from 0 to 4.7%. A significant increase of the A allele of the −238 SNP was seen in GD patients when compared with control subjects (9.6 vs 6.8%, respectively; P =0.003) and mirrored in the genotype distribution ( P =0.009). Furthermore, association of the –238 SNP appears not to be due to linkage disequilibrium of the known HLA-DRB1 * 03 associations with GD. This study has established accurate allele frequencies of TNF-α SNPs in a UK population and provides preliminary evidence for association of the TNF-α gene with GD.

Properties of deuterium (D) supersaturated surface layers (DSSLs) formed in tungsten (W), such as thickness, internal microstructures, and D retention, are experimentally investigated as a function of the incident ion energy, E i . W samples were exposed to D plasmas in the PISCES-A linear plasma device in a range of E i ∼ 45–175 eV, while other plasma exposure parameters were fixed: sample temperature, T s , ∼423 K, ion flux, Γ i , ∼1.2 × 10 21 m −2 s −1 , and fluence, Φ i , ∼3.0 × 10 24 m −2 . High-resolution, cross-sectional, transmission electron microscopy observations confirm that (1) a DSSL forms even at the lowest E i ∼ 45 eV, (2) the DSSL thickness, Δ t DSSL , is found to decrease with decreasing E i from ∼11–12 nm at E i ∼ 175 eV to ∼5–6 nm at ∼45 eV, and to agree with approximately the maximum implantation depth calculated using SDTrimSP, and (3) high-density D nanobubbles with a diameter of ∼1 nm or less exist inside the DSSL, which is deemed to validate a theory-predicted vacancy stabilization process due to trapping of a solute D atom(s). Utilizing a D areal density of ∼4.2 × 10 19 m −2 in the first 14 nm from the surface at E i ∼ 75 eV from nuclear reaction analysis and the measured E i dependence of Δ t DSSL , our previous laser-induced breakdown spectroscopy data is updated: both dynamic and static D retention increase with decreasing E i , and the D/W atomic fraction during plasma exposure reaches ∼0.3 at E i ∼ 45 eV. A possible DSSL formation mechanism is proposed.

We reply to the comment by Li et al (submitted to Nucl. Fusion with this response) on our recent paper Nishijima et al (2023 Nucl. Fusion 63 126003). In this response, we address the existence of an incident ion energy, E i, threshold for the deuterium (D) supersaturated surface layer (DSSL) formation with a newly conducted D plasma exposure experiment at E i ∼ 20 eV. It is also further demonstrated, based on new experiments where the ion flux, fluence, and sample temperature are scanned, that non-kinetic (ballistic) processes play a role in the DSSL formation and growth. In addition, the effect of impurities in our plasma is discussed also with a new analysis of the surface composition made after a D plasma exposure.

Timely medical assessment is integral to the safety and quality of healthcare delivery in acute medicine. Medical staff are an expensive resource. This study aimed to develop a modelling system that facilitated efficient workforce planning according to patient need on the acute medical unit. A realistic 24-hour ‘supply’ of junior doctors was calculated by adjusting the theoretical numbers on the rota for leave allowances, natural breaks and other ward duties by a combination of direct observation of working practice and junior doctor interviews. ‘Demand’ was analysed using detailed admission data. Supply and demand were then integrated with data from a survey of the time spent on the process of clerking and assessment of medical admissions. A robust modelling system that predicted the number of unclerked patients was developed. The utility of the model was assessed by demonstrating the impact of a regulation-compliant redesign of the rota using existing staff and by predicting the most efficient use of an additional shift. This simple modelling system has the potential to enhance quality of care and efficiency by linking workforce planning to patient need.

Abstract Properties of deuterium (D) supersaturated surface layers (DSSLs) formed in tungsten (W), such as thickness, internal microstructures, and D retention, are experimentally investigated as a function of the incident ion energy, E i . W samples were exposed to D plasmas in the PISCES-A linear plasma device in a range of E i ∼ 45–175 eV, while other plasma exposure parameters were fixed: sample temperature, T s , ∼423 K, ion flux, Γ i , ∼1.2 × 10 21 m −2 s −1 , and fluence, Φ i , ∼3.0 × 10 24 m −2 . High-resolution, cross-sectional, transmission electron microscopy observations confirm that (1) a DSSL forms even at the lowest E i ∼ 45 eV, (2) the DSSL thickness, Δ t DSSL , is found to decrease with decreasing E i from ∼11–12 nm at E i ∼ 175 eV to ∼5–6 nm at ∼45 eV, and to agree with approximately the maximum implantation depth calculated using SDTrimSP, and (3) high-density D nanobubbles with a diameter of ∼1 nm or less exist inside the DSSL, which is deemed to validate a theory-predicted vacancy stabilization process due to trapping of a solute D atom(s). Utilizing a D areal density of ∼4.2 × 10 19 m −2 in the first 14 nm from the surface at E i ∼ 75 eV from nuclear reaction analysis and the measured E i dependence of Δ t DSSL , our previous laser-induced breakdown spectroscopy data is updated: both dynamic and static D retention increase with decreasing E i , and the D/W atomic fraction during plasma exposure reaches ∼0.3 at E i ∼ 45 eV. A possible DSSL formation mechanism is proposed.

BackgroundPatients with chronic pain often lack the skills and resources necessary to manage this disease.ObjectiveTo develop a chronic pain self-management program reflecting community stakeholders’ priorities and to compare functional outcomes from training in two settings.DesignA parallel-group randomized trial.ParticipantsEligible subjects were 35–70 years of age, with chronic non-cancer pain treated with opioids for >2 months at two primary care and one HIV clinic serving low-income Hispanics.InterventionsIn one study arm, the 6-month program was delivered in monthly one-on-one clinic meetings by a community health worker (CHW) trained as a chronic pain health educator, and in the second arm, content experts gave eight group lectures in a nearby library.Main MeasuresFive times Sit-to-Stand test (5XSTS) assessed at baseline and 3 and 6 months. Other reported physical and cognitive measures include the 6-Min Walk (6 MW), Borg Perceived Effort Test (Borg Effort), 50-ft Speed Walk (50FtSW), SF-12 Physical Component Summary (SF-12 PCS), Patient-Specific Functional Scale (PSFS), and Symbol–Digit Modalities Test (SDMT). Intention-to-treat (ITT) analyses in mixed-effects models adjust for demographics, body mass index, maximum pain, study arm, and measurement time. Multiple imputation was used for sensitivity analyses.Key ResultsAmong 111 subjects, 53 were in the clinic arm and 58 in the community arm. In ITT analyses at 6 months, subjects in both arms performed the 5XSTS test faster (−4.9 s, P = 0.001) and improved scores on Borg Effort (−1, P = 0.02), PSFS (1.6, P < 0.001), and SDMT (5.9, P < 0.001). Only the clinic arm increased the 6 MW (172.4 ft, P = 0.02) and SF-12 PCS (6.2 points, P < 0.001). 50ftSW did not change (P = 0.15). Results were similar with multiple imputation. Five falls were possible adverse events.ConclusionsIn low-income subjects with chronic pain, physical and cognitive function improved significantly after self-management training from expert lectures in the community and in-clinic meetings with a trained health educator.