ß-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.

Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). Here, we identify ß-hydroxybutyrate (ßHB), a ketone body, as a regulator of protein solubility in the aging brain. ßHB is a small molecule metabolite which primarily provides an oxidative substrate for ATP during hypoglycemic conditions, and also regulates other cellular processes through covalent and noncovalent protein interactions. We demonstrate ßHB-induced protein insolubility across in vitro, ex vivo, and in vivo mouse systems. This activity is shared by select structurally similar metabolites, is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain in vivo after delivery of a ketone ester. Furthermore, this phenotype is selective for pathological proteins such as amyloid-ß, and exogenous ßHB ameliorates pathology in nematode models of amyloid-ß aggregation toxicity. We have generated a comprehensive atlas of the ßHB-induced protein insolublome ex vivo and in vivo using mass spectrometry proteomics, and have identified common protein domains within ßHB target sequences. Finally, we show enrichment of neurodegeneration-related proteins among ßHB targets and the clearance of these targets from mouse brain, likely via ßHB-induced autophagy. Overall, these data indicate a new metabolically regulated mechanism of proteostasis relevant to aging and AD.

Effects of antifouling compounds on the growth of macroalgae Undaria pinnatifida.

Seaweeds are some of the principal primary producers of marine environments, and they are important ecological elements of coastal ecosystems. The effects of harmful chemicals on seaweeds may adversely affect coastal ecosystems, hence we aimed to develop a new phytotoxicity test using the gametophytes of a common temperate kelp species, Undaria pinnatifida (KU-1630), for the widely used antifouling chemical substances Cybutryne, Diuron, Cu2+, and Zn2+. Toxicity to gametophytes of U. pinnatifida was assessed by comparing the relative growth rate (RGR) at the logarithmic growth phase. Fragmentation method, initial algal biomass, photon irradiance, and adhesive period were investigated for developing optimal test conditions. Cybutryne exposure tests were performed with seven replicates and control, the RGR ranging from 0.17 to 0.19, while mean 7-day EC50 and no observed effect concentration (NOEC) were 5.1 µg/L and 1.8 µg/L, respectively. The 7-day EC50 for other antifoulants was 14 µg/L for Diuron, 17 µg/L for Cu2+, and 1500 µg/L for Zn2+. This test method demonstrated high sensitivity and reproducibility, and it may be added to the routine methods used for toxicity evaluation of hazardous chemicals.

Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy in unresectable or metastatic mucosal melanoma: a retrospective, multicenter study of 329 Japanese cases (JMAC study).

BACKGROUND: Anti-programmed cell death protein 1 (PD-1) antibody monotherapy (PD1) has led to favorable responses in advanced non-acral cutaneous melanoma among Caucasian populations; however, recent studies suggest that this therapy has limited efficacy in mucosal melanoma (MCM). Thus, advanced MCM patients are candidates for PD1 plus anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) combination therapy (PD1 + CTLA4). Data on the efficacy of immunotherapy in MCM, however, are limited. We aimed to compare the efficacies of PD1 and PD1 + CTLA4 in Japanese advanced MCM patients. PATIENTS AND METHODS: We retrospectively assessed advanced MCM patients treated with PD1 or PD1 + CTLA4 at 24 Japanese institutions. Patient baseline characteristics, clinical responses (RECIST), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier analysis, and toxicity was assessed to estimate the efficacy and safety of PD1 and PD1 + CTLA4. RESULTS: Altogether, 329 patients with advanced MCM were included in this study. PD1 and PD1 + CTLA4 were used in 263 and 66 patients, respectively. Baseline characteristics were similar between both treatment groups, except for age (median age 71 versus 65 years; P < 0.001). No significant differences were observed between the PD1 and PD1 + CTLA4 groups with respect to objective response rate (26% versus 29%; P = 0.26) or PFS and OS (median PFS 5.9 months versus 6.8 months; P = 0.55, median OS 20.4 months versus 20.1 months; P = 0.55). Cox multivariate survival analysis revealed that PD1 + CTLA4 did not prolong PFS and OS (PFS: hazard ratio 0.83, 95% confidence interval 0.58-1.19, P = 0.30; OS: HR 0.89, 95% confidence interval 0.57-1.38, P = 0.59). The rate of ≥grade 3 immune-related adverse events was higher in the PD1 + CTLA4 group than in the PD1 group (53% versus 17%; P < 0.001). CONCLUSIONS: First-line PD1 + CTLA4 demonstrated comparable clinical efficacy to PD1 in Japanese MCM patients, but with a higher rate of immune-related adverse events.

Enhanced thermal conduction by surface phonon-polaritons.

Improving heat dissipation in increasingly miniature microelectronic devices is a serious challenge, as the thermal conduction in nanostructures is markedly reduced by increasingly frequent scattering of phonons on the surface. However, the surface could become an additional heat dissipation channel if phonons couple with photons forming hybrid surface quasiparticles called surface phonon-polaritons (SPhPs). Here, we experimentally demonstrate the formation of SPhPs on the surface of SiN nanomembranes and subsequent enhancement of heat conduction. Our measurements show that the in-plane thermal conductivity of membranes thinner than 50 nm doubles up as the temperature rises from 300 to 800 kelvin, while thicker membranes show a monotonic decrease. Our theoretical analysis shows that these thickness and temperature dependencies are fingerprints of SPhP contribution to heat conduction. The demonstrated thermal transport by SPhPs can be useful as a previously unidentified channel of heat dissipation in a variety of fields including microelectronics and silicon photonics.

Alteration in faecal bile acids, gut microbial composition and diversity after laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a well established treatment for severe obesity and type 2 diabetes. Although the gut microbiota is linked to the efficacy of LSG, the underlying mechanisms remain elusive. The effect of LSG for morbid obesity on the gut microbiota and bile acids was assessed here. METHODS: Severely obese subjects who were candidates for LSG were included and followed until 6 months after surgery. The composition and abundance of the microbiota and bile acids in faeces were assessed by 16S ribosomal RNA sequencing, quantitative PCR and liquid chromatography-mass spectrometry. RESULTS: In total, 28 patients with a mean(s.d.) BMI of 44·2(6·6) kg/m2 were enrolled. These patients had achieved excess weight loss of 53·2(19·0) per cent and showed improvement in metabolic diseases by 6 months after LSG, accompanied by an alteration in the faecal microbial community. The increase in α-diversity and abundance of specific taxa, such as Rikenellaceae and Christensenellaceae, was strongly associated with reduced faecal bile acid levels. These changes had a significant positive association with excess weight loss and metabolic alterations. However, the total number of faecal bacteria was lower in patients before (mean(s.d.) 10·26(0·36) log10 cells per g faeces) and after (10·39(0·29) log10 cells per g faeces) operation than in healthy subjects (10·83(0·27) log10 cells per g faeces). CONCLUSION: LSG is associated with a reduction in faecal bile acids and greater abundance of specific bacterial taxa and α-diversity that may contribute to the metabolic changes.

ANTECEDENTES: La gastrectomía vertical laparoscópica (laparoscopic sleeve gastrectomy, LSG) es un tratamiento bien establecido para la obesidad grave y la diabetes tipo 2. Aunque la microbiota intestinal se ha vinculado con la eficacia de LSG, los mecanismos subyacentes siguen siendo poco conocidos. En este estudio se evaluó el efecto de LSG en la obesidad mórbida sobre la microbiota del intestino y de los ácidos biliares (bile acids, BA). MÉTODOS: Tras la aprobación del Comité ético y la obtención del consentimiento informado, los sujetos con obesidad grave que eran candidatos para LSG fueron incluidos en el estudio y seguidos durante 6 meses después de la operación. Se evaluaron la composición y abundancia de la microbiota y BA en las heces mediante secuenciación del gen 16S rRNA, PCR cuantitativa y cromatografía líquida-espectrometría de masas. RESULTADOS: En total, 28 pacientes con una mediana (rango) del IMC de 43,9 kg/m2 (35,0-61,9) fueron reclutados y a los 6 meses tras una LSG, consiguieron una pérdida del exceso de peso de 47,3% (20,7-95,1) y mejoría de las enfermedades metabólicas acompañada de una alteración en la comunidad microbiana fecal. El aumento en la diversidad α y abundancia de especies taxonómicas específicas como Rikenellaceae y Christensenellaceae, se asociaba fuertemente con niveles fecales reducidos de BA. Estos cambios se asociaban de manera positiva y significativa con la pérdida del exceso de peso y las alteraciones metabólicas. Sin embargo, el número total de bacterias fecales en los pacientes fue inferior al de los sujetos sanos (10,84 log10 células/g heces (9,46-11,35)) antes de la operación (10,26 log10 células/g heces (9,44-10,91)) y después de la misma (10,42 log10 células/g heces (9,57-10,96)). CONCLUSIÓN: LSG se asoció con menos BA fecal y mayor abundancia de especies bacterianas específicas y diversidad α lo que puede contribuir a los cambios metabólicos.

A candidate-SNP retrospective cohort study for fracture risk in Japanese Thoroughbred racehorses.

Fractures are medical conditions that compromise the athletic potential of horses and/or the safety of jockeys. Therefore, the reduction of fracture risk is an important horse and human welfare issue. The present study used molecular genetic approaches to determine the effect of genetic risk for fracture at four candidate SNPs spanning the myostatin (MSTN) gene on horse chromosome 18. Among the 3706 Japanese Thoroughbred racehorses, 1089 (29.4%) had experienced fractures in their athletic life, indicating the common occurrence of this injury in Thoroughbreds. In the case/control association study, fractures of the carpus (carpal bones and distal radius) were statistically associated with g.65809482T/C (P = 1.17 x 10-8 ), g.65868604G/T (P = 2.66 x 10-9 ), and g.66493737C/T (P = 6.41 x 10-8 ). In the retrospective cohort study using 1710 racehorses born in 2000, the relative risk (RR) was highest for male horses at g.65868604G/T, based on the dominant allele risk model (RR = 2.251, 95% confidence interval 1.407-3.604, P = 0.00041), and for female horses at g.65868604G/T, based on the recessive allele risk model (RR = 2.313, 95% confidence interval 1.380-3.877, P = 0.00163). Considering the association of these SNPs with racing performance traits such as speed, these genotypes may affect the occurrence of carpus fractures in Japanese Thoroughbred racehorses as a consequence of the non-genetic influence of the genotype on the distance and/or intensity of racing and training. The genetic information presented here may contribute to the development of strategic training programs and racing plans for racehorses that improve their health and welfare.

A self-reported measurement scale on a potential component of competency in the healthcare staff engaged in the prevention and control of non-communicable disease in Fiji.

BACKGROUND: According to the World Health Organization, an estimated 80% or more deaths in Pacific island countries, including Fiji, were related to non-communicable diseases (NCDs). Although competency-based approaches have been effective for developing healthcare workers' capabilities, there are only a few reports on competency scales of healthcare workers for NCD prevention. We aimed to develop a self-reported measurement scale on a potential component of competency in the healthcare staff engaged in the prevention and control of NCDs in Fiji. METHODS: There were 378 Ministry of Health and Medical Services staff members working on NCD prevention and control in Fiji included in this study, which was a cross-sectional survey of social factors, working situation factors, and competency. Exploratory factor analysis was conducted to assess potential competency components, whereas Cronbach's α coefficient and analysis of variance were used to assess the validity and reliability of the scale items, respectively. Multivariate regression analyses were conducted to analyze the respondents' factor scores relative to social status and work situations. RESULTS: The factor analysis revealed 16 items that identified competency in four work types: 1) work management, 2) monitoring and evaluation, 3) community partnership, and 4) community diagnosis. The monitoring and evaluation roles were related to ethnic background, community partnership was related to religion, and community diagnosis was related to academic qualifications. CONCLUSIONS: Based on the results, we developed a competency scale for the four work types. This scale can help healthcare workers engage in better management of residents with NCDs in Fiji.

A case of nivolumab-induced acute-onset type 1 diabetes mellitus in melanoma.

Nivolumab, an anti-PD-1 antibody, is now considered an important therapeutic agent in several advanced malignancies. However, immune-related adverse events such as endocrinopathies have been reported with its use. Thyroid disorder and isolated adrenocorticotropic hormone deficiency have frequently been reported as nivolumab-induced immune-related adverse events. Another endocrinopathy is nivolumab-induced type 1 diabetes mellitus (t1dm), described as diabetes mellitus with rapid onset and complete insulin insufficiency, at times leading to fulminant t1dm. We report the case of a 68-year-old woman who developed pancreatic islet-related autoantibody-negative t1dm, possibly induced by nivolumab, under continuous glucocorticoid administration. She was treated with nivolumab for advanced malignant melanoma, concomitant with 10 mg prednisolone daily for thrombophlebitis tapered to 5 mg after 13 courses of nivolumab therapy. At approximately the 27th course of nivolumab therapy, she showed elevated plasma glucose levels despite preserved insulin secretion. A month later, she developed diabetic ketoacidosis. Her insulin secretion decreased and finally was exhausted. She was diagnosed with acute-onset rather than fulminant t1dm because of a rapidly progressive course to diabetic ketoacidosis during just more than 1 week. She is currently receiving insulin replacement. There has been no recurrence of the melanoma. Thus, nivolumab might induce autoimmune diabetes mellitus, with patients having t1dm-sensitive human leucocyte antigen being more susceptible even when receiving glucocorticoids. Physicians should be aware that nivolumab could potentially induce t1dm as a critical immune-related adverse event.

Brillouin Light Scattering by Magnetic Quasivortices in Cavity Optomagnonics.

A ferromagnetic sphere can support optical vortices in the form of whispering gallery modes and magnetic quasivortices in the form of magnetostatic modes with nontrivial spin textures. These vortices can be characterized by their orbital angular momenta. We experimentally investigate Brillouin scattering of photons in the whispering gallery modes by magnons in the magnetostatic modes, zeroing in on the exchange of the orbital angular momenta between the optical vortices and magnetic quasivortices. We find that the conservation of the orbital angular momentum results in different nonreciprocal behavior in the Brillouin light scattering. New avenues for chiral optics and optospintronics can be opened up by taking the orbital angular momenta as a new degree of freedom for cavity optomagnonics.

Aluminium nanopillars reduce thermal conductivity of silicon nanobeams.

In search of efficient thermoelectric nanostructures, many theoretical works predicted that nanopillars, placed on the surface of silicon membranes, nanobeams, or nanowires, can reduce the thermal conductivity of these nanostructures. To verify these predictions, we experimentally investigate heat conduction in suspended silicon nanobeams with periodic arrays of aluminium nanopillars. Our room temperature time-domain thermoreflectance experiments show that the nanobeams with nanopillars have 20% lower thermal conductivity as compared to pristine nanobeams. We discuss possible explanations of these data, including coherent effects, and conclude that the thermal conductivity is reduced mainly by phonon scattering at the pillar/beam interface due to the intermixing of aluminium and silicon atoms, as supported by the transmission electron microscopy. As this intermixing does not only reduce thermal conductivity but may also increase electrical conductivity, these nanostructures are exceptionally promising for thermoelectric applications.

Plutonium, 137Cs and uranium isotopes in Mongolian surface soils.

Plutonium (238Pu and 239,240Pu), 137Cs and plutonium activity ratios (238Pu/239,240Pu) as did uranium isotope ratio (235U/238U) were measured in surface soil samples collected in southeast Mongolia. The 239,240Pu and 137Cs concentrations in Mongolian surface soils (<53 µm of particle size) ranged from 0.42 ± 0.03 to 3.53 ± 0.09 mBq g-1 and from 11.6 ± 0.7 to 102 ± 1 mBq g-1, respectively. The 238Pu/239,240Pu activity ratios in the surface soils (0.013-0.06) coincided with that of global fallout. The 235U/238U atom ratios in the surface soil show the natural one. There was a good correlation between the 239,240Pu and 137Cs concentrations in the surface soils. We introduce the migration depth to have better understanding of migration behaviors of anthropogenic radionuclides in surface soil. We found a difference of the migration behavior between 239,240Pu and 137Cs from 137Cs/239,240Pu - 137Cs plots for the Mongolian and Tsukuba surface soils; plutonium in surface soil is migrated easier than 137Cs.

Quantitating the lateral skin stiffness by a new and versatile electro-mechanical instrument. Preliminary studies.

BACKGROUND: A new electro-mechanical device for measuring the lateral stiffness of the skin is now available. It basically allows to recording the forces that the skin opposes to a lateral displacement (1-2 mm) of a pinching type movement. Preliminary assays of this device to various skin sites and an artificial substrate aimed at defining its major characteristics (sensitivity, reproducibility, variations according to skin site). METHODS: The calibration of the device (Khelometer® ) and assessment of its reproducibility were carried out through the use of elastometer substrates of various stiffness's. The device was then used, in vivo, at different skin sites (scalp, inner and outer forearms, cheeks) of 213 healthy Japanese women of various ages. The short-time effect of a hydrating regimen (7% glycerol) was recorded on the outer forearm. RESULTS: This new device offers an appreciable reproducibility in vitro and in vivo (coefficient of variation of 2-4% and 5-14%, respectively). Unlike other biophysical methods, the Khelometer® can be easily applied onto the human scalp that shows a higher stiffness than the two other skin sites, increasing with age and presence of alopecia. In all the three studied skin sites, the impact of age leads to significantly higher lateral skin stiffness (LSS, expressed as N/mm) values. The latter were found significantly different between the two sides of the forearms where the outer (sun-exposed) side showed statistically slightly higher LSS, than the unexposed inner side. LSS values found on cheeks (≈0.5 N/mm) were about four times lower than those of the scalp (≈2 N/mm) and about half those of forearms (≈1 N/mm). The effect of a 7% glycerol based formula was recorded 20 min post application onto the forearm, leading to a slight drop in LSS (approx. 15%) as compared to a vehicle-applied skin site. CONCLUSION: These preliminary studies clearly indicate that this new device, applicable to any skin site, offers appreciable assets such as sensitivity and reproducibility. Accordingly, it appears as a new approach in the non-invasive biophysical measurements of the skin surface, in both advanced and applied research investigations.

Thinning of articular cartilage after joint unloading or immobilization. An experimental investigation of the pathogenesis in mice.

OBJECTIVE: Moderate mechanical stress generated by normal joint loading and movement is essential for the maintenance of healthy articular cartilage. However, the effects of reduced loading caused by the absence of weight bearing or joint motion on articular cartilage and subchondral bone is still poorly understood. We aimed to characterize morphological and metabolic responses of articular cartilage and subchondral bone to decreased mechanical stress in vivo. METHODS: Mice were subjected to periods of hindlimb unloading by tail suspension or external fixation of the knee joints. The articular surface was observed with digital microscope and the epiphyseal bone was assessed by micro-CT analysis. Articular cartilage and subchondral bone were further evaluated by histomorphometric, histochemical, and immunohistochemical analyses. RESULTS: The joint surface was intact, but thickness of both the total and uncalcified layer of articular cartilage were decreased both after joint unloading and immobilization. Subchondral bone atrophy with concomitant marrow expansion predisposed osteoclast activity at bone surface to invade into cartilaginous layer. Uncalcified cartilage showed decreased aggrecan content and increased aggrecanase expression. Alkaline phosphatase (ALP) activity was increased at uncalcified cartilage, whereas decreased at calcified cartilage. The distributions of hypertrophic chondrocyte markers remained unchanged. CONCLUSION: Thinning of articular cartilage induced by mechanical unloading may be mediated by metabolic changes in chondrocytes, including accelerated aggrecan catabolism and exquisitely modulated matrix mineralization, and cartilage matrix degradation and resorption by subchondral osteoclasts. Cartilage degeneration without chondrocyte hypertrophy under unloading condition indicate the possible existence of mechanism which is different from osteoarthritis pathogenesis.

Cavity Optomagnonics with Spin-Orbit Coupled Photons.

We experimentally implement a system of cavity optomagnonics, where a sphere of ferromagnetic material supports whispering gallery modes (WGMs) for photons and the magnetostatic mode for magnons. We observe pronounced nonreciprocity and asymmetry in the sideband signals generated by the magnon-induced Brillouin scattering of light. The spin-orbit coupled nature of the WGM photons, their geometrical birefringence, and the time-reversal symmetry breaking in the magnon dynamics impose the angular-momentum selection rules in the scattering process and account for the observed phenomena. The unique features of the system may find interesting applications at the crossroad between quantum optics and spintronics.

Pharmacokinetics of procaterol in thoroughbred horses.

Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 µg/kg) and oral (2.0 µg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 ± 0.23 L/kg, and the elimination half-life was 2.85 ± 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses.

Predictive factors for pericardial effusion identified by heart dose-volume histogram analysis in oesophageal cancer patients treated with chemoradiotherapy.

OBJECTIVE: To identify predictive factors for the development of pericardial effusion (PCE) in patients with oesophageal cancer treated with chemotherapy and radiotherapy (RT). METHODS: From March 2006 to November 2012, patients with oesophageal cancer treated with chemoradiotherapy (CRT) using the following criteria were evaluated: radiation dose >50 Gy; heart included in the radiation field; dose-volume histogram (DVH) data available for analysis; no previous thoracic surgery; and no PCE before treatment. The diagnosis of PCE was independently determined by two radiologists. Clinical factors, the percentage of heart volume receiving >5-60 Gy in increments of 5 Gy (V5-60, respectively), maximum heart dose and mean heart dose were analysed. RESULTS: A total of 143 patients with oesophageal cancer were reviewed retrospectively. The median follow-up by CT was 15 months (range, 2.1-72.6 months) after RT. PCE developed in 55 patients (38.5%) after RT, and the median time to develop PCE was 3.5 months (range, 0.2-9.9 months). On univariate analysis, DVH parameters except for V60 were significantly associated with the development of PCE (p < 0.001). No clinical factor was significantly related to the development of PCE. Recursive partitioning analysis including all DVH parameters as variables showed a V10 cut-off value of 72.8% to be the most influential factor. CONCLUSION: The present results showed that DVH parameters are strong independent predictive factors for the development of PCE in patients with oesophageal cancer treated with CRT. ADVANCES IN KNOWLEDGE: A heart dosage was associated with the development of PCE with radiation and without prophylactic nodal irradiation.

Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA.

Somatic mutations in the gene encoding the catalytic subunit of protein phosphatase 6 (Ppp6c) have been identified in malignant melanoma and are thought to function as a driver in B-raf- or N-ras-driven tumorigenesis. To assess the role of Ppp6c in carcinogenesis, we generated skin keratinocyte-specific Ppp6c conditional knockout mice and performed two-stage skin carcinogenesis analysis. Ppp6c deficiency induced papilloma formation with 7,12-dimethylbenz (a) anthracene (DMBA) only, and development of those papillomas was significantly accelerated compared with that seen following DMBA/TPA (12-O-tetradecanoylphorbol 13-acetate) treatment of wild-type mice. NF-κB activation either by tumor necrosis factor (TNF)-α or interleukin (IL)-1ß was enhanced in Ppp6c-deficient keratinocytes. Overall, we conclude that Ppp6c deficiency predisposes mice to skin carcinogenesis initiated by DMBA. This is the first report showing that such deficiency promotes tumor formation in mice.

The development and piloting of a leadership questionnaire for general dental practitioners: preliminary results from the North West of England and Tokyo.

OBJECTIVES: Key reforms in England and Japan have called for greater clinical leadership from general dental practitioners to deliver improvements in the quality of care for patients. In England, the reorganisation of the National Health Service has led to the development of Local Professional Networks to ensure services are clinically led, patient and outcome focused. In Japan, the rapidly changing demographics have led to calls for general dental practitioners to become more active in meeting the emerging population health challenges. Both require engagement at a strategic and a local level. However, little is known about what is meant by clinical leadership in dentistry or what training needs exist. The aim of this study was to develop and pilot a questionnaire to understand what general dental practitioners feel is important about clinical leadership and how they rate themselves. METHODS: A 61-item questionnaire was developed from the literature, an earlier qualitative study and refined through cognitive interviews. Questionnaires were distributed to general dental practitioners across the North West of England and Tokyo, using random sequence generation. For each item, the participant had to record whether they thought the statement was an important component of clinical leadership and how they rated themselves. Both were rated using a seven-point Likert scale. Data reduction was undertaken using principal component analysis to examine for factor loadings within the questionnaire. Differences in mean scores were also used to highlight substantive differences in how general dental practitioners rated the different components of leadership and how they rated themselves. RESULTS: The response rate for the pilot was low (22.9% and 7.5% for North West and Tokyo respectively). The items that were considered to be important in leadership reduced to two components in the North West (accounting for 62.1% of the total variance): 'How to lead' and 'How not to lead'. In Tokyo, 56.4% of the total variance was explained by three components: 'Demonstrating personal qualities', 'Working with others' and 'How not to lead'. When the self-rated items were reduced, three factors were found to be important in the North West: 'Working with others', 'Setting direction' and 'Managing services' (55.1% of the variance). 'Working with others', 'Demonstrating personal qualities', 'Pragmatism', 'Setting direction' and 'Improving services' were found to be important in Tokyo (52.8% of the variance). The questionnaire items relating to integrity, team-working and having a positive attitude during difficult times were rated highly by both groups. Items relating to providing vision for team, being assertive and having a positive attitude had the greatest mean difference, suggesting possible areas of training need. CONCLUSION: The nature of the pilot study and the poor response rate makes any conclusion difficult to infer. Among those that participated, leadership was understood to be more important at a practice level rather than at a strategic level. The questionnaire should be refined further based on the results of the pilot and the data reduction.