Thermoelectric performance of a metastable thin-film Heusler alloy.

Thermoelectric materials transform a thermal gradient into electricity. The efficiency of this process relies on three material-dependent parameters: the Seebeck coefficient, the electrical resistivity and the thermal conductivity, summarized in the thermoelectric figure of merit. A large figure of merit is beneficial for potential applications such as thermoelectric generators. Here we report the thermal and electronic properties of thin-film Heusler alloys based on Fe2V0.8W0.2Al prepared by magnetron sputtering. Density functional theory calculations suggest that the thin films are metastable states, and measurements of the power factor-the ratio of the Seebeck coefficient squared divided by the electrical resistivity-suggest a high intrinsic figure of merit for these thin films. This may arise from a large differential density of states at the Fermi level and a Weyl-like electron dispersion close to the Fermi level, which indicates a high mobility of charge carriers owing to linear crossing in the electronic bands.

Effect of X-ray tube on image quality and pancreatic ductal adenocarcinoma conspicuity in pancreatic protocol dual-energy CT.

AIM: To compare the radiation dose, image quality, and conspicuity of pancreatic ductal adenocarcinoma (PDAC) in pancreatic protocol dual-energy computed tomography (CT) between two X-ray tubes mounted in the same CT machine. MATERIAL AND METHODS: This retrospective study comprised 80 patients (median age, 73 years; 45 men) who underwent pancreatic protocol dual-energy CT from January 2019 to March 2022 using either old (Group A, n=41) or new (Group B, n=39) X-ray tubes mounted in the same CT machine. The imaging parameters were completely matched between the two groups, and CT data were reconstructed at 70 and 40 keV. The CT dose-index volume (CTDIvol); CT attenuation of the abdominal aorta, pancreas, and PDAC; background noise; and qualitative scores for the image noise, overall image quality, and PDAC conspicuity were compared between the two groups. RESULTS: The CTDIvol was lower in Group B than Group A (7.9 versus 9.2 mGy; p<0.001). The CT attenuation of all anatomical structures at 70 and 40 keV was comparable between the two groups (p=0.06-0.78). The background noise was lower in Group B than Group A (12 versus 14 HU at 70 keV, p=0.046; and 26 versus 30 HU at 40 keV, p<0.001). Qualitative scores for image noise and overall image quality at 70 and 40 keV and PDAC conspicuity at 40 keV were higher in Group B than Group A (p<0.001-0.045). CONCLUSION: The latest X-ray tube could reduce the radiation dose and improve image quality in pancreatic protocol dual-energy CT.

Comparison of the cardiometabolic profiles of adolescents conceived through ART with those of a non-ART cohort.

STUDY QUESTION: Is the cardiometabolic health of adolescents conceived through ART worse than that of their counterparts conceived without ART? SUMMARY ANSWER: The majority of cardiometabolic and vascular health parameters of adolescents conceived through ART are similar or more favourable, than those of their counterparts of similar age and conceived without ART. WHAT IS KNOWN ALREADY: It has been proposed that the cardiometabolic health of offspring conceived with ART may be unfavourable compared to that of their counterparts conceived without ART. The literature pertaining to cardiometabolic health of offspring conceived after ART is contradictory, but generally suggests unfavourable cardiometabolic health parameters, such as an increase in blood pressure (BP), vascular dysfunction and adiposity, as well as unfavourable glucose and lipid profiles. With over 8 million children and adults born through ART worldwide, it is important to investigate whether these early signs of adverse cardiometabolic differences persist into adolescence and beyond. STUDY DESIGN, SIZE, DURATION: The Growing Up Healthy Study (GUHS) is a prospective cohort study that recruited 303 adolescents and young adults conceived after ART (aged 13-21 years) and born between 1991 and 2001 in Western Australia. Their health parameters, including cardiometabolic factors, were assessed and compared with counterparts from the Raine Study Generation 2 (Gen2). The 2868 Gen2 participants were born 1989-1992 and are representative of the Western Australian adolescent population. At ∼17 years of age (2013-2017), 163 GUHS participants replicated assessments previously completed by Gen2 at a similar age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cardiometabolic parameters were compared between a total of 163 GUHS and 1457 Gen2 adolescents. Separate male (GUHS n = 81, Gen2 n = 735) and female (GUHS n = 82, Gen2 n = 722) analyses were conducted. Assessments consisted of a detailed questionnaire including health, lifestyle and demographic parameters, anthropometric assessments (height, weight, BMI, waist circumference and skinfold thickness), fasting serum biochemistry, arterial stiffness and BP (assessed using applanation tonometry). Abdominal ultrasonography was used to assess the presence and severity of hepatic steatosis, and thickness of abdominal fat compartments. Non-alcoholic fatty liver disease (NAFLD) was diagnosed if there was sonographic fatty liver in the absence of significant alcohol consumption. Chi2, Fisher's exact and Mann-Whitney U tests, performed in SPSS V25, examined cohort differences and generalized estimating equations adjusted for the following covariates: singleton vs non-singleton pregnancy, birthweight (z-score), gestational age, BMI, smoking, alcohol consumption in the past 6 months and parent cardiovascular status. Arterial stiffness measures and waist circumference were additionally adjusted for height, and female analyses were additionally adjusted for use of oral contraceptives in the preceding 6 months. MAIN RESULTS AND THE ROLE OF CHANCE: In adjusted analyses, GUHS females had a lower BMI (22.1 vs 23.3 kg/m2, P = 0.014), and thinner skinfolds (triceps, subscapular, mid-abdominal; 16.9 vs 18.7 mm, P = 0.021, 13.4 vs 15.0 mm, P = 0.027, 19.7 vs 23.2 mm, P < 0.001, respectively), whereas males were not significantly different. Waist circumference was lower in GUHS adolescents (males: 78.1 vs 81.3 cm, P = 0.008, females: 76.7 vs 83.3 cm, P = 0.007). There were no significant differences between the two groups in glucose, insulin, homeostatic model assessment for insulin resistance, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), alanine aminotransferase and high-sensitivity C-reactive protein in both sexes. In females, serum triglycerides were lower in GUHS adolescents (1.0 vs 1.2 mmol/l, P = 0.029). GUHS males had higher serum HDL-C (1.1 vs 1.0 mmol/l, P = 0.004) and a lower TC/HDL-C ratio (3.2 vs 3.6, P = 0.036). There were no significant differences in the prevalence of NAFLD or steatosis severity scores between the cohorts in males and females. GUHS females had less subcutaneous adipose tissue (9.4 vs 17.9 mm, P < 0.001), whereas GUHS males had greater visceral adipose thickness (44.7 vs 36.3 mm, P < 0.001). There was no significant difference in pre-peritoneal adipose thickness. Pulse wave velocity was lower in GUHS males (5.8 vs 6.3 m/s, P < 0.001) and heart rate corrected augmentation index was lower in GUHS females (-8.4 vs -2.7%, P = 0.048). There were no significant differences in BP or heart rate in males or females between the two groups. LIMITATIONS, REASONS FOR CAUTION: Despite the substantial study size and the unique study design of the ART cohort, we were unable to differentiate between different types of ART, due to the low number of ICSI cycles (e.g. IVF vs ICSI), draw definite conclusions, or relate the outcomes to the cause of infertility. Considering the differences in time points when both cohorts were studied, external factors could have changed, which could not be accounted for. Given the observational nature of this study, causation cannot be proven. WIDER IMPLICATIONS OF THE FINDINGS: Contrary to our hypothesis and previous findings focussing mainly on childhood, this study reports mostly similar or favourable cardiometabolic markers in adolescents conceived with ART compared to those conceived without ART. The greater visceral adipose thickness, particularly present in males, requires further investigation. While these findings are generally reassuring, future well-designed and appropriately powered studies are required to definitively address the issue of cardiometabolic health in ART adults. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by NHMRC project grant number 1042269 and R.J.H. received education grant funding support from Ferring Pharmaceuticals. R.J.H. is the Medical Director of Fertility Specialists of Western Australia and a shareholder in Western IVF. He has received educational sponsorship from MSD, Merck-Serono and Ferring Pharmaceuticals. P.B. is the Scientific Director of Concept Fertility Centre, Subiaco, Western Australia. J.L.Y. is the Medical Director of PIVET Medical Centre, Perth, Western Australia. TRIAL REGISTRATION NUMBER: N/A.

Analog of a Quantum Heat Engine Using a Single-Spin Qubit.

A quantum two-level system with periodically modulated energy splitting could provide a minimal universal quantum heat machine. We present the experimental realization and the theoretical description of such a two-level system as an impurity electron spin in a silicon tunnel field-effect transistor. In the incoherent regime, the system can behave analogously to either an Otto heat engine or a refrigerator. The coherent regime could be described as a superposition of those two regimes, producing specific interference fringes in the observed source-drain current.

Physical activity trajectories from childhood to late adolescence and their implications for health in young adulthood.

Physical activity has been associated with physical and mental health across the life course, yet few studies have used group-based trajectory modeling to examine the effect of longitudinal patterns of physical activity during childhood and adolescence on adult health outcomes. The Raine Study data from Gen2 follow-ups at 8, 10, 14, 17, 20, and 22 years collected between 1998 and 2014 were used. Latent class analysis identified trajectories using parent-reported physical activity for ages 8 to 17. Associations between trajectories and physical and mental health outcomes at ages 20 and 22 were explored, adjusting for current physical activity and considering sex interactions. Analysis in 2019 identified three trajectories: low (13%), mid (65%) and high (22%) physical activity (n = 1628). Compared to the low-activity trajectory, those in the high-activity trajectory had lower adiposity, insulin, HOMA-IR and fewer diagnosed disorders, higher HDL-cholesterol, and faster cognitive processing. For example, those in the high-activity trajectory had lower percent body fat at age 20 compared to those in the mid-activity (-4.2%, 95%CI: -5.8, -2.7) and low-activity (-9.5%, 95%CI: -11.7, -7.2) trajectories. Physical activity trajectories showed different associations between sexes for self-reported physical and mental health, BMI, systolic blood pressure, and depression symptoms. Being in the high- or mid-activity trajectory was associated with a more favorable cardiometabolic and mental health profile in young adulthood. Strategies are needed to help less active children to increase physical activity throughout childhood and adolescence to improve young adult health outcomes.

Features of the metabolic syndrome in late adolescence are associated with impaired testicular function at 20 years of age.

STUDY QUESTION: Are early signs of metabolic disorder in late adolescence associated with features of impaired testicular function many years before the majority seek parenthood? SUMMARY ANSWER: Adolescents with features of metabolic disorder at 17 years, or insulin resistance (IR) at 20 years of age, show impaired testicular function and altered hormone levels compared to those without metabolic disorder. WHAT IS KNOWN ALREADY: Controversial evidence suggests a recent decline in sperm production potentially linked to environmental influences, but its cause remains unclear. Concomitant increases in obesity and diabetes suggest that lifestyle factors may contribute to this decline in testicular function. Although obesity has been associated with adverse testicular function in some studies, it remains unclear whether poor testicular function merely reflects, or causes, poor metabolic health. If metabolic disorder were present in adolescence, prior to the onset of obesity, this may suggest that metabolic disorder maybe a precursor of impaired testicular function. STUDY DESIGN, SIZE, DURATION: The Western Australian Pregnancy Cohort (Raine) Study is a longitudinal study of children born in 1989-1991 who have undergone detailed physical assessments since birth (1454 male infants born). At 17 years of age, 490 boys underwent a hepatic ultrasound examination, serum cytokine assessment (n = 520) and a metabolic assessment (n = 544). A further metabolic assessment was performed at 20 years (n = 608). Testicular assessment was performed at 20 years; 609 had reproductive hormones measured, 404 underwent a testicular ultrasound and 365 produced a semen sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testicular volume was estimated by ultrasonography, and semen analysis was performed according to World Health Organization guidelines. Concentrations of LH, FSH and inhibin B (inhB) in serum were measured by immunoassay and total testosterone by liquid chromatography-mass spectrometry.At 17 years of age, a liver ultrasound examination was performed to determine the presence of non-alcoholic fatty liver disease (NAFLD), and serum analysed for the cytokines interleukin-18 and soluble tumour necrosis factor receptor 1 and 2 (sTNFR1, sTNFR2).At 17 and 20 years of age, fasting blood samples were analysed for serum liver enzymes, insulin, glucose, triglycerides (TG), total cholesterol, high density lipoprotein and low density lipoprotein cholesterol, high sensitivity C-reactive protein and uric acid. The homoeostatic model assessment (HOMA) was calculated and approximated IR was defined by a HOMA >4. Anthropometric data was collected and dual energy X-ray absorptiometry measurement performed for lean and total fat mass. As at this young age the prevalence of metabolic syndrome was expected to be low, a two-step cluster analysis was used using waist circumference, TGs, insulin, and systolic blood pressure to derive a distinct high-risk group with features consistent with the metabolic syndrome and increased cardiometabolic risk. MAIN RESULTS AND THE ROLE OF CHANCE: Men at age 17 years with increased cardiometabolic risk had lower concentrations of serum testosterone (medians: 4.0 versus 4.9 ng/mL) and inhB (193.2 versus 221.9 pg/mL) (P < 0.001 for both) compared to those within the low risk metabolic cluster. Men with ultrasound evidence of NAFLD (n = 45, 9.8%) had reduced total sperm output (medians: 68.0 versus 126.00 million, P = 0.044), testosterone (4.0 versus 4.7 ng/mL, P = 0.005) and inhB (209.1 versus 218.4 pg/mL, P = 0.032) compared to men without NAFLD.Men with higher concentrations of sTNFR1 at 17 years of age had a lower sperm output and serum concentration of inhB, with an increase in LH and FSH (all P < 0.05 after adjustment for age, BMI, abstinence and a history of cryptorchidism, varicocele, cigarette smoking, alcohol and drug use), compared to those without an elevated sTNFR1. Multivariable regression analysis, adjusting for confounders, demonstrated that men in the high-risk metabolic cluster at 20 years had a lower serum testosterone and inhB (P = 0.003 and P = 0.001, respectively). A HOMA-IR > 4 was associated with a lower serum testosterone (P = <0.001) and inhB (P = 0.010) and an increase in serum FSH (P = 0.015). LIMITATIONS, REASONS FOR CAUTION: This study is limited by the sample size and multiple comparisons, and causality cannot be proven from an observational study. Due to a 3-year interval between some metabolic assessments and assessment of testicular function, we cannot exclude the introduction of a bias into the study, as some of the participants and their testicular function will not have been fully mature at the 17-year assessment. WIDER IMPLICATIONS OF THE FINDINGS: Irrespective of a proven causation, our study findings are important in that a significant minority of the men, prior to seeking parenthood, presented co-existent features of metabolic disorder and signs of testicular impairment. Of particular note is that the presence of NAFLD at 17 years of age, although only present in a minority of men, was associated with an almost 50% reduction in sperm output at 20 years of age, and that the presence of IR at 20 years was associated with a 20% reduction in testicular volume. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Australian NHMRC (Grant Numbers 634457, 35351417 and 403981) and received support from the Raine Medical Research Foundation, The Telethon Kids Institute, University of Western Australia, Women and Infants Research Foundation, Curtin University and Edith Cowan University. D.A.D., J.E.D., N.M., L.A.A., R.-C.H., T.A.M., J.K.O., L.J.B. have nothing to declare. R.J.H. is Medical Director of Fertility Specialists of Western Australia, has equity interests in Western IVF, and has received grant support from MSD, Merck-Serono and Ferring Pharmaceuticals. RMcL has equity interests in the Monash IVF Group. R.J.N. has equity interests in FertilitySA, and has received grant support from Merck Serono and Ferring Pharmaceuticals. D.J.H. has received institutional grant funding (but no personal income) for investigator-initiated testosterone pharmacology studies from Lawley and Besins Healthcare and has provided expert testimony to anti-doping tribunals and for testosterone litigation.This abstract was awarded the Fertility Society of Australia clinical exchange award for the oral presentation at ESHRE, Barcelona, in 2018.

Quantum Interferometry with a g-Factor-Tunable Spin Qubit.

We study quantum interference effects of a qubit whose energy levels are continuously modulated. The qubit is formed by an impurity electron spin in a silicon tunneling field-effect transistor, and it is read out by spin blockade in a double-dot configuration. The qubit energy levels are modulated via its gate-voltage-dependent g factors, with either rectangular, sinusoidal, or ramp radio frequency waves. The energy-modulated qubit is probed by the electron spin resonance. Our results demonstrate the potential of spin qubit interferometry implemented in a silicon device and operated at a relatively high temperature.

Oral function and vertical jump height among healthy older people in Japan.

OBJECTIVE: Vertical jump height and oral function affect the general muscle condition. This study aimed to evaluate the association between vertical jump height and oral function among healthy older individuals. BASIC RESEARCH DESIGN: Cross-sectional analytic study. PARTICIPANTS: 231 independent older people (mean age, 74.4 ± 5.6 years) who participated in the Kyoto Elders Physical Fitness Measurement Research Project. Individuals with partial or complete edentulousness who did not use a prosthetic device or complained of oral/maxillofacial pain were excluded from the study. INTERVENTIONS: Grip strength was measured using a Smedley Hand Dynamometer. To measure masticatory performance, the participants were instructed to chew a gummy jelly on their habitual chewing side (left or right) for 20 s. Occlusal force, contact area, and pressure were also assessed. MAIN OUTCOME MEASURES: The outcome variable was vertical jump height. The predictor variables were physical status (age, body mass index, and grip strength), oral status (number of present teeth and denture use), and oral function (masticatory performance, occlusal force, occlusal contact area, occlusal pressure, and tongue pressure). These relationships were evaluated with univariate analysis, and then multiple regression analysis was performed with age as the covariate for each male and female participant. RESULTS: Vertical jump height was significantly associated with grip strength in both men and women. Moreover, in women, it was associated with masticatory performance, occlusal force, and occlusal contact area. CONCLUSIONS: Vertical jump height was closely associated with oral function among healthy older women.

Kidney enlargement and multiple liver cyst formation implicate mutations in PKD1/2 in adult sporadic polycystic kidney disease.

Distinguishing autosomal-dominant polycystic kidney disease (ADPKD) from other inherited renal cystic diseases in patients with adult polycystic kidney disease and no family history is critical for correct treatment and appropriate genetic counseling. However, for patients with no family history, there are no definitive imaging findings that provide an unequivocal ADPKD diagnosis. We analyzed 53 adult polycystic kidney disease patients with no family history. Comprehensive genetic testing was performed using capture-based next-generation sequencing for 69 genes currently known to cause hereditary renal cystic diseases including ADPKD. Through our analysis, 32 patients had PKD1 or PKD2 mutations. Additionally, 3 patients with disease-causing mutations in NPHP4, PKHD1, and OFD1 were diagnosed with an inherited renal cystic disease other than ADPKD. In patients with PKD1 or PKD2 mutations, the prevalence of polycystic liver disease, defined as more than 20 liver cysts, was significantly higher (71.9% vs 33.3%, P = .006), total kidney volume was significantly increased (median, 1580.7 mL vs 791.0 mL, P = .027) and mean arterial pressure was significantly higher (median, 98 mm Hg vs 91 mm Hg, P = .012). The genetic screening approach and clinical features described here are potentially beneficial for optimal management of adult sporadic polycystic kidney disease patients.

Pleth variability index can predict spinal anaesthesia-induced hypotension in patients undergoing caesarean delivery.

BACKGROUND: Spinal anaesthesia carries a risk of hypotension. We hypothesized that pleth variability index and perfusion index would assess maternal volume status, and thus, allow identification of patients at higher risk of developing hypotension after spinal anaesthesia for caesarean delivery. METHODS: Fifty patients undergoing elective caesarean delivery were enrolled. All patients received spinal anaesthesia with 0.5% hyperbaric bupivacaine (10 mg) and fentanyl (10 mcg). Blood pressure was measured every minute. Pleth variability index and perfusion index were automatically measured throughout the procedure using pulse oximetry on the index finger. In case of hypotension (systolic blood pressure below 90 mmHg or 80% of the baseline value), ephedrine 5 mg was administered. Receiver-operating characteristic and multivariate logistic regression analyses for spinal anaesthesia-induced hypotension were performed. RESULTS: Hypotension occurred in 32 patients (64%). The areas under the receiver-operating characteristic curve were 0.751 (95% confidence interval: 0.597-0.904) for pleth variability index before anaesthesia, 0.793 (95% confidence interval: 0.655-0.930) for pleth variability index after anaesthesia and 0.731 (95% confidence interval: 0.570-0.892) for perfusion index change (percent change in perfusion index induced by spinal anaesthesia). The optimal threshold value of pleth variability index (after anaesthesia) for predicting hypotension was 18% (sensitivity: 78.1%, specificity: 83.3%). Pleth variability index after spinal anaesthesia was an independent factor for hypotension (odds ratio: 1.21, P = 0.041). CONCLUSIONS: Pleth variability index after spinal anaesthesia was a good predictor of spinal anaesthesia-induced hypotension in patients undergoing caesarean delivery. In addition, perfusion index change after spinal anaesthesia has the potential to predict hypotension.

Body odour aldehyde reduction by acetic acid bacterial extract including enzymes: alcohol dehydrogenase and aldehyde dehydrogenase.

OBJECTIVE: The major causes of unpleasant human body odour are aldehydes produced by axillary-resident bacteria. There are many methods of body odour prevention; however, they all carry risks of destroying indigenous dermal bacteria that are necessary for the maintenance of the normal physical function of the skin. Furthermore, some methods cannot directly reduce the concentrations of substances that cause body odour. Therefore, a novel method of reducing body odour more safely and effectively is required. We focused on acetic acid bacterial enzymes, which can convert aldehydes into carboxylic acids, and investigated their effect on aldehydes and body odour. METHODS: Subjects with strong body odour were recruited using screening questionnaires. Acetic acid bacterial extract including enzymes was applied to subjects' skin, and their effects were evaluated by trained panellists and by quantitative aldehyde analysis using thermal detector gas chromatography/mass spectrometry. RESULTS: Acetic acid bacterial extract including enzymes decreased the ratio of dilution to threshold and the concentration of body odour-producing aldehydes dropped by up to 98.7%. CONCLUSION: These results indicate that simply applying acetic acid bacterial enzymes on the skin can reduce the concentration of aldehydes that cause unpleasant body odour by directly converting them into carboxylic acids. Therefore, acetic acid bacterial enzymes can potentially be developed into new products that do not destroy indigenous bacteria and yet can effectively reduce unpleasant body odour.

Nosocomial BK Polyomavirus Infection Causing Hemorrhagic Cystitis Among Patients With Hematological Malignancies After Hematopoietic Stem Cell Transplantation.

BK polyomavirus (BKPyV) is recognized as a pathogen that causes diseases such as hemorrhagic cystitis and nephritis after allogeneic hematopoietic stem cell transplantation (HSCT) or renal transplantation. BKPyV-associated disease is thought to occur through reactivation under immunosuppression. However, the possibility of its nosocomial transmission and the clinical significance of such transmission have not been elucidated. During a 6-month period, nine adult patients (median age: 47 years) who had hematological disorders and who were treated with HSCT (n = 7) or chemotherapy (n = 2) in a single hematology department developed hemorrhagic cystitis due to BKPyV infection. The polymerase chain reaction products of BKPyV DNA obtained from each patient were sequenced. Of the nine patients, six had subtype I, 2 had subtype IV, and 1 had subtype II or III. In the alignment of sequences, four and two of the six subtype I strains were completely homologous (100%). These results strongly suggest that BKPyV has the potential to cause nosocomial infection within a medical facility, especially among recipients of HSCT. Further studies are clearly warranted to elucidate the route(s) of BKPyV transmission in order to establish optimal infection control.

Cost-effectiveness of denosumab versus oral alendronate for elderly osteoporotic women in Japan.

We constructed a Markov microsimulation model among hypothetical cohorts of community-dwelling elderly osteoporotic Japanese women without prior hip or vertebral fractures over a lifetime horizon. Compared with weekly oral alendronate for 5 years, denosumab every 6 months for 5 years is cost-saving or cost-effective at a conventionally accepted threshold. INTRODUCTION: The objective of the study was to examine the cost-effectiveness of subcutaneous denosumab every 6 months for 5 years compared with weekly oral alendronate for 5 years in Japan. METHODS: We calculated incremental cost-effectiveness ratios [ICERs] (2016 US dollars [$] per quality-adjusted life year [QALY]), using a Markov microsimulation model among hypothetical cohorts of community-dwelling osteoporotic Japanese women without prior hip or vertebral fractures at various ages of therapy initiation (65, 70, 75, and 80 years) over a lifetime horizon from three perspectives: societal, healthcare sector, and government. RESULTS: Denosumab was cost-saving compared with alendronate at ages 75 and 80 years from any of the three perspectives. The ICERs of denosumab compared with alendronate were $25,700 and $5000 per QALY at ages 65 and 70 years from a societal perspective and did not exceed a willingness-to-pay of $50,000 per QALY from the other two perspectives. In deterministic sensitivity analyses, results were sensitive to changes in the effectiveness of denosumab for reducing hip fracture and clinical vertebral fracture and the rate ratio of non-persistence with denosumab compared to alendronate. In probabilistic sensitivity analyses, the probabilities of denosumab being cost-effective compared with alendronate were 89-100% at a willingness-to-pay of $50,000 per QALY. CONCLUSIONS: Among community-dwelling elderly osteoporotic women in Japan, denosumab every 6 months for 5 years is cost-saving or cost-effective at a conventionally accepted threshold of willingness-to-pay at all ages examined, compared with weekly alendronate for 5 years. This study provides insight to clinicians and policymakers regarding the relative economic value of osteoporosis treatments in elderly women.

Cost-effectiveness of combined oral bisphosphonate therapy and falls prevention exercise for fracture prevention in the USA.

We developed a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women without prior major osteoporotic fractures over a lifetime horizon. At ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a conventionally accepted threshold compared with bisphosphonates alone. INTRODUCTION: The purpose of this study was to examine the cost-effectiveness of the combined strategy of oral bisphosphonate therapy for 5 years and falls prevention exercise for 1 year compared with either strategy in isolation. METHODS: We calculated incremental cost-effectiveness ratios [ICERs] (2014 US dollars per quality-adjusted life year [QALY]), using a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women with different starting ages (65, 70, 75, and 80) without prior history of hip, vertebral, or wrist fractures over a lifetime horizon from the societal perspective. RESULTS: At ages 65, 70, 75, and 80, the combined strategy had ICERs of $202,020, $118,460, $46,870, and $17,640 per QALY, respectively, compared with oral bisphosphonate therapy alone. The combined strategy provided better health at lower cost than falls prevention exercise alone at ages 70, 75, and 80. In deterministic sensitivity analyses, results were particularly sensitive to the change in the opportunity cost of participants' time spent exercising. In probabilistic sensitivity analyses, the probabilities of the combined strategy being cost-effective compared with the next best alternative increased with age, ranging from 35 % at age 65 to 48 % at age 80 at a willingness-to-pay of $100,000 per QALY. CONCLUSIONS: Among community-dwelling US white women ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a willingness-to-pay of $100,000 per QALY, compared with oral bisphosphonate therapy only. This analysis will help clinicians and policymakers make better decisions about treatment options to reduce fracture risk.

FUT2 non-secretor status is associated with Type 1 diabetes susceptibility in Japanese children.

AIM: To examine the contribution of the FUT2 gene and ABO blood type to the development of Type 1 diabetes in Japanese children. METHODS: We analysed FUT2 variants and ABO genotypes in a total of 531 Japanese children diagnosed with Type 1 diabetes and 448 control subjects. The possible association of FUT2 variants and ABO genotypes with the onset of Type 1 diabetes was statistically examined. RESULTS: The se2 genotype (c.385A>T) of the FUT2 gene was found to confer susceptibility to Type 1A diabetes in a recessive effects model [odds ratio for se2/se2, 1.68 (95% CI 1.20-2.35); corrected P value = 0.0075]. CONCLUSIONS: The FUT2 gene contributed to the development of Type 1 diabetes in the present cohort of Japanese children.

Effect of imidafenacin on the urodynamic parameters of patients with indwelling bladder catheters due to spinal cord injury.

STUDY DESIGN: A retrospective study. OBJECTIVES: To investigate the effect of imidafenacin on the urodynamic parameters of patients with indwelling bladder catheters due to spinal cord injury (SCI). SETTING: Spinal center (Tokyo, Japan). METHODS: Imidafenacin was prescribed to 34 patients with SCI who had a low cystometric volume and/or detrusor compliance according to a urodynamic study. A low cystometric volume and detrusor compliance were defined as <200 ml and <20 ml cm-1 H2O, respectively. The urodynamic study was repeated 4 weeks after imidafenacin was prescribed. When the urodynamic parameters did not improve in the follow-up study, the dose of imidafenacin was increased twofold. Then the urodynamic study was repeated 4 weeks thereafter. We compared the urodynamic parameters before and after imidafenacin treatment. Complications such as vesico-urethral reflux (VUR) and autonomic dysreflexia (AD) were documented. RESULTS: Fifteen patients took 0.2 mg of imidafenacin daily, and 19 received 0.4 mg of imidafenacin daily. Imidafenacin increased the cystometric volume from 246.0 to 321.5 ml (median, P=0.002), detrusor compliance from 6.67 ml cm-1 H2O to 8.98 ml cm-1 H2O (median, P=0.012), and decreased the detrusor pressure from 37.0 cm H2O to 30.5 cm H2O (median, P=0.056). All three patients who had VUR fully recovered. Although 3 of 12 patients recovered from AD, 3 patients newly developed symptoms of AD. No patient withdrew from treatment due to adverse effects. CONCLUSION: Imidafenacin is a safe drug that may improve the urodynamic parameters of patients with SCI, and it possibly alleviates bladder complications.

Density-dependent effects of non-native brown trout Salmo trutta on the species-area relationship in stream fish assemblages.

The spatial scale and density-dependent effects of non-native brown trout Salmo trutta on species richness of fish assemblages were examined at 48 study sites in Mamachi Stream, a tributary of Chitose River, Hokkaido, Japan. The density of age ≥1 year S. trutta was high in the upstream side of the main stem of Mamachi Stream. Fish species richness increased with increasing area of study sites (habitat size), but the increasing magnitude of the species richness with area decreased with increasing age of ≥1 year S. trutta density. The relationships between age ≥1 year S. trutta, however, and presence-absence of each species seemed to be different among species. Species richness was also determined by location and physical environmental variables, i.e. it was high on the downstream side and in structurally complex environments.

Evaluation of antimicrobial stewardship (AS) for appropriate use of antimicrobial agents.

We implemented an antimicrobial stewardship (AS) program whereby pharmacists sought appropriate use of antimicrobial agents in January 2012. At that time, we targeted anti-methicillin-resistant Staphylococcus aureus (MRSA) agents and carbapenems; however, in January 2014, we added tazobactam/piperacillin (TAZ/PIPC). We evaluated outcomes using multilateral analyses. The average one-day dosage of carbapenems increased; however, the duration of administration and number of recipient patients decreased significantly (P < 0.01). Moreover, the percentage of patients receiving meropenem (MEPM), for whom the time above minimal inhibitory concentration (MIC) was 40% or higher increased (P < 0.01). In contrast, patient utilization of TAZ/PIPC increased significantly after targeting of carbapenems as specific antibacterial agents. However, after TAZ/PIPC was targeted as a specific antibacterial agent, the number of TAZ/PIPC administrations decreased significantly (P < 0.01). The duration of hospitalization and mortality rate in patients receiving specific antibacterial agents significantly decreased after implementation of the AS program (P < 0.01). In conclusion, pharmacist's interventions to provide AS and patient follow-up reduced improper use and promoted proper administration of antibacterial agents. Furthermore, AS was effective in improving patient prognoses and suppressing drug-resistant strains, as well as promoting effective treatment.