A molecular dynamics study of nuclear quantum effect on diffusivity of hydrogen molecule.

In this paper, the nuclear quantum effect of the hydrogen molecule on its diffusivity was analyzed using the molecular dynamics (MD) method. The centroid MD (CMD) method was applied to reproduce the time evolution of the molecules. The diffusion coefficient of hydrogen was calculated using the Green-Kubo method over a wide temperature region, and the temperature dependence of the quantum effect of the hydrogen molecule on its diffusivity was addressed. The calculated results were compared with classical MD results based on the principle of corresponding state (PCS). It was confirmed that the difference in the diffusion coefficient calculated in the CMD and classical MD methods was small, and the PCS appears to be satisfied on the temperature dependence of the diffusion coefficient, even though the quantum effect of the hydrogen molecules was taken into account. It was clarified that this result did not suggest that the quantum effect on the diffusivity of the hydrogen molecule was small but that the two changes in the intermolecular interaction of hydrogen due to the quantum effect offset each other. Moreover, it was found that this tendency was related to the temperature dependence of the ratio of the kinetic energy of the quantum fluctuational motion to the classical kinetic energy.

Inter-rater and intra-rater reliability outcomes of a rapid bacteria counting system with pressure ulcer samples.

OBJECTIVE: Evaluating bacterial load in pressure ulcers (PUs) is key to combat infection; therefore, using technologies to measure bacterial count can be particularly useful. A rapid bacteria counting system was recently developed and introduced to the wound care field. However, its reliability was not established. This cross-sectional study aimed to evaluate the inter-rater and intra-rater reliability of bacterial count using this rapid counting system. METHOD: We took bacterial swabs from patients with category I or greater PUs to assess inter- and intra-rater reliability. An assessor swabbed the longest axis of the PU once and bacterial counts were measured using a rapid bacteria counting system. To confirm the inter-rater and intra-rater reliability, intraclass correlation coefficients (ICCs) were calculated. RESULTS: We took 63 and 57 pairs of bacterial counts from 13 patients with 16 category I or greater PUs to assess inter- and intra-rater reliability, respectively. Overall ICCs [95% confidence intervals (CI)] for the bacterial counts were 0.83 [0.73-0.90, p<0.001, inter-rater reliability, n=63], and 0.89 [0.82-0.94, p< 0.001, intra-rater reliability, n=57]. CONCLUSION: A high level of reliability for counting bacterial numbers in PU sites was confirmed. The results should encourage clinicians and researchers to use this type of device for the real-time assessment of wound bacterial bioburden at the patient's bedside.

Publisher's Note: Search for Majorana Neutrinos Near the Inverted Mass Hierarchy Region with KamLAND-Zen [Phys. Rev. Lett. 117, 082503 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.082503.

Search for Majorana Neutrinos Near the Inverted Mass Hierarchy Region with KamLAND-Zen.

We present an improved search for neutrinoless double-beta (0νßß) decay of ^{136}Xe in the KamLAND-Zen experiment. Owing to purification of the xenon-loaded liquid scintillator, we achieved a significant reduction of the ^{110m}Ag contaminant identified in previous searches. Combining the results from the first and second phase, we obtain a lower limit for the 0νßß decay half-life of T_{1/2}^{0ν}>1.07×10^{26} yr at 90% C.L., an almost sixfold improvement over previous limits. Using commonly adopted nuclear matrix element calculations, the corresponding upper limits on the effective Majorana neutrino mass are in the range 61-165 meV. For the most optimistic nuclear matrix elements, this limit reaches the bottom of the quasidegenerate neutrino mass region.

Calcium-dependent intracellular signal pathways in primary cultured adipocytes and ANK3 gene variation in patients with bipolar disorder and healthy controls.

Bipolar disorder (BD) is a chronic psychiatric disorder of public health importance affecting >1% of the Swedish population. Despite progress, patients still suffer from chronic mood switches with potential severe consequences. Thus, early detection, diagnosis and initiation of correct treatment are critical. Cultured adipocytes from 35 patients with BD and 38 healthy controls were analysed using signal pathway reporter assays, that is, protein kinase C (PKC), protein kinase A (PKA), mitogen-activated protein kinases (extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK)), Myc, Wnt and p53. The levels of activated target transcriptional factors were measured in adipocytes before and after stimulation with lithium and escitalopram. Variations were analysed in the loci of 25 different single-nucleotide polymorphisms (SNPs). Activation of intracellular signals in several pathways analysed were significantly higher in patients than in healthy controls upon drug stimulation, especially with escitalopram stimulation of PKC, JNK and Myc, as well as lithium-stimulated PKC, whereas no meaningful difference was observed before stimulation. Univariate analyses of contingency tables for 80 categorical SNP results versus diagnoses showed a significant link with the ANK3 gene (rs10761482; likelihood ratio χ(2)=4.63; P=0.031). In a multivariate ordinal logistic fit for diagnosis, a backward stepwise procedure selected ANK3 as the remaining significant predictor. Comparison of the escitalopram-stimulated PKC activity and the ANK3 genotype showed them to add their share of the diagnostic variance, with no interaction (15% of variance explained, P<0.002). The study is cross-sectional with no longitudinal follow-up. Cohorts are relatively small with no medication-free patients, and there are no 'ill patient' controls. It takes 3 to 4 weeks of culture to expand adipocytes that may change epigenetic profiles but remove the possibility of medication effects. Abnormalities in the reactivity of intracellular signal pathways to stimulation and the ANK3 genotype may be associated with pathogenesis of BD. Algorithms using biological patterns such as pathway reactivity together with structural genetic SNP data may provide opportunities for earlier detection and effective treatment of BD.

Use of smartphone attached mobile thermography assessing subclinical inflammation: a pilot study.

OBJECTIVE: To verify the reliability and validity of FLIR ONE, a device connected to a smartphone, for the assessment of inflammation based on relative temperature increase compared with the thermography routinely used in pressure ulcer (PU) and diabetic foot assessment. METHOD: Participants in this pilot cross-sectional observational study were recruited from the patients in the PU team rounds and the diabetic foot outpatient clinic at the university hospital in January 2015. Cohen's kappa coefficient with its 95% confidence intervals was used to evaluate the criterion-related validity and inter- and intra-rater reliability for the thermal imaging assessment. For assessing criterion-related validity, a hand-held high-end infrared thermography device was used to provide reference data. Comparison of thermal images between the smartphone-connected device and the hand-held device was performed with both a 'predetermined range' and an 'automatically-set range.' For assessing inter-rater reliability, two assessors evaluated the thermal images taken by the mobile thermography. For assessing intra-rater reliability, one assessor evaluated the thermal images twice. The thermal images were shown to the assessors at random. RESULTS: Among 16 thermal images obtained from eight patients, kappa coefficients for each value were as follows: for the predetermined range and automatically-set range, respectively, the criterion-related validity was 1.00 (95% confidence interval 1.00-1.00) and 1.00 (95% confidence interval 1.00-1.00); the inter-rater reliability was 1.00 (95% confidence interval 1.00-1.00) and 1.00 (95% confidence interval 1.00-1.00); and the intra-rater reliability was 1.00 (95% confidence interval 1.00-1.00) and 1.00 (95% confidence interval 1.00-1.00). CONCLUSION: This pilot study suggests that FLIR ONE can work as an alternative device for assessing subclinical inflammation in PUs and the diabetic foot in clinical settings. Our results may facilitate clinicians in accepting the routine use of thermal imaging assessment at the patients' bedside.

Indocyanine Green Lymphography Findings in Primary Leg Lymphedema.

OBJECTIVES: Indocyanine green (ICG) lymphography has been reported to be useful for the evaluation of secondary lymphedema, but no study has reported characteristic findings of ICG lymphography in primary lymphedema. This study aimed to classify characteristic ICG lymphography patterns in primary lymphedema. METHODS: The study was a retrospective observational study. Thirty one primary lower extremity lymphedema (LEL) patients with a total of 62 legs were studied. ICG lymphography patterns were categorized according to the visibility of lymphatics and dermal backflow (DB) extension. Clinical demographics were compared with categorized ICG lymphography patterns. RESULTS: All symptomatic legs showed abnormal patterns, and all asymptomatic legs showed normal patterns on ICG lymphography. Abnormal lymphographic patterns could be classified into proximal DB (PDB), distal DB (DDB), less enhancement (LE), and no enhancement (NE) patterns. There were significant differences between PDB (16 patients), DDB (6 patients), LE (4 patients), and NE patterns (5 patients) in age (37.3 ± 18.3 vs. 61.8 ± 19.2 vs. 50.8 ± 27.7 vs. 29.2 ± 18.0 years, p = .035), onset of edema (23.9 ± 19.4 vs. 46.8 ± 27.0 vs. 43.0 ± 31.3 vs. 6.6 ± 14.2 years, p = .020), laterality (bilateral; 18.8% vs. 66.7% vs. 75.0% vs. 0%, p » .016), cellulitis history(56.3% vs. 100% vs. 25.0% vs. 0%, p » .007), and LEL index (292.2 ± 32.8 vs. 254.2 ± 28.6 vs. 243.3 ± 9.4 vs. 295.2 ± 44.8, p = .016). CONCLUSIONS: ICG lymphography findings in primary lymphedema could be classified into four patterns withdifferent patient characteristics.

Efficacy and safety of creatine supplementation in childhood-onset systemic lupus erythematosus: a randomized, double-blind, placebo-controlled, crossover trial.

INTRODUCTION: Creatine supplementation has emerged as a promising non-pharmacological therapeutic strategy to counteract muscle dysfunction and low lean mass in a variety of conditions, including in pediatric and rheumatic diseases. The objective of this study was to examine the efficacy and safety of creatine supplementation in childhood systemic lupus erythematosus (C-SLE). METHODS: C-SLE patients with mild disease activity (n = 15) received placebo or creatine supplementation in a randomized fashion using a crossover, double-blind, repeated-measures design. The participants were assessed at baseline and after 12 weeks in each arm, interspersed by an eight-week washout period. The primary outcomes were muscle function, as assessed by a battery of tests including one-maximum repetition (1-RM) tests, the timed-up-and-go test, the timed-stands test, and the handgrip test. Secondary outcomes included body composition, biochemical markers of bone remodeling, aerobic conditioning, quality of life, and physical capacity. Possible differences in dietary intake were assessed by three 24-hour dietary recalls. Muscle phosphorylcreatine content was measured through phosphorus magnetic resonance spectroscopy (31 P-MRS). The safety of the intervention was assessed by laboratory parameters, and kidney function was measured by (51)Cr-EDTA clearance. Additionally, self-reported adverse events were recorded throughout the trial. RESULTS: Intramuscular phosphorylcreatine content was not significantly different between creatine and placebo before or after the intervention (creatine-Pre: 20.5 ± 2.6, Post: 20.4 ± 4.1, placebo-Pre: 19.8 ± 2.0; Post: 20.2 ± 3.2 mmol/kg wet muscle; p = 0.70 for interaction between conditions). In addition, probably as a consequence of the lack of change in intramuscular phosphorylcreatine content, there were no significant changes between placebo and creatine for any muscle function and aerobic conditioning parameters, lean mass, fat mass, bone mass, and quality of life scores (p > 0.05). The (51)Cr-EDTA clearance was not altered by creatine supplementation and no side effects were noticed. CONCLUSION: A 12-week creatine supplementation protocol at 0.1 g/kg/d is well tolerated and free of adverse effects but did not affect intramuscular phosphorylcreatine, muscle function, free-fat mass or quality of life in non-active C-SLE patients. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT01217320.

Therapeutic strategy for lower limb lymphedema and lymphatic fistula after resection of a malignant tumor in the hip joint region: a case report.

Lymphatic fistula complicating lymphedema is thought to occur due to communication between lymph vessels and the skin, which has yet to be shown objectively. The objective of this case report is to show the pathology and treatment using simultaneous lymphatic fistula resection and lymphatico-venous anastomosis (LVA). A 40-year-old woman underwent extended resection and total hip arthroplasty for primitive neuroectodermal tumor in the right proximal femur 23 years ago. Right lower limb lymphedema developed immediately after surgery and lymphatic fistula appeared in the posterior thigh. On ICG lymphography, lymph reflux toward the distal side dispersing in a fan-shape reticular pattern from the lymphatic fistula region was noted after intracutaneous injection of ICG into the foot. We performed simultaneous lymphatic fistula resection and of LVA. Pathological examination showed that the epidermis and stratum corneum of the healthy skin were lost in the lymphatic fistula region. Dilated lymph vessels were open in this region. The examinations provide the first objective evidence that the cause of lymphatic fistula may be lymph reflux from lymphatic stems to precollectors through lymphatic perforators.

Frequency of HER2 expression of circulating tumour cells in patients with metastatic or recurrent gastrointestinal cancer.

BACKGROUND: The clinical significance of circulating tumour cell (CTC) detection in gastrointestinal (GI) cancer remains controversial and the molecular biological characteristics of CTCs are poorly understood. METHODS: A total of 87 patients with metastatic or recurrent GI cancer were prospectively enrolled. Circulating tumour cells and their HER2 status were assessed using the CellSearch System. RESULTS: Among the 62 CTC-positive cases, we found 22 discordant cases (35.5%). Among the HER2-negative primary tumours, 17 of 54 developed HER2-positive CTCs. Five of eight had HER2-negative CTCs among the HER2-positive primary tumours. CONCLUSION: The findings in the current study suggest that it is critical to evaluate the HER2 status of not only the primary tumour but also the CTCs because the metastasising tumour cells are the primary target of systemic therapy.

Characterization of 5C11-positive activated interferon-producing cells in patients with systemic lupus erythematosus.

OBJECTIVE: 5C11 antibody is a novel monoclonal antibody against human BST2 and can be used to detect activation of interferon-producing cells (IPCs). Activated IPCs, which produce large amounts of interferon-α (IFNα), are considered to play an important role in the pathogenesis of systemic lupus erythematosus (SLE). We investigated the characterization of 5C11-positive cells in patients with SLE. METHODS: The proportions of 5C11-positive cells among blood dendritic cell antigen 2 (BDCA-2)-, CD3-, CD19- and CD14-positive cells in peripheral blood from SLE patients (SLE-PBMCs) and healthy controls (control-PBMCs) were analyzed by flow cytometry. The effect of 5C11 antibody on IFNα production from SLE-PBMCs under stimulation with cytosine-phosphate-guanosine (CpG2216, bacterial oligonucleotide motif) was also examined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The proportions of 5C11-positive cells among BDCA-2-, CD3- and CD19-, but not CD14-positive cells in SLE-PBMCs were significantly increased compared to those in control-PBMCs (p < 0.0001, all). Especially, the number of 5C11-positive cells among BDCA-2-positive cells was significantly increased in SLE-PBMCs by about six-fold compared to that in control-PBMCs (p < 0.0001). 5C11 antibody inhibited IFNα production by SLE-PBMCs induced by CpG and the inhibition rates was 27% (p < 0.001). CONCLUSION: SLE patients had a significantly higher proportion of 5C11-positive cells among CD3 and CD19 cells, and especially BDCA-2 positive cells. The ability of 5C11 antibody to inhibit IFNα production from SLE-PBMCs warrants further investigation for its possible clinical application for the treatment of SLE.

Primary care and public health activities in select US health centers: documenting successes, barriers, and lessons learned.

OBJECTIVES: We examined primary care and public health activities among federally funded health centers, to better understand their successes, the barriers encountered, and the lessons learned. METHODS: We used qualitative and quantitative methods to collect data from 9 health centers, stratified by administrative division, urban-rural location, and race/ethnicity of patients served. Descriptive data on patient and institutional characteristics came from the Uniform Data System, which collects data from all health centers annually. We administered questionnaires and conducted phone interviews with key informants. RESULTS: Health centers performed well on primary care coordination and community orientation scales and reported conducting many essential public health activities. We identified specific needs for integrating primary care and public health: (1) more funding for collaborations and for addressing the social determinants of health, (2) strong leadership to champion collaborations, (3) trust building among partners, with shared missions and clear expectations of responsibilities, and (4) alignment and standardization of data collection, analysis, and exchange. CONCLUSIONS: Lessons learned from health centers should inform strategies to better integrate public health with primary care.

Counting-backward test for executive function in idiopathic normal pressure hydrocephalus.

OBJECTIVES: The aim of this study was to develop and validate a bedside test for executive function in patients with idiopathic normal pressure hydrocephalus (INPH). MATERIALS AND METHODS: Twenty consecutive patients with INPH and 20 patients with Alzheimer's disease (AD) were enrolled in this study. We developed the counting-backward test for evaluating executive function in patients with INPH. Two indices that are considered to be reflective of the attention deficits and response suppression underlying executive dysfunction in INPH were calculated: the first-error score and the reverse-effect index. Performance on both the counting-backward test and standard neuropsychological tests for executive function was assessed in INPH and AD patients. RESULTS: The first-error score, reverse-effect index and the scores from the standard neuropsychological tests for executive function were significantly lower for individuals in the INPH group than in the AD group. The two indices for the counting-backward test in the INPH group were strongly correlated with the total scores for Frontal Assessment Battery and Phonemic Verbal Fluency. The first-error score was also significantly correlated with the error rate of the Stroop colour-word test and the score of the go/no-go test. In addition, we found that the first-error score highly distinguished patients with INPH from those with AD using these tests. CONCLUSION: The counting-backward test is useful for evaluating executive dysfunction in INPH and for differentiating between INPH and AD patients. In particular, the first-error score may reflect deficits in the response suppression related to executive dysfunction in INPH.

New method for quantitative assessment of airway calibre using a stereovision fibreoptic bronchoscope.

BACKGROUND: We have developed a new bronchoscopy system with two independent lenses at the tip of the device. This enables measurement of object size using the principle of triangulation. This study was performed to assess the accuracy of this system. METHODS: The accuracy of the bronchoscopy system was confirmed by measuring the diameters of four plastic tubes and 36 airway calibres in 12 surgical patients under general anaesthesia. The measured diameters of the tubes and airway tracts were compared with the manufactured diameters of tubes and those measured by high-resolution computed tomography (HRCT)-based virtual bronchoscopy, respectively. RESULTS: Using the new bronchoscope system, tube diameters, 9, 12, 15, and 19 mm, were measured as 9.9 (0.7), 12.8 (1.4), 16.3 (1.6), and 20.1 (2.0) mm, respectively. Airway calibres obtained by a stereovision bronchoscopy and HRCT-based virtual bronchoscopy were 8.66 (4.31) and 9.38 (5.09) mm, respectively. There is a significant correlation between airway calibres with the two measurement methods (r=0.975, P<0.01). CONCLUSIONS: We have confirmed that this new bronchoscopy system could provide relatively accurate quantitative data. This new system may be useful in the clinic to measure airway dimension and lesion sizes such as tumours.

Direct growth of horizontally aligned carbon nanotubes between electrodes and its application to field-effect transistors.

This paper presents direct growth of horizontally-aligned carbon nanotubes (CNTs) between two predefined various inter-spacing up to tens of microns of electrodes (pads) and its use as CNT field-effect transistors (CNT-FETs). Using the conventional photolithography technique followed by thin film evaporation and lift off, the catalytic electrodes (pads) were prepared, consisting of Pt, Al and Fe triple layers on SiO2/Si substrate. The grown CNTs were horizontally-aligned across the catalytic electrodes on the modified gold image furnace hot stage (thermal CVD) at 800 degrees C by using an alcohol vapor as the carbon source. Scanning and transmission electron microcopies (SEM/TEM) were used to observe the structure, growth direction and density of CNTs, while Raman spectrum analysis was used to indicate the degree of amorphous impurity and diameter of CNTs. Both single- and multi-wall CNTs with diameters of 1.1-2.2 nm were obtained and the CNT density was controlled by thickness of Fe catalytic layer. Following horizontally-aligned growth of CNTs, the electrical properties of back-gate CNT-FETs were measured and showd p-type conduction behaviors of FET.

Characteristics of prolonged luteal phase identified by milk progesterone concentrations and its effects on reproductive performance in Holstein cows.

A database of milk progesterone profiles consisting 497 lactations in 3 dairy herds from northern and western regions of Japan was used to identify the characteristics and associated risk factors for prolonged luteal phase (PLP) and its effects on subsequent reproductive performance in high-producing Holstein cows. Milk samples were collected twice weekly and progesterone concentrations in whole milk were determined by ELISA. Herds were visited monthly and examined by vaginoscopy and transrectal palpation. Resumption of ovarian cyclicity within 35 d postpartum followed by regular cycles was considered normal. Prolonged luteal phase was defined when progesterone concentrations were ≥5 ng/mL for ≥20 d of duration in any cycle postpartum. Delay of first ovulation to 35 to 60 d (delayed first ovulation type I), >60 d (delayed first ovulation type II), a luteal phase of <14 d except in the first cycle (short luteal phase), and the absence of luteal activity >14 d between 2 cycles (cessation of cyclicity) were the other categories of abnormal ovarian resumptions considered. The overall incidence of PLP in the 3 herds was 11.9% and a significantly higher proportion of PLP was observed in the first cycle postpartum compared with the second and third cycles. Approximately 83% of the PLP were 20 to 28 d in duration, and maximum progesterone concentration was significantly higher when PLP lasted >35 d compared with PLP of 20 to 35 d in duration. Higher parity, commencement of luteal activity≤28 d postpartum, and postpartum complications significantly increased the occurrence of PLP within 90 d postpartum. Cows with PLP showed reduced conception rate to first artificial insemination (AI) and reduced pregnancy proportions within 100, 150, and 210 d postpartum. Based on survival analysis, PLP was associated with a 56% reduction in relative pregnancy rate and a 36% reduction in AI submission rate. Cows that experienced PLP had a longer interval from calving to first AI (74 d) and from calving to pregnancy (141 d) than cows without PLP (53 and 80 d), respectively. In conclusion, 11.9% of lactations had PLP, of which approximately two-thirds were seen in the first cycle postpartum. Most of the PLP were 20 to 28 d in duration. Higher parity, postpartum complications, and early commencement of luteal activity postpartum increased the risk for PLP. Occurrence of PLP adversely affected fertility by reducing pregnancy proportions and extending calving to conception interval.

Four cases of postrenal renal failure induced by renal stone associated with rotavirus infection.

Rotavirus (RV) is a common pathogen that causes acute gastroenteritis in childhood. Some cases with RV infection also have prerenal renal failure induced by dehydration associated with vomiting and diarrhea. Here, we report 4 patients with RV infection who developed postrenal renal failure induced by urinary tract obstruction with uroammoniac calculi or crystals. The patients did not have metabolic disorders or abnormalities of the urinary tract, and increased urinary excretion of uric acid was not recognized at discharge. In addition, no abnormalities in the uric acid transporter (URAT1) were found in any of the patients. Uric acid stone formation was considered to have originated from the low pH caused by dehydration and the increase of urinary uric acid excretion from damaged cells.