Attenuated relationship between salivary oxytocin levels and attention to social information in adolescents and adults with autism spectrum disorder: a comparative study.

BACKGROUND: Previous research studies have assessed the relationship between attention to social information and peripheral (e.g., plasma and salivary) oxytocin (OT) levels in typically developing (TD) children and children with autism spectrum disorder (ASD). A relationship between them was observed in TD children, but not in children with ASD. However, this relationship remains unexamined in other age groups. To clarify whether this lack of association is maintained throughout development in individuals with ASD, we aimed to assess the relationship between salivary OT levels and attention to social information in adolescents and adults with and without ASD. METHODS: We recruited male adolescents and adults with ASD (n = 17) and TD participants (n = 24). Using the all-in-one eye-tracking system Gazefinder, we measured the percentage fixation time allocated to social information. We also measured the salivary OT levels and Autism Spectrum Quotient (AQ) of participants. Subsequently, we confirmed group differences and conducted a correlation analysis to investigate the relationships between these three measures. RESULTS: Salivary OT levels did not show any significant difference between the ASD and TD groups and were negatively correlated with the AQ in the whole-group analysis, but not in within-group analysis. Individuals with ASD had significantly lower percentage fixation times than did TD individuals for eye regions in human faces with/without mouth motion, for upright biological motion, and for people regions in the people and geometry movies. The percentage of fixation for geometric shapes in the people and geometry movies was significantly higher in the ASD than in the TD group. In the TD group, salivary OT levels were positively correlated with percentage fixation times for upright biological motion and people and negatively correlated with inverted biological motion and geometry. However, no significant correlations were found in the ASD group. CONCLUSIONS: Our exploratory results suggest that salivary OT levels in adolescents and adults with ASD are less indicative of attention to social stimuli than they are in TD adolescents and adults. It is suggested that their association is slightly weaker in adolescents and adults with ASD and that this attenuated relationship appears to be maintained throughout development.

Microscopic gain analysis of modulation-doped GeSn/SiGeSn quantum wells: epitaxial design toward high-temperature lasing.

Threshold carrier densities of GeSn quantum well (QW) lasers and the physical reason of low-temperature lasing of current GeSn laser are investigated through the comparison of threshold carrier densities of conventional III-V QW lasers. Electrons distributed over L-band is the main cause of decreased gain for GeSn QWs. To increase the gain (and improve the laser characteristics), a modulation-doped GeSn QW is proposed and the material gain is analyzed based on many-body theory for both qualitative and quantitative simulation. Significant gain increase can be expected for n-type modulation doping QWs. The doping condition for elevated temperature lasing is discussed and it was found that material gain curve similar to III-V QW is obtained for GeSn QW with n-type modulation doping of 6 × 1018 cm-3. It was also found that unlike III-V QW lasers, n-type modulation doping is more effective for high-speed operation in terms of differential gain than p-type modulation doping.

Risk of heat illness in men and women: A systematic review and meta-analysis.

BACKGROUND: Heat illness (HI) is a growing global concern; its incidence has risen dramatically across the world in recent years. The individual factors whereby elevated core temperature produces HI are not well-understood. Given known physiological differences between men and women pertaining to temperature regulation, we hypothesized that women would be at increased risk of HI than men. OBJECTIVES: We aimed to determine the relative risk of HI in women compared with men through an exhaustive literature review and meta-analysis. METHODS: We search PubMed and Ovid Medline databases from inception to Apr 2017. Search terms included all permutations of sex and heat illness (including heatstroke and exertional heat illness) with no language restrictions. We included adult or adolescent human data reporting comparable male and female HI rates. One reviewer identified and screened titles and abstracts. Two independent reviewers applied eligibility criteria. Disagreements were resolved with a third reviewer. RESULTS: Of 5888 articles identified by searches, 36 were included in the systematic review and 22 in the meta-analysis. The mean (standard deviation) quality score was 3.31(1.25)/5. Overall the rate among women was consistently lower than men across the lifespan. The male: female pooled IRR was 2.28 (p < 0.001, 95% CI: 1.66-3.16). There was modest heterogeneity (between-studies variance (τ2) = 0.02). The rates did not differ significantly when corrected for severity or occupation. DISCUSSION: The rate of HI was significantly increased in men compared with women. Risk for HI might be conferred by psychological and behavioral factors rather than physiological ones. Further research is required to delineate which groups are at greatest risk, leading to the development of mitigation strategies against HI. OTHER: No funding was received. The authors acknowledge the support of the UK Women in Ground Close Combat Review. The Study was registered with PROSPREO CRD42017064739.

Respiratory impedance is correlated with airway narrowing in asthma using three-dimensional computed tomography.

BACKGROUND: Respiratory impedance comprises the resistance and reactance of the respiratory system and can provide detailed information on respiratory function. However, details of the relationship between impedance and morphological airway changes in asthma are unknown. OBJECTIVE: We aimed to evaluate the correlation between imaging-based airway changes and respiratory impedance in patients with asthma. METHODS: Respiratory impedance and spirometric data were evaluated in 72 patients with asthma and 29 reference subjects. We measured the intraluminal area (Ai) and wall thickness (WT) of third- to sixth-generation bronchi using three-dimensional computed tomographic analyses, and values were adjusted by body surface area (BSA, Ai/BSA, and WT/the square root (√) of BSA). RESULTS: Asthma patients had significantly increased respiratory impedance, decreased Ai/BSA, and increased WT/√BSA, as was the case in those without airflow limitation as assessed by spirometry. Ai/BSA was inversely correlated with respiratory resistance at 5 Hz (R5) and 20 Hz (R20). R20 had a stronger correlation with Ai/BSA than did R5. Ai/BSA was positively correlated with forced expiratory volume in 1 second/forced vital capacity ratio, percentage predicted forced expiratory volume in 1 second, and percentage predicted mid-expiratory flow. WT/√BSA had no significant correlation with spirometry or respiratory impedance. CONCLUSIONS & CLINICAL RELEVANCE: Respiratory resistance is associated with airway narrowing.

Si-based Mach-Zehnder wavelength/mode multi/demultiplexer for a WDM/MDM transmission system.

We propose and experimentally demonstrate a low-loss and low-crosstalk Mach-Zehnder mode/wavelength multi/demultiplexer for WDM/MDM transmission based on a Si-photonics platform. A broadband 3-dB mode divider, which is also newly devised here, makes it possible to compose a Mach-Zehnder filter for "mode" and "wavelength" simultaneously. Transmission characteristics of fabricated 3-dB mode dividers are in excellent agreement with theoretical results. Mach-Zehnder filters using the 3-dB mode divider with a free spectral range (FSR) of 20 and 1 nm are also fabricated and the modal crosstalk is less than -24 dB in the 40-nm wavelength range for the MZ filter with an FSR of 20 nm. The tuning of the peak wavelength position by the TiN heater is also demonstrated.

Evaluation of serum IgE in peach-allergic patients with systemic reaction by using recombinant Pru p 7 (gibberellin-regulated protein).

BACKGROUND: Lipid transfer protein (LTP) is a major fruit allergen. It has, however, recently been revealed that the systemic reaction in peach-allergic patients is related not only to LTP (Pru p 3) but also to gibberellin-regulated protein (Pru p 7). We investigated recombinant Pru p 7 (rPru p 7) for its potential use in worldwide standardization for the diagnosis of peach allergy. METHODS: Natural Pru p 7 (nPru p 7) was purified from peach crude extract using a monoclonal antibody affinity column. Complementary DNA for Pru p 7 was cloned and expressed in Escherichia coli and Pichia pastoris. Serum immunoglobulin (Ig) E in peach-allergic patients was examined by enzyme-linked immunosorbent assay (ELISA) using nPru p 7 and rPru p 7 (E. coli product: erPru p 7 and P. pastoris product: prPru p 7). RESULTS: Peach-allergic patients (n=27) were diagnosed and categorized into oral reaction (n=10) or systemic reaction (n=17). The nPru p 7 positivity based on serum IgE levels was 52% in the systemic-reaction group and 0% in the oral-reaction group (P<0.05). In the systemic-reaction group, there was no significant difference in reactivity between nPru p 7 and prPru p 7, but the reactivity of erPru p 7 was significantly lower than those of nPru p 7 and prPru p 7 (P<0.05). CONCLUSIONS: We found that prPru p 7 exhibited reactivity in ELISA comparable to that of nPru p 7 for the diagnosis of peach allergy with systemic reaction.

Outcomes of fulvestrant therapy among japanese women with advanced breast cancer: a retrospective multicenter cohort study (JBCRG-C06; Safari).

PURPOSE: This retrospective study evaluated the effect of clinical background and treatment line on time to treatment failure (TTF) in advanced/metastatic breast cancer (AMBC) patients receiving F500 in Japan (UMIN 000015168). METHODS: Patients who commenced F500 treatment were registered at 16 sites in Japan. Correlations between baseline clinicopathological factors, treatment line, and TTF were investigated by Kaplan-Meier analysis. TTF data were analyzed using univariate analysis and multivariate analysis with a Cox proportional hazards model. RESULTS: Data for 1072 patients were available; 1031 patients (96.2%) were evaluable for efficacy. F500 was administered as first-line treatment in 2.0%, second-line in 22.7%, third-line in 26.7%, and ≥fourth-line in 48.6% patients. Median TTF was 5.4 months. Multivariate analysis found that earlier F500 use (first and second vs. third vs. ≥fourth line; hazard ratio (HR) = 0.80, 95% confidence interval (CI) 0.74-0.86; P < 0.001), longer period from AMBC diagnosis to F500 use (≥3 vs. <3 years; HR 0.60, 95% CI 0.51-0.70; P < 0.001), and no prior palliative chemotherapy administered for unresectable or metastatic breast cancer (no vs. yes; HR 0.69, 95% CI 0.60-0.80; P < 0.001) were associated with significantly longer TTF. Among 691 patients, where information on histologic/nuclear grade was available, a low grade was also associated with a longer TTF, but this finding was not maintained among patients with recurrent breast cancer (N = 558). Among women with recurrent breast cancer, a longer DFI between a patient's initial breast cancer diagnosis and their recurrence was associated with a longer TTF on F500 therapy. CONCLUSIONS: Our study showed that treatment period of F500 was longer when used in earlier-line treatment. For patients on F500, TTF was also longer for patients who had not received prior palliative chemotherapy and for those who had a longer period from their AMBC diagnosis to F500 use.

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.

Predictive values of egg-specific IgE by two commonly used assay systems for the diagnosis of egg allergy in young children: a prospective multicenter study.

BACKGROUND: Specific IgE (sIgE) is often used to predict oral food challenge (OFC) outcomes in food allergy, but interpretation of the results may vary depending on the assay method employed and the patient population tested. The aim of this study was to use two commercial assay systems to determine egg-sIgE values predictive of allergy within the most common populations treated at pediatric clinics. METHODS: In a multicenter prospective study, 433 children with suspected or confirmed egg allergy underwent oral challenge (OFC) using cooked egg (CE) and raw egg (RE) powders to diagnose either true allergy in 1-year-old (group A, n = 220) or tolerance in 2- to 6-year-old (group B, n = 213). Egg white (EW)- and ovomucoid (OM)-sIgE values were measured using the ImmunoCAP(®) sIgE (ImmunoCAP) and the IMMULITE(®) 2000 3 gAllergy(™) (3gAllergy) systems. Children were recruited from six primary care clinics and 18 hospitals in Japan. RESULTS: Receiver-operating characteristic (ROC) curve analysis yielded similar areas under the curve (AUC) for the two assays (0.7-0.8). The optimal cutoff values and the probability curves (PCs) of the sIgE by the two assays to predict CE and RE OFC outcomes were determined for both groups. Values for 3gAllergy were higher than for ImmunoCAP; however, correlation of sIgE and predicted probability calculated by PCs were strong between the two methods. CONCLUSIONS: Cutoff values and PCs for egg-sIgE established using both ImmunoCAP and 3gAllergy may be useful for predicting egg allergy in early childhood patient populations.

Variants associated with autoimmune Type 1 diabetes in Japanese children: implications for age-specific effects of cis-regulatory haplotypes at 17q12-q21.

AIMS: The aim of this study was to clarify the significance of previously reported susceptibility variants in the development of autoimmune Type 1 diabetes in non-white children. Tested variants included rs2290400, which has been linked to Type 1 diabetes only in one study on white people. Haplotypes at 17q12-q21 encompassing rs2290400 are known to determine the susceptibility of early-onset asthma by affecting the expression of flanking genes. METHODS: We genotyped 63 variants in 428 Japanese people with childhood-onset autoimmune Type 1 diabetes and 457 individuals without diabetes. Possible association between variants and age at diabetes onset was examined using age-specific quantitative trait locus analysis and ordered-subset regression analysis. RESULTS: Ten variants, including rs2290400 in GSDMB, were more frequent among the people with Type 1 diabetes than those without diabetes. Of these, rs689 in INS and rs231775 in CTLA4 yielded particularly high odds ratios of 5.58 (corrected P value 0.001; 95% CI 2.15-14.47) and 1.64 (corrected P value 5.3 × 10-5 ; 95% CI 1.34-2.01), respectively. Age-specific effects on diabetes susceptibility were suggested for rs2290400; heterozygosity of the risk alleles was associated with relatively early onset of diabetes, and the allele was linked to the phenotype exclusively in the subgroup of age at onset ≤ 5.0 years. CONCLUSIONS: The results indicate that rs2290400 in GSDMB and polymorphisms in INS and CTLA4 are associated with the risk of Type 1 diabetes in Japanese children. Importantly, cis-regulatory haplotypes at 17q12-q21 encompassing rs2290400 probably determine the risk of autoimmune Type 1 diabetes predominantly in early childhood.

Exchange-Induced Spin Blockade in a Two-Electron Double Quantum Dot.

We have experimentally identified the exchange-induced spin blockade in a GaAs double quantum dot. The transport is suppressed only when the eigenstates are well-defined singlet and triplet states, and thus sensitive to dynamic nuclear-spin polarization that causes singlet-triplet mixing. This gives rise to unusual current spectra, such as a sharp current dip and an asymmetric current profile near the triplet resonance of a double quantum dot. Numerical simulations suggest that the current dip is a signature of identical nuclear-spin polarization in the two dots, which is attractive for coherent spin manipulations in a material with nuclear spins.

Development and evaluation of MALDI-TOF MS-based serotyping for Streptococcus pneumoniae.

Surveillance of Streptococcus pneumoniae serotypes is important for the successful implementation of vaccination strategies to prevent the spread of invasive pneumococcal diseases. The standard method of serotyping of pneumococcal isolates is the phenotypic Neufeld test, which is cost- and labor-intensive. Recently, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been implemented as a rapid, simple and inexpensive method for identifying species. We evaluated the performance of MALDI-TOF MS for serotyping ten major serotypes of S. pneumoniae in Japan (serotypes 3, 6B, 15A, 15C, 19A, 19 F, 23A, 24 F, 35B and 38) using the Biotyper and ClinProTools. After optimizing the settings, we validated their serotyping performance for serotypes 3, 15A and 19A using a separate set of isolates that were not used in the creation of the classification algorithms. A total of 574 isolates of S. pneumoniae collected from Japanese nationwide surveillance studies were included. Of these, 407 isolates belonged to the ten major serotypes. Biotyper and ClinProTools correctly identified 77.9 % and 84.0 %, respectively, of the ten major serotype isolates. The validation analysis included a total of 113 isolates of the serotypes 3, 15A and 19A isolates. Biotyper and ClinProTools correctly identified 85.0 % and 69.9 % of the validation cohort isolates, respectively. MALDI-TOF MS has the potential to discriminate the ten major S. pneumoniae serotypes prevalent in Japan.

Very-low-voltage operation of Mach-Zehnder interferometer-type electroabsorption modulator using asymmetric couplers.

We have proposed and developed a new type of electroabsorption modulator (EAM) that employs both optical absorption and interferometric extinction. The EAM operates at a record low voltage of 0.2 V at 25.8-Gbit/s modulation, which can reduce optical transmitter power consumption and allows the adoption of cost-effective CMOS drivers.

From serendipitous assembly to controlled synthesis of 3d-4f single-molecule magnets.

Learning from serendipitous assembly, we have prepared a new family of designed 3d-4f Mn6Ln complexes. The dynamics of relaxation of the magnetization via alternating-current magnetic susceptibility for the new Mn6Ln complexes 1 (Ln = La), 2 (Ln = Tb), and 4 (Ln = Dy) have been studied down to 0.2 K.

Comprehensive validation of early diagnostic algorithms for myocardial infarction in the emergency department.

OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.

Coherent zero-state and pi-state in an exciton-polariton condensate array.

The effect of quantum statistics in quantum gases and liquids results in observable collective properties among many-particle systems. One prime example is Bose-Einstein condensation, whose onset in a quantum liquid leads to phenomena such as superfluidity and superconductivity. A Bose-Einstein condensate is generally defined as a macroscopic occupation of a single-particle quantum state, a phenomenon technically referred to as off-diagonal long-range order due to non-vanishing off-diagonal components of the single-particle density matrix. The wavefunction of the condensate is an order parameter whose phase is essential in characterizing the coherence and superfluid phenomena. The long-range spatial coherence leads to the existence of phase-locked multiple condensates in an array of superfluid helium, superconducting Josephson junctions or atomic Bose-Einstein condensates. Under certain circumstances, a quantum phase difference of pi is predicted to develop among weakly coupled Josephson junctions. Such a meta-stable pi-state was discovered in a weak link of superfluid 3He, which is characterized by a 'p-wave' order parameter. The possible existence of such a pi-state in weakly coupled atomic Bose-Einstein condensates has also been proposed, but remains undiscovered. Here we report the observation of spontaneous build-up of in-phase ('zero-state') and antiphase ('pi-state') 'superfluid' states in a solid-state system; an array of exciton-polariton condensates connected by weak periodic potential barriers within a semiconductor microcavity. These in-phase and antiphase states reflect the band structure of the one-dimensional polariton array and the dynamic characteristics of metastable exciton-polariton condensates.

Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians.

AIMS/HYPOTHESIS: FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. METHODS: All studies published on the association between FTO-rs9939609 (or proxy [r (2) > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. RESULTS: The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10(-19)), overweight by 1.13-fold/allele (p = 1.0 × 10(-11)) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10(-8)). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10(-5)). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m(2) per allele (p = 2.8 × 10(-17)), WHR by 0.003/allele (p = 1.2 × 10(-6)), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations. CONCLUSIONS/INTERPRETATION: FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.

Magnetic-field dependence of tunnel couplings in carbon nanotube quantum dots.

By means of sequential and cotunneling spectroscopy, we study the tunnel couplings between metallic leads and individual levels in a carbon nanotube quantum dot. The levels are ordered in shells consisting of two doublets with strong- and weak-tunnel couplings, leading to gate-dependent level renormalization. By comparison to a one- and two-shell model, this is shown to be a consequence of disorder-induced valley mixing in the nanotube. Moreover, a parallel magnetic field is shown to reduce this mixing and thus suppress the effects of tunnel renormalization.

Association of genetic variants for susceptibility to obesity with type 2 diabetes in Japanese individuals.

AIMS/HYPOTHESIS: In populations of East Asian descent, we performed a replication study of loci previously identified in populations of European descent as being associated with obesity measures such as BMI and type 2 diabetes. METHODS: We genotyped 14 single nucleotide polymorphisms (SNPs) from 13 candidate loci that had previously been identified by genome-wide association meta-analyses for obesity measures in Europeans. Genotyping was done in 18,264 participants from two general Japanese populations. For SNPs showing an obesity association in Japanese individuals, we further examined diabetes associations in up to 6,781 cases and 7,307 controls from a subset of the original, as well as from additional populations. RESULTS: Significant obesity associations (p < 0.1 two-tailed, concordant direction with previous reports) were replicated for 11 SNPs from the following ten loci in Japanese participants: SEC16B, TMEM18, GNPDA2, BDNF, MTCH2, BCDIN3D-FAIM2, SH2B1-ATP2A1, FTO, MC4R and KCTD15. The strongest effect was observed at TMEM18 rs4854344 (p = 7.1 × 10(-7) for BMI). Among the 11 SNPs showing significant obesity association, six were also associated with diabetes (OR 1.05-1.17; p = 0.04-2.4 × 10(-7)) after adjustment for BMI in the Japanese. When meta-analysed with data from the previous reports, the BMI-adjusted diabetes association was found to be highly significant for the FTO locus in East Asians (OR 1.13; 95% CI 1.09-1.18; p = 7.8 × 10(-10)) with substantial inter-ethnic heterogeneity (p = 0.003). CONCLUSIONS/INTERPRETATION: We confirmed that ten candidate loci are associated with obesity measures in the general Japanese populations. Six (of ten) loci exert diabetogenic effects in the Japanese, although relatively modest in size, and independently of increased adiposity.