Background. Orally administered antiviral therapy for genital herpes improves the time to lesion healing and resolves symptoms during an outbreak. Although traditional therapy for a recurrent episode ...for healthy adults has consisted of twice-daily dosing for 5 days, recent studies have indicated that shorter courses of antiviral therapy are effective. This study was conducted to assess the efficacy and safety of a patient-initiated, single-day regimen of famciclovir therapy, compared with placebo, in immunocompetent adult patients with recurrent genital herpes. Methods. This multicenter, multinational, randomized, double-blind, parallel-group, placebo-controlled study compared single-day, patient-initiated oral famciclovir (1000 mg given twice daily) with placebo for the treatment of recurrent genital herpes. Patients were instructed to initiate therapy within 6 h after onset of prodromal symptoms or genital herpes lesions. Results. Famciclovir reduced (P <.001) the time to healing of nonaborted lesions (i.e., those that did not progress beyond the papule stage) (median time, 4.3 vs. 6.1 days) and all nonaborted and aborted lesions (median time, 3.5 vs. 5.0 days), compared with placebo. The proportion of patients with aborted lesions was larger in the famciclovir group than in the placebo group (23.3% vs. 12.7%; P =.003). Adverse events in the famciclovir group were infrequent overall; most were of mild-to-moderate severity and were similar to adverse events in the placebo group. Conclusions. A single-day regimen of patient-initiated famciclovir treatment was well tolerated and safe, and the healing of recurrent genital herpes lesions occurred ∼2 days faster than with placebo. Moreover, single-day famciclovir treatment stopped the development or progression of lesions beyond the papule stage. This convenient single-day regimen has the potential for improving patient compliance and satisfaction with therapy.
Increasing evidence suggests that distinct inflammatory cytokines convert forkhead box protein P3 (FOXP3+) regulatory T-cells (Tregs) into IL-17-producing cells (Th17 cells) in vitro. However, this ...functional plasticity has not been examined in the pathogenesis of periodontal disease. In this study, we analyzed the IL-17A+FOXP3+ cells present in periodontitis lesions to determine the association between Treg conversion and the pathogenesis of periodontitis. The immunohistochemical analysis of gingival tissues demonstrated that the numbers of Th17 cells (IL-17A+FOXP3−) and Tregs (IL-17A−FOXP3+) were greater in periodontitis lesions than in gingivitis lesions. We further identified a small number of IL-17A+FOXP3+ cells in periodontitis lesions but not in gingivitis lesions. The flow cytometry analysis of CD4+ T-cell lines established from gingival tissues and the peripheral blood of periodontitis patients showed that the proportion of Tregs was reduced and the proportion of IL-17A+FOXP3+ cells among all FOXP3+ cells was elevated in gingival tissue T-cell lines relative to the proportions in peripheral blood T-cell lines. Our findings indicate that Treg-Th17 conversion may occur in periodontitis lesions. Further studies addressing the role of Treg conversion during inflammatory responses against periodontopathic bacteria are needed.
JLDG is a data-grid for the lattice QCD (LQCD) community in Japan. Several large research groups in Japan have been working on lattice QCD simulations using supercomputers distributed over distant ...sites. The JLDG provides such collaborations with an efficient method of data management and sharing. File servers installed on 9 sites are connected to the NII SINET VPN and are bound into a single file system with the GFarm. The file system looks the same from any sites, so that users can do analyses on a supercomputer on a site, using data generated and stored in the JLDG at a different site. We present a brief description of hardware and software of the JLDG, including a recently developed subsystem for cooperating with the HPCI shared storage, and report performance and statistics of the JLDG. As of April 2015, 15 research groups (61 users) store their daily research data of 4.7PB including replica and 68 million files in total. Number of publications for works which used the JLDG is 98. The large number of publications and recent rapid increase of disk usage convince us that the JLDG has grown up into a useful infrastructure for LQCD community in Japan.
Abstract
Although previous studies have suggested the involvement of dopamine (DA) and noradrenaline (NA) neurotransmissions in the autism spectrum disorder (ASD) pathophysiology, few studies have ...examined these neurotransmissions in individuals with ASD in vivo. Here, we investigated DA D1 receptor (D1R) and noradrenaline transporter (NAT) binding in adults with ASD (n = 18) and neurotypical controls (n = 20) by utilizing two different PET radioligands, 11CSCH23390 and (S,S)-18FFMeNER-D2, respectively. We found no significant group differences in DA D1R (striatum, anterior cingulate cortex, and temporal cortex) or NAT (thalamus and pons) binding. However, in the ASD group, there were significant negative correlations between DA D1R binding (striatum, anterior cingulate cortex and temporal cortex) and the “attention to detail” subscale score of the Autism Spectrum Quotient. Further, there was a significant positive correlation between DA D1R binding (temporal cortex) and emotion perception ability assessed by the neurocognitive battery. Associations of NAT binding with empathic abilities and executive function were found in controls, but were absent in the ASD group. Although a lack of significant group differences in binding might be partly due to the heterogeneity of ASD, our results indicate that central DA and NA function might play certain roles in the clinical characteristics of ASD.
We study spatial isovector meson correlators in Nf=2 QCD with dynamical domain-wall fermions on 323×8 lattices at temperatures T=220–380 MeV. We measure the correlators of spin-one (J=1) operators ...including vector, axial-vector, tensor and axial-tensor. Restoration of chiral U(1)A and SU(2)L×SU(2)R symmetries of QCD implies degeneracies in vector–axial-vector (SU(2)L×SU(2)R) and tensor–axial-tensor (U(1)A) pairs, which are indeed observed at temperatures above Tc. Moreover, we observe an approximate degeneracy of all J=1 correlators with increasing temperature. This approximate degeneracy suggests emergent SU(2)CS and SU(4) symmetries at high temperatures, that mix left- and right-handed quarks.
Abnormal trajectory of brain development has been suggested by previous structural magnetic resonance imaging and head circumference findings in autism spectrum disorders (ASDs); however, the ...neurochemical backgrounds remain unclear. To elucidate neurochemical processes underlying aberrant brain growth in ASD, we conducted a comprehensive literature search and a meta-analysis of (1)H-magnetic resonance spectroscopy ((1)H-MRS) studies in ASD. From the 22 articles identified as satisfying the criteria, means and s.d. of measure of N-acetylaspartate (NAA), creatine, choline-containing compounds, myo-Inositol and glutamate+glutamine in frontal, temporal, parietal, amygdala-hippocampus complex, thalamus and cerebellum were extracted. Random effect model analyses showed significantly lower NAA levels in all the examined brain regions but cerebellum in ASD children compared with typically developed children (n=1295 at the maximum in frontal, P<0.05 Bonferroni-corrected), although there was no significant difference in metabolite levels in adulthood. Meta-regression analysis further revealed that the effect size of lower frontal NAA levels linearly declined with older mean age in ASD (n=844, P<0.05 Bonferroni-corrected). The significance of all frontal NAA findings was preserved after considering between-study heterogeneities (P<0.05 Bonferroni-corrected). This first meta-analysis of (1)H-MRS studies in ASD demonstrated robust developmental changes in the degree of abnormality in NAA levels, especially in frontal lobes of ASD. Previously reported larger-than-normal brain size in ASD children and the coincident lower-than-normal NAA levels suggest that early transient brain expansion in ASD is mainly caused by an increase in non-neuron tissues, such as glial cell proliferation.
In the Phase III PATRICIA study (NCT00122681), the human papillomavirus (HPV)‐16/18 AS04‐adjuvanted vaccine (Cervarix®, GlaxoSmithKline Biologicals) was highly efficacious against HPV‐16/18 ...infections and precancerous lesions in women HPV‐16/18 deoxyribose nucleic acid (DNA) negative and seronegative at baseline. We present further data on vaccine efficacy (VE) against HPV‐16/18 in the total vaccinated cohort including women who may have been exposed to HPV‐16/18 infection before vaccination. In women with no evidence of current or previous HPV‐16/18 infection (DNA negative and seronegative), VE was 90.3% (96.1% confidence interval: 87.3–92.6) against 6‐month persistent infection (PI), 91.9% (84.6–96.2) against cervical intraepithelial neoplasia (CIN)1+ and 94.6% (86.3–98.4) against CIN2+ 97.7% (91.1–99.8) when using the HPV type assignment algorithm (TAA). In women HPV‐16/18 DNA negative but with serological evidence of previous HPV‐16/18 infection (seropositive), VE was 72.3% (53.0–84.5) against 6‐month PI, 67.2% (10.9–89.9) against CIN1+, and 68.8% (−28.3–95.0) against CIN2+ 88.5% (10.8–99.8) when using TAA. In women with no evidence of current HPV‐16/18 infection (DNA negative), regardless of their baseline HPV‐16/18 serological status, VE was 88.7% (85.7–91.1) against 6‐month PI, 89.1% (81.6–94.0) against CIN1+ and 92.4% (84.0–97.0) against CIN2+ 97.0% (90.6–99.5) when using TAA. In women who were DNA positive for one vaccine type, the vaccine was efficacious against the other vaccine type. The vaccine did not impact the outcome of HPV‐16/18 infections present at the time of vaccination. Vaccination was generally well tolerated regardless of the woman's HPV‐16/18 DNA or serological status at entry.
Abstract
The chiral susceptibility, or the first derivative of the chiral condensate with respect to the quark mass, is often used as a probe for the QCD phase transition since the chiral condensate ...is an order parameter of SU(2)L × SU(2)R symmetry breaking. However, the chiral condensate also breaks the axial U(1) symmetry, which is usually not studied as it is already broken by the anomaly and apparently has little impact on the transition. We investigate the susceptibilities in the scalar and pseudoscalar channels in order to quantify how much the axial U(1) breaking contributes to the chiral phase transition. Employing a chirally symmetric lattice Dirac operator and its eigenmode decomposition, we separate the axial U(1) breaking effects from others. Our result in two-flavor QCD indicates that both of the connected and disconnected chiral susceptibilities are dominated by axial U(1) breaking at temperatures T ≳ 190 MeV after the quadratically divergent constant is subtracted.
Groups are essential elements of society, and humans, by nature, commonly manifest intergroup bias (i.e., behave more positively toward an ingroup member than toward an outgroup member). Despite the ...growing evidence of various types of altered decision-making in individuals with autism spectrum disorder (ASD), their behavior under the situation involving group membership remains largely unexplored. By modifying a third-party punishment paradigm, we investigated intergroup bias in individuals with ASD and typical development (TD). In our experiment, participants who were considered as the third party observed a dictator game wherein proposers could decide how to distribute a provided amount of money while receivers could only accept unconditionally. Participants were confronted with two different group situations: the proposer was an ingroup member and the recipient was an outgroup member (IN/OUT condition) or the proposer was an outgroup member and the recipient was an ingroup member (OUT/IN condition). Participants with TD punished proposers more severely when violating social norms in the OUT/IN condition than in IN/OUT condition, indicating that their decisions were influenced by the intergroup context. This intergroup bias was attenuated in individuals with ASD. Our findings deepen the understanding of altered decision-making and socioeconomic behaviors in individuals with ASD.
Ti–15V–3Al–3Cr–3Sn (Ti–15–3) is one of the important practical titanium alloys with high cold deformability and high mechanical strength, but its wear resistance is poor. This paper reports the ...formation of wear-resistant and adhesive ceramic coatings on Ti–15–3 by two-step plasma electrolytic oxidation (PEO). The PEO of Ti–15–3 has been carried out first in alkaline aluminate electrolyte to form a wear-resistant oxide layer and then in acid electrolyte containing both phosphoric acid and sulfuric acid to improve adhesion of the coating. The coating formed in the alkaline aluminate electrolyte is more than 10μm thick, and highly crystalline. The main phase is Al2TiO5. This coating shows high wear resistance, but is not adherent to substrate due to the development of a number of voids and pores in the oxide layer close to the substrate. A new oxide layer with amorphous structure is formed next to the substrate in the subsequent PEO in the acid electrolyte, during which the voids are filled with a new oxide formed in the acid electrolyte, reducing the porosity. As a consequence, the adhesion of the coating is markedly improved without deteriorating the high wear resistance.
► Two-step PEO was carried out to form a wear-resistant coating on Ti–15V–3Al–3Cr–3Sn. ► The first step PEO in alkaline aluminate electrolyte formed a wear-resistant coating. ► The second step PEO in acid electrolyte improved the coating adhesion markedly. ► During the second step PEO, voids near the alloy/coating interface were healed.
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