Publisher Correction: Electron magnetic reconnection without ion coupling in Earth's turbulent magnetosheath.

Change history: In this Letter, the y-axis values in Fig. 3f should go from 4 to -8 (rather than from 4 to -4), the y-axis values in Fig. 3h should appear next to the major tick marks (rather than the minor ticks), and in Fig. 1b, the arrows at the top and bottom of the electron-scale current sheet were going in the wrong direction; these errors have been corrected online.

Electron magnetic reconnection without ion coupling in Earth's turbulent magnetosheath.

Magnetic reconnection in current sheets is a magnetic-to-particle energy conversion process that is fundamental to many space and laboratory plasma systems. In the standard model of reconnection, this process occurs in a minuscule electron-scale diffusion region1,2. On larger scales, ions couple to the newly reconnected magnetic-field lines and are ejected away from the diffusion region in the form of bi-directional ion jets at the ion Alfvén speed3-5. Much of the energy conversion occurs in spatially extended ion exhausts downstream of the diffusion region 6 . In turbulent plasmas, which contain a large number of small-scale current sheets, reconnection has long been suggested to have a major role in the dissipation of turbulent energy at kinetic scales7-11. However, evidence for reconnection plasma jetting in small-scale turbulent plasmas has so far been lacking. Here we report observations made in Earth's turbulent magnetosheath region (downstream of the bow shock) of an electron-scale current sheet in which diverging bi-directional super-ion-Alfvénic electron jets, parallel electric fields and enhanced magnetic-to-particle energy conversion were detected. Contrary to the standard model of reconnection, the thin reconnecting current sheet was not embedded in a wider ion-scale current layer and no ion jets were detected. Observations of this and other similar, but unidirectional, electron jet events without signatures of ion reconnection reveal a form of reconnection that can drive turbulent energy transfer and dissipation in electron-scale current sheets without ion coupling.

Observational Evidence for Stochastic Shock Drift Acceleration of Electrons at the Earth's Bow Shock.

The first-order Fermi acceleration of electrons requires an injection of electrons into a mildly relativistic energy range. However, the mechanism of injection has remained a puzzle both in theory and observation. We present direct evidence for a novel stochastic shock drift acceleration theory for the injection obtained with Magnetospheric Multiscale observations at the Earth's bow shock. The theoretical model can explain electron acceleration to mildly relativistic energies at high-speed astrophysical shocks, which may provide a solution to the long-standing issue of electron injection.

Disturbance of the Front Region of Magnetic Reconnection Outflow Jets due to the Lower-Hybrid Drift Instability.

A 3D fully kinetic simulation shows that the lower-hybrid drift instability disturbs the front of magnetic reconnection outflow jets and additionally causes energy dissipation. The result is very consistent with a disturbance observed at the dipolarization front (DF) in Earth's magnetotail by the Magnetospheric Multiscale (MMS) mission. A fully kinetic dispersion relation solver, validated by the MMS observations, further predicts that the disturbance of the reconnection jet front could occur over different parameter regimes in space plasmas including Earth's DF and solar flares.

Comparing treatments for basal cell carcinoma in terms of long-term treatment-failure: a network meta-analysis.

Although many variations of guidelines have been released, there is limited research that compares multiple treatment strategies for basal cell carcinoma (BCC). The aim of this study was to systematically review the studies reporting on multiple treatments for BCC with systematic review and network meta-analyses. Search formulas for databases, such as PubMed, EMBASE, Web of Science Core Collection and Cochrane Central Register of Controlled Trials, were created with the support of Cochrane Japan. The patient-level and tumour-level meta-analyses were performed for both the long-term treatment-failure and treatment-success. Of the 1464 studies identified from the database and hand searches, 14 met our inclusion criteria. These 14 studies included 2524 patients and 1738 tumours. Our study indicated that the incidence of treatment-failure of invasive treatments such as surgery and Mohs micrographic surgery was significantly lower than that of superficial therapies such as cryotherapy, photodynamic therapy, radiotherapy or topical therapies, in the patient-level and the tumour-level analyses, despite histological-type and pretreatment. Relapse of BCC may be a low life-threatening risk, and there are merits of non-surgical treatment. However, the significant difference in the recurrence rate is essential. Our study can provide useful guidance to clinicians in selecting treatment options for BCC.

Differential Cross Section and Photon-Beam Asymmetry for the γ[over →]p → π

Differential cross sections and photon-beam asymmetries for the γ[over →]p→π^{-}Δ^{++}(1232) reaction have been measured for 0.7

A novel HYLS1 homozygous mutation in living siblings with Joubert syndrome.

The p.Asp211Gly homozygous HYLS1 mutation is so far known to cause only hydrolethalus syndrome, a lethal malformation syndrome. We report living sibling patients with a homozygous no-stop mutation in exon 4 of HYLS1, NM_145014.2:c.900A>C (p.Ter300TyrextTer11) in the second decade of life. The proband has Joubert syndrome (JS). The younger brother also has JS and an enlarged posterior fossa that was initially diagnosed as Dandy-Walker malformation. The present mutation is unique as it affects the stop codon. The product protein HYLS1 plays an essential role in the formation of the primary cilium. This report provides insight into the spectrum of disorders involving midline brain defects closely related to cilium dysfunction or ciliopathy.

Randomized clinical trial comparing long-term quality of life for Billroth I versus Roux-en-Y reconstruction after distal gastrectomy for gastric cancer.

BACKGROUND: Patients' quality of life (QoL) deteriorates remarkably after gastrectomy. Billroth I reconstruction following distal gastrectomy has the physiological advantage of allowing food to pass through the duodenum. It was hypothesized that Billroth I reconstruction would be superior to Roux-en-Y reconstruction in terms of long-term QoL after distal gastrectomy. This study compared two reconstructions in a multicentre prospective randomized clinical trial to identify the optimal reconstruction procedure. METHODS: Between January 2009 and September 2010, patients who underwent gastrectomy for gastric cancer were randomized during surgery to Billroth I or Roux-en-Y reconstruction. The primary endpoint was assessment of QoL using the Functional Assessment of Cancer Therapy - Gastric (FACT-Ga) questionnaire 36 months after surgery. RESULTS: A total of 122 patients were enrolled in the study, 60 to Billroth I and 62 to Roux-en-Y reconstruction. There were no differences between the two groups in terms of postoperative complications or mortality, and no significant differences in FACT-Ga total score (P = 0·496). Symptom scales such as epigastric fullness (heaviness), diarrhoea and fatigue were significantly better in the Billroth I group at 36 months after gastrectomy (heaviness, P = 0·040; diarrhoea, P = 0·046; fatigue, P = 0·029). The rate of weight loss in the third year was lower for patients in the Billroth I group (P = 0·046). CONCLUSION: The choice of anastomotic reconstruction after distal gastrectomy resulted in no difference in long-term QoL in patients with gastric cancer. REGISTRATION NUMBER: NCT01065688 (http://www.clinicaltrials.gov).

DFT-based ab initio MD simulation of the ionic conduction in doped ZrO2 systems under epitaxial strain.

The oxygen ionic conduction in ZrO2 systems under tensile epitaxial strain was investigated by performing ab initio molecular dynamics (MD) calculations based on density functional theory (DFT) to elucidate the essential factors in the colossal ionic conductivity observed in the yttria stabilized ZrO2 (YSZ)/SrTiO3 heterostructure. Three factors were evaluated: lattice strain, oxygen vacancies, and dopants. Phonon calculations based on density functional perturbation theory (DFPT) were used to obtain the most stable structure for nondoped ZrO2 under 7% tensile strain along the a- and b-axes. This structure has the space group Pbcn, which is entirely different from that of cubic ZrO2, suggesting that previous ab initio MD calculations assuming cubic ZrO2 may have overestimated the ionic conductivity due to relaxation from the initial structure to the stable structure (Pbcn). Our MD calculations revealed that the ionic conductivity is enhanced only when tensile strain and oxygen vacancies are incorporated, although the presently obtained diffusion constant is far below the range for the colossal ionic conduction experimentally observed. The enhanced ionic conductivity is due to the combined effects of oxygen sublattice formation induced by strain and deformation of this sublattice by oxygen vacancies.

Genetic variants of immunoglobulin γ and κ chains influence humoral immunity to the cancer-testis antigen XAGE-1b (GAGED2a) in patients with non-small cell lung cancer.

GM (γ marker) allotypes, genetic variants of immunoglobulin γ chains, have been reported to be associated strongly with susceptibility to lung cancer, but the mechanism(s) underlying this association is not known. One mechanism could involve their contribution to humoral immunity to lung tumour-associated antigens. In this study, we aimed to determine whether particular GM and KM (κ marker) allotypes were associated with antibody responsiveness to XAGE-1b, a highly immunogenic lung tumour-associated cancer-testis antigen. Sera from 89 patients with non-small cell lung cancer (NSCLC) were allotyped for eight GM and two KM determinants and characterized for antibodies to a synthetic XAGE-1b protein. The distribution of various GM phenotypes was significantly different between XAGE-1b antibody-positive and -negative patients (P = 0·023), as well as in the subgroup of XAGE-1b antigen-positive advanced NSCLC (P = 0·007). None of the patients with the GM 1,17 21 phenotype was positive for the XAGE-1b antibody. In patients with antigen-positive advanced disease, the prevalence of GM 1,2,17 21 was significantly higher in the antibody-positive group than in those who lacked the XAGE-1b antibody (P = 0·026). This phenotype also interacted with a particular KM phenotype: subjects with GM 1,2,17 21 and KM 3,3 phenotypes were almost four times (odds ratio = 3·8) as likely to be positive for the XAGE-1b antibody as the subjects who lacked these phenotypes. This is the first report presenting evidence for the involvement of immunoglobulin allotypes in immunity to a cancer-testis antigen, which has important implications for XAGE-1b-based immunotherapeutic interventions in lung adenocarcinoma.

Expression of B7-H3, a potential factor of tumor immune evasion in combination with the number of regulatory T cells, affects against recurrence-free survival in breast cancer patients.

BACKGROUND: In the tumor microenvironment, factors inhibiting the targeting of cancer cells by activated T cells have recently been noted. B7-H3 belongs to the B7 superfamily of immune regulatory ligands and plays an important role in the adaptive immune response of co-inhibitory/stimulatory factors in regulating T cells. However, the degree to which B7-H3 directly affects tumor immune evasion mechanisms remains unclear, particularly in patients with breast cancer. Regulatory T cells (Tregs) are known as a key player in the inhibition of immune mechanisms. The present study demonstrated that expression of B7-H3 on tumor cells and the number of Tregs in the tumor microenvironment independently affected prognosis in breast cancer patients. METHODS: We immunohistochemically investigated the presence of B7-H3 and forkhead box P3 (Foxp3)-positive Tregs in pathological specimens from 90 patients with breast cancer. RESULTS: Positive B7-H3 expression was associated with shorter recurrence-free survival (RFS) (p = 0.014). A higher percentage of Foxp3-positive cells also correlated with shorter RFS (p = 0.039). Multivariate analysis showed B7-H3 as an independent factor on RFS. Foxp3 expression in tumor-infiltrating lymphocytes (TILs) correlated significantly with larger tumor size (>2 cm), expression of human epidermal growth factor receptor 2 (HER2), and higher nuclear grade (p = 0.003, p < 0.001, p = 0.001, respectively). No correlation was identified between expression of B7-H3 and the percentage of Foxp3-positive TILs. CONCLUSIONS: B7-H3 and Foxp3 can be regarded as markers of poor prognosis in breast cancer. These expressions were not correlated, suggesting that B7-H3 expression plays an independent role in tumor immune evasion, regardless of Tregs.

Influence of neutralizing antibodies to adalimumab and infliximab on the treatment of psoriasis.

BACKGROUND: Current treatment with biologics has produced dramatic therapeutic effects in patients with psoriasis, although these agents occasionally decrease in efficacy. One of the main factors responsible for this attenuation is attributed to the development of antidrug antibodies (ADAs). OBJECTIVES: To analyse the relationship between serum drug concentrations, the presence of ADAs and treatment efficacy of adalimumab and infliximab, and to determine the optimal use of these biologics. METHODS: This was a 1-year prospective study in the dermatology departments of Kobe University Hospital and collaborating hospitals. All patients starting a regimen of adalimumab and infliximab for psoriasis were included. We measured the serum concentration of the drugs and titres of antibodies to adalimumab and infliximab, as well as the Psoriasis Area and Severity Index scores at weeks 0, 4, 12, 24 and 48 during the first year of treatment. RESULTS: We observed a 50% positive rate of ADAs to adalimumab, and a 41% positive rate of ADAs to infliximab. The titres of ADAs showed a wide range from low to high titres. In the high-titre groups, the patients exhibited a decreased clinical response, and demonstrated a negative correlation between titre and clinical response. However, an equivalent therapeutic effect was observed between the low-titre group and the group with no antibodies detected for adalimumab. For infliximab, the patients with ADAs showed decreased clinical response. An apparent negative correlation between antibody production and reduced clinical response was observed. CONCLUSIONS: Two biologics, adalimumab and infliximab, showed different therapeutic behaviour. The measurement of ADAs and drug concentrations has important implications for treatment with biologics.

Effect of occlusal rehabilitation on spatial memory and hippocampal neurons after long-term loss of molars in rats.

Experimental loss of occlusal support caused by the extraction or grinding of molar teeth has been reported to foment the impairment of learning and memory in laboratory animals. The purpose of this study was to examine the effect of occlusal reconstruction after long-term loss of molars on spatial memory by using 8-arm radial maze and by assessing histopathological changes of neuron density in the hippocampus. Experimental dentures were inserted into the oral cavities of molarless rats to recover the occlusal support. Age-matched groups of control, molarless and denture-wearing rats were trained to perform the maze tasks. The difference of the error incidence in the maze task was evaluated between three groups. The difference of neuron density between three groups was also evaluated at the end of the maze task. Serum corticosterone levels were also measured to estimate the chronic stress, which could be caused by extraction, insertion of the experimental denture or any experimental procedure. The error incidence in the denture-wearing group was significantly higher than that of the control group, but significantly lower than that of the molarless group. Significant differences of neuron density were observed between three groups in each of the hippocampal CA1, CA3 and DG subfields. No significant difference of the serum corticosterone levels between three groups could be observed. From the results of this study, it was suggested that the recovery of occlusal support would bring amelioration of cognitive impairment concomitant with long period loss of molars in rats.

Spin-density matrix elements for γp→K*0Σ+ at Eγ=1.85-3.0 GeV with evidence for the κ(800) meson exchange.

The exclusive reaction γp→K(+)π(-)Σ(+) was measured for the first time using linearly polarized photons at beam energies from 1.85 to 2.96 GeV. Angular distributions in the rest frame of the K(+)π(-) system were fitted to extract spin-density matrix elements of the K(*0) decay. The measured parity spin asymmetry shows that natural-parity exchange is dominant in this reaction. This result clearly indicates the need for t-channel exchange of the κ(800) scalar meson.

Clinical potential of diagnostic methods for the rapid diagnosis of Mycoplasma pneumoniae pneumonia in adults.

The purpose of the present study was to evaluate the accuracy and usefulness of three rapid diagnostic methods, ImmunoCard Mycoplasma kit, chest high-resolution computed tomography (HRCT) findings, and the Japanese Respiratory Society (JRS) scoring system (including six parameters), for the early presumptive diagnosis of Mycoplasma pneumoniae pneumonia in adults. We performed three rapid diagnostic methods at the same time in four pneumonia groups: 68 cases with M. pneumoniae pneumonia, 133 cases with Streptococcus pneumoniae pneumonia, 30 cases with Haemophilus influenzae pneumonia, and 20 cases with Legionella pneumonia. The sensitivity and specificity were 35% and 68% for ImmunoCard, 73% and 85% with HRCT, and 83% and 90% with the JRS scoring system, respectively. Among the three rapid diagnostic methods, the JRS scoring system was the most useful tool for initiating the administration of adequate antibiotic therapy for probable M. pneumoniae pneumonia. We suggest that M. pneumoniae pneumonia should be suspected when there is a correlation of more than five parameters in the JRS scoring system (99% specificity). If there is a correlation of three or four parameters in the JRS scoring system, chest computed tomography (CT) findings are helpful for the presumptive diagnosis of M. pneumoniae pneumonia.

Abnormal fast activity before the onset of West syndrome.

In our sequential EEG study performed on 68 infants with various pre- and perinatal brain insults, we found peculiar abnormal fast activity (AFAs) in 12 patients. 9 of the 12 patients with AFAs later developed West syndrome (WS) compared with only 3 of the 56 patients without AFAs (p<0.001, χ(2) test). We analyzed these AFAs using EEG topography, and compared them with ictal fast activity (IFA) corresponding to tonic spasms observed later in the same patients after they had developed WS. We also investigated the clinical and EEG features in these patients. AFAs were first observed commonly at 4-5 months of CA, before the onset of WS. AFA topographic maps revealed posterior predominance in 11 of the 12 patients; IFA maps also showed posterior predominance but were more widely distributed. We propose that, though AFAs and IFAs are different, they share certain aspects of their pathophysiology, and that the maturational process of the occipital cortex plays an important role in the shared aspects. Since AFAs are observed before the onset of WS, they can be considered a sign that WS is imminent.