Cortical and cerebellar activation induced by reflexive and voluntary saccades

Reflexive saccades are driven by visual stimulation whereas voluntary saccades require volitional control. Behavioral and lesional studies suggest that there are two separate mechanisms involved in the generation of these two types of saccades. This study investigated differences in cerebral and cerebellar activation between reflexive and self-paced voluntary saccadic eye movements using functional magnetic resonance imaging. In two experiments (whole brain and cerebellum) using the same paradigm, differences in brain activations induced by reflexive and self-paced voluntary saccades were assessed. Direct comparison of the activation patterns showed that the frontal eye fields, parietal eye field, the motion-sensitive area (MT/V5), the precuneus (V6), and the angular and the cingulate gyri were more activated in reflexive saccades than in voluntary saccades. No significant difference in activation was found in the cerebellum. Our results suggest that the alleged separate mechanisms for saccadic control of reflexive and self-paced voluntary are mainly observed in cerebral rather than cerebellar areas

Association of PPARγ2 polymorphisms with carcass and meat quality traits in a Pietrain x Jinhua F2 population

The PPARγ2 gene is a key regulator of both proliferation and preadipocyte differentiation in mammals. Herein its genotype and allele frequencies were analyzed using PCR-SSCP in eight pig breeds (N = 416). Two kinds of polymorphisms of the PPARγ2 gene were detected, including a previously reported shift SNP A177G (Met59Val) in exon 1 and a novel silent mutation G876A in exon 5. The results revealed that European pig breeds carry a higher allele A frequency at the A177G locus and a fixed GG genotype at the G876A locus. Allele A at the G876A locus was only found in Jinhua pigs. The association between haplotype (A177G/G876A) and carcass and meat quality traits was analyzed in a Pietrain x Jinhua F2 population (N = 248). The PPARγ2 gene was found to be significantly associated with backfat thickness at the shoulder (p < 0.05), 6–7th ribs (p < 0.01), last rib (p < 0.01), gluteus medius (p <0.05) and ham weight (p < 0.01). Significant effects of different haplotypes on ham weight and backfat thickness at the 6–7th ribs, last rib, and gluteus medius were also observed

Performance of the first prototype of the CALICE scintillator strip electromagnetic calorimeter

A first prototype of a scintillator strip-based electromagnetic calorimeter was built, consisting of 26 layers of tungsten absorber plates interleaved with planes of 45x10x3 mm3 plastic scintillator strips. Data were collected using a positron test beam at DESY with momenta between 1 and 6 GeV/c. The prototype's performance is presented in terms of the linearity and resolution of the energy measurement. These results represent an important milestone in the development of highly granular calorimeters using scintillator strip technology. This technology is being developed for a future linear collider experiment, aiming at the precise measurement of jet energies using particle flow techniques

Quantitative and spatial analysis of CD8+/PD-1 tumor-infiltrating lymphocytes as a predictive biomarker for clinical response of melanoma in-transit metastases to topical immunotherapy

Background: Melanoma in-transit metastases (ITMs) are a challenge to treat and associated with systemic disease and poor prognosis. Topical diphencyprone (DPCP), a potent contact sensitizer, is an established treatment for melanoma ITMs. This exploratory study investigated the utility of BRAF mutation status, CD8, PD-1, PD-L1, and TILs distribution as biomarkers for response of ITMs to topical immunotherapy (DPCP).  Methods: The ITM deposits of 40 patients treated with DPCP were subjected to biomarker analysis for BRAF status, CD8 and PD-1 expression on tumor-infiltrating lymphocytes (TILs), and tumor PD-L1 expression. Response to DPCP and overall survival (OS) were compared by biomarker status.  Results: After 12 weeks, 10 patients (25%) had a complete response, 12 patients (30%) had a partial response, and 18 patients (45%) had no response. No significant association was found between any individual biomarker and response to DPCP or OS. The BRAF mutation rate was 25% (10/40). All the patients with a complete response had BRAF wild-type tumor. Peritumoral CD8+ T-cells were associated with complete response (P = 0.041). Both CD8+ and PD-1 expressions were highly correlated (P < 0.0001), and the highest levels of PD-1 expression were detected at the peritumoral interface (P = 0.0004). Only two cases were PD-L1-positive, and both had a complete response to DPCP (P = 0.043).  Conclusion: Patients who have BRAF wild-type tumor are more likely to experience a complete response to DPCP. Peritumoral TILs and PD-1 expressions may predict a better response to DPCP. Expression of PD-L1 may be associated with a complete response to DPCP. A larger prospective study is required

A Reliability-Generalization Study of Journal Peer Reviews: A Multilevel Meta-Analysis of Inter-Rater Reliability and Its Determinants

Background: This paper presents the first meta-analysis for the inter-rater reliability (IRR) of journal peer reviews. IRR is defined as the extent to which two or more independent reviews of the same scientific document agree. Methodology/Principal Findings: Altogether, 70 reliability coefficients (Cohen’s Kappa, intra-class correlation [ICC], and Pearson product-moment correlation [r]) from 48 studies were taken into account in the meta-analysis. The studies were based on a total of 19,443 manuscripts; on average, each study had a sample size of 311 manuscripts (minimum: 28, maximum: 1983). The results of the meta-analysis confirmed the findings of the narrative literature reviews published to date: The level of IRR (mean ICC/r 2 =.34, mean Cohen’s Kappa =.17) was low. To explain the study-to-study variation of the IRR coefficients, meta-regression analyses were calculated using seven covariates. Two covariates that emerged in the metaregression analyses as statistically significant to gain an approximate homogeneity of the intra-class correlations indicated that, firstly, the more manuscripts that a study is based on, the smaller the reported IRR coefficients are. Secondly, if the information of the rating system for reviewers was reported in a study, then this was associated with a smaller IRR coefficient than if the information was not conveyed. Conclusions/Significance: Studies that report a high level of IRR are to be considered less credible than those with a low level o

Molecular imaging of inflammation and intraplaque vasa vasorum: A step forward to identification of vulnerable plaques?

Current developments in cardiovascular biology and imaging enable the noninvasive molecular evaluation of atherosclerotic vascular disease. Intraplaque neovascularization sprouting from the adventitial vasa vasorum has been identified as an independent predictor of intraplaque hemorrhage and plaque rupture. These intraplaque vasa vasorum result from angiogenesis, most likely under influence of hypoxic and inflammatory stimuli. Several molecular imaging techniques are currently available. Most experience has been obtained with molecular imaging using positron emission tomography and single photon emission computed tomography. Recently, the development of targeted contrast agents has allowed molecular imaging with magnetic resonance imaging, ultrasound and computed tomography. The present review discusses the use of these molecular imaging techniques to identify inflammation and intraplaque vasa vasorum to identify vulnerable atherosclerotic plaques at risk of rupture and thrombosis. The available literature on molecular imaging techniques and molecular targets associated with inflammation and angiogenesis is discussed, and the clinical applications of molecular cardiovascular imaging and the use of molecular techniques for local drug delivery are addressed

Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN

Observation of a New Excited Beauty Strange Baryon Decaying to Ξb- π+π-

The Ξb-π+π- invariant mass spectrum is investigated with an event sample of proton-proton collisions at s=13 TeV, collected by the CMS experiment at the LHC in 2016-2018 and corresponding to an integrated luminosity of 140 fb-1. The ground state Ξb- is reconstructed via its decays to J/ψΞ- and J/ψΛK-. A narrow resonance, labeled Ξb(6100)-, is observed at a Ξb-π+π- invariant mass of 6100.3±0.2(stat)±0.1(syst)±0.6(Ξb-) MeV, where the last uncertainty reflects the precision of the Ξb- baryon mass. The upper limit on the Ξb(6100)- natural width is determined to be 1.9 MeV at 95% confidence level. The low Ξb(6100)- signal yield observed in data does not allow a measurement of the quantum numbers of the new state. However, following analogies with the established excited Ξc baryon states, the new Ξb(6100)- resonance and its decay sequence are consistent with the orbitally excited Ξb- baryon, with spin and parity quantum numbers JP=3/2-