Medical students’ views about having different types of problem-based learning tutors

Background At Norwich Medical School, Year 3 or 4 medical students taking a year out of the 5-year undergraduate MBBS degree to do a master’s degree in clinical education worked as near-peer problem-based learning (PBL) tutors for students in Year 2. Peer-assisted learning has been shown to benefit both peer tutors and tutees; in this study, experiences of students with near-peer PBL tutors were compared to students with other types of PBL tutor. Methods Using existing student evaluation data, we compared student views about PBL tutor performance, PBL group functioning, and overall satisfaction with PBL learning experience according to whether their PBL tutor/s were (1) a single near-peer tutor (later-year MB BS student), (2) a single staff tutor, (3) multiple staff tutors, or (4) multiple newly qualified doctor tutors. Results Results indicated that students’ evaluation of tutor performance was more positive for near-peer PBL tutors compared to both groups of staff tutors for most areas evaluated. Additionally, students’ evaluation of overall satisfaction with PBL was more positive for near-peer PBL tutors compared to multiple staff tutors. Tutor performance for multiple staff tutors was evaluated less positively compared to both single staff and multiple newly qualified doctor groups. But there were no statistically significant differences between the four groups regarding PBL group functioning. Conclusion Near-peer PBL tutors perform comparably or better to staff PBL tutors in salient measures of tutor performance and group functioning. We conclude that medical students find near-peer PBL tutors to be an acceptable addition to the PBL tutor workforce

Wnt5a induces ROR1 to complex with HS1 to enhance migration of chronic lymphocytic leukemia cells.

ROR1 (receptor tyrosine kinase-like orphan receptor 1) is a conserved, oncoembryonic surface antigen expressed in chronic lymphocytic leukemia (CLL). We found that ROR1 associates with hematopoietic-lineage-cell-specific protein 1 (HS1) in freshly isolated CLL cells or in CLL cells cultured with exogenous Wnt5a. Wnt5a also induced HS1 tyrosine phosphorylation, recruitment of ARHGEF1, activation of RhoA and enhanced chemokine-directed migration; such effects could be inhibited by cirmtuzumab, a humanized anti-ROR1 mAb. We generated truncated forms of ROR1 and found its extracellular cysteine-rich domain or kringle domain was necessary for Wnt5a-induced HS1 phosphorylation. Moreover, the cytoplamic, and more specifically the proline-rich domain (PRD), of ROR1 was required for it to associate with HS1 and allow for F-actin polymerization in response to Wnt5a. Accordingly, we introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1 PRD at positions 784, 808, 826, 841 or 850 in potential SH3-binding motifs. In contrast to wild-type ROR1, or other ROR1P→︀A mutants, ROR1P(841)A had impaired capacity to recruit HS1 and ARHGEF1 to ROR1 in response to Wnt5a. Moreover, Wnt5a could not induce cells expressing ROR1P(841)A to phosphorylate HS1 or activate ARHGEF1, and was unable to enhance CLL-cell motility. Collectively, these studies indicate HS1 plays an important role in ROR1-dependent Wnt5a-enhanced chemokine-directed leukemia-cell migration

Baby MIND: A magnetised spectrometer for the WAGASCI experiment

The WAGASCI experiment being built at the J-PARC neutrino beam line will measure the difference in cross sections from neutrinos interacting with a water and scintillator targets, in order to constrain neutrino cross sections, essential for the T2K neutrino oscillation measurements. A prototype Magnetised Iron Neutrino Detector (MIND), called Baby MIND, is being constructed at CERN to act as a magnetic spectrometer behind the main WAGASCI target to be able to measure the charge and momentum of the outgoing muon from neutrino charged current interactions.Comment: Poster presented at NuPhys2016 (London, 12-14 December 2016). Title + 4 pages, LaTeX, 6 figure

Synchronization of the Distributed Readout Frontend Electronics of the Baby MIND Detector

Baby MIND is a new downstream muon range detector for the WGASCI experiment. This article discusses the distributed readout system and its timing requirements. The paper presents the design of the synchronization subsystem and the results of its test

Baby MIND Experiment Construction Status

Baby MIND is a magnetized iron neutrino detector, with novel design features, and is planned to serve as a downstream magnetized muon spectrometer for the WAGASCI experiment on the T2K neutrino beam line in Japan. One of the main goals of this experiment is to reduce systematic uncertainties relevant to CP-violation searches, by measuring the neutrino contamination in the anti-neutrino beam mode of T2K. Baby MIND is currently being constructed at CERN, and is planned to be operational in Japan in October 2017.Comment: Poster presented at NuPhys2016 (London, 12-14 December 2016). 4 pages, LaTeX, 7 figure

Baby MIND: A magnetized segmented neutrino detector for the WAGASCI experiment

T2K (Tokai-to-Kamioka) is a long-baseline neutrino experiment in Japan designed to study various parameters of neutrino oscillations. A near detector complex (ND280) is located 280~m downstream of the production target and measures neutrino beam parameters before any oscillations occur. ND280's measurements are used to predict the number and spectra of neutrinos in the Super-Kamiokande detector at the distance of 295~km. The difference in the target material between the far (water) and near (scintillator, hydrocarbon) detectors leads to the main non-cancelling systematic uncertainty for the oscillation analysis. In order to reduce this uncertainty a new WAter-Grid-And-SCintillator detector (WAGASCI) has been developed. A magnetized iron neutrino detector (Baby MIND) will be used to measure momentum and charge identification of the outgoing muons from charged current interactions. The Baby MIND modules are composed of magnetized iron plates and long plastic scintillator bars read out at the both ends with wavelength shifting fibers and silicon photomultipliers. The front-end electronics board has been developed to perform the readout and digitization of the signals from the scintillator bars. Detector elements were tested with cosmic rays and in the PS beam at CERN. The obtained results are presented in this paper.Comment: In new version: modified both plots of Fig.1 and added one sentence in the introduction part explaining Baby MIND role in WAGASCI experiment, added information for the affiliation

An SU(N) Mott insulator of an atomic Fermi gas realized by large-spin Pomeranchuk cooling

The Hubbard model, containing only the minimum ingredients of nearest neighbor hopping and on-site interaction for correlated electrons, has succeeded in accounting for diverse phenomena observed in solid-state materials. One of the interesting extensions is to enlarge its spin symmetry to SU(N>2), which is closely related to systems with orbital degeneracy. Here we report a successful formation of the SU(6) symmetric Mott insulator state with an atomic Fermi gas of ytterbium (173Yb) in a three-dimensional optical lattice. Besides the suppression of compressibility and the existence of charge excitation gap which characterize a Mott insulating phase, we reveal an important difference between the cases of SU(6) and SU(2) in the achievable temperature as the consequence of different entropy carried by an isolated spin. This is analogous to Pomeranchuk cooling in solid 3He and will be helpful for investigating exotic quantum phases of SU(N) Hubbard system at extremely low temperatures.Comment: 20 pages, 6 figures, to appear in Nature Physic

Insights from Amphioxus into the Evolution of Vertebrate Cartilage

Central to the story of vertebrate evolution is the origin of the vertebrate head, a problem difficult to approach using paleontology and comparative morphology due to a lack of unambiguous intermediate forms. Embryologically, much of the vertebrate head is derived from two ectodermal tissues, the neural crest and cranial placodes. Recent work in protochordates suggests the first chordates possessed migratory neural tube cells with some features of neural crest cells. However, it is unclear how and when these cells acquired the ability to form cellular cartilage, a cell type unique to vertebrates. It has been variously proposed that the neural crest acquired chondrogenic ability by recruiting proto-chondrogenic gene programs deployed in the neural tube, pharynx, and notochord. To test these hypotheses we examined the expression of 11 amphioxus orthologs of genes involved in neural crest chondrogenesis. Consistent with cellular cartilage as a vertebrate novelty, we find that no single amphioxus tissue co-expresses all or most of these genes. However, most are variously co-expressed in mesodermal derivatives. Our results suggest that neural crest-derived cartilage evolved by serial cooption of genes which functioned primitively in mesoderm

Cc Chemokine Receptor (Ccr)3/Eotaxin Is Followed by Ccr4/Monocyte-Derived Chemokine in Mediating Pulmonary T Helper Lymphocyte Type 2 Recruitment after Serial Antigen Challenge in Vivo

Isolated peripheral blood CD4 cells from allergic individuals express CC chemokine receptor (CCR)3 and CCR4 after expansion in vitro. In addition, human T helper type 2 (Th2) cells polarized in vitro selectively express CCR3 and CCR4 at certain stages of activation/differentiation and respond preferentially to the ligands eotaxin and monocyte-derived chemokine (MDC). However, controversy arises when the in vivo significance of this distinct expression is discussed. To address the functional role of CCR3/eotaxin and CCR4/MDC during the in vivo recruitment of Th2 cells, we have transferred effector Th cells into naive mice to induce allergic airway disease. Tracking of these cells after repeated antigen challenge has established that both CCR3/eotaxin and CCR4/MDC axes contribute to the recruitment of Th2 cells to the lung, demonstrating the in vivo relevance of the expression of these receptors on Th2 cells. We have shown that involvement of the CCR3/eotaxin pathway is confined to early stages of the response in vivo, whereas repeated antigen stimulation results in the predominant use of the CCR4/MDC pathway. We propose that effector Th2 cells respond to both CCR3/eotaxin and CCR4/MDC pathways initially, but that a progressive increase in CCR4-positive cells results in the predominance of the CCR4/MDC axis in the long-term recruitment of Th2 cells in vivo

The EMIF-AD Multimodal Biomarker Discovery study: design, methods and cohort characteristics.

There is an urgent need for novel, noninvasive biomarkers to diagnose Alzheimer's disease (AD) in the predementia stages and to predict the rate of decline. Therefore, we set up the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study. In this report we describe the design of the study, the methods used and the characteristics of the participants. Participants were selected from existing prospective multicenter and single-center European studies. Inclusion criteria were having normal cognition (NC) or a diagnosis of mild cognitive impairment (MCI) or AD-type dementia at baseline, age above 50 years, known amyloid-beta (Aβ) status, availability of cognitive test results and at least two of the following materials: plasma, DNA, magnetic resonance imaging (MRI) or cerebrospinal fluid (CSF). Targeted and untargeted metabolomic and proteomic analyses were performed in plasma, and targeted and untargeted proteomics were performed in CSF. Genome-wide SNP genotyping, next-generation sequencing and methylation profiling were conducted in DNA. Visual rating and volumetric measures were assessed on MRI. Baseline characteristics were analyzed using ANOVA or chi-square, rate of decline analyzed by linear mixed modeling. We included 1221 individuals (NC n = 492, MCI n = 527, AD-type dementia n = 202) with a mean age of 67.9 (SD 8.3) years. The percentage Aβ+ was 26% in the NC, 58% in the MCI, and 87% in the AD-type dementia groups. Plasma samples were available for 1189 (97%) subjects, DNA samples for 929 (76%) subjects, MRI scans for 862 (71%) subjects and CSF samples for 767 (63%) subjects. For 759 (62%) individuals, clinical follow-up data were available. In each diagnostic group, the APOE ε4 allele was more frequent amongst Aβ+ individuals (p < 0.001). Only in MCI was there a difference in baseline Mini Mental State Examination (MMSE) score between the A groups (p < 0.001). Aβ+ had a faster rate of decline on the MMSE during follow-up in the NC (p < 0.001) and MCI (p < 0.001) groups. The characteristics of this large cohort of elderly subjects at various cognitive stages confirm the central roles of Aβ and APOE ε4 in AD pathogenesis. The results of the multimodal analyses will provide new insights into underlying mechanisms and facilitate the discovery of new diagnostic and prognostic AD biomarkers. All researchers can apply for access to the EMIF-AD MBD data by submitting a research proposal via the EMIF-AD Catalog