Use of an Innovative Interprofessional Mini-Series Movie to Train Preceptors

Objectives: To evaluate the effectiveness of the innovative “Preceptor Mini-Series: Adventures in Interprofessional Precepting” movie program in training pharmacy preceptors on interprofessional competencies and to determine pharmacy preceptors’ perceptions of the effectiveness of the Mini-Series format. Methods: Chronicled by two preceptor experts, the Mini-Series movie follows the challenges of pharmacy, nursing, and medicine students and their preceptor during six-week experiential rotations. Pharmacy preceptors were invited to events held at movie theatres or local classrooms in three different cities. Participants were asked to provide basic demographic information and answer four “pre-program” and “post-program” survey questions focused on working in an interprofessional environment on a 5 point scale, 1=strongly disagree, 5=strongly agree. The post-program survey also included six additional questions to assess participant’s attitudes toward the effectiveness of this medium. Results: Fifty-eight (58) individuals attended the movie events. The majority had more than ten years of preceptor experience (n = 21, 36.2%), were female preceptors (n = 40, 69.0%), and practiced in an interprofessional environment (n = 48, 82.8%). The participants’ scores on all four interprofessional confidence level questions were significantly increased after viewing the Mini-Series movie and the overall mean increased from 4.47 (pre-confidence level) to 4.79 (post-confidence level, p < 0.001). There were no significant differences of confidence levels based on gender, location, or number of students a preceptor took on rotation each year. However, participants with fewer years of preceptor experience (0-10 years) had a significantly higher perceived learning score than those with more preceptor experience (>10 years) (4.89 vs. 4.63, p = 0.020). The mean for satisfaction (4.9, 3 questions) was slightly higher than the means for perceived learning (4.8, 1 question), and instructional approach (4.87, 3 questions). Implications: After program completion, pharmacy preceptors indicated an increase in confidence level for precepting in an interprofessional environment. The Mini-Series movie program also yielded positive feedback on its delivery format and suggests the medium may be effective to use for similar future training initiatives. Conflict of Interest The authors report no conflicts of interest or financial incentives to disclose related to this project. Dr. Craig D. Cox conceptualized, developed, and directed the Mini-Seriesprogram described in the manuscript. All funding for and all income generated by the program studied is the property of the Texas Tech University Health Sciences Center School of Pharmacy.   Type: Original Researc

Exotic quantum holonomy induced by degeneracy hidden in complex parameter space

An adiabatic change of a bound state along a closed circuit in the parameter space can induces holonomies not only in the phase of the state, but also in the associated eigenspace and eigenvalue. The former is the well-known Berry phase while the latter, namely the exotic holonomy, is found a decade ago and its origin has not been understood yet. By extending the parameter into the complex number, the correspondence of the exotic holonomies and the degeneracy of the non-Hermitian Hamiltonian, or the exceptional points, is revealed. We show that this explains all the known non-trivial characteristics of the exotic holonomies.Comment: 4 pages, 1 figur

Investigation of gene–environment interactions in relation to tic severity

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies.This research was funded by National Institute of Mental Health (NIMH) grant R01MH092293 (to GAH and JAT) and NJCTS (New Jersey Center for Tourette Syndrome and Associated Disorders; to GAH and JAT). This work was also supported by grants from the Judah Foundation, the Tourette Association of America, National Institute of Health (NIH) Grants NS40024, NS016648, MH079489, MH073250, the American Recovery and Re-investment Act (ARRA) Grants NS040024-07S1; NS16648-29S1; NS040024-09S1; MH092289; MH092290; MH092291; MH092292; R01MH092293; MH092513; MH092516; MH092520; MH071507; MH079489; MH079487; MH079488; and MH079494. Dr. Mir has received grants from the Instituto de Salud Carlos III (PI10/01674, PI13/01461), the Consejería de Economía, Innovación, Ciencia y Empresa de la Junta de Andalucía (CVI-02526, CTS-7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0741/2010, PI-0437-2012, PI-0471-2013), the Sociedad Andaluza de Neurología, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña and the Jaques and Gloria Gossweiler Foundation. Dr. Morer has received grants from the Fundacion Alicia Koplowitz and belongs to the research group of the Comissionat per Universitats i Recerca del Departmanent d’Innovacio (DIUE) 2009SGR1119. Dr. Münchau has received grants from the Deutsche Forschungsgemeinschaft (DFG: MU 1692/3-1, MU 1692/4-1 and FOR 2698). This study was also supported by a Grant from the National Institute for Environmental Health Science (R01 ES021462)

Reproducible safety and efficacy of atezolizumab plus bevacizumab for HCC in clinical practice: Results of the AB-real study

IMbrave150 has established the superiority of atezolizumab plus bevacizumab over sorafenib in patients with unresectable hepatocellular carcinoma (HCC)

Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent–child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case–control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive–compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes

Timing of host feeding drives rhythms in parasite replication

Circadian rhythms enable organisms to synchronise the processes underpinning survival and reproduction to anticipate daily changes in the external environment. Recent work shows that daily (circadian) rhythms also enable parasites to maximise fitness in the context of ecological interactions with their hosts. Because parasite rhythms matter for their fitness, understanding how they are regulated could lead to innovative ways to reduce the severity and spread of diseases. Here, we examine how host circadian rhythms influence rhythms in the asexual replication of malaria parasites. Asexual replication is responsible for the severity of malaria and fuels transmission of the disease, yet, how parasite rhythms are driven remains a mystery. We perturbed feeding rhythms of hosts by 12 hours (i.e. diurnal feeding in nocturnal mice) to desynchronise the hosts' peripheral oscillators from the central, light-entrained oscillator in the brain and their rhythmic outputs. We demonstrate that the rhythms of rodent malaria parasites in day-fed hosts become inverted relative to the rhythms of parasites in night-fed hosts. Our results reveal that the hosts' peripheral rhythms (associated with the timing of feeding and metabolism), but not rhythms driven by the central, light-entrained circadian oscillator in the brain, determine the timing (phase) of parasite rhythms. Further investigation reveals that parasite rhythms correlate closely with blood glucose rhythms. In addition, we show that parasite rhythms resynchronise to the altered host feeding rhythms when food availability is shifted, which is not mediated through rhythms in the host immune system. Our observations suggest that parasites actively control their developmental rhythms. Finally, counter to expectation, the severity of disease symptoms expressed by hosts was not affected by desynchronisation of their central and peripheral rhythms. Our study at the intersection of disease ecology and chronobiology opens up a new arena for studying host-parasite-vector coevolution and has broad implications for applied bioscience

Synaptic processes and immune-related pathways implicated in Tourette syndrome

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS

Study of \Omega_c^0 and \Omega_c^{*0} Baryons at Belle

We report results from a study of the charmed double strange baryons \Omega_c^0 and \Omega_c^{*0} at Belle. The \Omega_c^0 is reconstructed using the \Omega_c^0 --> \Omega^- \pi^+ decay mode, and its mass is measured to be (2693.6 \pm 0.3 {+1.8 \atop -1.5}) MeV/c^2. The \Omega_c^{*0} baryon is reconstructed in the \Omega_c^0 \gamma mode. The mass difference M_{\Omega_c^{*0}} - M_{\Omega_c^0} is measured to be (70.7 \pm 0.9 {+0.1 \atop -0.9}) MeV/c^2. The analysis is performed using 673 fb^{-1} of data on and near the \Upsilon(4S) collected with the Belle detector at the KEKB asymmetric-energy e^+e^- collider.Comment: 11 pages, 5 figures, prepared for 34th International Conference on High Energy Physics (ICHEP 08), Philadelphia, PA, 29 Jul - 5 Aug 200

Identification of a transitional fibroblast functional phenotype in very early rheumatoid arthritis

Objectivesandnbsp;Synovial fibroblasts actively regulate the inflammatory infiltrate by communicating with neighbouring endothelial cells (EC). Surprisingly, little is known about how the development of rheumatoid arthritis (RA) alters these immunomodulatory properties. We examined the effects of phase of RA and disease outcome (resolving vs persistence) on fibroblast crosstalk with EC and regulation of lymphocyte recruitment. Methodsandnbsp;Fibroblasts were isolated from patients without synovitis, with resolving arthritis, very early RA (VeRA; symptom andle;12andthinsp;weeks) and established RA undergoing joint replacement (JRep) surgery. Endothelial-fibroblast cocultures were formed on opposite sides of porous filters. Lymphocyte adhesion from flow, secretion of soluble mediators and interleukin 6 (IL-6) signalling were assessed. Resultsandnbsp;Fibroblasts from non-inflamed and resolving arthritis were immunosuppressive, inhibiting lymphocyte recruitment to cytokine-treated endothelium. This effect was lost very early in the development of RA, such that fibroblasts no longer suppressed recruitment. Changes in IL-6 and transforming growth factor beta 1 (TGF-andbeta;1) signalling appeared critical for the loss of the immunosuppressive phenotype. In the absence of exogenous cytokines, JRep, but not VeRA, fibroblasts activated endothelium to support lymphocyte. Conclusionsandnbsp;In RA, fibroblasts undergo two distinct changes in function: first a loss of immunosuppressive responses early in disease development, followed by the later acquisition of a stimulatory phenotype. Fibroblasts exhibit a transitional functional phenotype during the first 3 months of symptoms that contributes to the accumulation of persistent infiltrates. Finally, the role of IL-6 and TGF-andbeta;1andnbsp;changes from immunosuppressive in resolving arthritis to stimulatory very early in the development of RA. Early interventions targeting andlsquo;pathogenicandrsquo; fibroblasts may be required in order to restore protective regulatory processes.</p