I’ll Be Back: Post‐Purchase Activities and ROI

What kinds of services and support should be expected after the sale? Vendors are increasingly providing postsale services to their customers, typically in the form of account development. This panel discussion examined experiences that vendors, libraries, and consortia have had with one another, including which services have been beneficial, and explored future enhancements that will benefit libraries and users. The panelists provided specific examples of past collaborations, including customized trainings, usage analysis, and professional development events. Panelists discussed topics of interest to librarians and vendors with a focus on ways to get the best ROI out of library resources. Librarians and publishers on the panel highlighted the important role that each side has in improving ROI and marketing the resources to the library community

Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo

Meeting Abstracts: Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo Clearwater Beach, FL, USA. 9-11 June 201

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Functional connectivity and upper limb function in patients after pediatric arterial ischemic stroke with contralateral corticospinal tract wiring.

To develop individualized motor rehabilitation, knowledge of the relationship between neuroplastic reorganization and motor recovery after pediatric arterial ischemic stroke (AIS) is crucial. Thus, we investigated functional connectivity in patients after AIS with good motor outcome and in patients with hemiparesis compared with typically developing peers. We included 18 patients (n = 9 with hemiparesis, n = 9 with good motor outcome) with pediatric AIS in the chronic phase (≥ 2 years after diagnosis, diagnosed > 16 years) and 18 peers matched by age and gender. Participants underwent a standardized motor assessment, single-pulse transcranial magnetic stimulation to determine the type of corticospinal tract wiring, and resting-state functional magnetic resonance imaging to examine motor network connectivity. Corticospinal tract wiring was contralateral in all participants. Patients with hemiparesis had lower interhemispheric connectivity strength compared with patients with good clinical outcome and peers. Patients with good clinical outcome had higher intrahemispheric connectivity strength compared with peers. Further, higher intrahemispheric connectivity was related to better motor outcome in patients. Our findings suggest that better motor outcome after pediatric AIS is related to higher motor network connectivity strength. Thus, resting-state functional connectivity might be predictive for motor recovery after pediatric AIS

Prenatal exome sequencing and impact on perinatal outcome: cohort study

ObjectivesFirst, to determine the uptake of prenatal exome sequencing (pES) and the diagnostic yield of pathogenic (causative) variants in a UK tertiary fetal medicine unit following the introduction of the NHS England Rapid Exome Sequencing Service for fetal anomalies testing (R21 pathway). Second, to identify how the decision to proceed with pES and identification of a causative variant affect perinatal outcomes, specifically late termination of pregnancy (TOP) at or beyond 22 weeks' gestation.MethodsThis was a retrospective cohort study of anomalous fetuses referred to the Liverpool Women's Hospital Fetal Medicine Unit between 1 March 2021 and 28 February 2022. pES was performed as part of the R21 pathway. Trio exome sequencing was performed using an Illumina next-generation sequencing platform assessing coding and splice regions of a panel of 974 prenatally relevant genes and 231 expert reviewed genes. Data on demographics, phenotype, pES result and perinatal outcome were extracted and compared. Descriptive statistics and the χ-square or Fisher's exact test were performed using IBM SPSS version 28.0.1.0.ResultsIn total, 72 cases were identified and two-thirds of eligible women (n = 48) consented to trio pES. pES was not feasible in one case owing to a low DNA yield and, therefore, was performed in 47 cases. In one-third of cases (n = 24), pES was not proposed or agreed. In 58.3% (14/24) of these cases, this was because invasive testing was declined and, in 41.7% (10/24) of cases, women opted for testing and underwent chromosomal microarray analysis only. The diagnostic yield of pES was 23.4% (11/47). There was no overall difference in the proportion of women who decided to have late TOP in the group in which pES was agreed compared with the group in which pES was not proposed or agreed (25.0% (12/48) vs 25.0% (6/24); P = 1.0). However, the decision to have late TOP was significantly more frequent when a causative variant was detected compared with when pES was uninformative (63.6% (7/11) vs 13.9% (5/36); P ConclusionsThis study demonstrates the potential impact of identification of a causative variant by pES on decision to have late TOP. As the R21 pathway continues to evolve, we urge clinicians and policymakers to consider introducing earlier screening for anomalies, developing robust guidance for late TOP and ensuring optimized support for couples. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology

Neural correlates of mirror movements in children with arterial ischemic stroke

Background: Mirror movements (MM) in pediatric stroke patients are related to abnormal ipsilateral Corticospinal Tract (CST). Whilst children with contralateral CST wiring may also present with MM, the role of interhemispheric interactions remains unknown. Here, we investigated the role of interhemispheric inhibition, facilitation and functional connectivity on MM in children with contralateral CST after arterial ischemic stroke. Patients and Methods: 16 patients with pediatric stroke and contralateral CST wiring were included. Participants underwent multimodal examination including dual-pulse transcranial magnetic stimulation to measure interhemispheric inhibition (10 milliseconds interstimulus interval, measured on the flexor digitorum superficialis) and resting-state functional MRI to assess motor network functional connectivity between primary motor cortices. MM were measured with the Woods and Teuber scale in each hand (hand opening and closing, finger opposition and sequential finger movement). We conducted non-parametric correlation analysis and interpreted r-values as absent (0.75). Results: Higher MM-scores in the affected hand were related to (1) lower interhemispheric functional connectivity between the primary motor cortices (r = −0.48, p = 0.06), (2) higher inhibition from the non-lesioned to the lesioned hemisphere (r = 0.65, p = 0.01) and (3) slightly higher facilitation from the lesioned to the non-lesioned hemisphere (r = 0.36, p = 0.27). MM-scores in the non-affected hand were higher with facilitation from the lesioned to the non-lesioned hemisphere (r = 0.76, p = 0.006). Conclusion: In children with arterial ischemic stroke and contralateral CST wiring, the active motor cortex may facilitate the contralateral motor cortex and increase the occurrence of MM, highlighting the importance of interhemispheric interactions for this phenomenon

Challenging the "leaky pipeline" in faculties of medicine : action plans and strategies of four Swiss universities

In the last few decades, the percentage of women graduating in medicine has increased gradually in North America and in Europe [1, 2]. With this process of “feminisation” of medicine, various aspects such as the clustering of female and male physicians in different specialties, salary inequalities, working hours preferences and implications for the practice of medicine and for patients were observed [3–5]. However, at the same time a “leaky pipeline” was identified within the academic track of medicine: the underrepresentation of women at higher professorial levels and leadership positions in medical faculties [1, 6]. Unlike the progress observed in other disciplines, such as humanities and social sciences, with a similar feminisation trend, in medicine advances have been described as “incomplete and inadequate” [6]. In 2013 to 2014 in the US, women represented almost half of all matriculants (47%) [1]. However, at the faculty level finally only 38% were women with 21% full women professors [1]. The contrast is even more striking in Switzerland: women made up 61% of students in 2014, but represented only 17% of professors [7, 8]. Within this highly gender unequal context, measures promoting female faculty seem particularly needed in Switzerland. This article addresses efforts to combat women’s underrepresentation in leading academic medicine positions by describing and analysing the action plans implemented within the faculties of four of the largest Swiss universities: Basel, Geneva, Lausanne and Zurich. Geneva and Lausanne represent faculties of the French-speaking part of Switzerland, whereas Basel and Zurich are located in the German-speaking part. After describing the obstacles to women’s advancement in leadership positions in medicine identified in the research literature, the article presents the main theoretical approaches adopted to counter these inequalities. We then present the case studies of the four Swiss faculties of medicine where action plans were implemented within the frame of the Swiss Federal Equal Opportunity at Universities Program, which ran from 2013 to 2016. Focusing on the innovative faculty-based actions undertaken, we discuss the advantages of combining strategies that empower women with those that change institutions by modifying their structure and culture to advance gender equality

Genotype and tumor locus determine expression profile of pseudohypoxic pheochromocytomas and paragangliomas

Contains fulltext : 118484.pdf (publisher's version ) (Open Access)Pheochromocytomas (PHEOs) and paragangliomas (PGLs) related to mutations in the mitochondrial succinate dehydrogenase (SDH) subunits A, B, C, and D, SDH complex assembly factor 2, and the von Hippel-Lindau (VHL) genes share a pseudohypoxic expression profile. However, genotype-specific differences in expression have been emerging. Development of effective new therapies for distinctive manifestations, e.g., a high rate of malignancy in SDHB- or predisposition to multifocal PGLs in SDHD patients, mandates improved stratification. To identify mutation/location-related characteristics among pseudohypoxic PHEOs/PGLs, we used comprehensive microarray profiling (SDHB: n = 18, SDHD-abdominal/thoracic (AT): n = 6, SDHD-head/neck (HN): n = 8, VHL: n = 13). To avoid location-specific bias, typical adrenal medulla genes were derived from matched normal medullas and cortices (n = 8) for data normalization. Unsupervised analysis identified two dominant clusters, separating SDHB and SDHD-AT PHEOs/PGLs (cluster A) from VHL PHEOs and SDHD-HN PGLs (cluster B). Supervised analysis yielded 6937 highly predictive genes (misclassification error rate of 0.175). Enrichment analysis revealed that energy metabolism and inflammation/fibrosis-related genes were most pronouncedly changed in clusters A and B, respectively. A minimum subset of 40 classifiers was validated by quantitative real-time polymerase chain reaction (quantitative real-time polymerase chain reaction vs. microarray: r = 0.87). Expression of several individual classifiers was identified as characteristic for VHL and SDHD-HN PHEOs and PGLs. In the present study, we show for the first time that SDHD-HN PGLs share more features with VHL PHEOs than with SDHD-AT PGLs. The presented data suggest novel subclassification of pseudohypoxic PHEOs/PGLs and implies cluster-specific pathogenic mechanisms and treatment strategies