133 research outputs found
Prof-in-a-Box: using internet-videoconferencing to assist students in the gross anatomy laboratory
BACKGROUND: The optimal learning environment for gross anatomy is the dissection laboratory. The Prof-in-a-Box (PiB) system has been developed where an anatomist using distance-learning technologies 'helps' students in a dissection laboratory at a different site. METHODS: The PiB system consists of: (1) an anatomist in his/her office with a computer and video camera; (2) a computer and 2 video cameras in the lab; (3) iChat AV software; (4) a secure server to host the PiB-student 'consultation'. The PiB system allows the students and faculty to interact via audio and video providing an environment where questions can be asked and answered and anatomical structures can be identified 'at a distance' in real-time. The PiB system was set up at a prosected cadaver and made available for student use during 'office hours'. RESULTS: 25–30% of the students used the PiB system. Anatomical structures were identified, questions answered and demonstrations given 'at a distance' using the system. Students completed an optional questionnaire about the PiB system at the end of the semester. Results of the questionnaire indicate that the students were enthusiastic about the PiB system and wanted its use to be expanded in the future. CONCLUSION: Many of the functions of a faculty member in the gross anatomy dissection laboratory can be performed 'at a distance' using the PiB system. This suggests that a geographically dispersed faculty could assist in providing instruction in the dissection labs at multiple medical schools without needing to be physically present
Ross Gyre variability modulates oceanic heat supply toward the West Antarctic continental shelf
C.J.P., G.A.M., M.R.M., L.D.T., and S.T.G. were supported by NSF PLR-1425989 and OPP-1936222 (Southern Ocean Carbon and Climate Observations and Modeling project). C.J.P. received additional support from a NOAA Climate & Global Change Postdoctoral Fellowship. G.A.M. received additional support from UKRI Grant Ref. MR/W013835/1. G.E.M. was supported by NSF OPP-2220969. R.Q.P. was supported by the High Meadows Environmental Institute Internship Program. R.M. was supported by the General Sir John Monash Foundation. A.F.T. was supported by NSF OPP-1644172 and NASA grant 80NSSC21K0916. M.R.M. also acknowledges funding from NSF awards OCE-1924388 and OPP-2319829 and NASA awards 80NSSC22K0387 and 80NSSC20K1076.West Antarctic Ice Sheet mass loss is a major source of uncertainty in sea level projections. The primary driver of this melting is oceanic heat from Circumpolar Deep Water originating offshore in the Antarctic Circumpolar Current. Yet, in assessing melt variability, open ocean processes have received considerably less attention than those governing cross-shelf exchange. Here, we use Lagrangian particle release experiments in an ocean model to investigate the pathways by which Circumpolar Deep Water moves toward the continental shelf across the Pacific sector of the Southern Ocean. We show that Ross Gyre expansion, linked to wind and sea ice variability, increases poleward heat transport along the gyre’s eastern limb and the relative fraction of transport toward the Amundsen Sea. Ross Gyre variability, therefore, influences oceanic heat supply toward the West Antarctic continental slope. Understanding remote controls on basal melt is necessary to predict the ice sheet response to anthropogenic forcing.Publisher PDFPeer reviewe
Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukemia
Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2DBCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered.This work was supported in part by
the American Lebanese Syrian Associated Charities of St. Jude Children’s Research
Hospital; by a Stand Up to Cancer Innovative Research Grant and St. Baldrick’s
Foundation Scholar Award (to C.G.M.); by a St. Baldrick’s Consortium Award (S.P.H.),
by a Leukemia and Lymphoma Society Specialized Center of Research grant (S.P.H. and
C.G.M.), by a Lady Tata Memorial Trust Award (I.I.), by a Leukemia and Lymphoma
Society Special Fellow Award and Alex’s Lemonade Stand Foundation Young Investigator
Awards (K.R.), by an Alex’s Lemonade Stand Foundation Award (M.L.) and by
National Cancer Institute Grants CA21765 (St Jude Cancer Center Support Grant), U01
CA157937 (C.L.W. and S.P.H.), U24 CA114737 (to Dr Gastier-Foster), NCI Contract
HHSN261200800001E (to Dr Gastier-Foster), U10 CA180820 (ECOG-ACRIN
Operations) and CA180827 (E.P.); U10 CA180861 (C.D.B. and G.M.); U24 CA196171
(The Alliance NCTN Biorepository and Biospecimen Resource); CA145707 (C.L.W. and
C.G.M.); and grants to the COG: U10 CA98543 (Chair’s grant and supplement to
support the COG ALL TARGET project), U10 CA98413 (Statistical Center) and U24
CA114766 (Specimen Banking). This project has been funded in whole or in part with
Federal funds from the National Cancer Institute, National Institutes of Health, under
Contract Number HHSN261200800001E
Asthma in the elderly: what we know and what we have yet to know
In the past, asthma was considered mainly as a childhood disease. However, asthma is an important cause of morbidity and mortality in the elderly nowadays. In addition, the burden of asthma is more significant in the elderly than in their younger counterparts, particularly with regard to mortality, hospitalization, medical costs or health-related quality of life. Nevertheless, asthma in the elderly is still been underdiagnosed and undertreated. Therefore, it is an imperative task to recognize our current challenges and to set future directions. This project aims to review the current literature and identify unmet needs in the fields of research and practice for asthma in the elderly. This will enable us to find new research directions, propose new therapeutic strategies, and ultimately improve outcomes for elderly people with asthma. There are data to suggest that asthma in older adults is phenotypically different from young patients, with potential impact on the diagnosis, assessment and management in this population. The diagnosis of AIE in older populations relies on the same clinical findings and diagnostic tests used in younger populations, but the interpretation of the clinical data is more difficult. The challenge today is to encourage new research in AIE but to use the existing knowledge we have to make the diagnosis of AIE, educate the patient, develop a therapeutic approach to control the disease, and ultimately provide a better quality of life to our elderly patients
Social media marketing strategy: definition, conceptualization, taxonomy, validation, and future agenda
Although social media use is gaining increasing importance as a component of firms’ portfolio of strategies, scant research has systematically consolidated and extended knowledge on social media marketing strategies (SMMSs). To fill this research gap, we first define SMMS, using social media and marketing strategy dimensions. This is followed by a conceptualization of the developmental process of SMMSs, which comprises four major components, namely drivers, inputs, throughputs, and outputs. Next, we propose a taxonomy that classifies SMMSs into four types according to their strategic maturity level: social commerce strategy, social content strategy, social monitoring strategy, and social CRM strategy. We subsequently validate this taxonomy of SMMSs using information derived from prior empirical studies, as well with data collected from in-depth interviews and a quantitive survey among social media marketing managers. Finally, we suggest fruitful directions for future research based on input received from scholars specializing in the field
Absorbing customer knowledge: how customer involvement enables service design success
Customers are a knowledge resource outside of the firm that can be utilized for new service success by involving them in the design process. However, existing research on the impact of customer involvement (CI) is inconclusive. Knowledge about customers’ needs and on how best to serve these needs (articulated in the service concept) is best obtained from customers themselves. However, codesign runs the risk of losing control of the service concept. This research argues that of the processes of external knowledge, acquisition (via CI), customer knowledge assimilation, and concept transformation form a capability that enables the firm to exploit customer knowledge in the form of a successful new service. Data from a survey of 126 new service projects show that the impact of CI on new service success is fully mediated by customer knowledge assimilation (the deep understanding of customers’ latent needs) and concept transformation (the modification of the service concept due to customer insights). However, its impact is more nuanced. CI exhibits an “∩”-shaped relationship with transformation, indicating there is a limit to the beneficial effect of CI. Its relationship with assimilation is “U” shaped, suggesting a problem with cognitive inertia where initial learnings are ignored. Customer knowledge assimilation directly impacts success, while concept transformation only helps success in the presence of resource slack. An evolving new service design is only beneficial if the firm has the flexibility to adapt to change
Evaluation of Candidate Stromal Epithelial Cross-Talk Genes Identifies Association between Risk of Serous Ovarian Cancer and TERT, a Cancer Susceptibility “Hot-Spot”
We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs) in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC). In the discovery stage, cases with epithelial ovarian cancer (n = 675) and controls (n = 1,162) were genotyped at 1,536 SNPs using an Illumina GoldenGate assay. Based on Positive Predictive Value estimates, three SNPs—PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616—were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with Pper-allele<0.05 in the discovery stage were selected for replication in a subset of five OCAC studies (n = 1,233 serous invasive cases; n = 3,364 controls). The discovery stage associations in PODXL, ITGA6, and MMP3 were attenuated in the larger replication set (adj. Pper-allele≥0.5). However genotypes at TERT rs7726159 were associated with ovarian cancer risk in the smaller, five-study replication study (Pper-allele = 0.03). Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. ORper-allele 1.14 (1.04–1.24) p = 0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe
Molecular characterisation and clinical outcome of B-cell precursor acute lymphoblastic leukaemia with IG-MYC rearrangement
Rarely, immunophenotypically immature B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) carries an immunoglobulin-MYC rearrangement (IG-MYC-r). This can result in diagnostic confusion with Burkitt lymphoma/leukaemia and use of unproven individualised treatment schedules. Here we contrast the molecular characteristics of these conditions and investigate historic clinical outcome data. We identified 90 cases registered on a national BCP-ALL clinical trial/registry. Where present, diagnostic material underwent cytogenetic, exome, methylome and transcriptome analysis. Outcome was analysed to define 3-year event free survival (EFS) and overall survival (OS). IG-MYC-r was identified in diverse cytogenetic backgrounds, co-existing with either: established BCP-ALL specific abnormalities (high hyperdiploidy n=3, KMT2A-rearrangement n=6, iAMP21 n=1, BCR-ABL n=1); BCL2/BCL6-rearrangements (n=15); or, most commonly, as the only defining feature (n=64). Within this final group, precursor-like V(D)J breakpoints predominated (8/9) and KRAS mutations were common (5/11). DNA methylation identified a cluster of V(D)J rearranged cases, clearly distinct from Burkitt leukaemia/lymphoma. Children with IG-MYC-r within that subgroup had 3-year EFS of 47% and OS of 60%, representing a high-risk BCP-ALL. To develop effective management strategies this patient group must be allowed access to contemporary, minimal residual disease adapted, prospective clinical trial protocols
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