Interprofessional education: an overview of six initiatives across the schools of health at a single university

The benefits of interprofessional education (IPE) amongst health professionals are well documented, however, the implementation of interprofessional initiatives across the USA is inconsistent. This report describes the development and content of a number of IPE initiatives that are in the early stages of development and implementation at the University of California, Davis, USA. The article describes several important factors that were found to be necessary for the initial implementation of these IPE initiatives. Evaluation data from these initiatives, which is providing a range of positive outcomes, are also presented and discussed in relation to the wider IPE literature

Functional analysis of structural variants in single cells using Strand-seq

Somatic structural variants (SVs) are widespread in cancer, but their impact on disease evolution is understudied due to a lack of methods to directly characterize their functional consequences. We present a computational method, scNOVA, which uses Strand-seq to perform haplotype-aware integration of SV discovery and molecular phenotyping in single cells by using nucleosome occupancy to infer gene expression as a readout. Application to leukemias and cell lines identifies local effects of copy-balanced rearrangements on gene deregulation, and consequences of SVs on aberrant signaling pathways in subclones. We discovered distinct SV subclones with dysregulated Wnt signaling in a chronic lymphocytic leukemia patient. We further uncovered the consequences of subclonal chromothripsis in T cell acute lymphoblastic leukemia, which revealed c-Myb activation, enrichment of a primitive cell state and informed successful targeting of the subclone in cell culture, using a Notch inhibitor. By directly linking SVs to their functional effects, scNOVA enables systematic single-cell multiomic studies of structural variation in heterogeneous cell populations

Towards an operational production of 300m resolution biophysical products in the Copernicus Global Land Service,

International audienc

Operating the Copernicus Global Land Service

International audienc

Malnutrition predicts clinical outcome in patients with neuroendocrine neoplasias

Malnutrition is a common problem in oncologic diseases influencing treatment outcomes, treatment complications, quality of life and survival. The potential role of malnutrition has not yet systematically been studied in neuroendocrine neoplasms (NEN), which due to growing prevalence and additional therapeutic options provide an increasing clinical challenge for diagnosis and management. The aim of this cross-sectional observational study, which included a long-term follow-up, was therefore to define the prevalence of malnutrition in 203 patients with NEN using various methodological approaches and to analyze the short- and long-term outcome of malnourished patients. A detailed subgroup analysis was also performed to define risk factors for poorer outcome. By applying malnutrition screening scores 21-25% of NEN-patients were at risk of or demonstrated manifest malnutrition. This was confirmed by anthropometric measurements, determination of serum surrogate parameters such as albumin and bioelectrical impedance analysis particularly phase angle α. Length of hospital stay (LoS) was significantly longer in malnourished NEN-patients while long-term overall survival was highly significantly reduced. Patients with high-grade (G3) neuroendocrine carcinomas, progressive disease and undergoing chemotherapy were at particular risk for malnutrition associated with a poorer outcome. Multivariate analysis confirmed the important and highly significant role of malnutrition as an independent prognostic factor for NEN besides proliferative capacity (G3-NEC). Malnutrition is therefore an underrecognized problem in NEN-patients, which should systematically be diagnosed by widely available standard methods such Nutritional Risk Screening (NRS) score, serum albumin levels and bioelectrical impedance analysis (BIA) and treated to improve both short- and long-term outcomes

The operational 333 m biophysical products of the Copernicus Global Land Service. In J. Sobrino

International audienc

Cell-type-specific consequences of mosaic structural variants in hematopoietic stem and progenitor cells

The functional impact and cellular context of mosaic structural variants (mSVs) in normal tissues is understudied. Utilizing Strand-seq, we sequenced 1,133 single-cell genomes from 19 human donors of increasing age, and discovered the heterogeneous mSV landscapes of hematopoietic stem and progenitor cells. While mSVs are continuously acquired throughout life, expanded subclones in our cohort are confined to individuals >60. Cells already harboring mSVs are more likely to acquire additional somatic structural variants, including megabase-scale segmental aneuploidies. Capitalizing on comprehensive single-cell micrococcal nuclease digestion with sequencing reference data, we conducted high-resolution cell-typing for eight hematopoietic stem and progenitor cells. Clonally expanded mSVs disrupt normal cellular function by dysregulating diverse cellular pathways, and enriching for myeloid progenitors. Our findings underscore the contribution of mSVs to the cellular and molecular phenotypes associated with the aging hematopoietic system, and establish a foundation for deciphering the molecular links between mSVs, aging and disease susceptibility in normal tissues

Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states

Single-cell genomics technology has transformed our understanding of complex cellular systems. However, excessive cost and a lack of strategies for the purification of newly identified cell types impede their functional characterization and large-scale profiling. Here, we have generated high-content single-cell proteo-genomic reference maps of human blood and bone marrow that quantitatively link the expression of up to 197 surface markers to cellular identities and biological processes across all main hematopoietic cell types in healthy aging and leukemia. These reference maps enable the automatic design of cost-effective high-throughput cytometry schemes that outperform state-of-the-art approaches, accurately reflect complex topologies of cellular systems and permit the purification of precisely defined cell states. The systematic integration of cytometry and proteo-genomic data enables the functional capacities of precisely mapped cell states to be measured at the single-cell level. Our study serves as an accessible resource and paves the way for a data-driven era in cytometry.This work was supported financially by the Emerson foundation grant 643577 (to L.V.), grant PID2019-108082GA-I00 from the Spanish Ministry of Science, Innovation and Universities (MCIU/AEI/FEDER, UE), the German Bundesministerium für Bildung und Forschung (BMBF) through the Juniorverbund in der Systemmedizin ‘LeukoSyStem’ (FKZ 01ZX1911D to L.V., S.H. and S.R.), SFB873, FOR2674 and FOR2033 funded by the Deutsche Forschungsgemeinschaft (DFG), the ERC Consolidator Grant METACELL (773089) (to T.A.) and the José Carreras Foundation for Leukemia Research (grant no. DCJLS 20 R/2017 to L.V., A.T. and S.H.). L.V. acknowledges the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and ‘the CERCA Programme/Generalitat de Cataluny