Conceptual framework for an episode of rehabilitative care after hip fracture surgery

Researchers face a challenge when evaluating the effectiveness of rehabilitation after hip fracture surgery. Reported outcomes of rehabilitation will vary depending on the endpoint of the episode of care. Evaluation at an inappropriate endpoint may suggest a lack of effectiveness leading to the underuse of rehabilitation that could improve outcomes. The purpose of this paper is to describe a conceptual framework for a continuum-care-episode of rehabilitation after hip fracture surgery. We propose definitions for the index event, endpoint, and service scope of the episode. We discuss challenges in defining the episode of care, operationalizing the episode, and next steps for researchers. The episode described is intended to apply to all patients eligible for entry to rehabilitation after hip fracture and includes most functional recovery endpoints. This framework will provide a guide for rehabilitation researchers when designing and interpreting evaluations of the effectiveness of rehabilitation after hip fracture. Evaluation of all potential care episodes facilitates transparency in reporting of outcomes enabling researchers to determine the true effectiveness of rehabilitation after hip fracture surgery

Functional brain defects in a mouse model of a chromosomal t(1;11) translocation that disrupts DISC1 and confers increased risk of psychiatric illness

A balanced t(1;11) translocation that directly disrupts DISC1 is linked to schizophrenia and affective disorders. We previously showed that a mutant mouse, named Der1, recapitulates the effect of the translocation upon DISC1 expression. Here, RNAseq analysis of Der1 mouse brain tissue found enrichment for dysregulation of the same genes and molecular pathways as in neuron cultures generated previously from human t(1;11) translocation carriers via the induced pluripotent stem cell route. DISC1 disruption therefore apparently accounts for a substantial proportion of the effects of the t(1;11) translocation. RNAseq and pathway analysis of the mutant mouse predicts multiple Der1-induced alterations converging upon synapse function and plasticity. Synaptosome proteomics confirmed that the Der1 mutation impacts synapse composition, and electrophysiology found reduced AMPA:NMDA ratio in hippocampal neurons, indicating changed excitatory signalling. Moreover, hippocampal parvalbumin-positive interneuron density is increased, suggesting that the Der1 mutation affects inhibitory control of neuronal circuits. These phenotypes predict that neurotransmission is impacted at many levels by DISC1 disruption in human t(1;11) translocation carriers. Notably, genes implicated in schizophrenia, depression and bipolar disorder by large-scale genetic studies are enriched among the Der1-dysregulated genes, just as we previously observed for the t(1;11) translocation carrier-derived neurons. Furthermore, RNAseq analysis predicts that the Der1 mutation primarily targets a subset of cell types, pyramidal neurons and interneurons, previously shown to be vulnerable to the effects of common schizophrenia-associated genetic variants. In conclusion, DISC1 disruption by the t(1;11) translocation may contribute to the psychiatric disorders of translocation carriers through commonly affected pathways and processes in neurotransmission

The importance of Real-Life research in Respiratory Medicine: Manifesto of the Respiratory Effectiveness Group:Endorsed by the International Primary Care Respiratory Group and the World Allergy Organization

status: publishe

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Conceptual framework for an episode of rehabilitative care after hip fracture surgery

Researchers face a challenge when evaluating the effectiveness of rehabilitation after hip fracture surgery. Reported outcomes of rehabilitation will vary depending on the endpoint of the episode of care. Evaluation at an inappropriate endpoint may suggest a lack of effectiveness leading to the underuse of rehabilitation that could improve outcomes. The purpose of this paper is to describe a conceptual framework for a continuum-care-episode of rehabilitation after hip fracture surgery. We propose definitions for the index event, endpoint, and service scope of the episode. We discuss challenges in defining the episode of care, operationalizing the episode, and next steps for researchers. The episode described is intended to apply to all patients eligible for entry to rehabilitation after hip fracture and includes most functional recovery endpoints. This framework will provide a guide for rehabilitation researchers when designing and interpreting evaluations of the effectiveness of rehabilitation after hip fracture. Evaluation of all potential care episodes facilitates transparency in reporting of outcomes enabling researchers to determine the true effectiveness of rehabilitation after hip fracture surgery

North American Carbon Program (NACP) regional interim synthesis: Terrestrial biospheric model intercomparison

Understanding of carbon exchange between terrestrial ecosystems and the atmosphere can be improved through direct observations and experiments, as well as through modeling activities. Terrestrial biosphere models (TBMs) have become an integral tool for extrapolating local observations and understanding to much larger terrestrial regions. Although models vary in their specific goals and approaches, their central role within carbon cycle science is to provide a better understanding of the mechanisms currently controlling carbon exchange. Recently, the North American Carbon Program (NACP) organized several interim-synthesis activities to evaluate and inter-compare models and observations at local to continental scales for the years 2000–2005. Here, we compare the results from the TBMs collected as part of the regional and continental interim-synthesis (RCIS) activities. The primary objective of this work is to synthesize and compare the 19 participating TBMs to assess current understanding of the terrestrial carbon cycle in North America. Thus, the RCIS focuses on model simulations available from analyses that have been completed by ongoing NACP projects and other recently published studies. The TBM flux estimates are compared and evaluated over different spatial (1◦ × 1◦ and spatially aggregated to different regions) and temporal (monthly and annually) scales. The range in model estimates of net ecosystem productivity (NEP) for North America is much narrower than estimates of productivity or respiration, with estimates of NEP varying between −0.7 and 2.2 PgC yr−1, while gross primary productivity and heterotrophic respiration vary between 12.2 and 32.9 PgC yr−1 and 5.6 and 13.2 PgC yr−1, respectively. The range in estimates from the models appears to be driven by a combination of factors, including the representation of photosynthesis, the source and of environmental driver data and the tempora

The MOSDEF survey: The dependence of H α-to-UV SFR ratios on SFR and size at z ∼2

We perform an aperture-matched analysis of dust-corrected H α and UV star formation rates (SFRs) using 303 star-forming galaxies with spectroscopic redshifts 1.36 < zspec < 2.66 from the MOSFIRE Deep Evolution Field survey. By combining H α and H β emission line measurements with multiwaveband resolved Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey/3D-HST imaging, we directly compare dust-corrected H α and UV SFRs, inferred assuming a fixed attenuation curve shape and constant SFHs, within the spectroscopic aperture. Previous studies have found that H α and UV SFRs inferred with these assumptions generally agree for typical star-forming galaxies, but become increasingly discrepant for galaxies with higher SFRs (Z100 M⊙ yr-1), with H α-to-UV SFR ratios being larger for these galaxies. Our analysis shows that this trend persists even after carefully accounting for the apertures over which H α and UV-based SFRs (and the nebular and stellar continuum reddening) are derived. Furthermore, our results imply that H α SFRs may be higher in the centres of large galaxies (i.e. where there is coverage by the spectroscopic aperture) compared to their outskirts, which could be indicative of inside-out galaxy growth. Overall, we suggest that the persistent difference between nebular and stellar continuum reddening and high H α-to-UV SFR ratios at the centres of large galaxies may be indicative of a patchier distribution of dust in galaxies with high SFRs. © 2021 The Author(s).Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]