A prospective cohort study examining medical and social factors associated with engagement in life activities following total hip replacement

Objectives: Studies show limited improvement in the frequency of engaging in life activities after joint replacement. However, there is a paucity of research that has examined factors, including other life events, which influence engagement following total hip replacement (THR). This research sought to identify factors associated with engaging in life activities following THR. Methods: A prospective cohort study was conducted with 376 people who had a THR for osteoarthritis (OA). Data were collected pre-surgery and 1 year post-surgery. The primary outcome was change in frequency in engagement in life activities (Late Life Disability Index (LLDI): higher scores indicate higher frequency of engagement (range 0e80)). Analyses included multivariable regression. Factors considered included: positive/negative life events, a new comorbidity, another joint replacement and complications post-surgery. Results: Participants' mean age was 64 years; 46% were male. 68% of participants had at least one comorbidity pre-surgery; 36% reported at least one new comorbidity after surgery. The mean change in LLDI frequency was an increase of 6.29 (+/- 8.10). 36% reported one or more positive impact life events in the year following surgery; 63% reported one or more negative life events. The number of positive life events (beta=1.24; 95% CI: 0.49, 1.99) was significantly associated with change in LLDI frequency after adjusting for age, sex, education, body mass index (BMI), comorbidities pre-surgery, number of symptomatic joints and pre-surgery pain and function, LLDI limitations and depression. Conclusions: These findings highlight the significant influence of social factors and life circumstances on engagement in life activities following THR. (C) 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.Peer reviewe

ICOS is required for the generation of both central and effector CD4⁺ memory T-cell populations following acute bacterial infection

Interactions between ICOS and ICOS ligand (ICOSL) are essential for the development of T follicular helper (Tfh) cells and thus the formation and maintenance of GC reactions. Given the conflicting reports on the requirement of other CD4(+) T‐cell populations for ICOS signals, we have employed a range of in vivo approaches to dissect requirements for ICOS signals in mice during an endogenous CD4(+) T‐cell response and contrasted this with CD28 signals. Genetic absence of ICOSL only modestly reduced the total number of antigen‐specific CD4(+) T cells at the peak of the primary response, but resulted in a severely diminished number of both T central memory and T effector memory cells. Treatment with blocking anti‐ICOS mAb during the primary response recapitulated these effects and caused a more substantial reduction than blocking CD28 signals with CTLA4Ig. During the memory phase of the response further signals through ICOS or CD28 were not required for survival. However, upon secondary challenge only Tfh cell expansion remained heavily ICOS‐dependent, while CD28 signals were required for optimal expansion of all subsets. These data demonstrate the importance of ICOS signals specifically for memory CD4(+) T‐cell formation, while highlighting the potential of therapeutically targeting this pathway

Improved Noninterferometric Test of Collapse Models Using Ultracold Cantilevers

Spontaneous collapse models predict that a weak force noise acts on any mechanical system, as a consequence of the collapse of the wave function. Significant upper limits on the collapse rate have been recently inferred from precision mechanical experiments, such as ultracold cantilevers and the space mission LISA Pathfinder. Here, we report new results from an experiment based on a high- Q cantilever cooled to millikelvin temperatures, which is potentially able to improve the current bounds on the continuous spontaneous localization (CSL) model by 1 order of magnitude. High accuracy measurements of the cantilever thermal fluctuations reveal a nonthermal force noise of unknown origin. This excess noise is compatible with the CSL heating predicted by Adler. Several physical mechanisms able to explain the observed noise have been ruled out

S6K1 regulates hematopoietic stem cell self-renewal and leukemia maintenance.

Hyperactivation of the mTOR pathway impairs hematopoietic stem cell (HSC) functions and promotes leukemogenesis. mTORC1 and mTORC2 differentially control normal and leukemic stem cell functions. mTORC1 regulates p70 ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E–binding (eIF4E-binding) protein 1 (4E-BP1), and mTORC2 modulates AKT activation. Given the extensive crosstalk that occurs between mTORC1 and mTORC2 signaling pathways, we assessed the role of the mTORC1 substrate S6K1 in the regulation of both normal HSC functions and in leukemogenesis driven by the mixed lineage leukemia (MLL) fusion oncogene MLL-AF9. We demonstrated that S6K1 deficiency impairs self-renewal of murine HSCs by reducing p21 expression. Loss of S6K1 also improved survival in mice transplanted with MLL-AF9–positive leukemic stem cells by modulating AKT an

Seasonality of soil water exchange in the soybean growing season in southern Brazil

The processes of water transfer in the soil-plant-atmosphere system are strongly affected by soil use and management. Differences in the dynamics of soil water transfer between no-tillage (NT) and conventional tillage (CT) practices during a soybean (Glycine max) growing season in southern Brazil were assessed in this study. All the water balance components were analyzed during the soybean growing season (2009/2010). Rainfall, runoff, soil water storage and hydro-physical soil properties were analyzed under two tillage systems. The land-atmosphere water vapor exchanges, obtained from eddy covariance stations, were analyzed with regard to the soybean agroecosystem. Characterizations of soil water storage were also formulated in the 2006/2007 and 2008/2009 soybean growing seasons under the NT system. During the periods without rain, the soil water content under NT was greater than under CT. The soil superficial layer, more porous under NT, contributed to less runoff during rainy events. Moreover, under NT conditions the water supply was always high, between 0.2 - 0.5 m. The total evapotranspiration in the soybean agroecosystem growing season was 410.8 mm