Physical fitness interventions for nonambulatory stroke survivors: A mixed-methods systematic review and meta-analysis

IntroductionPhysical fitness training after stroke is recommended in guidelines across the world, but evidence pertains mainly to ambulatory strokesurvivors. Non-ambulatory stroke survivors (FAC score ≤2) are atincreased risk of recurrent stroke due to limited physical activity. This systematic review aimed to synthesise evidence regarding case fatality, effects, experiences and feasibility of fitness training for non-ambulatory stroke survivors.MethodsEight major databases were searched for any type of study design. Two independent reviewers selected studies, extracted data and assessed study quality, using published tools. Random-effects meta-analysis was used. Following their separate analysis, qualitative and quantitative data were synthesised using a published framework.ResultsOf 13,614 records, 33 studies involving 910 non-ambulatory participants met inclusion criteria. Most studies were of moderatequality. Interventions comprised assisted walking (25 studies), cycleergometer training (5 studies) and other training (3 studies), mainly in acute settings. Case fatality did not differ between intervention (1.75%) and control (0.88%) groups (95% CI 0.13-3.78, P=0.67). Compared with control interventions, assisted walking significantly improved: fat mass, peak heart rate, peak oxygen uptake and walking endurance, maximum walking speed and mobility at intervention end, and walking endurance, balance, mobility and independent walking at follow-up. Cycle ergometry significantly improved peak heart rate, work load, peak ventilation, peakcarbon dioxide production, HDL cholesterol, fasting insulin and fasting glucose and independence at intervention end. Effectiveness of other training could not be established. There were insufficient qualitative data to draw conclusions about participants’ experiences, but those reported were positive. There were few intervention-related adverse events and drop-out rate ranged from 12-20%.ConclusionsFindings suggest safety, effectiveness and feasibility of adapted fitness training for screened non-ambulatory stroke survivors. Further research needs to investigate the clinical and cost-effectiveness as well as experiences of fitness training - especially for chronic stroke survivors in community settings

Monitoring the Future Panel Study annual report: National data on substance use among adults ages 19 to 60, 1976-2021.

http://deepblue.lib.umich.edu/bitstream/2027.42/175555/1/mtfpanelreport2022.pdfSEL

The Impact of Realistic Age Structure in Simple Models of Tuberculosis Transmission

Background : Mathematical models of tuberculosis (TB) transmission have been used to characterize disease dynamics, investigate the potential effects of public health interventions, and prioritize control measures. While previous work has addressed the mathematical description of TB natural history, the impact of demography on the behaviour of TB models has not been assessed. Methods : A simple model of TB transmission, with alternative assumptions about survivorship, is used to explore the effect of age structure on the prevalence of infection, disease, basic reproductive ratio and the projected impact of control interventions. We focus our analytic arguments on the differences between constant and exponentially distributed lifespans and use an individual-based model to investigate the range of behaviour arising from realistic distributions of survivorship. Results : The choice of age structure and natural (non-disease related) mortality strongly affects steady-state dynamics, parameter estimation and predictions about the effectiveness of control interventions. Since most individuals infected with TB develop an asymptomatic latent infection and never progress to active disease, we find that assuming a constant mortality rate results in a larger reproductive ratio and an overestimation of the effort required for disease control in comparison to using more realistic age-specific mortality rates. Conclusions : Demographic modelling assumptions should be considered in the interpretation of models of chronic infectious diseases such as TB. For simple models, we find that assuming constant lifetimes, rather than exponential lifetimes, produces dynamics more representative of models with realistic age structure

Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples

Background: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. Methodology: We developed and implemented an optimized mutation profiling platform (“OncoMap”) to interrogate ∼400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. Conclusions: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of “actionable” cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Genomic Analysis of Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma.

Neoadjuvant therapy followed by surgery is the standard of care for locally advanced esophageal adenocarcinoma (EAC). Unfortunately, response to neoadjuvant chemotherapy (NAC) is poor (20-37%), as is the overall survival benefit at five years (9%). The EAC genome is complex and heterogeneous between patients, and it is not yet understood whether specific mutational patterns may result in chemotherapy sensitivity or resistance. To identify associations between genomic events and response to NAC in EAC, a comparative genomic analysis was performed in 65 patients with extensive clinical and pathological annotation using whole-genome sequencing (WGS). We defined response using Mandard Tumor Regression Grade (TRG), with responders classified as TRG1-2 (n = 27) and non-responders classified as TRG4-5 (n =38). We report a higher non-synonymous mutation burden in responders (median 2.08/Mb vs. 1.70/Mb, p = 0.036) and elevated copy number variation in non-responders (282 vs. 136/patient, p < 0.001). We identified copy number variants unique to each group in our cohort, with cell cycle (CDKN2A, CCND1), c-Myc (MYC), RTK/PIK3 (KRAS, EGFR) and gastrointestinal differentiation (GATA6) pathway genes being specifically altered in non-responders. Of note, NAV3 mutations were exclusively present in the non-responder group with a frequency of 22%. Thus, lower mutation burden, higher chromosomal instability and specific copy number alterations are associated with resistance to NAC

Mutant Versions of the S. cerevisiae Transcription Elongation Factor Spt16 Define Regions of Spt16 That Functionally Interact with Histone H3

In eukaryotic cells, the highly conserved FACT (FAcilitates Chromatin Transcription) complex plays important roles in several chromatin-based processes including transcription initiation and elongation. During transcription elongation, the FACT complex interacts directly with nucleosomes to facilitate histone removal upon RNA polymerase II (Pol II) passage and assists in the reconstitution of nucleosomes following Pol II passage. Although the contribution of the FACT complex to the process of transcription elongation has been well established, the mechanisms that govern interactions between FACT and chromatin still remain to be fully elucidated. Using the budding yeast Saccharomyces cerevisiae as a model system, we provide evidence that the middle domain of the FACT subunit Spt16 – the Spt16-M domain – is involved in functional interactions with histone H3. Our results show that the Spt16-M domain plays a role in the prevention of cryptic intragenic transcription during transcription elongation and also suggest that the Spt16-M domain has a function in regulating dissociation of Spt16 from chromatin at the end of the transcription process. We also provide evidence for a role for the extreme carboxy terminus of Spt16 in functional interactions with histone H3. Taken together, our studies point to previously undescribed roles for the Spt16 M-domain and extreme carboxy terminus in regulating interactions between Spt16 and chromatin during the process of transcription elongation

Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years

To compare the prevalence of cognitive, neurological, and behavioral outcomes at 10 years of age in 428 girls and 446 boys who were born extremely preterm (EP)

The Faraday Effect Tracker of Coronal and Heliospheric Structures (FETCH) instrument

There continue to be open questions regarding the solar wind and coronal mass ejections (CMEs). For example: how do magnetic fields within CMEs and corotating/stream interaction regions (CIRs/SIRs) evolve in the inner heliosphere? What is the radially distributed magnetic profile of shock-driving CMEs? What is the internal magnetic structure of CMEs that cause magnetic storms? It is clear that these questions involve the magnetic configurations of solar wind and transient interplanetary plasma structures, for which we have limited knowledge. In order to better understand the origin of the magnetic field variability in steady-state structures and transient events, it is necessary to probe the magnetic field in Earth-directed structures/disturbances. This is the goal of the Multiview Observatory for Solar Terrestrial Science (MOST) mission (Gopalswamy et al., 2022). For MOST to answer the aforementioned questions, we propose the instrument concept of the Faraday Effect Tracker of Coronal and Heliospheric structures (FETCH), a simultaneous quad-line-of-sight polarization radio remote-sensing instrument. With FETCH, spacecraft radio beams passing through the Sun–Earth line offer the possibility of obtaining information of plasma conditions via analysis of radio propagation effects such as Faraday rotation and wave dispersion, which provide information of the magnetic field and total electron content (TEC). This is the goal of the FETCH instrument, one of ten instruments proposed to be hosted on the MOST mission. The MOST mission will provide an unprecedented opportunity to achieve NASA’s heliophysics science goal to “explore and characterize the physical processes in the space environment from the Sun” (Gopalswamy et al., 2022)