Rehabilitation definition for research purposes. A global stakeholders’ initiative by Cochrane Rehabilitation

Negrini S, Selb M, Kiekens C, et al. Rehabilitation definition for research purposes. A global stakeholders initiative by Cochrane Rehabilitation. European Journal of Physical and Rehabilitation Medicine . 2022.Since its foundation, Cochrane Rehabilitation has faced challenges with rehabilitation definitions because existing definitions did not indicate what rehabilitation includes and what it excludes. We aimed to develop a comprehensive and shared rehabilitation definition for research purposes to: 1) support the conduct of primary studies and systematic reviews, and 2) identify relevant systematic reviews for knowledge translation purposes. We performed a multimodal study including seven preliminary research and discussion papers, four Consensus Meetings and three Delphi rounds with 80 rehabilitation stakeholders. The Delphi Study aimed to obtain agreement, refine and complete the items composing the definition and meanings of rehabilitation. These stakeholders covered 5 continents, representing 11 global and continental rehabilitation organizations, 11 scientific journals, 4 Cochrane Networks and 3 Cochrane Groups, and included invited experts, and representatives of low middle-income countries (LMICs) and consumers. We had a 70% to 82.5% response rate to the three Delphi rounds, during which participants responded to all items (100%) and provided relevant comments (range 5.5-50% per item). This participation led to several refinements to the rehabilitation definition through three preliminary versions, and the final items reached an agreement between 88.9% and 100%. We structured the definition using the PICO (Population, Intervention, Comparison, Outcome) framework. We concluded that "In a health care context," rehabilitation is defined as a "multimodal, person-centered, collaborative process" (Intervention-general), including interventions targeting a person's "capacity (by addressing body structures, functions, and activities/participation) and/or contextual factors related to performance" (Intervention-specific) with the goal of "optimizing" the "functioning" (Outcome) of "persons with health conditions currently experiencing disability or likely to experience disability, or persons with disability" (Population). Rehabilitation requires that all the items of the definition are satisfied. We defined a "rehabilitation intervention" as "any intervention provided within the rehabilitation process." We developed a rehabilitation definition for research purposes achieving a broad agreement with global stakeholders. This definition provides explicit criteria to define rehabilitation. Using the proposed definition will improve rehabilitation research by standardizing the description of interventions. Our definition may require revision in the future, as further research enhances understanding and communication of the essence and complexity of rehabilitation

Optimality of mutation and selection in germinal centers

The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. To resolve these conflicts, we present a coarse-grained model to calculate the B cell population development in affinity maturation, which allows a comprehensive analysis of its parameter space to look for optimal values of mutation rate, selection strength, and initial antibody-antigen binding level that maximize the affinity improvement. With these optimized parameters, the model is compatible with the experimental observations such as the ~100-fold affinity improvements, the number of mutations, the hypermutation rate, and the "all or none" phenomenon. Moreover, we study the reasons behind the optimal parameters. The optimal mutation rate, in agreement with the hypermutation rate in vivo, results from a tradeoff between accumulating enough beneficial mutations and avoiding too many deleterious or lethal mutations. The optimal selection strength evolves as a balance between the need for affinity improvement and the requirement to pass the population bottleneck. These findings point to the conclusion that germinal centers have been optimized by evolution to generate strong affinity antibodies effectively and rapidly. In addition, we study the enhancement of affinity improvement due to B cell migration between germinal centers. These results could enhance our understandings to the functions of germinal centers.Comment: 5 figures in main text, and 4 figures in Supplementary Informatio

Towards the glueball spectrum from unquenched lattice QCD

We use a variational technique to study heavy glueballs on gauge configurations generated with 2+1 flavours of ASQTAD improved staggered fermions. The variational technique includes glueball scattering states. The measurements were made using 2150 configurations at 0.092 fm with a pion mass of 360 MeV. We report masses for 10 glueball states. We discuss the prospects for unquenched lattice QCD calculations of the oddballs.Comment: 19 pages, 4 tables and 8 figures. One figure added. Now matches the published versio

High sero-prevalence of caseous lymphadenitis identified in slaughterhouse samples as a consequence of deficiencies in sheep farm management in the state of Minas Gerais, Brazil

<p>Abstract</p> <p>Background</p> <p>Caseous lymphadenitis (CLA), caused by <it>Corynebacterium pseudotuberculosis</it>, is one of the most important diseases of sheep and goats, causing considerable economic losses for herd owners.</p> <p>Results</p> <p>We assessed the seroprevalence of infection with <it>C. pseudotuberculosis </it>in 805 sheep from 23 sheep farms that supply slaughterhouses in the state of Minas Gerais; we also analyzed management practices that could be associated with CLA occurrence, used on these and nearby farms that also supplied animals to the slaughterhouse (n = 60). The serum samples for assaying CLA infection were taken at the slaughterhouse. Frequency of infection with <it>C. pseudotuberculosis </it>was estimated at 43.7%, and farm frequency was estimated at 100%. Management practices were analyzed through a questionnaire. All farmers (60/60) had extensive/semi-extensive rearing system; 70.0% (42/60) identified sheep individually; 11.7% (7/60) had periodical technical assistance; 41.7% (25/60) disinfected the facilities; 86.7% (52/60) used barbed wire fences and did not implement adequate CLA control measures; only 11.7% (7/60) of breeders reported vaccination against <it>C. pseudotuberculosis</it>; 13.3% (8/60) took note of animals with clinical signs of CLA; 1.7% (1/60) opened and sanitized abscesses, and isolated the infected animals; 10.0% (6/60) knew the zoonotic potential of this disease and 1.7% (1/60) of the farmers culled animals in case of recurrence of abscesses.</p> <p>Conclusions</p> <p>It can be concluded that <it>C. pseudotuberculosis </it>infection is widely spread in sheep flocks in Minas Gerais state in Brazil and that there is a lack of good management measures and vaccination, allowing transmission of this infectious agent throughout the production network.</p

Participation and satisfaction after spinal cord injury: results of a vocational and leisure outcome study

Study design: Survey. Objectives: Insight in (1) the changes in participation in vocational and leisure activities and (2) satisfaction with the current participation level of people with spinal cord injuries (SCIs) after reintegration in society. Design: Descriptive analysis of data from a questionnaire. Setting: Rehabilitation centre with special department for patients with SCIs, Groningen, The Netherlands. Subjects: A total of 57 patients with traumatic SCI living in the community, who were admitted to the rehabilitation centre two to 12 years before the current assessment. Main outcome measures: Changes in participation in activities; current life satisfaction; support and unmet needs. Results: Participation expressed in terms of hours spent on vocational and leisure activities changed to a great extent after the SCI. This was mainly determined by a large reduction of hours spent on paid work. While 60% of the respondents successfully reintegrated in work, many changes took place in the type and extent of the job. Loss of work was partially compensated with domestic and leisure activities. Sports activities were reduced substantially. The change in participation level and compensation for the lost working hours was not significantly associated with the level of SCI-specific health problems and disabilities. As was found in other studies, most respondents were satisfied with their lives. Determinants of a negative life satisfaction several years following SCI were not easily indicated. Reduced quality of life was particularly related to an unsatisfactory work and leisure situation. Conclusions: Most people with SCI in this study group were able to resume work and were satisfied with their work and leisure situation

Sensory Electrical Stimulation Improves Foot Placement during Targeted Stepping Post-Stroke

Proper foot placement is vital for maintaining balance during walking, requiring the integration of multiple sensory signals with motor commands. Disruption of brain structures post-stroke likely alters the processing of sensory information by motor centers, interfering with precision control of foot placement and walking function for stroke survivors. In this study, we examined whether somatosensory stimulation, which improves functional movements of the paretic hand, could be used to improve foot placement of the paretic limb. Foot placement was evaluated before, during, and after application of somatosensory electrical stimulation to the paretic foot during a targeted stepping task. Starting from standing, twelve chronic stroke participants initiated movement with the non-paretic limb and stepped to one of five target locations projected onto the floor with distances normalized to the paretic stride length. Targeting error and lower extremity kinematics were used to assess changes in foot placement and limb control due to somatosensory stimulation. Significant reductions in placement error in the medial–lateral direction (p = 0.008) were observed during the stimulation and post-stimulation blocks. Seven participants, presenting with a hip circumduction walking pattern, had reductions (p = 0.008) in the magnitude and duration of hip abduction during swing with somatosensory stimulation. Reductions in circumduction correlated with both functional and clinical measures, with larger improvements observed in participants with greater impairment. The results of this study suggest that somatosensory stimulation of the paretic foot applied during movement can improve the precision control of foot placement

Iron Age and Anglo-Saxon genomes from East England reveal British migration history

British population history has been shaped by a series of immigrations, including the early Anglo-Saxon migrations after 400 CE. It remains an open question how these events affected the genetic composition of the current British population. Here, we present whole-genome sequences from 10 individuals excavated close to Cambridge in the East of England, ranging from the late Iron Age to the middle Anglo-Saxon period. By analysing shared rare variants with hundreds of modern samples from Britain and Europe, we estimate that on average the contemporary East English population derives 38% of its ancestry from Anglo-Saxon migrations. We gain further insight with a new method, rarecoal, which infers population history and identifies fine-scale genetic ancestry from rare variants. Using rarecoal we find that the Anglo-Saxon samples are closely related to modern Dutch and Danish populations, while the Iron Age samples share ancestors with multiple Northern European populations including Britain

Non-classical ProIL-1beta activation during mammary gland infection is pathogen-dependent but caspase-1 independent

Infection of the mammary gland with live bacteria elicits a pathogen-specific host inflammatory response. To study these host-pathogen interactions wild type mice, NF-kappaB reporter mice as well as caspase-1 and IL-1beta knockout mice were intramammarily challenged with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The murine mastitis model allowed to compare the kinetics of the induced cytokine protein profiles and their underlying pathways. In vivo and ex vivo imaging showed that E. coli rapidly induced NF-kappaB inflammatory signaling concomitant with high mammary levels of TNF-alpha, IL-1 alpha and MCP-1 as determined by multiplex analysis. In contrast, an equal number of S. aureus bacteria induced a low NF-kappaB activity concomitant with high mammary levels of the classical IL-1beta fragment. These quantitative and qualitative differences in local inflammatory mediators resulted in an earlier neutrophil influx and in a more extensive alveolar damage post-infection with E. coli compared to S. aureus. Western blot analysis revealed that the inactive proIL-1beta precursor was processed into pathogen-specific IL-1beta fragmentation patterns as confirmed with IL-1beta knockout animals. Additionally, caspase-1 knockout animals allowed to investigate whether IL-1beta maturation depended on the conventional inflammasome pathway. The lack of caspase-1 did not prevent extensive proIL-1beta fragmentation by either of S. aureus or E. coli. These non-classical IL-1beta patterns were likely caused by different proteases and suggest a sentinel function of IL-1beta during mammary gland infection. Thus, a key signaling nodule can be defined in the differential host innate immune defense upon E. coli versus S. aureus mammary gland infection, which is independent of caspase-1

Examining the Decline in the C~IV Content of the Universe over 4.3 ≲ z ≲ 6.3 using the E-XQR-30 Sample

Intervening C iv absorbers are key tracers of metal-enriched gas in galaxy haloes over cosmic time. Previous studies suggest that the C iv cosmic mass density (⁠[Math Processing Error]⁠) decreases slowly over 1.5 [Math Processing Error] 5 before declining rapidly at z ≳ 5, but the cause of this downturn is poorly understood. We characterize the [Math Processing Error] evolution over 4.3 ≲ z ≲ 6.3 using 260 absorbers found in 42 XSHOOTER spectra of z ∼ 6 quasars, of which 30 come from the ESO Large Program XQR-30. The large sample enables us to robustly constrain the rate and timing of the downturn. We find that [Math Processing Error] decreases by a factor of 4.8 ± 2.0 over the ∼300 Myr interval between z ∼ 4.7 and ∼5.8. The slope of the column density (log N) distribution function does not change, suggesting that C iv absorption is suppressed approximately uniformly across 13.2 ≤ log N/cm−2 &lt; 15.0. Assuming that the carbon content of galaxy haloes evolves as the integral of the cosmic star formation rate density (with some delay due to stellar lifetimes and outflow travel times), we show that chemical evolution alone could plausibly explain the fast decline in [Math Processing Error] over 4.3 ≲ z ≲ 6.3. However, the C iv/C ii ratio decreases at the highest redshifts, so the accelerated decline in [Math Processing Error] at z ≳ 5 may be more naturally explained by rapid changes in the gas ionization state driven by evolution of the UV background towards the end of hydrogen reionization

Workshop to identify critical windows of exposure for children's health: neurobehavioral work group summary.

This paper summarizes the deliberations of a work group charged with addressing specific questions relevant to risk estimation in developmental neurotoxicology. We focused on eight questions. a) Does it make sense to think about discrete windows of vulnerability in the development of the nervous system? If it does, which time periods are of greatest importance? b) Are there cascades of developmental disorders in the nervous system? For example, are there critical points that determine the course of development that can lead to differences in vulnerabilities at later times? c) Can information on critical windows suggest the most susceptible subgroups of children (i.e., age groups, socioeconomic status, geographic areas, race, etc.)? d) What are the gaps in existing data for the nervous system or end points of exposure to it? e) What are the best ways to examine exposure-response relationships and estimate exposures in vulnerable life stages? f) What other exposures that affect development at certain ages may interact with exposures of concern? g) How well do laboratory animal data predict human response? h) How can all of this information be used to improve risk assessment and public health (risk management)? In addressing these questions, we provide a brief overview of brain development from conception through adolescence and emphasize vulnerability to toxic insult throughout this period. Methodological issues focus on major variables that influence exposure or its detection through disruptions of behavior, neuroanatomy, or neurochemical end points. Supportive evidence from studies of major neurotoxicants is provided