Minimal clinically-important differences for the "Liverpool Osteoarthritis in Dogs" (LOAD) and the "Canine Orthopedic Index" (COI) in dogs with osteoarthritis.

ObjectiveOsteoarthritis is the most common joint disease in companion animals. Several client-report outcome measures (CROMs) have been developed and validated to monitor patients and their response to treatment. However, estimates for minimal clinically-important differences for these CROMs in the context of osteoarthritis have not been published.Patients and methodsData from the Clínica Veterinária de Cães (Portuguese Gendarmerie Canine Clinic) clinical records were extracted. Baseline and 30-day post-treatment follow-up data from 296 dogs treated for hip osteoarthritis were categorized based on an anchor question, and estimates of minimal clinically-important differences (MCIDs) using distribution-based and anchor-based methods were performed.ResultsFor the LOAD, the anchor-based methods provided a MCID estimate range of -2.5 to -9.1 and the distribution-based methods from 1.6 to 4.2. For the COI, the anchor-based methods provided a MCID estimate range of -4.5 to -16.6 and the distribution-based methods from 2.3 to 2.4. For the dimensions of COI, values varied from -0.5 to -4.9 with the anchor-based methods and from 0.6 to 2.7 with the distribution-based methods. Receiver operator characteristic curves provided areas under the curve >0.7 for the COI, indicating an acceptable cut-off point, and >0.8 for the LOAD, indicating an excellent cut-off point.ConclusionOur estimates of MCIDs for dogs with OA were consistent with previously proposed values of -4 for the LOAD and -14 for the COI in a post-surgical intervention context. ROC curve data suggest that LOAD may more reliably differentiate between anchor groups. We also presented estimates from COI of -4 for Stiffness, Function, and Gait and -3 for quality of life. These estimates can be used for research and patient monitoring

miramap a collective awareness platform to support open policy making and the integration of the citizens perspective in urban planning and governance

The chapter intends to explore an innovative approach for a more inclusive and sustainable urban planning and governance through the use of the ICT matched with a participatory process. It describes the transition process from a pilot project (Crowdmapping Mirafiori Sud/CMMS) headed by the Politecnico di Torino in 2013 in the Mirafiori Sud district of Turin (Italy)—whose aim was to design and test an open-source crowdmapping platform to identify and categorize, aggregating large amounts of user-generated inputs, the nature, the location and the consistency of the obstacles, which prevent vulnerable categories to use the public space in their neighbourhood—to the set up of a proper governing tool (MiraMap) to enhance open policy-making and the integration of the citizens' perspective through their effective engagement. Such platform is expected to have very concrete impacts both in empowering citizens, supporting grassroots processes and practices, sharing knowledge and in allowing policy options and design to become more informed and targeted. The methodology and the technological implementation supporting the creation of the platform have been developed by a multidisciplinary research team (urban planners, architects, sociologists, engineers, computer scientists, legal experts) in consultation with—and with the support of—the local public administration and the community-based organizations

mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype

Senescent cells secrete a combination of factors collectively known as the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence and activates an immune surveillance response, but it can also show pro-tumorigenic properties and contribute to age-related pathologies. In a drug screen to find new SASP regulators, we uncovered the mTOR inhibitor rapamycin as a potent SASP suppressor. Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1. In turn, MAPKAPK2 phosphorylates the RNA-binding protein ZFP36L1 during senescence, inhibiting its ability to degrade the transcripts of numerous SASP components. Consequently, mTOR inhibition or constitutive activation of ZFP36L1 impairs the non-cell-autonomous effects of senescent cells in both tumour-suppressive and tumour-promoting contexts. Altogether, our results place regulation of the SASP as a key mechanism by which mTOR could influence cancer, age-related diseases and immune responses

Validity of the Dictionary of Occupational Titles for Assessing Upper Extremity Work Demands

Objectives: The Dictionary of Occupational Titles (DOT) is used in vocational rehabilitation to guide decisions about the ability of a person with activity limitations to perform activities at work. The DOT has categorized physical work demands in five categories. The validity of this categorization is unknown. Aim of this study was to investigate whether the DOT could be used validly to guide decisions for patients with injuries to the upper extremities. Four hypotheses were tested. Methods: A database including 701 healthy workers was used. All subjects filled out the Dutch Musculoskeletal Questionnaire, from which an Upper Extremity Work Demands score (UEWD) was derived. First, relation between the DOT-categories and UEWD-score was analysed using Spearman correlations. Second, variance of the UEWD-score in occupational groups was tested by visually inspecting boxplots and assessing kurtosis of the distribution. Third, it was investigated whether occupations classified in one DOT-category, could significantly differ on UEWD-scores. Fourth, it was investigated whether occupations in different DOT-categories could have similar UEWD-scores using Mann Whitney U-tests (MWU). Results: Relation between the DOT-categories and the UEWD-score was weak (r(sp) = 0.40; p < .01). Overlap between categories was found. Kurtosis exceeded +/- 1.0 in 3 occupational groups, indicating large variance. UEWD-scores were significantly different within one DOT-category (MWU = 1.500; p < .001). UEWD scores between DOT-categories were not significantly different (MWU = 203.000; p = .49). Conclusion: All four hypotheses could not be rejected. The DOT appears to be invalid for assessing upper extremity work demands

Wrist fracture management and the role of surgical care practitioner through the patient’s journey

The presentation of this case study involves an exploration of the patient's journey in detail after having a traumatic wrist fracture, which is recognised as one of the most common fractures encountered daily in emergency services by junior doctors and practitioners. However, this article not only analyses the medical guidance for this type of case, but also the importance of the surgical care practitioner role in trauma and orthopaedics. All practitioners attending patients in emergency services are required to develop a good knowledge of anatomy, physiology, patient’s examination technique, classifications and consequently being aware of the possible surgical options for treatment of the fracture. They will also need to fully understand the legal implications of consent to ensure safe practice

Women Born Preterm or with Inappropriate Weight for Gestational Age Are at Risk of Subsequent Gestational Diabetes and Pre-Eclampsia

Introduction: Low birthweight, which can be caused by inappropriate intrauterine growth or prematurity, is associated with development of gestational diabetes mellitus (GDM) as well as pre-eclampsia later in life, but the relative effects of prematurity and inappropriate intrauterine growth remain uncertain. Methods: Through nation-wide registries we identified all Danish mothers in the years 1989–2007. Two separate cohorts consisting mothers born 1974–1977 (n = 84219) and 1978–1981 (n = 32376) were studied, due to different methods o

Final analysis of a trial of M72/AS01E vaccine to prevent tuberculosis

Background Results of an earlier analysis of a trial of the M72/AS01E candidate vaccine against Mycobacterium tuberculosis showed that in infected adults, the vaccine provided 54.0% protection against active pulmonary tuberculosis disease, without evident safety concerns. We now report the results of the 3-year final analysis of efficacy, safety, and immunogenicity. Methods From August 2014 through November 2015, we enrolled adults 18 to 50 years of age with M. tuberculosis infection (defined by positive results on interferon-γ release assay) without evidence of active tuberculosis disease at centers in Kenya, South Africa, and Zambia. Participants were randomly assigned in a 1:1 ratio to receive two doses of either M72/AS01E or placebo, administered 1 month apart. The primary objective was to evaluate the efficacy of M72/AS01E to prevent active pulmonary tuberculosis disease according to the first case definition (bacteriologically confirmed pulmonary tuberculosis not associated with human immunodeficiency virus infection). Participants were followed for 3 years after the second dose. Participants with clinical suspicion of tuberculosis provided sputum samples for polymerase-chain-reaction assay, mycobacterial culture, or both. Humoral and cell-mediated immune responses were evaluated until month 36 in a subgroup of 300 participants. Safety was assessed in all participants who received at least one dose of M72/AS01E or placebo. Results A total of 3575 participants underwent randomization, of whom 3573 received at least one dose of M72/AS01E or placebo, and 3330 received both planned doses. Among the 3289 participants in the according-to-protocol efficacy cohort, 13 of the 1626 participants in the M72/AS01E group, as compared with 26 of the 1663 participants in the placebo group, had cases of tuberculosis that met the first case definition (incidence, 0.3 vs. 0.6 cases per 100 person-years). The vaccine efficacy at month 36 was 49.7% (90% confidence interval [CI], 12.1 to 71.2; 95% CI, 2.1 to 74.2). Among participants in the M72/AS01E group, the concentrations of M72-specific antibodies and the frequencies of M72-specific CD4+ T cells increased after the first dose and were sustained throughout the follow-up period. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups. Conclusions Among adults infected with M. tuberculosis, vaccination with M72/AS01E elicited an immune response and provided protection against progression to pulmonary tuberculosis disease for at least 3 years. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598. opens in new tab.

Neural responses in parietal and occipital areas in response to visual events are modulated by prior multisensory stimuli

The effect of multi-modal vs uni-modal prior stimuli on the subsequent processing of a simple flash stimulus was studied in the context of the audio-visual 'flash-beep' illusion, in which the number of flashes a person sees is influenced by accompanying beep stimuli. EEG recordings were made while combinations of simple visual and audio-visual stimuli were presented. The experiments found that the electric field strength related to a flash stimulus was stronger when it was preceded by a multi-modal flash/beep stimulus, compared to when it was preceded by another uni-modal flash stimulus. This difference was found to be significant in two distinct timeframes--an early timeframe, from 130-160 ms, and a late timeframe, from 300-320 ms. Source localisation analysis found that the increased activity in the early interval was localised to an area centred on the inferior and superior parietal lobes, whereas the later increase was associated with stronger activity in an area centred on primary and secondary visual cortex, in the occipital lobe. The results suggest that processing of a visual stimulus can be affected by the presence of an immediately prior multisensory event. Relatively long-lasting interactions generated by the initial auditory and visual stimuli altered the processing of a subsequent visual stimulus.status: publishe