711 research outputs found

    The Bobath Clinical Reasoning Framework: A systems science approach to the complexity of neurodevelopmental conditions, including cerebral palsy

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    The current recommended developmental Bobath practice within the Bobath Clinical Reasoning Framework (BCRF) can be conceptualized using the lens of systems science, thereby providing a holistic perspective on the interrelatedness and interconnectedness of the variables associated with childhood-onset disability. The BCRF is defined as an in-depth clinical reasoning framework that can be applied to help understand the relationships between the domains of the International Classification of Functioning, Disability and Health, how those domains can be influenced, and how they impact each other. The BCRF is a transdisciplinary observational system and practical reasoning approach that results in an intervention plan. This provides a holistic understanding of the complexity of situations associated with disorders such as cerebral palsy (CP) and the basis for the lifelong management and habilitation of people living with neurological disorders. The clinical reasoning used by the BCRF draws on the important contextual factors of the individual and their social environment, primarily the family unit. It is rooted in an understanding of the interrelationships between typical and atypical development, pathophysiology (sensorimotor, cognitive, behavioural), and neuroscience, and the impact of these body structure and function constructs on activity and participation. The systems science model integral to the BCRF is a useful way forward in understanding and responding to the complexity of CP, the overarching goal being to optimize the lived experience of any individual in any context

    A current perspective on cancer immune therapy: Step‑by‑step approach to constructing the magic bullet

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    Immunotherapy is the new trend in cancer treatment due to the selectivity, long lasting effects, and demonstrated improved overall survival and tolerance, when compared to patients treated with conventional chemotherapy. Despite these positive results, immunotherapy is still far from becoming the perfect magic bullet to fight cancer, largely due to the facts that immunotherapy is not effective in all patients nor in all cancer types. How and when will immunotherapy overcome these hurdles? In this review we take a step back to walk side by side with the pioneers of immunotherapy in order to understand what steps need to be taken today to make immunotherapy effective across all cancers. While early scientists, such as Coley, elicited an unselective but effective response against cancer, the search for selectivity pushed immunotherapy to the side in favor of drugs focused on targeting cancer cells. Fortunately, the modern era would revive the importance of the immune system in battling cancer by releasing the brakes or checkpoints (anti-CTLA-4 and anti-PD-1/PD-L1) that have been holding the immune system at bay. However, there are still many hurdles to overcome before immunotherapy becomes a universal cancer therapy. For example, we discuss how the redundant and complex nature of the immune system can impede tumor elimination by teeter tottering between different polarization states: one eliciting anti-cancer effects while the other promoting cancer growth and invasion. In addition, we highlight the incapacity of the immune system to choose between a fight or repair action with respect to tumor growth. Finally we combine these concepts to present a new way to think about the immune system and immune tolerance, by introducing two new metaphors, the “push the accelerator” and “repair the car” metaphors, to explain the current limitations associated with cancer immunotherapyThis work was supported by NIH R00 CA154605 and Louisiana Board of Regents LEQSF(2016-17)-RD-C-14 (H.L.M.), a Rámon y Cajal Merit Award from the Ministerio de Economía y Competitividad, Spain (B.S.Jr) and a Clinic and Laboratory Integration Program (CLIP) grant from the Cancer Research Institute, NY (B.S.Jr)

    HQET at order 1/m1/m: II. Spectroscopy in the quenched approximation

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    Using Heavy Quark Effective Theory with non-perturbatively determined parameters in a quenched lattice calculation, we evaluate the splittings between the ground state and the first two radially excited states of the BsB_s system at static order. We also determine the splitting between first excited and ground state, and between the BsB_s^* and BsB_s ground states to order 1/mb1/m_b. The Generalized Eigenvalue Problem and the use of all-to-all propagators are important ingredients of our approach.Comment: (1+18) pages, 3 figures (4 pdf files); pdflatex; v2: corrections to table 1, results unaffecte

    Elastic Properties of 4–6 nm-thick Glassy Carbon Thin Films

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    Glassy carbon is a disordered, nanoporous form of carbon with superior thermal and chemical stability in extreme environments. Freestanding glassy carbon specimens with 4–6 nm thickness and 0.5 nm average pore size were synthesized and fabricated from polyfurfuryl alcohol precursors. Elastic properties of the specimens were measured in situ inside a scanning electron microscope using a custom-built micro-electro-mechanical system. The Young’s modulus, fracture stress and strain values were measured to be about 62 GPa, 870 MPa and 1.3%, respectively; showing strong size effects compared to a modulus value of 30 GPa at the bulk scale. This size effect is explained on the basis of the increased significance of surface elastic properties at the nanometer length-scale

    Growing old, yet staying young: The role of telomeres in bats' exceptional longevity

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    Understanding aging is a grand challenge in biology. Exceptionally long-lived animals have mechanisms that underpin extreme longevity. Telomeres are protective nucleotide repeats on chromosome tips that shorten with cell division, potentially limiting life span. Bats are the longest-lived mammals for their size, but it is unknown whether their telomeres shorten. Using >60 years of cumulative mark-recapture field data, we show that telomeres shorten with age inRhinolophus ferrumequinumandMiniopterus schreibersii, but not in the bat genus with greatest longevity,Myotis. As in humans, telomerase is not expressed inMyotis myotisblood or fibroblasts. Selection tests on telomere maintenance genes show thatATMandSETX, which repair and prevent DNA damage, potentially mediate telomere dynamics inMyotisbats. Twenty-one telomere maintenance genes are differentially expressed inMyotis, of which 14 are enriched for DNA repair, and 5 for alternative telomere-lengthening mechanisms. We demonstrate how telomeres, telomerase, and DNA repair genes have contributed to the evolution of exceptional longevity inMyotisbats, advancing our understanding of healthy aging

    Risk factors of one year increment of coronary calcifications and survival in hemodialysis patients

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    <p>Abstract</p> <p>Background</p> <p>Heart and coronary calcifications in hemodialysis patients are of very common occurrence and linked to cardiovascular events and mortality. Several studies have been published with similar results. Most of them were mainly cross-sectional and some of the prospective protocols were aimed to evaluate the results of the control of altered biochemical parameters of mineral disturbances with special regard to serum calcium, phosphate and CaxP with the use of calcium containing and calcium free phosphate chelating agents. The aim of the present study was to evaluate in hemodialysis patients classic and some non classic risk factors as predictors of calcification changes after one year and to evaluate the impact of progression on survival.</p> <p>Methods</p> <p>81 patients on hemodialysis were studied, with a wide age range and HD vintage. Several classic parameters and some less classic risk factors were studied like fetuin-A, CRP, 25-OHD and leptin. Calcifications, as Agatston scores, were evaluated with Multislice CT basally and after 12-18 months.</p> <p>Results</p> <p>Coronary artery calcifications were observed in 71 of 81 patients. Non parametric correlations between Agatston scores and Age, HD Age, PTH and CRP were significant. Delta increments of Agatston scores correlated also with serum calcium, CaxP, Fetuin-A, triglycerides and serum albumin. Logistic regression analysis showed Age, PTH and serum calcium as important predictors of Delta Agatston scores. LN transformation of the not normally distributed variables restricted the significant correlations to Age, BMI and CRP. Considering the Delta Agatston scores as dependent, significant predictors were Age, PTH and HDL. A strong association was found between basal calcification scores and Delta increment at one year. By logistic analysis, the one year increments in Agatston scores were found to be predictors of mortality. Diabetic and hypertensive patients have significantly higher Delta scores.</p> <p>Conclusions</p> <p>Progression of calcification is of common occurrence, with special regard to elevated basal scores, and is predictive of survival. Higher predictive value of survival is linked to the one year increment of calcification scores. Some classic and non classic risk factors play an important role in progression. Some of them could be controlled with appropriate management with possible improvement of mortality.</p

    Medicines containing codeine: perspectives of medical professionals in the Republic of Ireland

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    Aims: The aim of the study was to examine prescribing professional's perceptions on prescribed and OTC medicines, containing codeine in the Republic of Ireland. A secondary aim was to examine perceptions on codeine dependence, screening and treatment. Methods: A cross sectional study of a nationally representative group of prescribing professionals was conducted using a questionnaire containing a number of open and closed ended items. Data were analysed using SPSS version 21 and content analysis techniques. Results: 398 medical professionals participated in the study giving a response rate of 18%. 77% of respondents agreed to routinely review patient prescribed codeine. 59% of respondents routinely asked patients about their use of OTC medicines and 50% documented use of OTC codeine in their patients' medical notes. 93% indicated concern about the potential to purchase codeine from multiple sources. 88% implied that patients did not fully understand the risks of taking OTC medicine containing codeine. Only 21% of respondents were confident in identifying codeine dependence without being informed by the patient and 11.4% agreed to having suitable screening methods in practice. 76% indicated that they would like more instruction on prescribing addictive medicines. Conclusion: Policy should examine the need for greater public health awareness on codeine use and should examine the role of OTC and internet sales in the development of dependence. Further consideration should be given to training and support for those who prescribe addictive medicines in practice

    Carotid artery calcification at the initiation of hemodialysis is a risk factor for cardiovascular events in patients with end-stage renal disease: a cohort study

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    <p>Abstract</p> <p>Background</p> <p>Vascular calcification has been recognized as a risk factor for cardiovascular (CV) events in patients with end-stage renal disease (ESRD). However, the association of carotid artery calcification (CAAC) with CV events remains unknown. The aim of this study was to elucidate whether CAAC is associated with composite CV events in ESRD patients.</p> <p>Methods</p> <p>One-hundred thirty-three patients who had been started on hemodialysis between 2004 and 2008 were included in this retrospective cohort study. These patients received multi-detector computed tomography to assess CAAC at the initiation of hemodialysis. Composite CV events, including ischemic heart disease, heart failure, cerebrovascular diseases, and CV deaths after the initiation of hemodialysis, were examined in each patient.</p> <p>Results</p> <p>CAAC was found in 94 patients (71%). At the end of follow-up, composite CV events were seen in 47 patients: ischemic heart disease in 20, heart failure in 8, cerebrovascular disease in 12, and CV deaths in 7. The incidence of CAAC was 87% in patients with CV events, which was significantly higher than the rate (62%) in those without. Kaplan-Meier analysis showed a significant increase in composite CV events in patients with CAAC compared with those without CAAC (p = 0.001, log-rank test). Univariate analysis using a Cox hazards model showed that age, smoking, common carotid artery intima-media thickness and CAAC were risk factors for composite CV events. In multivariate analysis, only CAAC was a significant risk factor for composite CV events (hazard ratio, 2.85; 95% confidence interval, 1.18-8.00; p = 0.02).</p> <p>Conclusions</p> <p>CAAC is an independent risk factor for CV events in ESRD patients. The assessment of CAAC at the initiation of hemodialysis is useful for predicting the prognosis.</p

    Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

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    Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

    Early readmission and length of hospitalization practices in the Dialysis Outcomes and Practice Patterns Study (DOPPS)

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    Background:  Rising hospital care costs have created pressure to shorten hospital stays and emphasize outpatient care. This study tests the hypothesis that shorter median length of stay (LOS) as a dialysis facility practice is associated with higher rates of early readmission. Methods:  Readmission within 30 days of each hospitalization was evaluated for participants in the Dialysis Outcomes and Practice Patterns Study, an observational study of randomly selected hemodialysis patients in the United States (142 facilities, 5095 patients with hospitalizations), five European countries (101 facilities, 2281 patients with hospitalizations), and Japan (58 facilities, 883 patients with hospitalizations). Associations between median facility LOS (estimated from all hospitalizations at the facility and interpreted as a dialysis facility practice pattern) and odds of readmission were assessed using logistic regression, adjusted for patient characteristics and the LOS of each index hospitalization. Results:  Risk of readmission was directly and significantly associated with LOS of the index hospitalization (adjusted odds ratio [AOR] 1.005 per day in median facility LOS, p = 0.007) and inversely associated with median facility LOS (AOR = 0.974 per day, p = 0.016). This latter association was strongest for US hemodialysis centers (AOR = 0.954 per day, p = 0.015). Conclusions:  Dialysis facilities with shorter median hospital LOS for their patients have higher odds of readmission, particularly in the United States, where there is greater pressure to shorten LOS. The determinants and consequences of practices related to hospital LOS for hemodialysis patients should be further studied.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73641/1/j.1492-7535.2004.01107.x.pd
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