258 research outputs found

    Decontextualizing contextual inversion

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    Contextual inversion, introduced as an analytical tool by David Lewin, is a concept of wide reach and value in music theory and analysis, at the root of neo-Riemannian theory as well as serial theory, and useful for a range of analytical applications. A shortcoming of contextual inversion as it is currently understood, however, is, as implied by the name, that the transformation has to be defined anew for each application. This is potentially a virtue, requiring the analyst to invest the transformational system with meaning in order to construct it in the first place. However, there are certainly instances where new transformational systems are continually redefined for essentially the same purposes. This paper explores some of the most common theoretical bases for contextual inversion groups and considers possible definitions of inversion operators that can apply across set class types, effectively decontextualizing contextual inversions.Accepted manuscrip

    Generation of tumour-specific cytotoxic T-cell clones from histocompatibility leucocyte antigen-identical siblings of patients with melanoma

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    Lymphodepletion and infusion of autologous expanded tumour-infiltrating lymphocytes is effective therapy for patients with malignant melanoma. Antitumour responses are likely to be mediated by HLA class I- and II-restricted immune responses directed at tumour antigens. We assessed whether the peripheral blood of normal HLA-matched siblings of patients with melanoma could be used to generate lymphocytes with antimelanoma activity for adoptive immunotherapy after allogeneic blood or marrow transplantation. Melanoma cell lines were derived from two donors and were used to stimulate the mononuclear cells of three HLA-identical siblings. CD4+ clones dominated cultures. Of these, approximately half were directly cytotoxic towards recipient melanoma cells and secreted interferon-Îł in response to tumour stimulation. More than half of the noncytotoxic clones also secreted interferon-Îł after melanoma stimulation. No CD4+ clones responded to stimulation with recipient haemopoietic cells. The majority of CD8+ clones directly lysed recipient melanoma, but did not persist in long-term culture in vitro. No crossreactivity with recipient haemopoietic cells was observed. The antigenic target of one CD4+ clone was determined to be an HLA-DR11-restricted MAGE-3 epitope. Antigenic targets of the remaining clones were not elucidated, but appeared to be restricted through a non-HLA-DR class II molecule. We conclude that the blood of allogeneic HLA-matched sibling donors contains melanoma-reactive lymphocyte precursors directed at tumour-associated antigens. Adoptive immunotherapy with unselected or ex vivo-stimulated donor lymphocytes after allogeneic stem cell transplantation has a rational basis for the treatment of malignant melanoma

    Chronic non-specific low back pain - sub-groups or a single mechanism?

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    Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

    Mechanosensitivity during lower extremity neurodynamic testing is diminished in individuals with Type 2 Diabetes Mellitus and peripheral neuropathy: a cross sectional study

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    <p>Abstract</p> <p>Background</p> <p>Type 2 Diabetes Mellitus (T2DM) and diabetic symmetrical polyneuropathy (DSP) impact multiple modalities of sensation including light touch, temperature, position sense and vibration perception. No study to date has examined the mechanosensitivity of peripheral nerves during limb movement in this population. The objective was to determine the unique effects T2DM and DSP have on nerve mechanosensitivity in the lower extremity.</p> <p>Methods</p> <p>This cross-sectional study included 43 people with T2DM. Straight leg raise neurodynamic tests were performed with ankle plantar flexion (PF/SLR) and dorsiflexion (DF/SLR). Hip flexion range of motion (ROM), lower extremity muscle activity and symptom profile, intensity and location were measured at rest, first onset of symptoms (P1) and maximally tolerated symptoms (P2).</p> <p>Results</p> <p>The addition of ankle dorsiflexion during SLR testing reduced the hip flexion ROM by 4.3° ± 6.5° at P1 and by 5.4° ± 4.9° at P2. Individuals in the T2DM group with signs of severe DSP (n = 9) had no difference in hip flexion ROM between PF/SLR and DF/SLR at P1 (1.4° ± 4.2°; paired t-test p = 0.34) or P2 (0.9° ± 2.5°; paired t-test p = 0.31). Movement induced muscle activity was absent during SLR with the exception of the tibialis anterior during DF/SLR testing. Increases in symptom intensity during SLR testing were similar for both PF/SLR and DF/SLR. The addition of ankle dorsiflexion induced more frequent posterior leg symptoms when taken to P2.</p> <p>Conclusions</p> <p>Consistent with previous recommendations in the literature, P1 is an appropriate test end point for SLR neurodynamic testing in people with T2DM. However, our findings suggest that people with T2DM and severe DSP have limited responses to SLR neurodynamic testing, and thus may be at risk for harm from nerve overstretch and the information gathered will be of limited clinical value.</p

    Does targeting manual therapy and/or exercise improve patient outcomes in nonspecific low back pain? A systematic review

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    <p>Abstract</p> <p>Background</p> <p>A central element in the current debate about best practice management of non-specific low back pain (NSLBP) is the efficacy of targeted versus generic (non-targeted) treatment. Many clinicians and researchers believe that tailoring treatment to NSLBP subgroups positively impacts on patient outcomes. Despite this, there are no systematic reviews comparing the efficacy of targeted versus non-targeted manual therapy and/or exercise. This systematic review was undertaken in order to determine the efficacy of such targeted treatment in adults with NSLBP.</p> <p>Method</p> <p>MEDLINE, EMBASE, Current Contents, AMED and the Cochrane Central Register of Controlled Trials were electronically searched, reference lists were examined and citation tracking performed. Inclusion criteria were randomized controlled trials of targeted manual therapy and/or exercise for NSLPB that used trial designs capable of providing robust information on targeted treatment (treatment effect modification) for the outcomes of activity limitation and pain. Included trials needed to be hypothesis-testing studies published in English, Danish or Norwegian. Method quality was assessed using the criteria recommended by the Cochrane Back Review Group.</p> <p>Results</p> <p>Four high-quality randomized controlled trials of targeted manual therapy and/or exercise for NSLBP met the inclusion criteria. One study showed statistically significant effects for short-term outcomes using McKenzie directional preference-based exercise. Research into subgroups requires much larger sample sizes than traditional two-group trials and other included studies showed effects that might be clinically important in size but were not statistically significant with their samples sizes.</p> <p>Conclusions</p> <p>The clinical implications of these results are that they provide very cautious evidence supporting the notion that treatment targeted to subgroups of patients with NSLBP may improve patient outcomes. The results of the studies included in this review are too patchy, inconsistent and the samples investigated are too small for any recommendation of any treatment in routine clinical practice to be based on these findings. The research shows that adequately powered controlled trials using designs capable of providing robust information on treatment effect modification are uncommon. Considering how central the notion of targeted treatment is to manual therapy principles, further studies using this research method should be a priority for the clinical and research communities.</p

    Motor control or graded activity exercises for chronic low back pain? A randomised controlled trial

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    Background: Chronic low back pain remains a major health problem in Australia and around the world. Unfortunately the majority of treatments for this condition produce small effects because not all patients respond to each treatment. It appears that only 25-50% of patients respond to exercise. The two most popular types of exercise for low back pain are graded activity and motor control exercises. At present however, there are no guidelines to help clinicians select the best treatment for a patient. As a result, time and money are wasted on treatments which ultimately fail to help the patient
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