Does a modified STarT Back Tool predict outcome with a broader group of musculoskeletal patients than back pain? A secondary analysis of cohort data.

OBJECTIVES: The STarT Back Tool has good predictive performance for non-specific low back pain in primary care. We therefore aimed to investigate whether a modified STarT Back Tool predicted outcome with a broader group of musculoskeletal patients, and assessed the consequences of using existing risk-group cut-points across different pain regions. SETTING: Secondary analysis of prospective data from 2 cohorts: (1) outpatient musculoskeletal physiotherapy services (PhysioDirect trial n=1887) and (2) musculoskeletal primary-secondary care interface services (SAMBA study n=1082). PARTICIPANTS: Patients with back, neck, upper limb, lower limb or multisite pain with a completed modified STarT Back Tool (baseline) and 6-month physical health outcome (Short Form 36 (SF-36)). OUTCOMES: Area under the receiving operator curve (AUCs) tested discriminative abilities of the tool's baseline score for identifying poor 6-month outcome (SF-36 lower tertile Physical Component Score). Risk-group cut-points were tested using sensitivity and specificity for identifying poor outcome using (1) Youden's J statistic and (2) a clinically determined rule that specificity should not fall below 0.7 (false-positive rate <30%). RESULTS: In PhysioDirect and SAMBA, poor 6-month physical health was 18.5% and 28.2%, respectively. Modified STarT Back Tool score AUCs for predicting outcome in back pain were 0.72 and 0.79, neck 0.82 and 0.88, upper limb 0.79 and 0.86, lower limb 0.77 and 0.83, and multisite pain 0.83 and 0.82 in PhysioDirect and SAMBA, respectively. Differences between pain region AUCs were non-significant. Optimal cut-points to discriminate low-risk and medium-risk/high-risk groups depended on pain region and clinical services. CONCLUSIONS: A modified STarT Back Tool similarly predicts 6-month physical health outcome across 5 musculoskeletal pain regions. However, the use of consistent risk-group cut-points was not possible and resulted in poor sensitivity (too many with long-term disability being missed) or specificity (too many with good outcome inaccurately classified as 'at risk') for some pain regions. The draft tool is now being refined and validated within a new programme of research for a broader musculoskeletal population. TRIAL REGISTRATION NUMBER: ISRCTN55666618; Post results

The Foraging Tunnel System of the Namibian Desert Termite, Baucaliotermes hainesi

The harvester termite, Baucaliotermes hainesi (Fuller) (Termitidae: Nasutitermitinae), is an endemic in southern Namibia, where it collects and eats dry grass. At the eastern, landward edge of the Namib Desert, the nests of these termites are sometimes visible above ground surface, and extend at least 60 cm below ground. The termites gain access to foraging areas through underground foraging tunnels that emanate from the nest. The looseness of the desert sand, combined with the hardness of the cemented sand tunnels allowed the use of a gasolinepowered blower and soft brushes to expose tunnels lying 5 to 15 cm below the surface. The tunnels form a complex system that radiates at least 10 to 15 m from the nest with crossconnections between major tunnels. At 50 to 75 cm intervals, the tunnels are connected to the surface by vertical risers that can be opened to gain foraging access to the surrounding area. Foraging termites rarely need to travel more than a meter on the ground surface. The tunnels swoop up and down forming high points at riser locations, and they have a complex architecture. In the center runs a smooth, raised walkway along which termites travel, and along the sides lie pockets that act as depots where foragers deposit grass pieces harvested from the surface. Presumably, these pieces are transported to the nest by a second group of termites. There are also several structures that seem to act as vertical highways to greater depths, possibly even to moist soil. A census of a single nest revealed about 45,000 termites, of which 71% were workers, 9% soldiers and 6% neotenic supplementary reproductives. The nest consisted of a hard outer “carapace” of cemented sand, with a central living space of smooth, sweeping arches and surfaces. A second species of termite, Promirotermes sp. nested in the outer carapace

Development and initial validation of the bronchiectasis exacerbation and symptom tool (BEST)

BACKGROUND: Recurrent bronchiectasis exacerbations are related to deterioration of lung function, progression of the disease, impairment of quality of life, and to an increased mortality. Improved detection of exacerbations has been accomplished in chronic obstructive pulmonary disease through the use of patient completed diaries. These tools may enhance exacerbation reporting and identification. The aim of this study was to develop a novel symptom diary for bronchiectasis symptom burden and detection of exacerbations, named the BEST diary. METHODS: Prospective observational study of patients with bronchiectasis conducted at Ninewells Hospital, Dundee. We included patients with confirmed bronchiectasis by computed tomography, who were symptomatic and had at least 1 documented exacerbation of bronchiectasis in the previous 12\u2009months to participate. Symptoms were recorded daily in a diary incorporating cough, sputum volume, sputum colour, dyspnoea, fatigue and systemic disturbance scored from 0 to 26. RESULTS: Twenty-one patients were included in the study. We identified 29 reported (treated exacerbations) and 23 unreported (untreated) exacerbations over 6-month follow-up. The BEST diary score showed a good correlation with the established and validated questionnaires and measures of health status (COPD Assessment Test, r =\u20090.61, p =\u20090.0037, Leicester Cough Questionnaire, r =\u2009-\u20090.52,p =\u20090.0015, St Georges Respiratory Questionnaire, r =\u20090.61,p &lt;\u20090.0001 and 6\u2009min walk test, r =\u2009-\u20090.46,p =\u20090.037). The mean BEST score at baseline was 7.1 points (SD 2.2). The peak symptom score during exacerbation was a mean of 16.4 (3.1), and the change from baseline to exacerbation was a mean of 9.1 points (SD 2.5). Mean duration of exacerbations based on time for a return to baseline symptoms was 15.3\u2009days (SD 5.7). A minimum clinically important difference of 4 points is proposed. CONCLUSIONS: The BEST symptom diary has shown concurrent validity with current health questionnaires and is responsive at onset and recovery from exacerbation. The BEST diary may be useful to detect and characterise exacerbations in bronchiectasis clinical trials

Factor structure and validity of the shoulder pain and disability index in a population-based study of people with shoulder symptoms

Background: The Shoulder Pain and Disability Index (SPADI) is a self-administered questionnaire that aims to measure pain and disability associated with shoulder disease. The aim of the present study was to investigate the construct validity and factor structure of the SPADI in a population-based study of patients with self-reported chronic shoulder symptoms. Methods: The North West Adelaide Health Study is a representative longitudinal cohort study of people aged 18 years and over. The original sample was randomly selected and recruited by telephone interview. Overall, 3 206 participants returned to the clinic during the second stage (2004-2006) and were asked to report whether they had pain, aching or stiffness on most days in either of their shoulders. Data was also collected on body mass index and shoulder range of motion (ROM) and demographic factors. The SPADI (numeric rating scale) was administered to participants with shoulder symptoms. Principal components factor analysis, with varimax rotation of factor loadings, was used to assess subscale structure of SPADI. Correlations between the SPADI, shoulder ROM and SF-36 were performed. Results: Overall, 22.3% of participants indicated that they had pain, aching or stiffness in either of their shoulders. SPADI results were available for 588 of participants with current shoulder symptoms. The internal consistency of the SPADI subscales were high (Cronbach's alpha > 0.92). Two factors, explaining 61.4% of the total variance were extracted by factor analysis. These were interpreted as disability and pain respectively. There was a strong negative correlation between SPADI disability subscale scores and shoulder range of motion. SPADI disability, but not pain, subscale scores were correlated with age. Conclusions: The SPADI is a valid measure to assess pain and disability in people with shoulder pain in a population-based study. In this setting, the SPADI had a bidimensional structure with both pain and disability subscales.Catherine L Hill, Susan Lester, Anne W Taylor, Michael E Shanahan, Tiffany K Gil

The complete linkage disequilibrium test: a test that points to causative mutations underlying quantitative traits

<p>Abstract</p> <p>Background</p> <p>Genetically, SNP that are in complete linkage disequilibrium with the causative SNP cannot be distinguished from the causative SNP. The Complete Linkage Disequilibrium (CLD) test presented here tests whether a SNP is in complete LD with the causative mutation or not. The performance of the CLD test is evaluated in 1000 simulated datasets.</p> <p>Methods</p> <p>The CLD test consists of two steps i.e. analysis I and analysis II. Analysis I consists of an association analysis of the investigated region. The log-likelihood values from analysis I are next ranked in descending order and in analysis II the CLD test evaluates differences in log-likelihood ratios between the best and second best markers. Under the null-hypothesis distribution, the best SNP is in greater LD with the QTL than the second best, while under the alternative-CLD-hypothesis, the best SNP is alike-in-state with the QTL. To find a significance threshold, the test was also performed on data excluding the causative SNP. The 5^th, 10^thand 50^thhighest T_CLDvalue from 1000 replicated analyses were used to control the type-I-error rate of the test at p = 0.005, p = 0.01 and p = 0.05, respectively.</p> <p>Results</p> <p>In a situation where the QTL explained 48% of the phenotypic variance analysis I detected a QTL in 994 replicates (p = 0.001), where 972 were positioned in the correct QTL position. When the causative SNP was excluded from the analysis, 714 replicates detected evidence of a QTL (p = 0.001). In analysis II, the CLD test confirmed 280 causative SNP from 1000 simulations (p = 0.05), i.e. power was 28%. When the effect of the QTL was reduced by doubling the error variance, the power of the test reduced relatively little to 23%. When sequence data were used, the power of the test reduced to 16%. All SNP that were confirmed by the CLD test were positioned in the correct QTL position.</p> <p>Conclusions</p> <p>The CLD test can provide evidence for a causative SNP, but its power may be low in situations with closely linked markers. In such situations, also functional evidence will be needed to definitely conclude whether the SNP is causative or not.</p

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

The racist bodily imaginary: the image of the body-in-pieces in (post)apartheid culture

This paper outlines a reoccurring motif within the racist imaginary of (post)apartheid culture: the black body-in-pieces. This disturbing visual idiom is approached from three conceptual perspectives. By linking ideas prevalent in Frantz Fanon’s description of colonial racism with psychoanalytic concepts such as Lacan’s notion of the corps morcelé, the paper offers, firstly, an account of the black body-in-pieces as fantasmatic preoccupation of the (post)apartheid imaginary. The role of such images is approached, secondly, through the lens of affect theory which eschews a representational ‘reading’ of such images in favour of attention to their asignifying intensities and the role they play in effectively constituting such bodies. Lastly, Judith Butler’s discussion of war photography and the conditions of grievability introduces an ethical dimension to the discussion and helps draw attention to the unsavory relations of enjoyment occasioned by such images

Dimethyl sulfoxide blocks herpes simplex virus-1 productive infection in vitro acting at different stages with positive cooperativity. Application of micro-array analysis

BACKGROUND: Dimethyl sulfoxide (DMSO) is frequently used at a concentration of up to 95% in the formulation of antiherpetic agents because of its properties as a skin penetration enhancer. Here, we have analyzed the effect of DMSO on several parameters of Herpes Simplex Virus replication. METHODS: Productive infection levels of HSV-1 were determined by plaque assay or by reporter gene activity, and its DNA replication was estimated by PCR. Transcript levels were evaluated with HSV-specific DNA micro-arrays. RESULTS: DMSO blocks productive infection in vitro in different cell types with a 50% inhibitory concentration (IC(50)) from 0.7 to 2% depending upon the multiplicity of infection. The concentration dependence exhibits a Hill coefficient greater than 1, indicating that DMSO blocks productive infection by acting at multiple different points (mechanisms of action) with positive cooperativity. Consistently, we identified at least three distinct temporal target mechanisms for inhibition of virus growth by DMSO. At late stages of infection, DMSO reduces virion infectivity, and markedly inhibits viral DNA replication. A third mode of action was revealed using an oligonucleotide-based DNA microarray system for HSV. These experiments showed that DMSO reduced the transcript levels of many HSV-1 genes; including several genes coding for proteins involved in forming and assembling the virion. Also, DMSO markedly inhibited some but not all early transcripts indicating a previously unknown mode for inhibiting the early phase of HSV transcription-replication cycle. CONCLUSION: These observations suggest that DMSO itself may have a role in the anti-herpetic activity of formulations utilizing it as a dispersant

Goal Priming in Dieters: Recent Insights and Applications

What are the psychological mechanisms that make dieting so challenging in our food-rich living environment? Social psychological research on goal priming provides a useful framework for answering this question, as well as implications for how to enhance dieting success. This review presents and discusses recent research which shows that attractive food cues prime the hedonic eating goal in dieters, and thus facilitate overeating. However, external cues priming the goal of weight control can be used to offset these effects and thus to facilitate dieting success, as is demonstrated in both field and laboratory experiments. In addition, recent strategies to prevent hedonic effects of attractive food, such as mindful attention, can facilitate self-regulation. These recent advances in our understanding of dieting behavior have theoretical and practical implications for how successful dieting can be facilitated, both by means of individual strategies, as well as by environmental changes