An analytic and systematic framework for estimating metabolic flux ratios from 13C tracer experiments

<p>Abstract</p> <p>Background</p> <p>Metabolic fluxes provide invaluable insight on the integrated response of a cell to environmental stimuli or genetic modifications. Current computational methods for estimating the metabolic fluxes from ¹³<it>C </it>isotopomer measurement data rely either on manual derivation of analytic equations constraining the fluxes or on the numerical solution of a highly nonlinear system of isotopomer balance equations. In the first approach, analytic equations have to be tediously derived for each organism, substrate or labelling pattern, while in the second approach, the global nature of an optimum solution is difficult to prove and comprehensive measurements of external fluxes to augment the ¹³<it>C </it>isotopomer data are typically needed.</p> <p>Results</p> <p>We present a novel analytic framework for estimating metabolic flux ratios in the cell from ¹³<it>C </it>isotopomer measurement data. In the presented framework, equation systems constraining the fluxes are derived automatically from the model of the metabolism of an organism. The framework is designed to be applicable with all metabolic network topologies, ¹³<it>C </it>isotopomer measurement techniques, substrates and substrate labelling patterns.</p> <p>By analyzing nuclear magnetic resonance (NMR) and mass spectrometry (MS) measurement data obtained from the experiments on glucose with the model micro-organisms <it>Bacillus subtilis </it>and <it>Saccharomyces cerevisiae </it>we show that our framework is able to automatically produce the flux ratios discovered so far by the domain experts with tedious manual analysis. Furthermore, we show by <it>in silico </it>calculability analysis that our framework can rapidly produce flux ratio equations – as well as predict when the flux ratios are unobtainable by linear means – also for substrates not related to glucose.</p> <p>Conclusion</p> <p>The core of ¹³<it>C </it>metabolic flux analysis framework introduced in this article constitutes of flow and independence analysis of metabolic fragments and techniques for manipulating isotopomer measurements with vector space techniques. These methods facilitate efficient, analytic computation of the ratios between the fluxes of pathways that converge to a common junction metabolite. The framework can been seen as a generalization and formalization of existing tradition for computing metabolic flux ratios where equations constraining flux ratios are manually derived, usually without explicitly showing the formal proofs of the validity of the equations.</p

Physical function and self-rated health status as predictors of mortality: results from longitudinal analysis in the ilSIRENTE study

<p>Abstract</p> <p>Background</p> <p>Physical function measures have been shown to predict negative health-related events in older persons, including mortality. These markers of functioning may interact with the self-rated health (SRH) in the prediction of events. Aim of the present study is to compare the predictive value for mortality of measures of physical function and SRH status, and test their possible interactions.</p> <p>Methods</p> <p>Data are from 335 older persons aged ≥ 80 years (mean age 85.6 years) enrolled in the "Invecchiamento e Longevità nel Sirente" (<it>ilSIRENTE</it>) study. The predictive values for mortality of 4-meter walk test, Short Physical Performance Battery (SPPB), hand grip strength, Activities of Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and a SRH scale were compared using proportional hazard models. Kaplan-Meier survival curves for mortality and Receiver Operating Characteristic (ROC) curve analyses were also computed to estimate the predictive value of the independent variables of interest for mortality (alone and in combination).</p> <p>Results</p> <p>During the 24-month follow-up (mean 1.8 years), 71 (21.2%) events occurred in the study sample. All the tested variables were able to significantly predict mortality. No significant interaction was reported between physical function measures and SRH. The SPPB score was the strongest predictor of overall mortality after adjustment for potential confounders (per SD increase; HR 0.64; 95%CI 0.48–0.86). A similar predictive value was showed by the SRH (per SD increase; HR 0.76; 95%CI 0.59–0.97). The chair stand test was the SPPB subtask showing the highest prognostic value.</p> <p>Conclusion</p> <p>All the tested measures are able to predict mortality with different extents, but strongest results were obtained from the SPPB and the SRH. The chair stand test may be as useful as the complete SPPB in estimating the mortality risk.</p

Comparing two intramedullary devices for treating trochanteric fractures: A prospective study

<p>Abstract</p> <p>Background</p> <p>Intertrochanteric fractures are surgically treated by using different methods and implants. The optional type of surgical stabilization is still under debate. However, between devices with the same philosophy, different design characteristics may substantially influence fracture healing. This is a prospective study comparing the complication and final functional outcome of two intramedullary devices, the intramedullary hip screw (IMHS) and the ENDOVIS nail.</p> <p>Materials and methods</p> <p>Two hundred fifteen patients were randomized on admission in two treatment groups. Epidemiology features and functional status was similar between two treatment groups. Fracture stability was assessed according to the Evan's classification. One hundred ten patients were treated with IMHS and 105 with ENDOVIS nail.</p> <p>Results</p> <p>There were no significant statistical differences between the two groups regarding blood loss, transfusion requirements and mortality rate. In contrast, the number of total complications was significantly higher in the ENDOVIS nail group. Moreover, the overall functional and walking competence was superior in the patients treated with the IMHS nail.</p> <p>Conclusions</p> <p>These results indicate that the choice of the proper implant plays probably an important role in the final outcome of surgical treatment of intertrochanteric fractures. IMHS nail allows for accurate surgical technique, for both static and dynamic compression and high rotational stability. IMHS nail proved more reliable in our study regarding nail insertion and overall uncomplicated outcome.</p

The Effect of Auditory Distraction on the Useful Field of View in Hearing Impaired Individuals and its implications for driving

This study assessed whether the increased demand of listening in hearing impaired individuals exacerbates the detrimental impact of auditory distraction on a visual task (useful field of view test), relative to normally hearing listeners. Auditory distraction negatively affects this visual task, which is linked with various driving performance outcomes. Hearing impaired and normally hearing participants performed useful field of view testing with and without a simultaneous listening task. They also undertook a cognitive test battery. For all participants, performing the visual and auditory tasks together reduced performance on each respective test. For a number of subtests, hearing impaired participants showed poorer visual task performance, though not to a statistically significant extent. Hearing impaired participants were significantly poorer at a reading span task than normally hearing participants and tended to score lower on the most visually complex subtest of the visual task in the absence of auditory task engagement. Useful field of view performance is negatively affected by auditory distraction, and hearing loss may present further problems, given the reductions in visual and cognitive task performance suggested in this study. Suggestions are made for future work to extend this study, given the practical importance of the findings

Body mass index, muscle strength and physical performance in older adults from eight cohort studies: the HALCyon programme.

Objective To investigate the associations of body mass index (BMI) and grip strength with objective measures of physical performance (chair rise time, walking speed and balance) including an assessment of sex differences and non-linearity. Methods Cross-sectional data from eight UK cohort studies (total N = 16 444) participating in the Healthy Ageing across the Life Course (HALCyon) research programme, ranging in age from 50 to 90+ years at the time of physical capability assessment, were used. Regression models were fitted within each study and meta-analysis methods used to pool regression coefficients across studies and to assess the extent of heterogeneity between studies. Results Higher BMI was associated with poorer performance on chair rise (N = 10 773), walking speed (N = 9 761) and standing balance (N = 13 921) tests. Higher BMI was associated with stronger grip strength in men only. Stronger grip strength was associated with better performance on all tests with a tendency for the associations to be stronger in women than men; for example, walking speed was higher by 0.43 cm/s (0.14, 0.71) more per kg in women than men. Both BMI and grip strength remained independently related with performance after mutual adjustment, but there was no evidence of effect modification. Both BMI and grip strength exhibited non-linear relations with performance; those in the lowest fifth of grip strength and highest fifth of BMI having particularly poor performance. Findings were similar when waist circumference was examined in place of BMI. Conclusion Older men and women with weak muscle strength and high BMI have considerably poorer performance than others and associations were observed even in the youngest cohort (age 53). Although causality cannot be inferred from observational cross-sectional studies, our findings suggest the likely benefit of early assessment and interventions to reduce fat mass and improve muscle strength in the prevention of future functional limitations

Work-life balance in the police: the development of a self-management competency framework

Purpose Addressing a gap in the current work–life balance (WLB) literature regarding individual-focused approaches to inform interventions, we elicited behaviors used to self-manage WLB to draw up a competency-based WLB framework for relevant learnable knowledge, skills, and abilities (KSAs; Hoffmann, Eur J Ind Train 23:275–285, 1999) and mapping this against extant WLB frameworks. Design/Methodology/Approach Our participants were from a major UK police force, which faces particular challenges to the work–life interface through job demands and organizational cutbacks, covering a range of operational job roles, including uniformed officers and civilian staff. We took a mixed methods approach starting with semi-structured interviews to elicit 134 distinct behaviors (n = 20) and used a subsequent card sort task (n = 10) to group these into categories into 12 behavioral themes; and finally undertook an online survey (n = 356) for an initial validation. Findings Item and content analysis reduced the behaviors to 58, which we analyzed further. A framework of eight competencies fits the data best; covering a range of strategies, including Boundary Management, Managing Flexibility, and Managing Expectations. Implications The WLB self-management KSAs elicited consist of a range of solution-focused behaviors and strategies, which could inform future WLB-focused interventions, showing how individuals may negotiate borders effectively in a specific environment. Originality/Value A competence-based approach to WLB self-management is new, and may extend existing frameworks such as Border Theory, highlighting a proactive and solution-focused element of effective behaviors

Randomized controlled trial of postoperative exercise rehabilitation program after lumbar spine fusion: study protocol

Abstract Background Lumbar spine fusion (LSF) effectively decreases pain and disability in specific spinal disorders; however, the disability rate following surgery remains high. This, combined with the fact that in Western countries the number of LSF surgeries is increasing rapidly it is important to develop rehabilitation interventions that improve outcomes. Methods/design In the present RCT-study we aim to assess the effectiveness of a combined back-specific and aerobic exercise intervention for patients after LSF surgery. One hundred patients will be randomly allocated to a 12-month exercise intervention arm or a usual care arm. The exercise intervention will start three months after surgery and consist of six individual guidance sessions with a physiotherapist and a home-based exercise program. The primary outcome measures are low back pain, lower extremity pain, disability and quality of life. Secondary outcomes are back function and kinesiophobia. Exercise adherence will also be evaluated. The outcome measurements will be assessed at baseline (3&#8201;months postoperatively), at the end of the exercise intervention period (15&#8201;months postoperatively), and after a 1-year follow-up. Discussion The present RCT will evaluate the effectiveness of a long-term rehabilitation program after LSF. To our knowledge this will be the first study to evaluate a combination of strength training, control of the neutral lumbar spine position and aerobic training principles in rehabilitation after LSF. Trial registration ClinicalTrials.gov Identifier NCT00834015peerReviewe

Training Genetic Counsellors to Deliver an Innovative Therapeutic Intervention: their views and experience of facilitating multi-family discussion groups

Innovations in clinical genetics have increased diagnosis, treatment and prognosis of inherited genetic conditions (IGCs). This has led to an increased number of families seeking genetic testing and / or genetic counselling and increased the clinical load for genetic counsellors (GCs). Keeping pace with biomedical discoveries, interventions are required to support families to understand, communicate and cope with their Inherited Genetic Condition. The Socio-Psychological Research in Genomics (SPRinG) collaborative have developed a new intervention, based on multi-family discussion groups (MFDGs), to support families affected by IGCs and train GCs in its delivery. A potential challenge to implementing the intervention was whether GCs were willing and able to undergo the training to deliver the MFDG. In analysing three multi-perspective interviews with GCs, this paper evaluates the training received. Findings suggests that MFDGs are a potential valuable resource in supporting families to communicate genetic risk information and can enhance family function and emotional well-being. Furthermore, we demonstrate that it is feasible to train GCs in the delivery of the intervention and that it has the potential to be integrated into clinical practice. Its longer term implementation into routine clinical practice however relies on changes in both organisation of clinical genetics services and genetic counsellors' professional development