The role of agonist and antagonist muscles in explaining isometric knee extension torque variation with hip joint angle.

PURPOSE: The biarticular rectus femoris (RF), operating on the ascending limb of the force-length curve, produces more force at longer lengths. However, experimental studies consistently report higher knee extension torque when supine (longer RF length) compared to seated (shorter RF length). Incomplete activation in the supine position has been proposed as the reason for this discrepancy, but differences in antagonistic co-activation could also be responsible due to altered hamstrings length. We examined the role of agonist and antagonist muscles in explaining the isometric knee extension torque variation with changes in hip joint angle. METHOD: Maximum voluntary isometric knee extension torque (joint MVC) was recorded in seated and supine positions from nine healthy males (30.2 ± 7.7 years). Antagonistic torque was estimated using EMG and added to the respective joint MVC (corrected MVC). Submaximal tetanic stimulation quadriceps torque was also recorded. RESULT: Joint MVC was not different between supine (245 ± 71.8 Nm) and seated (241 ± 69.8 Nm) positions and neither was corrected MVC (257 ± 77.7 and 267 ± 87.0 Nm, respectively). Antagonistic torque was higher when seated (26 ± 20.4 Nm) than when supine (12 ± 7.4 Nm). Tetanic torque was higher when supine (111 ± 31.9 Nm) than when seated (99 ± 27.5 Nm). CONCLUSION: Antagonistic co-activation differences between hip positions do not account for the reduced MVC in the supine position. Rather, reduced voluntary knee extensor muscle activation in that position is the major reason for the lower MVC torque when RF is lengthened (hip extended). These findings can assist standardising muscle function assessment and improving musculoskeletal modelling applications

Inorganic Becomings:Situating the Anthropocene in Puchuncaví

In this choral essay we, an assorted group of academics interested in inorganic life and matter, explore a mode of thinking and feeling with our objects of inquiry—chemicals, waste, cement, gas, and the “project” as a particular form of circulation and enactment of materials and things. To experiment with alternative modes of knowing, we went to Puchuncaví, the largest, oldest, and most polluting industrial compound in Chile, to encounter the inorganic through and with its inorganicness and to attend to the situated, historicized, and political composition of both our materials and our experiences. Thinking of this as a collective provocation, we do not rehearse a conventional argument. Its parts are connected but only partially. There is no dramatic arc but rather an attempt at composing an atmosphere through which our thought and feelings are invoked. We have made visible the authorship behind each of the stories recounted here to celebrate the multivocality of our collaboration and to rehearse a nonabstracted mode of attention to Puchuncaví and the inorganic forces and entities we encountered there. We connect our irritations and speculations with the Anthropocene precisely as a way of summoning the multiple violences, many of them of planetary reach, that have to be denounced when situating our knowledge practices in Puchuncaví. Thinking about the ethico-political challenges of research in territories that have been, and are being, transformed under the weighty history of contamination and that are lived in and lived with by generations of beings (human and otherwise), we call in our concluding remarks for an enhanced pedagogy of care born of our inherited pasts and of engagement, interest, and becoming as response-ability

Pertussis resurgence in Toronto, Canada: a population-based study including test-incidence feedback modeling

<p>Abstract</p> <p>Background</p> <p>Pertussis continues to challenge medical professionals; recently described increases in incidence may be due to age-cohort effects, vaccine effectiveness, or changes in testing patterns. Toronto, Canada has recently experienced increases in pertussis incidence, and provides an ideal jurisdiction for evaluating pertussis epidemiology due to centralized testing. We evaluated pertussis trends in Toronto using all available specimen data, which allowed us to control for changing testing patterns and practices.</p> <p>Methods</p> <p>Data included all pertussis culture and PCR test records for Greater Toronto from 1993 to 2007. We estimated incidence trends using Poisson regression models; complex relationships between disease incidence and test submission were explored with vector autoregressive models.</p> <p>Results</p> <p>From 1993 to 2007, 26988 specimens were submitted for testing; 2545 (9.4%) were positive. Pertussis incidence was 2 per 100,000 from 1993 to 2004 and increased to 10 per 100,000 from 2005-2007, with a concomitant 6-fold surge in test specimen submissions after the introduction of a new, more sensitive PCR assay. The relative change in incidence was less marked after adjustment for testing volumes. Bidirectional feedbacks between test positivity and test submissions were identified.</p> <p>Conclusions</p> <p>Toronto's recent surge in pertussis reflects a true increase in local disease activity; the apparent size of the outbreak has likely been magnified by increasing use of pertussis testing by clinicians, and by improved test sensitivity since 2005. These findings may be applicable to changes in pertussis epidemiology that have been noted elsewhere in North America.</p

Cost-Effectiveness of Adolescent Pertussis Vaccination for The Netherlands: Using an Individual-Based Dynamic Model

BACKGROUND: Despite widespread immunization programs, a clear increase in pertussis incidence is apparent in many developed countries during the last decades. Consequently, additional immunization strategies are considered to reduce the burden of disease. The aim of this study is to design an individual-based stochastic dynamic framework to model pertussis transmission in the population in order to predict the epidemiologic and economic consequences of the implementation of universal booster vaccination programs. Using this framework, we estimate the cost-effectiveness of universal adolescent pertussis booster vaccination at the age of 12 years in the Netherlands. METHODS/PRINCIPAL FINDINGS: We designed a discrete event simulation (DES) model to predict the epidemiological and economic consequences of implementing universal adolescent booster vaccination. We used national age-specific notification data over the period 1996-2000--corrected for underreporting--to calibrate the model assuming a steady state situation. Subsequently, booster vaccination was introduced. Input parameters of the model were derived from literature, national data sources (e.g. costing data, incidence and hospitalization data) and expert opinions. As there is no consensus on the duration of immunity acquired by natural infection, we considered two scenarios for this duration of protection (i.e. 8 and 15 years). In both scenarios, total pertussis incidence decreased as a result of adolescent vaccination. From a societal perspective, the cost-effectiveness was estimated at €4418/QALY (range: 3205-6364 € per QALY) and €6371/QALY (range: 4139-9549 € per QALY) for the 8- and 15-year protection scenarios, respectively. Sensitivity analyses revealed that the outcomes are most sensitive to the quality of life weights used for pertussis disease. CONCLUSIONS/SIGNIFICANCE: To our knowledge we designed the first individual-based dynamic framework to model pertussis transmission in the population. This study indicates that adolescent pertussis vaccination is likely to be a cost-effective intervention for The Netherlands. The model is suited to investigate further pertussis booster vaccination strategies

Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients

Cancer recurrence times from a branching process model

As cancer advances, cells often spread from the primary tumor to other parts of the body and form metastases. This is the main cause of cancer related mortality. Here we investigate a conceptually simple model of metastasis formation where metastatic lesions are initiated at a rate which depends on the size of the primary tumor. The evolution of each metastasis is described as an independent branching process. We assume that the primary tumor is resected at a given size and study the earliest time at which any metastasis reaches a minimal detectable size. The parameters of our model are estimated independently for breast, colorectal, headneck, lung and prostate cancers. We use these estimates to compare predictions from our model with values reported in clinical literature. For some cancer types, we find a remarkably wide range of resection sizes such that metastases are very likely to be present, but none of them are detectable. Our model predicts that only very early resections can prevent recurrence, and that small delays in the time of surgery can significantly increase the recurrence probability.Comment: 26 pages, 9 figures, 4 table

The influence of exercise training status on antigen-stimulated IL-10 production in whole blood culture and numbers of circulating regulatory T cells

The final publication is available at springerlink.com.Highly trained athletes are associated with high resting antigen-stimulated whole blood culture interleukin (IL)-10 production. The purpose of the present study was to examine the effects of training status on resting circulating T regulatory (T) cell counts and antigen-stimulated IL-10 production and the effect of acute bout of exercise on the T response. Forty participants volunteered to participate and were assigned to one of the four groups: sedentary (SED), recreationally active (REC), sprint-trained athletes and endurance-trained athletes (END). From the resting blood sample, CD4CD25CD127 T cells and in vitro antigen-stimulated IL-10 production were assessed. Ten REC subjects performed 60 min cycling at 70 % of maximal oxygen uptake and blood samples for T analysis were collected post- and 1 h post-exercise. IL-10 production was greater in END compared with the other groups (P < 0.05). END had a higher T percentage of total lymphocyte count compared with SED (P < 0.05). A smaller proportion of T CD4 cells were observed in SED compared with all other groups (P < 0.05). IL-10 production significantly correlated with the proportion of T within the total lymphocyte population (r = 0.51, P = 0.001). No effect of acute exercise was evident for T cell counts in the REC subjects (P > 0.05). Our results demonstrate that high training loads in END are associated with greater resting IL-10 production and T cell count and suggest a possible mechanism for depression of immunity commonly reported in athletes engaged in high training loads. © 2013 Springer-Verlag Berlin Heidelberg

The self-organizing fractal theory as a universal discovery method: the phenomenon of life

A universal discovery method potentially applicable to all disciplines studying organizational phenomena has been developed. This method takes advantage of a new form of global symmetry, namely, scale-invariance of self-organizational dynamics of energy/matter at all levels of organizational hierarchy, from elementary particles through cells and organisms to the Universe as a whole. The method is based on an alternative conceptualization of physical reality postulating that the energy/matter comprising the Universe is far from equilibrium, that it exists as a flow, and that it develops via self-organization in accordance with the empirical laws of nonequilibrium thermodynamics. It is postulated that the energy/matter flowing through and comprising the Universe evolves as a multiscale, self-similar structure-process, i.e., as a self-organizing fractal. This means that certain organizational structures and processes are scale-invariant and are reproduced at all levels of the organizational hierarchy. Being a form of symmetry, scale-invariance naturally lends itself to a new discovery method that allows for the deduction of missing information by comparing scale-invariant organizational patterns across different levels of the organizational hierarchy