Adaptive Remodeling of Achilles Tendon: A Multi-scale Computational Model

While it is known that musculotendon units adapt to their load environments, there is only a limited understanding of tendon adaptation in vivo. Here we develop a computational model of tendon remodeling based on the premise that mechanical damage and tenocyte-mediated tendon damage and repair processes modify the distribution of its collagen fiber lengths. We explain how these processes enable the tendon to geometrically adapt to its load conditions. Based on known biological processes, mechanical and strain-dependent proteolytic fiber damage are incorporated into our tendon model. Using a stochastic model of fiber repair, it is assumed that mechanically damaged fibers are repaired longer, whereas proteolytically damaged fibers are repaired shorter, relative to their pre-damage length. To study adaptation of tendon properties to applied load, our model musculotendon unit is a simplified three-component Hill-type model of the human Achilles-soleus unit. Our model results demonstrate that the geometric equilibrium state of the Achilles tendon can coincide with minimization of the total metabolic cost of muscle activation. The proposed tendon model independently predicts rates of collagen fiber turnover that are in general agreement with in vivo experimental measurements. While the computational model here only represents a first step in a new approach to understanding the complex process of tendon remodeling in vivo, given these findings, it appears likely that the proposed framework may itself provide a useful theoretical foundation for developing valuable qualitative and quantitative insights into tendon physiology and pathology

Prehospital Intubation and Outcome in Traumatic Brain Injury-Assessing Intervention Efficacy in a Modern Trauma Cohort.

BACKGROUND: Prehospital intubation in traumatic brain injury (TBI) focuses on limiting the effects of secondary insults such as hypoxia, but no indisputable evidence has been presented that it is beneficial for outcome. The aim of this study was to explore the characteristics of patients who undergo prehospital intubation and, in turn, if these parameters affect outcome. MATERIAL AND METHODS: Patients ≥15 years admitted to the Department of Neurosurgery, Stockholm, Sweden with TBI from 2008 through 2014 were included. Data were extracted from prehospital and hospital charts, including prospectively collected Glasgow Outcome Score (GOS) after 12 months. Univariate and multivariable logistic regression models were employed to examine parameters independently correlated to prehospital intubation and outcome. RESULTS: A total of 458 patients were included (n = 178 unconscious, among them, n = 61 intubated). Multivariable analyses indicated that high energy trauma, prehospital hypotension, pupil unresponsiveness, mode of transportation, and distance to the hospital were independently correlated with intubation, and among them, only pupil responsiveness was independently associated with outcome. Prehospital intubation did not add independent information in a step-up model versus GOS (p = 0.154). Prehospital reports revealed that hypoxia was not the primary cause of prehospital intubation, and that the procedure did not improve oxygen saturation during transport, while an increasing distance from the hospital increased the intubation frequency. CONCLUSION: In this modern trauma cohort, prehospital intubation was not independently associated with outcome; however, hypoxia was not a common reason for prehospital intubation. Prospective trials to assess efficacy of prehospital airway intubation will be difficult due to logistical and ethical considerations

Is the Soleus a Sentinel Muscle for Impaired Aerobic Capacity in Heart Failure?

Purpose: Skeletal muscle wasting is well documented in chronic heart failure (CHF). This article provides a more detailed understanding of the morphology behind this muscle wasting and the relation between muscle morphology, strength, and exercise capacity in CHF. We investigated the effect of CHF on lower limb lean mass, detailed muscle–tendon architecture of the individual triceps surae muscles (soleus (SOL), medial gastrocnemius, and lateral gastrocnemius) and how these parameters relate to exercise capacity and strength. Methods: Eleven patients with CHF and 15 age-matched controls were recruited. Lower limb lean mass was assessed by dual energy x-ray absorptiometry and the architecture of skeletal muscle and tendon properties by ultrasound. Plantarflexor strength was assessed by dynamometry. Results: Patients with CHF exhibited approximately 25% lower combined triceps surae volume and physiological cross-sectional area (PCSA) compared with those of control subjects (P < 0.05), driven in large part by reductions in the SOL. Only the SOL volume and the SOL and medial gastrocnemius physiological cross-sectional area were statistically different between groups after normalizing to lean body mass and body surface area, respectively. Total lower limb lean mass did not differ between CHF and control subjects, further highlighting the SOL specificity of muscle wasting in CHF. Moreover, the volume of the SOL and plantarflexor strength correlated strongly with peak oxygen uptake (V˙O2peak) in patients with CHF. Conclusions: These findings suggest that the SOL may be a sentinel skeletal muscle in CHF and provide a rationale for including plantarflexor muscle training in CHF care

Soleus Muscle as a Surrogate for Health Status in Human Heart Failure

We propose the hypothesis that soleus muscle function may provide a surrogate measure of functional capacity in patients with heart failure. We summarize literature pertaining to skeletal muscle as a locus of fatigue and present our recent findings, using in vivo imaging in combination with biomechanical experimentation and modeling, to reveal novel structure-function relationships in chronic heart failure skeletal muscle and gait

Gait analysis in chronic heart failure: The calf as a locus of impaired walking capacity

Reduced walking capacity, a hallmark of chronic heart failure (CHF), is strongly correlated with hospitalization and morbidity. The aim of this work was to perform a detailed biomechanical gait analysis to better identify mechanisms underlying reduced walking capacity in CHF. Inverse dynamic analyses were conducted in CHF patients and age- and exercise level-matched control subjects on an instrumented treadmill at self-selected treadmill walking speeds and at speeds representing +20% and -20% of the subjects' preferred speed. Surprisingly, no difference in preferred speed was observed between groups, possibly explained by an optimization of the mechanical cost of transport in both groups (the mechanical cost to travel a given distance; J/kg/m). The majority of limb kinematics and kinetics were also similar between groups, with the exception of greater ankle dorsiflexion angles during stance in CHF. Nevertheless, over two times greater ankle plantarflexion work during stance and per distance traveled is required for a given triceps surae muscle volume in CHF patients. This, together with a greater reliance on the ankle compared to the hip to power walking in CHF patients, especially at faster speeds, may contribute to the earlier onset of fatigue in CHF patients. This observation also helps explain the high correlation between triceps surae muscle volume and exercise capacity that has previously been reported in CHF. Considering the key role played by the plantarflexors in powering walking and their association with exercise capacity, our findings strongly suggest that exercise-based rehabilitation in CHF should not omit the ankle muscle group

Is 'Opt-Out HIV Testing' a real option among pregnant women in rural districts in Kenya?

PMTCT allows people living with HIV to actualize childbearing. However, it also complicates motherhood, as the medical consequences and public health implications of non-adherence to PMTCT service recommendations disrupt socio-cultural expectations of childbearing and parenthood. This thesis aimed to study childbearing and adherence to PMTCT interventions focusing on how women living with HIV realize motherhood in Kenya. We sought to answer how women on ART experience motherhood and how motherhood aggravate adherence to PMTCT services Methods: A quantitative cross sectional study (I) with a questionnaire survey conducted among pregnant women at their first visit to antenatal clinic to study consent to HIV testing and three qualitative studies analyzed with content analysis (II and IV) and narrative structuring (III) were included. Qualitative interviews were performed with women living with HIV who were pregnant, recently delivered and those actively planning a pregnancy to explore views and experiences when seeking a pregnancy (II), the reasoning and deciding about adherence to PMTCT (III) and how motherhood interferes with HIV treatment (IV). Results: ‘Striving for motherhood’ was the overriding theme describing the desire of women on ART to be parents while negotiating the challenges of living with HIV (IIV). Children improve women’s position in society and are a sign of a happy and fulfilled life (II-IV). Of 900 pregnant women surveyed at their first visit to antenatal care clinic, only 17% understood that HIV testing is optional (I). Making an informed decision to decline HIV testing was associated with knowing that testing was optional (OR=5.44, 95%CI 3.44-8.59), not having a stable relationship with the child’s father (OR=1.76, 95%CI 1.02-3.03), and not having discussed HIV testing with a partner before the ANC visit (OR=2.64 95%CI 1.79-3.86). Socio-economic affluence and residence influence behaviors such as no condom use, non-disclosure of HIV infection, use of traditional medicine simultaneously with ART, home delivery and stigma and discrimination from partners, family and community, all of which undermine adherence to PMTCT services (II-IV). Structural shortcomings in PMTCT result in the lack of antiretroviral HIV medicines, practice of mixed infant feeding and missed appointments (I, III, IV). Conclusion: Motherhood is achieved at the cost of striving to balance socio-cultural expectations of childbearing that also conceals their HIV infection at the cost of nonadherence to PMTCT recommendations. Being infected with HIV does not remove the desire of motherhood and related socio-cultural demands. It is important to acknowledge the significance childbearing among women infected with HIV to improve adherence. Women with chronic illness such as HIV-infection who are dependent on continuous medication and health check-ups struggle to balance the desire for children with the needs related to their illness and the expectations of being a ‘good mother’

No Bad Slides: Scientific Presentations for All Audiences

Over the last several decades several factors have produced a communication crisis in biomedical research. The field has grown larger, specialization has increased, there are more non-native English speakers, wireless technology diverts audiences, and easy-to-use presentation software has led to slide proliferation. As a result, scientists spend increasing amounts of time in incomprehensible presentations. This talk will provide an overarching strategy for developing a scientific presentation. The talk will outline methods for developing a compelling narrative and converting that narrative into visually effective slides that articulate the essential technical message. It will review strategies for adapting talks to audiences with different levels of expertise. Speaker Bio: David Rubenson is the Administrative Director of the Stanford Cancer Institute since 2009. He also spent 7 years as Director of Special Projects at City of Hope where he helped physicians and scientists develop presentations. This talk was presented on April 14, 2016 at the Fred Hutchinson Cancer Research Center

To infinity and beyond: Children generalize the successor function to all possible numbers years after learning to count

Recent accounts of number word learning posit that when children learn to accurately count sets (i.e., become "cardinal principle" or "CP" knowers), they have a conceptual insight about how the count list implements the successor function - i.e., that every natural number *n *has a successor defined as *n+1* (Carey, 2004, 2009; Sarnecka & Carey, 2008). However, recent studies suggest that knowledge of the successor function emerges sometime after children learn to accurately count, though it remains unknown when this occurs, and what causes this developmental transition. We tested knowledge of the successor function in 100 children aged 4 through 7 and asked how age and counting ability are related to: (1) children's ability to infer the successors of all numbers in their count list, and (2) knowledge that *all *numbers have a successor. We found that children do not acquire these two facets of the successor function until they are about 5.5 or 6 years of age - roughly 2 years after they learn to accurately count sets and become CP-knowers. These findings show that acquisition of the successor function is highly protracted, providing the strongest evidence yet that it cannot drive the cardinal principle induction. We suggest that counting experience, as well as knowledge of recursive counting structures, may instead drive the learning of the successor function