Microwear, mechanics and the feeding adaptations of Australopithecus africanus

Recent studies of dental microwear and craniofacial mechanics have yielded contradictory interpretations regarding the feeding ecology and adaptations of Australopithecus africanus. As part of this debate, the methods used in the mechanical studies have been criticized. In particular, it has been claimed that finite element analysis has been poorly applied to this research question. This paper responds to some of these mechanical criticisms, highlights limitations of dental microwear analysis, and identifies avenues of future research.

Changes in respiratory mechanics and gas exchange during the acute respiratory distress syndrome

BACKGROUND: The time course of impairment of respiratory mechanics and gas exchange in the acute respiratory distress syndrome (ARDS) remains poorly defined. We assessed the changes in respiratory mechanics and gas exchange during ARDS. We hypothesized that due to the changes in respiratory mechanics over time, ventilatory strategies based on rigid volume or pressure limits might fail to prevent overdistension throughout the disease process. METHODS: Seventeen severe ARDS patients {PaO2/FiO2 10.1 (9.2-14.3) kPa; 76 (69-107) mmHg [median (25th-75th percentiles)] and bilateral infiltrates} were studied during the acute, intermediate, and late stages of ARDS (at 1-3, 4-6 and 7 days after diagnosis). Severity of lung injury, gas exchange, and hemodynamics were assessed. Pressure-volume (PV) curves of the respiratory system were obtained, and upper and lower inflection points (UIP, LIP) and recruitment were estimated. RESULTS: (1) UIP decreased from early to established (intermediate and late) ARDS [30 (28-30) cmH2O, 27 (25-30) cmH2O and 25 (23-28) cmH2O (P=0.014)]; (2) oxygenation improved in survivors and in patients with non-pulmonary etiology in late ARDS, whereas all patients developed hypercapnia from early to established ARDS; and (3) dead-space ventilation and pulmonary shunt were larger in patients with pulmonary etiology during late ARDS. CONCLUSION: We found a decrease in UIP from acute to established ARDS. If applied to our data, the inspiratory pressure limit advocated by the ARDSnet (30 cmH2O) would produce ventilation over the UIP, with a consequent increased risk of overdistension in 12%, 43% and 65% of our patients during the acute, intermediate and late phases of ARDS, respectively. Lung protective strategies based on fixed tidal volume or pressure limits may thus not fully avoid the risk of lung overdistension throughout ARDS.

New aspects of airway mechanics in pre-term infants

High-frequency respiratory impedance data measured noninvasively by the high-speed interrupter technique (HIT), particularly the first antiresonance frequency (f(ar,1)), is related to airway wall mechanics. The aim of this study was to evaluate the feasibility and repeatability of HIT in unsedated pre-term infants, and to compare values of f(ar,1) from 18 pre-term (post-conceptional age 32-37 weeks, weight 1,730-2,910 g) and 18 full-term infants (42-47 weeks, 3,920-5,340 g). Among the pre-term infants, there was good short-term repeatability of f(ar,1) within a single sleep epoch (mean (sd) coefficient of variance: 8 (1.7)%), but 95% limits of agreement for repeated measures of f(ar,1) after 3-8 h were relatively wide (-41 Hz; 37 Hz). f(ar,1) was significantly lower in pre-term infants (199 versus 257 Hz), indicating that wave propagation characteristics in pre-term airways are different from those of full-term infants. The present authors suggest that this is consistent with developmental differences in airway wall structure and compliance, including the influence of the surrounding tissue. Since flow limitation is determined by wave propagation velocity and airway cross-sectional area, it was hypothesised that the physical ability of the airways to carry large flows is fundamentally different in pre-term than in full-term infants.

The treatment of spasticity with Delta9-tetrahydrocannabinol in persons with spinal cord injury

STUDY DESIGN: Open label study to determine drug dose for a randomized double-blind placebo-controlled parallel study. OBJECTIVES: To assess the efficacy and side effects of oral Delta(9)-tetrahydrocannabinol (THC) and rectal THC-hemisuccinate (THC-HS) in SCI patients. SETTING: REHAB Basel, Switzerland. METHOD: Twenty-five patients with SCI were included in this three-phase study with individual dose adjustment, each consisting of 6 weeks. Twenty-two participants received oral THC open label starting with a single dose of 10 mg (Phase 1, completed by 15 patients). Eight subjects received rectal THC-HS (Phase 2, completed by seven patients). In Phase 3, six patients were treated with oral THC and seven with placebo. Major outcome parameters were the spasticity sum score (SSS) using the Modified Ashworth Scale (MAS) and self-ratings of spasticity. RESULTS: Mean daily doses were 31 mg with THC and 43 mg with THC-HS. Mean SSS for THC decreased significantly from 16.72 (+/-7.60) at baseline to 8.92 (+/-7.14) on day 43. Similar improvement was seen with THC-HS. We observed a significant improvement of SSS with active drug (P=0.001) in the seven subjects who received oral THC in Phase 1 and placebo in Phase 3. Major reasons for drop out were increase of pain and psychological side effects. CONCLUSION: THC is an effective and safe drug in the treatment of spasticity. At least 15-20 mg per day were needed to achieve a therapeutic effect.

The PRO-AGE study: an international randomised controlled study of health risk appraisal for older persons based in general practice

BACKGROUND: This paper describes the study protocol, the recruitment, and base-line data for evaluating the success of randomisation of the PRO-AGE (PRevention in Older people-Assessment in GEneralists' practices) project. METHODS/DESIGN: A group of general practitioners (GPs) in London (U.K.), Hamburg (Germany) and Solothurn (Switzerland) were trained in risk identification, health promotion, and prevention in older people. Their non-disabled older patients were invited to participate in a randomised controlled study. Participants allocated to the intervention group were offered the Health Risk Appraisal for Older Persons (HRA-O) instrument with a site-specific method for reinforcement (London: physician reminders in electronic medical record; Hamburg: one group session or two preventive home visits; Solothurn: six-monthly preventive home visits over a two-year period). Participants allocated to the control group received usual care. At each site, an additional group of GPs did not receive the training, and their eligible patients were invited to participate in a concurrent comparison group. Primary outcomes are self-reported health behaviour and preventative care use at one-year follow-up. In Solothurn, an additional follow-up was conducted at two years. The number of older persons agreeing to participate (% of eligible persons) in the randomised controlled study was 2503 (66.0%) in London, 2580 (53.6%) in Hamburg, and 2284 (67.5%) in Solothurn. Base-line findings confirm that randomisation of participants was successful, with comparable characteristics between intervention and control groups. The number of persons (% of eligible) enrolled in the concurrent comparison group was 636 (48.8%) in London, 746 (35.7%) in Hamburg, and 1171 (63.0%) in Solothurn. DISCUSSION: PRO-AGE is the first large-scale randomised controlled trial of health risk appraisal for older people in Europe. Its results will inform about the effects of implementing HRA-O with different methods of reinforcement.

Development, feasibility and performance of a health risk appraisal questionnaire for older persons

BACKGROUND: Health risk appraisal is a promising method for health promotion and prevention in older persons. The Health Risk Appraisal for the Elderly (HRA-E) developed in the U.S. has unique features but has not been tested outside the United States. METHODS: Based on the original HRA-E, we developed a scientifically updated and regionally adapted multilingual Health Risk Appraisal for Older Persons (HRA-O) instrument consisting of a self-administered questionnaire and software-generated feed-back reports. We evaluated the practicability and performance of the questionnaire in non-disabled community-dwelling older persons in London (U.K.) (N = 1090), Hamburg (Germany) (N = 804), and Solothurn (Switzerland) (N = 748) in a sub-sample of an international randomised controlled study. RESULTS: Over eighty percent of invited older persons returned the self-administered HRA-O questionnaire. Fair or poor self-perceived health status and older age were correlated with higher rates of non-return of the questionnaire. Older participants and those with lower educational levels reported more difficulty in completing the HRA-O questionnaire as compared to younger and higher educated persons. However, even among older participants and those with low educational level, more than 80% rated the questionnaire as easy to complete. Prevalence rates of risks for functional decline or problems were between 2% and 91% for the 19 HRA-O domains. Participants' intention to change health behaviour suggested that for some risk factors participants were in a pre-contemplation phase, having no short- or medium-term plans for change. Many participants perceived their health behaviour or preventative care uptake as optimal, despite indications of deficits according to the HRA-O based evaluation. CONCLUSION: The HRA-O questionnaire was highly accepted by a broad range of community-dwelling non-disabled persons. It identified a high number of risks and problems, and provided information on participants' intention to change health behaviour.

Volume dependence of high-frequency respiratory mechanics in healthy adults

Respiratory system input impedance (Zrs) at low to medium frequencies below 100 Hz, and study of its volume dependence, have been used extensively to quantify airway and tissue mechanics. Zrs at high oscillation frequencies including the first antiresonant frequency (far,1) may contain important information about airway mechanics. Changes in high-frequency Zrs with lung volume have not been studied. The volume-dependent behavior of high-frequency Zrs, specifically far,1 and respiratory system resistance at first antiresonance (Rrs(far,1)), was characterized in 16 healthy adults. Zrs was measured with a forced oscillation signal (5-302.5 Hz) through a wavetube setup. To track Zrs, subjects performed slow deep inspiratory and expiratory maneuvers over 30-s measurements, during which average impedance was calculated over 0.4-s intervals, with successive overlapping estimates every 0.156 s. Flow was measured using a pneumotachometer and integrated to obtain volume. Transpulmonary pressure dependence (Ptp) of Zrs was separately determined in five subjects. Both far,1 and Rrs(far,1) decreased with increasing lung volume and Ptp, consistent with an increase in airway caliber and decreased airway wall compliance as volume increased. These characterizations provide insight into airway mechanics, and are furthermore a necessary first step toward determining whether volume dependence of the first antiresonance is altered in disease.

Effect of atazanavir versus other protease inhibitor-containing antiretroviral therapy on endothelial function in HIV-infected persons: randomised controlled trial

OBJECTIVE: Impaired endothelial function was demonstrated in HIV-infected persons on protease inhibitor (PI)-containing antiretroviral therapy, probably due to altered lipid metabolism. Atazanavir is a PI causing less atherogenic lipoprotein changes. This study determined whether endothelial function improves after switching from other PI to atazanavir. DESIGN: Randomised, observer-blind, treatment-controlled trial. SETTING: Three university-based outpatient clinics. PATIENTS: 39 HIV-infected persons with suppressed viral replication on PI-containing regimens and fasting low-density lipoprotein (LDL)-cholesterol greater than 3 mmol/l. INTERVENTION: Patients were randomly assigned to continue the current PI or change to unboosted atazanavir. MAIN OUTCOME MEASURES: Endpoints at week 24 were endothelial function assessed by flow-mediated dilation (FMD) of the brachial artery, lipid profiles and serum inflammation and oxidative stress parameters. RESULTS: Baseline characteristics and mean FMD values of the two treatment groups were comparable (3.9% (SD 1.8) on atazanavir versus 4.0% (SD 1.5) in controls). After 24 weeks' treatment, FMD decreased to 3.3% (SD 1.4) and 3.4% (SD 1.7), respectively (all p = ns). Total cholesterol improved in both groups (p<0.0001 and p = 0.01, respectively) but changes were more pronounced on atazanavir (p = 0.05, changes between groups). High-density lipoprotein and triglyceride levels improved on atazanavir (p = 0.03 and p = 0.003, respectively) but not in controls. Serum inflammatory and oxidative stress parameters did not change; oxidised LDL improved significantly in the atazanavir group. CONCLUSIONS: The switch from another PI to atazanavir in treatment-experienced patients did not result in improvement of endothelial function despite significantly improved serum lipids. Atherogenic lipid profiles and direct effects of antiretroviral drugs on the endothelium may affect vascular function. Trial registration number: NCT00447070.

Advanced mechanics of materials with microstructure

The study of advanced materials aimed at improving human life has been performed since time immemorial. Such studies have created everlasting and greatly revered monuments and have helped revolutionize transportation by ushering the age of lighter–than–air flying machines. Hence a study of the mechanical behavior of advanced materials can pave way for their use for mankind’s benefit. In this school of thought, the aim of this dissertation is to broadly perform two investigations. First, an efficient modeling approach is established to predict the elastic response of cellular materials with distributions of cell geometries. Cellular materials find important applications in structural engineering. The approach does not require complex and time-consuming computational techniques usually associated with modeling such materials. Unlike most current analytical techniques, the modeling approach directly accounts for the cellular material microstructure. The approach combines micropolar elasticity theory and elastic mixture theory to predict the elastic response of cellular materials. The modeling approach is applied to the two dimensional balsa wood material. Predicted properties are in good agreement with experimentally determined properties, which emphasizes the model’s potential to predict the elastic response of other cellular solids, such as open cell and closed cell foams. The second topic concerns intraneural ganglion cysts which are a set of medical conditions that result in denervation of the muscles innervated by the cystic nerve leading to pain and loss of function. Current treatment approaches only temporarily alleviate pain and denervation which, however, does not prevent cyst recurrence. Hence, a mechanistic understanding of the pathogenesis of intraneural ganglion cysts can help clinicians understand them better and therefore devise more effective treatment options. In this study, an analysis methodology using finite element analysis is established to investigate the pathogenesis of intraneural ganglion cysts. Using this methodology, the propagation of these cysts is analyzed in their most common site of occurrence in the human body i.e. the common peroneal nerve. Results obtained using finite element analysis show good correlation with clinical imaging patterns thereby validating the promise of the method to study cyst pathogenesis.

Development of a continuum mechanics model of passive skeletal muscle

Skeletal muscle force evaluation is difficult to implement in a clinical setting. Muscle force is typically assessed through either manual muscle testing, isokinetic/isometric dynamometry, or electromyography (EMG). Manual muscle testing is a subjective evaluation of a patient’s ability to move voluntarily against gravity and to resist force applied by an examiner. Muscle testing using dynamometers adds accuracy by quantifying functional mechanical output of a limb. However, like manual muscle testing, dynamometry only provides estimates of the joint moment. EMG quantifies neuromuscular activation signals of individual muscles, and is used to infer muscle function. Despite the abundance of work performed to determine the degree to which EMG signals and muscle forces are related, the basic problem remains that EMG cannot provide a quantitative measurement of muscle force. Intramuscular pressure (IMP), the pressure applied by muscle fibers on interstitial fluid, has been considered as a correlate for muscle force. Numerous studies have shown that an approximately linear relationship exists between IMP and muscle force. A microsensor has recently been developed that is accurate, biocompatible, and appropriately sized for clinical use. While muscle force and pressure have been shown to be correlates, IMP has been shown to be non-uniform within the muscle. As it would not be practicable to experimentally evaluate how IMP is distributed, computational modeling may provide the means to fully evaluate IMP generation in muscles of various shapes and operating conditions. The work presented in this dissertation focuses on the development and validation of computational models of passive skeletal muscle and the evaluation of their performance for prediction of IMP. A transversly isotropic, hyperelastic, and nearly incompressible model will be evaluated along with a poroelastic model.

Effects of cognitive behavioral stress management on HIV-1 RNA, CD4 cell counts and psychosocial parameters of HIV-infected persons

OBJECTIVE: To determine the effects of cognitive-behavioral stress management (CBSM) training on clinical and psychosocial markers in HIV-infected persons. METHODS: A randomized controlled trial in four HIV outpatient clinics of 104 HIV-infected persons taking combination antiretroviral therapy (cART), measuring HIV-1 surrogate markers, adherence to therapy and well-being 12 months after 12 group sessions of 2 h CBSM training. RESULTS: Intent-to-treat analyses showed no effects on HIV-1 surrogate markers in the CBSM group compared with the control group: HIV-1 RNA < 50 copies/ml in 81.1% [95% confidence interval (CI), 68.0-90.6] and 74.5% (95% CI, 60.4-85.7), respectively (P = 0.34), and mean CD4 cell change from baseline of 53.0 cells/microl (95% CI, 4.1-101.8) and 15.5 cells/microl (95% CI, -34.3 to 65.4), respectively (P = 0.29). Self-reported adherence to therapy did not differ between groups at baseline (P = 0.53) or at 12 month's post-intervention (P = 0.47). Significant benefits of CBSM over no intervention were observed in mean change of quality of life scores: physical health 2.9 (95% CI, 0.7-5.1) and -0.2 (95% CI, -2.1 to 1.8), respectively (P = 0.05); mental health 4.8 (95% CI, 1.8-7.3) and -0.5 (95% CI, -3.3 to 2.2) (P = 0.02); anxiety -2.1 (95% CI, -3.6 to -1.0) and 0.3 (95% CI, -0.7 to 1.4), respectively (P = 0.002); and depression -2.1 (95% CI, -3.2 to -0.9) and 0.02 (95% CI, -1.0 to 1.1), respectively (P = 0.001). Alleviation of depression and anxiety symptoms were most pronounced among participants with high psychological distress at baseline. CONCLUSION: CBSM training of HIV-infected persons taking on cART does not improve clinical outcome but has lasting effects on quality of life and psychological well-being.

Developing ICF Core Sets for persons with sleep disorders based on the International Classification of Functioning, Disability and Health

BACKGROUND: With the International Classification of Functioning, Disability and Health (ICF), we can now rely on a globally agreed-upon framework and system for classifying the typical spectrum of problems in the functioning of persons given the environmental context in which they live. ICF Core Sets are subgroups of ICF items selected to capture those aspects of functioning that are most likely to be affected by sleep disorders. OBJECTIVE: The objective of this paper is to outline the developmental process for the ICF Core Sets for Sleep. METHODS: The ICF Core Sets for Sleep will be defined at an ICF Core Sets Consensus Conference, which will integrate evidence from preliminary studies, namely (a) a systematic literature review regarding the outcomes used in clinical trials and observational studies, (b) focus groups with people in different regions of the world who have sleep disorders, (c) an expert survey with the involvement of international clinical experts, and (d) a cross-sectional study of people with sleep disorders in different regions of the world. CONCLUSION: The ICF Core Sets for Sleep are being designed with the goal of providing useful standards for research, clinical practice and teaching. It is hypothesized that the ICF Core Sets for Sleep will stimulate research that leads to an improved understanding of functioning, disability, and health in sleep medicine. It is of further hope that such research will lead to interventions and accommodations that improve the restoration and maintenance of functioning and minimize disability among people with sleep disorders throughout the world.