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The impact force experienced by a runner when his/her foot makes contact with the ground has been the subject of much research. This force is called the ground reaction force (GRF), and has been measured by several groups. In parallel with this, mathematical models have been developed to simulate GRFs in order to investigate various effects on this, such as the parameters of the human body and types of running shoe soles. Lumped parameter models have been developed by several researchers with limited success, because they are either constrained to model translational motion, or become complicated if they include rotational motion. This paper proposes a new approach based on modes of vibration, which encompasses the simplicity of the lumped parameter approach, without the motion constraints. The GRF is decomposed into contributions due to the various vibration modes of the system. To achieve this, a linear system is required, so a Zener model, which is used to model viscoelastic materials, is employed as the ground reaction model. The modal modelling approach is described in detail using established lumped parameter models used to predict the GRF. It is then applied to four experimental data sets from the literature, where it is shown that at most three modes are required to model GRF data accurately. Two of these modes are oscillatory modes and one is a non-oscillatory exponentially decaying mode. In general, it is shown that the modal model can capture the dynamics of each measured GRF independently of speed and running style., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Treating tuberculosis (TB) requires a multidrug course of treatment lasting 6 months, or longer for drug-resistant TB, which is difficult to complete and often not well tolerated. Treatment failure and recurrence after end-of-treatment can have devastating consequences, including progressive debilitation, death, the transmission of Mycobacterium tuberculosis - the infectious agent responsible for causing TB - to others, and may be associated with the development of drug-resistant TB. The burden on health systems is important, with severe economic consequences. Vaccines have the potential to serve as immunotherapeutic adjuncts to antibiotic treatment regimens for TB. A therapeutic vaccine for TB patients, administered towards completion of a prescribed course of drug therapy or at certain time(s) during treatment, could improve outcomes through immune-mediated control and even clearance of bacteria, potentially prevent re-infection, and provide an opportunity to shorten and simplify drug treatment regimens. The preferred product characteristics (PPC) for therapeutic TB vaccines described in this document are intended to provide guidance to scientists, funding agencies, public and private sector organizations developing such vaccine candidates. This document presents potential clinical end-points for evidence generation and discusses key considerations about potential clinical development strategies., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The development of adhesives that can be applied and create strong bonds underwater is a significant challenge for materials engineering. When the adhesive is intended for biomedical applications, further criteria, such as biocompatibility, must be met. Current biomedical adhesive technologies do not meet these needs. In response, we designed a bioinspired protein system that shows promise to achieve biocompatible underwater adhesion coupled with environmentally responsive behavior that is "smart" - that is, it can be tuned to suit a specific application. The material, ELY 16 , is constructed from an elastin-like polypeptide (ELP) that can be produced in high yields from Escherichia coli and can coacervate in response to environmental factors such as temperature, pH, and salinity. To confer wet adhesion, we utilized design principles from marine organisms such as mussels and sandcastle worms. When expressed, ELY 16 is rich in tyrosine. Upon modification with the tyrosinase enzyme to form mELY 16 , the tyrosine residues are converted to 3,4-dihydroxyphenylalanine (DOPA). Both ELY 16 and mELY 16 exhibit cytocompatibility and significant dry adhesion strength (>2 MPa). Modification with DOPA increases protein adsorption to glass and provides moderate adhesion strength (∼240 kPa) in a highly humid environment. Furthermore, this ELP exhibits a tunable phase transition behavior that can be formulated to coacervate in physiological conditions and provides a convenient mechanism for application underwater. Finally, mELY 16 possesses significantly higher adhesion strength in dry, humid, and underwater environments compared with a commercially available fibrin sealant. To our knowledge, mELY 16 provides the strongest bonds of any rationally designed protein when used completely underwater, and its high yields make it more viable for commercial application compared to natural adhesive proteins. In conclusion, this ELP shows great potential to be a new "smart" underwater adhesive., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Although exercise and strength training have been shown to be protective against falls in older adults (aged 65 years and older), evidence for the role of leisure-time physical activity (LTPA) in the prevention of falls and resulting injuries in middle-aged adults (aged 45-64 years) is lacking. In the present study, we investigate the association between self-reported engagement in LTPA and the frequency of falls and fall-related injuries among middle-aged and older adults, while controlling for key sociodemographic and health characteristics., Methods: Nationally representative data from the 2010 U.S. Behavioral Risk Factor Surveillance Survey were analyzed in April 2014 to examine the number of adults aged ≥45 years who self-reported their fall experience in the previous 3 months and any injuries that resulted from those falls. We then evaluated the association between LTPA and self-reported falls and injuries across three age strata (45-54, 55-64, and ≥65 years). The two main self-reported outcome measures were (1) frequency of falls in the 3 months prior to the survey interview date and (2) the number of injuries resulting from these falls. Prevalence ratios (PRs) and 95% CIs were calculated using Poisson regression models with robust SEs., Results: Of 340,680 survey participants aged ≥45 years, 70.7% reported engaging in LTPA, and 17% reported one or more falls. Among those reporting a fall within 3 months, 25.6% experienced one injurious fall (fall resulting in an injury) and 8.4% reported two or more injurious falls. Controlling for sociodemographic and health characteristics, among adults aged 45-54 years, those who engaged in LTPA were significantly less likely to report one fall (PR=0.90, 95% CI=0.81, 0.99); two or more falls (PR=0.84, 95% CI=0.77, 0.93); one injurious fall (PR=0.88, 95% CI=0.78, 0.99); and two or more injurious falls (PR=0.69, 95% CI=0.58, 0.83) than those who did not exercise. A similar protective effect of LTPA on reporting falls and injuries was noted for adults aged 55-64 and ≥65 years., Conclusions: Similar to older adults, middle-aged adults who engage in LTPA report fewer falls and fall-related injuries. Upon further confirmation of the relationship between LTPA and falls among middle-aged adults, fall prevention interventions could be developed for this population., (Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

There are nearly ten million new cases and 1.4 million deaths from tuberculosis (TB) each year, and the 90-year old bacille calmette-guérin (BCG) vaccine in widespread use appears to have minimal impact on the worldwide incidence, despite demonstrating reasonable efficacy against complications of infant TB and death. Novel vaccine development has accelerated in the past ten years, with at least 16 candidates entering human trials, and a few vaccines have entered into Phase 2b efficacy studies. However, different vaccines may be needed due to the varying disease states (naïve, latently infected, or active), the ages affected (infants, adolescents and young adults, the elderly), and patient health status (HIV and immunocompromised patients especially). Modeling has shown that mass vaccination of latently infected populations, especially adolescents and young adults, will likely have the largest impact on new infection rates. At present, research and development of TB vaccines is hampered by the lack of validated animal models, the absence of correlates of immunity and a human challenge model, as well as by the size and cost of Proof-of-Concept clinical trials. Nonetheless, ongoing research and clinical studies should remove many of these barriers over the next five years, and lead to an increased understanding of the pathogenicity of Mycobacterium tuberculosis and what may constitute protective immunity during various stages of infection and disease., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In this review, published peer-reviewed preclinical studies using prime-boost tuberculosis (TB) vaccine regimens in animal challenge models for tuberculosis have been evaluated. These studies have been divided into groups that describe prime-boost vaccine combinations that performed better than, equivalent to, or worse than the currently used BCG vaccine. Review of the data has revealed interesting findings, including that more than half of the published studies using BCG as a prime combined with a novel boost vaccine give better efficacy than BCG alone and that the greatest reduction in Mycobacterium tuberculosis (M.tb.) colonization of animal tissues is provided by viral vectored vaccines delivered intranasally. Careful evaluation of these data should assist in defining the value of prime-boost regimens for advancement into human TB vaccine trials and stimulate the development of criteria for choosing which vaccine candidates should be studied further., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Infection with Mycobacterium tuberculosis continues to be a major public health burden in most developing parts of the world and efforts to develop effective strategies for containing the disease remain a priority. It has long been evident that effective mass vaccination programmes are a cost effective and efficient approach to controlling communicable diseases in a public health setting and tuberculosis (TB) continues to be a major target. One approach with increasing acceptance is based upon on live mycobacterial vaccines, either as recombinant BCG or rationally attenuated M. tuberculosis, thus generating a new live TB vaccine. The Geneva Consensus published in March 2005 set out the opinion on priorities and requirements for developing live mycobacterial vaccines for Phase I trials. In the intervening period much progress has been made in both preclinical and clinical development of new TB vaccines and has provided the impetus for organising the second Geneva Consensus (held at WHO headquarters, April 2009) to discuss issues, including: i. Explore the regulatory requirements for live TB vaccines to enter Phase I trials, in particular those based on attenuated M. tuberculosis. Particular attention was paid to the characterisation and safety package likely to be required, including issues of attenuation, the presence of antibiotic resistance markers in live vaccines and the nature of any attenuated vaccine phenotype. ii. To identify the general criteria for further clinical development from Phase I through to Phase III. iii. Obtain a perspective of the regulatory landscape of developing countries where Phase II and III trials are to be held. iv. Review manufacturing considerations for live TB vaccines and relevance of the WHO and European Pharmacopeia guidelines and requirements for BCG vaccine. v. Consider requirements and associated issues related to the use of these new vaccines within an existing BCG vaccination programme., (Copyright 2010. Published by Elsevier Ltd.. All rights reserved.)

As the disease caused by Mycobacterium tuberculosis continues to be a burden, which the world continues to suffer, there is a concerted effort to find new vaccines to combat this problem. Of the various vaccines strategies, one viable option is the development of live mycobacterial vaccines. A meeting with researchers, regulatory bodies, vaccines developers and manufactures was held to consider the challenges and progress, which has been achieved with live mycobacterial vaccines (either modified BCG or attenuated M. tuberculosis). Discussion led to the production of a consensus document of the proposed entry criteria for Phase I clinical trials of candidate live mycobacterial vaccines. The vaccine must be characterised thoroughly to prove identity and consistency, as clinical trial lots are prepared. In pre-clinical studies, greater protective efficacy as well as improved safety potential relative to BCG should be considered when assessing potential vaccine candidates. A standard way to measure the protective efficacy to facilitate comparison between vaccine candidates was suggested. Additional safety criteria and verification of attenuation must be considered for attenuated M. tuberculosis. Two non-reverting independent mutations are recommended for such vaccines. When entering Phase I trials, enrollment should be based upon an acceptable characterisation of the study population regarding mycobacterium status and exclude HIV(+) individuals. BCG could be used as a comparator for blinding during the trials and to properly assess vaccine-specific adverse reactions, while assays are being developed to assess immunogenicity of vaccines. The proposed criteria suggested in this consensus document may facilitate the movement of the most promising vaccine candidates to the clinic and towards control of tuberculosis.

Fetal mouse raphe and hippocampal tissue (from embryos with crown-rump length (CRL) 13-16 mm) was transplanted into adult and aged isogenetic mice to study the growth of serotonergic fibers between host and donor tissue. A specific antibody against serotonin (5-HT) was used to immunocytochemically visualize 5-HT containing cell bodies and fibers. Unilateral fetal transplants into the hippocampi of adult (4-6 mo.) or aged (24 mo.) mice matured and sent out processes which very densely innervated the transplant tissue itself and extended into the host hippocampus. The termination of these fibers was consistent with the known 5-HT-hippocampal lamination pattern in normal animals. Qualitative comparisons suggested that the density of outgrowth into adult hippocampus was greater than into aged hippocampus. Conversely, adult 5-HT neurons send sprouts into fetal hippocampal tissue transplanted into the lateral ventricle. Therefore, immunocytochemical procedures can be used to monitor outgrowth from the fetal tissue to the host and ingrowth from the adult host to the fetal tissue. Furthermore, the apparent normal 5-HT lamination pattern produced by fetal raphe axons in adult hippocampus is consistent with reports that neuronal transplantation is effective in reversing the anatomical and behavioral deficits produced by homotypic denervation of a terminal field.

The effects of aging on catecholamine concentrations in heart ventricle, aorta, and adrenal gland were evaluated in two inbred mouse strains (C57BL/6J and DBA/2J) and an F1 hybrid (B6D2F1). The effects of aging on ventricular norepinephrine (NE) levels were found to be strain specific; only the C57BL/6J strain showed a significant decline in ventricular NE levels with age. Though all strains showed a decline in ventricular epinephrine (EPI) levels with age, the magnitude of the decrease varied between strains. An age-related increase in ventricular dopamine (DA) levels was observed in each of the strains. Although strain differences in catecholamine levels were also observed in aorta and adrenal gland, no age-related changes in catecholamine concentrations were noted in any of the strains. The findings indicate strain and organ specific changes in the effects of aging on catecholamine concentrations in peripheral organs.