The anisotropic hyperelastic biomechanical response of the vocal ligament and implications for frequency regulation: A case study

One of the primary mechanisms to vary one's vocal frequency is through vocal fold length changes. As stress and deformation are linked to each other, it is hypothesized that the anisotropy in the biomechanical properties of the vocal fold tissue would affect the phonation characteristics. A biomechanical model of vibrational frequency rise during vocal fold elongation is developed which combines an advanced biomechanical characterization protocol of the vocal fold tissue with continuum beam models. Biomechanical response of the tissue is related to a microstructurally informed, anisotropic, nonlinear hyperelastic constitutive model. A microstructural characteristic (the dispersion of collagen) was represented through a statistical orientation function acquired from a second harmonic generation image of the vocal ligament. Continuum models of vibration were constructed based upon Euler–Bernoulli and Timoshenko beam theories, and applied to the study of the vibration of a vocal ligament specimen. From the natural frequency predictions in dependence of elongation, two competing processes in frequency control emerged, i.e., the applied tension raises the frequency while simultaneously shear deformation lowers the frequency. Shear becomes much more substantial at higher modes of vibration and for highly anisotropic tissues. The analysis was developed as a case study based on a human vocal ligament specimen

Biostratigraphic Evidence Relating to the Age-Old Question of Hannibal's Invasion of Italy, II: Chemical Biomarkers and Microbial Signatures

Open access article. Creative Commons Attribution 4.0 International License (CC BY 4.0) appliesAs discussed in Part I, a large accumulation of mammalian faeces at the mire site in the upper Guil Valley near Mt. Viso, dated to 2168 cal 14C yr., provides the first evidence of the passage of substantial but indeterminate numbers of mammals within the time frame of the Punic invasion of Italia. Specialized organic biomarkers bound up in a highly convoluted and bioturbated bed constitute an unusual anomaly in a histosol comprised of fibric and hemist horizons that are usually expected to display horizontal bedding. The presence of deoxycholic acid and ethylcoprostanol derived from faecal matter, coupled with high relative numbers of Clostridia 16S rRNA genes, suggests a substantial accumulation of mammalian faeces at the site over 2000 years ago. The results reported here constitute the first chemical and biological evidence of the passage of large numbers of mammals, possibly indicating the route of the Hannibalic army at this time. Combined with the geological analysis reported in Part I, these data provide a background supporting the need for further historical archaeological exploration in this area.Ye

Biostratigraphic Evidence Relating to the Age-Old Question of Hannibal's Invasion of Italy, I: History and Geological Reconstruction

Controversy over the alpine route that Hannibal of Carthage followed from the Rhône Basin into Italia has raged amongst classicists and ancient historians for over two millennia. The motivation for identifying the route taken by the Punic Army through the Alps lies in its potential for identifying sites of historical archaeological significance and for the resolution of one of history's most enduring quandaries. Here, we present stratigraphic, geochemical and microbiological evidence recovered from an alluvial floodplain mire located below the Col de la Traversette (~3000 m asl—above sea level) on the French/Italian border that potentially identifies the invasion route as the one originally proposed by Sir Gavin de Beer (de Beer 1974). The dated layer is termed the MAD bed (mass animal deposition) based on disrupted bedding, greatly increased organic carbon and key/specialized biological components/compounds, the latter reported in Part II of this paper. We propose that the highly abnormal churned up (bioturbated) bed was contaminated by the passage of Hannibal's animals, possibly thousands, feeding and watering at the site, during the early stage of Hannibal's invasion of Italia (218 bc)

Cure or control: complying with biomedical regime of diabetes in Cameroon

<p>Abstract</p> <p>Background</p> <p>The objective of the study was to explore the cultural aspect of compliance, its underlying principles and how these cultural aspects can be used to improve patient centred care for diabetes in Cameroon.</p> <p>Methods</p> <p>We used participant observation to collect data from a rural and an urban health district of Cameroon from June 2001 to June 2003. Patients were studied in their natural settings through daily interactions with them. The analysis was inductive and a continuous process from the early stages of fieldwork.</p> <p>Results</p> <p>The ethnography revealed a lack of basic knowledge about diabetes and diabetes risk factors amongst people with diabetes. The issue of compliance was identified as one of the main themes in the process of treating diabetes. Compliance emerged as part of the discourse of healthcare providers in clinics and filtered into the daily discourses of people with diabetes. The clinical encounters offered treatment packages that were socially inappropriate therefore rejected or modified for most of the time by people with diabetes. Compliance to biomedical therapy suffered a setback for four main reasons: dealing with competing regimes of treatment; coming to terms with biomedical treatment of diabetes; the cost of biomedical therapy; and the impact of AIDS on accepting weight loss as a lifestyle measure in prescription packages. People with diabetes had fears about and negative opinions of accepting certain prescriptions that they thought could interfere with their accustomed social image especially that which had to do with bridging their relationship with ancestors and losing weight in the era of HIV/AIDS.</p> <p>Conclusion</p> <p>The cultural pressures on patients are responsible for patients' partial acceptance of and adherence to prescriptions. Understanding the self-image of patients and their background cultures are vital ingredients to improve diabetes care in low-income countries of Sub-Sahara Africa like Cameroon.</p

A Role for TLR4 in Clostridium difficile Infection and the Recognition of Surface Layer Proteins

Clostridium difficile is the etiological agent of antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis in humans. The role of the surface layer proteins (SLPs) in this disease has not yet been fully explored. The aim of this study was to investigate a role for SLPs in the recognition of C. difficile and the subsequent activation of the immune system. Bone marrow derived dendritic cells (DCs) exposed to SLPs were assessed for production of inflammatory cytokines, expression of cell surface markers and their ability to generate T helper (Th) cell responses. DCs isolated from C3H/HeN and C3H/HeJ mice were used in order to examine whether SLPs are recognised by TLR4. The role of TLR4 in infection was examined in TLR4-deficient mice. SLPs induced maturation of DCs characterised by production of IL-12, TNFα and IL-10 and expression of MHC class II, CD40, CD80 and CD86. Furthermore, SLP-activated DCs generated Th cells producing IFNγ and IL-17. SLPs were unable to activate DCs isolated from TLR4-mutant C3H/HeJ mice and failed to induce a subsequent Th cell response. TLR4−/− and Myd88−/−, but not TRIF−/− mice were more susceptible than wild-type mice to C. difficile infection. Furthermore, SLPs activated NFκB, but not IRF3, downstream of TLR4. Our results indicate that SLPs isolated from C. difficile can activate innate and adaptive immunity and that these effects are mediated by TLR4, with TLR4 having a functional role in experimental C. difficile infection. This suggests an important role for SLPs in the recognition of C. difficile by the immune system

Biomechanical influences on the vibration of human vocal fold tissue

This investigation attempts to shed light on phonation from a solid mechanics (i.e. biomechanics) perspective. The global hypothesis is that the biomechanical properties of the vocal fold lamina propria are critical to understanding phonatory mechanisms. The contributions of this research can be summarized into two main categories: (1) using optical measurements of vocal fold tensile deformation to determine spatial heterogeneities in the biomechanical properties and the implications of said heterogeneities to phonation, and (2) measuring the vocal fold biomechanical anisotropy and subsequently exploring the effects of the anisotropy on vocal fold vibration through models (computational and analytical). The biomechanical properties were examined using in vitro experiments of human vocal fold cover and vocal ligament specimens isolated from excised larynges. In one study, an improved uniaxial testing protocol was used involving optical measurements of the actual tissue deformation (not simply the applied displacement). The initial longitudinal elastic modulus was found to be considerably higher if determined based on optical displacement measurements than typical values reported in the literature. Also, digital image correlation (DIC) was used to obtain the entire spatial deformation field for a ligament specimen. DIC results revealed that the elastic modulus was very heterogeneous, being approximately 10 times higher at the mid-point of the vocal ligament than in the anterior and posterior macula flavae regions. However, it was discovered that the modulus heterogeneity was much greater in specimens from non-smokers as opposed to those from smokers. Additionally, microstructural images revealed that the collagen fibers were less aligned and less dense at the mid-membranous location in smokers than in non-smokers, which may support the biomechanical heterogeneity findings. The strong modulus gradient is proposed to have a functional role of enabling more complete glottal close which was verified through a finite element eigenmode analysis. A new protocol was developed to enable empirical measurements of the biomechanical anisotropy (i.e. longitudinal elastic modulus to longitudinal shear modulus ratio) within a single specimen by conducting uniaxial tensile and transverse indentation experiments. In the unstretched state, the anisotropy was discovered to be substantially impact the vibration characteristics through transversely isotropic finite element models and analytical Timoshenko beam models. Finally, the anisotropy was represented in a microstructural, anisotropic, nonlinear, hyperelastic constitutive model (Gasser-Ogden-Holzapfel model). Multiphoton microscopy images of a vocal ligament specimen\u27s micro-architecture were analyzed and the degree of collagen fiber dispersion was quantified. The natural frequencies of vibration were predicted using Euler-Bernoulli and Timoshenko beam models in dependence of the neuromuscular elongation of the ligament. The primary factor influencing the natural frequencies as the anisotropy increased was transverse shear deformation