The Influence of Fallback Foods on Great Ape Tooth Enamel

Lucas and colleagues recently proposed a model based on fracture and deformation concepts to describe how mammalian tooth enamel may be adapted to the mechanical demands of diet (Lucas et al.: Bioessays 30[2008] 374-385). Here we review the applicability of that model by examining existing data on the food mechanical properties and enamel morphology of great apes (Pan, Pongo, and Gorilla). Particular attention is paid to whether the consumption of fallback foods is likely to play a key role in influencing great ape enamel morphology. Our results suggest that this is indeed the case. We also consider the implications of this conclusion on the evolution of the dentition of extinct hominins

Fracture in teeth—a diagnostic for inferring bite force and tooth function

Teeth are brittle and highly susceptible to cracking. We propose that observations of such cracking can be used as a diagnostic tool for predicting bite force and inferring tooth function in living and fossil mammals. Laboratory tests on model tooth structures and extracted human teeth in simulated biting identify the principal fracture modes in enamel. Examination of museum specimens reveals the presence of similar fractures in a wide range of vertebrates, suggesting that cracks extended during ingestion or mastication. The use of ‘fracture mechanics’ from materials engineering provides elegant relations for quantifying critical bite forces in terms of characteristic tooth size and enamel thickness. The role of enamel microstructure in determining how cracks initiate and propagate within the enamel (and beyond) is discussed. The picture emerges of teeth as damage-tolerant structures, full of internal weaknesses and defects and yet able to contain the expansion of seemingly precarious cracks and fissures within the enamel shell. How the findings impact on dietary pressures forms an undercurrent of the study

Expanding ART for Treatment and Prevention of HIV in South Africa: Estimated Cost and Cost-Effectiveness 2011-2050

Background: Antiretroviral Treatment (ART) significantly reduces HIV transmission. We conducted a cost-effectiveness analysis of the impact of expanded ART in South Africa. Methods: We model a best case scenario of 90% annual HIV testing coverage in adults 15-49 years old and four ART eligibility scenarios: CD4 count <200 cells/mm3(current practice), CD4 count <350, CD4 count <500, all CD4 levels. 2011-2050 outcomes include deaths, disability adjusted life years (DALYs), HIV infections, cost, and cost per DALY averted. Service and ART costs reflect South African data and international generic prices. ART reduces transmission by 92%. We conducted sensitivity analyses. Results: Expanding ART to CD4 count <350 cells/mm3prevents an estimated 265,000 (17%) and 1.3 million (15%) new HIV infections over 5 and 40 years, respectively. Cumulative deaths decline 15%, from 12.5 to 10.6 million; DALYs by 14% from 109 to 93 million over 40 years. Costs drop $504 million over 5 years and$3.9 billion over 40 years with breakeven by 2013. Compared with the current scenario, expanding to <500 prevents an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. Expanding to all CD4 levels decreases HIV infections by 3.3 million (45%) and costs by $10 billion over 40 years, with breakeven by 2023. By 2050, using higher ART and monitoring costs, all CD4 levels saves$0.6 billion versus current; other ART scenarios cost $9-194 per DALY averted. If ART reduces transmission by 99$17.5 billion. Sensitivity analyses suggest that poor retention and predominant acute phase transmission reduce DALYs averted by 26% and savings by 7%. Conclusion: Increasing the provision of ART to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden. Feasibility including HIV testing and ART uptake, retention, and adherence should be evaluated

Detection of Tuberculosis in HIV-Infected and -Uninfected African Adults Using Whole Blood RNA Expression Signatures: A Case-Control Study

BACKGROUND: A major impediment to tuberculosis control in Africa is the difficulty in diagnosing active tuberculosis (TB), particularly in the context of HIV infection. We hypothesized that a unique host blood RNA transcriptional signature would distinguish TB from other diseases (OD) in HIV-infected and -uninfected patients, and that this could be the basis of a simple diagnostic test. METHODS AND FINDINGS: Adult case-control cohorts were established in South Africa and Malawi of HIV-infected or -uninfected individuals consisting of 584 patients with either TB (confirmed by culture of Mycobacterium tuberculosis [M.TB] from sputum or tissue sample in a patient under investigation for TB), OD (i.e., TB was considered in the differential diagnosis but then excluded), or healthy individuals with latent TB infection (LTBI). Individuals were randomized into training (80%) and test (20%) cohorts. Blood transcriptional profiles were assessed and minimal sets of significantly differentially expressed transcripts distinguishing TB from LTBI and OD were identified in the training cohort. A 27 transcript signature distinguished TB from LTBI and a 44 transcript signature distinguished TB from OD. To evaluate our signatures, we used a novel computational method to calculate a disease risk score (DRS) for each patient. The classification based on this score was first evaluated in the test cohort, and then validated in an independent publically available dataset (GSE19491). In our test cohort, the DRS classified TB from LTBI (sensitivity 95%, 95% CI [87-100]; specificity 90%, 95% CI [80-97]) and TB from OD (sensitivity 93%, 95% CI [83-100]; specificity 88%, 95% CI [74-97]). In the independent validation cohort, TB patients were distinguished both from LTBI individuals (sensitivity 95%, 95% CI [85-100]; specificity 94%, 95% CI [84-100]) and OD patients (sensitivity 100%, 95% CI [100-100]; specificity 96%, 95% CI [93-100]). Limitations of our study include the use of only culture confirmed TB patients, and the potential that TB may have been misdiagnosed in a small proportion of OD patients despite the extensive clinical investigation used to assign each patient to their diagnostic group. CONCLUSIONS: In our study, blood transcriptional signatures distinguished TB from other conditions prevalent in HIV-infected and -uninfected African adults. Our DRS, based on these signatures, could be developed as a test for TB suitable for use in HIV endemic countries. Further evaluation of the performance of the signatures and DRS in prospective populations of patients with symptoms consistent with TB will be needed to define their clinical value under operational conditions. Please see later in the article for the Editors' Summary

Fatigue Sensitivity of Y-TZP to Microscale Sharp-Contact Flaws

The strength degrading effects of sharp-contact damage are examined for Y-TZP ceramic plates bonded to a plastic substrate. Contacts are made with Vickers and Berkovich diamond indenters at low loads (0.1 N to 100 N) in the ceramic lower surfaces prior to bonding to the substrates. The indentations remain in the subthreshold region, that is, without visible corner radial cracks, over the lower region (\u3c 10 N) of the load range. A concentrated load is then applied sinusoidally to the ceramic upper surface, with the loading axis centered on the subsurface indentation flaw, thereby subjecting the flaw to cyclic tension. Relative to polished surfaces, the indentations diminish the single-cycle strength by an amount that increases with increasing indentation load. The critical number of cycles required to cause failure from the indentation flaws is then measured at specified maximum lower surface tensile stresses. At each indentation load, the strength of the ceramic plates diminishes with increased cycling. The scale of degradation is compared with that from previous studies on Y-TZP surfaces containing larger-scale surface damage: sandblast damage, as used in dental crown preparation; and blunt-contact trauma from a spherical indenter at 3000 N. These other damage modes are shown to be equivalent in their strength-degrading capacity to diamond pyramid indentations in the microscale load range 0.1 N to 1 N, attesting to the highly deleterious nature of sharp particulate contacts. The mechanism of fatigue is considered in terms of microcrack evolution within the indentation damage zone

In Situ Observations of Toughening Processes in Alumina Reinforced with Silicon Carbide Whiskers

An in situ study is made of crack interfaces in composites of alumina reinforced with silicon carbide whiskers. Both qualitative observations of the whisker-bridging micro-mechanisms and quantitative measurements of the crack profile are made to assess the specific role of the whiskers on the toughness curve (T-curve or R-curve). At small crackwall separations the whiskers act as elastic restraints to the point of rupture. In some cases the whiskers remain in frictional contact with the alumina matrix over large pullout distances (more than 1 μm) corresponding to a bridging zone approaching 1 mm. The results are discussed in relation to existing models of whisker reinforcement and published long-crack T-curve data

In Situ Measurements of Bridged Crack Interfaces in the Scanning Electron Microscope

A device for in situ SEM examination of crack propagation during loading of compact tension specimens is described, with a specific demonstration on an alumina ceramic. The device facilitates direct qualitative observations of the inception and subsequent frictional pullout of grain-localized bridges at the crack interface. Quantitative data on the bridging mechanism are obtained from measurements of the crack-opening displacements behind the crack tip. The crack profile is found to be closer to linear than parabolic at the bridged interface. Deconvolution of these crack-opening data allow for an evaluation of the closure tractions operative at the crack walls within the bridging zone, and thence the R-curve