Tensile Overload and Stress Intensity Shielding Investigations by Ultrasound

Growth of a fatigue crack is modified according to the development of contacts between the crack faces [1,2] creating shielding, thus canceling a portion of the crack driving force. These contacts develop through a number of mechanisms, including plastic deformation, sliding of the faces with respect to each other and the collection of debris such as oxide particles [3]. Compressive stresses are created on either side of the partially contacting crack faces resulting in opening loads that must be overcome in order to apply a driving force at the crack tip. In this way, the crack tip is shielded from a portion of the applied load, thus creating the need for modification [1] of the applied stress intensity range from ΔK = KImax − KImin to ΔKeff = KImax − KIsh. Determination of the contact size and density in the region of closure from ultrasonic transmission and diffraction experiments [4] has allowed estimation of the magnitude of Kish on a crack grown under constant ΔK conditions. The calculation has since [5] been extended to fatigue cracks grown with a tensile overload block. The calculation was also successful in predicting the growth rate of the crack after reinitiation had occurred. This paper reports the further extension to the effects of a variable ΔK on fatigue crack growth. In addition, this paper presents preliminary results on detection of the tightly closed crack extension present during the growth retardation period after application of a tensile overload as well as an observation of the crack surface during reinitiation of growth that presents some interesting questions

C/EBPβ-Thr217 Phosphorylation Signaling Contributes to the Development of Lung Injury and Fibrosis in Mice

mice are refractory to Bleomycin-induced lung fibrosis the molecular mechanisms remain unknown. Here we show that blocking the ribosomal S-6 kinase (RSK) phosphorylation of the CCAAT/Enhancer Binding Protein (C/EBP)-β on Thr217 (a RSK phosphoacceptor) with either a single point mutation (Ala217), dominant negative transgene or a blocking peptide containing the mutated phosphoacceptor ameliorates the progression of lung injury and fibrosis induced by Bleomycin in mice. mice with a cell permeant, C/EBPβ peptide that inhibits phosphorylation of C/EBPβ on Thr217 (40 µg instilled intracheally on day-2 and day-6 after the single Bleomycin dose) also blocked the progression of lung injury and fibrosis induced by Bleomycin. Phosphorylation of human C/EBPβ on Thr266 (human homologue phosphoacceptor) was induced in collagen-activated human lung fibroblasts in culture as well as in activated lung fibroblasts in situ in lungs of patients with severe lung fibrosis but not in control lungs, suggesting that this signaling pathway may be also relevant in human lung injury and fibrosis.These data suggest that the RSK-C/EBPβ phosphorylation pathway may contribute to the development of lung injury and fibrosis

Systematic literature review of determinants of sedentary behaviour in older adults:a DEDIPAC study

BACKGROUND: Older adults are the most sedentary segment of society and high sedentary time is associated with poor health and wellbeing outcomes in this population. Identifying determinants of sedentary behaviour is a necessary step to develop interventions to reduce sedentary time. METHODS: A systematic literature review was conducted to identify factors associated with sedentary behaviour in older adults. Pubmed, Embase, CINAHL, PsycINFO and Web of Science were searched for articles published between 2000 and May 2014. The search strategy was based on four key elements: (a) sedentary behaviour and its synonyms; (b) determinants and its synonyms (e.g. correlates, factors); (c) types of sedentary behaviour (e.g. TV viewing, sitting, gaming) and (d) types of determinants (e.g. environmental, behavioural). Articles were included in the review if specific information about sedentary behaviour in older adults was reported. Studies on samples identified by disease were excluded. Study quality was rated by means of QUALSYST. The full review protocol is available from PROSPERO (PROSPERO 2014: CRD42014009823). The analysis was guided by the socio-ecological model framework. RESULTS: Twenty-two original studies were identified out of 4472 returned by the systematic search. These included 19 cross-sectional, 2 longitudinal and 1 qualitative studies, all published after 2011. Half of the studies were European. The study quality was generally high with a median of 82 % (IQR 69-96 %) using Qualsyst tool. Personal factors were the most frequently investigated with consistent positive association for age, negative for retirement, obesity and health status. Only four studies considered environmental determinants suggesting possible association with mode of transport, type of housing, cultural opportunities and neighbourhood safety and availability of places to rest. Only two studies investigated mediating factors. Very limited information was available on contexts and sub-domains of sedentary behaviours. CONCLUSION: Few studies have investigated determinants of sedentary behaviour in older adults and these have to date mostly focussed on personal factors, and qualitative studies were mostly lacking. More longitudinal studies are needed as well as inclusion of a broader range of personal and contextual potential determinants towards a systems-based approach, and future studies should be more informed by qualitative work

A Dynamical Analysis of the Suitability of Prehistoric Spheroids from the Cave of Hearths as Thrown Projectiles

Spheroids are ball-shaped stone objects found in African archaeological sites dating from 1.8 million years ago (Early Stone Age) to at least 70,000 years ago (Middle Stone Age). Spheroids are either fabricated or naturally shaped stones selected and transported to places of use making them one of the longest-used technologies on record. Most hypotheses about their use suggest they were percussive tools for shaping or grinding other materials. However, their size and spherical shape make them potentially useful as projectile weapons, a property that, uniquely, humans have been specialised to exploit for millions of years. Here we show (using simulations of projectile motions resulting from human throwing) that 81% of a sample of spheroids from the late Acheulean (Bed 3) at the Cave of Hearths, South Africa afford being thrown so as to inflict worthwhile damage to a medium-sized animal over distances up to 25 m. Most of the objects have weights that produce optimal levels of damage from throwing, rather than simply being as heavy as possible (as would suit other functions). Our results show that these objects were eminently suitable for throwing, and demonstrate how empirical research on behavioural tasks can inform and constrain our theories about prehistoric artefacts

Explicit Logic Circuits Discriminate Neural States

The magnitude and apparent complexity of the brain's connectivity have left explicit networks largely unexplored. As a result, the relationship between the organization of synaptic connections and how the brain processes information is poorly understood. A recently proposed retinal network that produces neural correlates of color vision is refined and extended here to a family of general logic circuits. For any combination of high and low activity in any set of neurons, one of the logic circuits can receive input from the neurons and activate a single output neuron whenever the input neurons have the given activity state. The strength of the output neuron's response is a measure of the difference between the smallest of the high inputs and the largest of the low inputs. The networks generate correlates of known psychophysical phenomena. These results follow directly from the most cost-effective architectures for specific logic circuits and the minimal cellular capabilities of excitation and inhibition. The networks function dynamically, making their operation consistent with the speed of most brain functions. The networks show that well-known psychophysical phenomena do not require extraordinarily complex brain structures, and that a single network architecture can produce apparently disparate phenomena in different sensory systems

Can osseous landmarks in the distal medial humerus be used to identify the attachment sites of ligaments and tendons: paleopathologic–anatomic imaging study in cadavers

Objective: To describe osseous landmarks that allow identification of the attachments of the ligaments and tendons in the distal medial aspect of the humerus. Materials and methods: Reliable osseous landmarks in the distal medial aspect of the humerus were identified in 34 well-preserved specimens from a paleopathologic collection. These osseous landmarks were then sought in magnetic resonance (MR) images of ten cadaveric elbow specimens so that the ease of their visualization and optimal imaging plane could be assessed. To assign these osseous landmarks to specific attachments of the tendons and ligaments in the distal medial humerus, we cut the specimens in slices and photographed and examined them. Subsequently, the prevalence of these osseous landmarks as well as the attachment sites of the tendons and ligaments in this location was determined. Results: We determined ten reliable osseous landmarks in the distal medial aspect of the humerus, their prevalence and ease of identification, and their relationship to the attachments of the tendons and ligaments at the medial distal humerus. Conclusion: It is possible to use osseous landmarks at the distal medial humerus to facilitate identification of the different attachments of tendons and ligaments when MR images of the elbow are assesse

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Reproducibility of quantitative F-18-3'-deoxy-3'-fluorothymidine measurements using positron emission tomography

Positron emission tomography (PET) using F-18-3'-deoxy-3'-fluorothymidine ([F-18]FLT) allows noninvasive monitoring of tumour proliferation. For serial imaging in individual patients, good reproducibility is essential. The purpose of the present study was to evaluate the reproducibility of quantitative [F-18]FLT measurements. Nine patients with non-small-cell lung cancer (NSCLC) and six with head-and-neck cancer (HNC) underwent [F-18]FLT PET twice within 7 days prior to therapy. The maximum pixel value (SUVmax) and a threshold defined volume (SUV41%) were defined for all delineated lesions. The plasma to tumour transfer constant (K-i) was estimated using both Patlak graphical analysis and nonlinear regression (NLR). NLR was also used to estimate k(3), which, at least in theory, selectively reflects thymidine kinase 1 activity. The level of agreement between test and retest values was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. All primary tumours and > 90% of clinically suspected locoregional metastases could be delineated. In total, 24 lesions were defined. NLR-derived K-i, Patlak-derived K-i, SUV41% and SUVmax showed excellent reproducibility with ICCs of 0.92, 0.95, 0.98 and 0.93, and SDs of 16%, 12%, 7% and 11%, respectively. Reproducibility was poor for k(3) with an ICC of 0.43 and SD of 38%. Quantitative [F-18]FLT measurements are reproducible in both NSCLC and HNC patients. When monitoring response in individual patients, changes of more than 15% in SUV41%, 20-25% in SUVmax and Patlak-derived K-i, and 32% in NLR3k-derived K-i are likely to represent treatment effect

MODEM: a comprehensive approach to modelling outcome and costs impacts of interventions for dementia. Protocol paper

Background The MODEM project (A comprehensive approach to MODelling outcome and costs impacts of interventions for DEMentia) explores how changes in arrangements for the future treatment and care of people living with dementia, and support for family and other unpaid carers, could result in better outcomes and more efficient use of resources. Methods MODEM starts with a systematic mapping of the literature on effective and (potentially) cost-effective interventions in dementia care. Those findings, as well as data from a cohort, will then be used to model the quality of life and cost impacts of making these evidence-based interventions more widely available in England over the period from now to 2040. Modelling will use a suite of models, combining microsimulation and macrosimulation methods, modelling the costs and outcomes of care, both for an individual over the life-course from the point of dementia diagnosis, and for individuals and England as a whole in a particular year. Project outputs will include an online Dementia Evidence Toolkit, making evidence summaries and a literature database available free to anyone, papers in academic journals and other written outputs, and a MODEM Legacy Model, which will enable local commissioners of services to apply the model to their own populations. Discussion Modelling the effects of evidence-based cost-effective interventions and making this information widely available has the potential to improve the health and quality of life both of people with dementia and their carers, while ensuring that resources are used efficiently

Smad4-expression is decreased in breast cancer tissues: a retrospective study

BACKGROUND: Although transforming growth factor β (TGF-β) typically inhibits proliferation of epithelial cells, consistent with a tumor suppressor activity, it paradoxically also exhibits pro-metastatic activity in the later stages of carcinogenesis. Since tumors often display altered TGF-β signaling, particularly involving the Smad-pathway, we investigated the role of Smad4-expression in breast cancer. METHODS: Smad4 expression was investigated by immunohistochemistry in formalin-fixed, paraffin-embedded tissue from 197 samples of primary breast cancer obtained between 1986 and 1998. The prognostic value of Smad4-expression was analyzed. RESULTS: Smad4 expression was found to be reduced in lobular and ductal breast carcinoma as compared to surrounding uninvolved lobular and ductal breast epithelia (p < 0.001, n = 50). Smad4-expression correlated positively with expression of TGF-β-receptor I (p < 0.001, n = 197) and TGF-β-receptor II (p < 0.001, n = 197), but showed no significant correlation with tumor size, metastases, nodal status, histological grade, histological type, or estrogen receptor expression. While not achieving statistical significance, there was a trend towards longer survival times in patients with Smad4 negative tumors. CONCLUSION: According to the suggested role of Smad4 as a tumor suppressor we observed that expression of Smad4 is lower in human breast cancer than in surrounding breast epithelium. However, we also observed a trend towards longer survival times in Smad4-negative patients, indicating the complex role of TGF-β signaling in tumor progression