The complexities of breast cancer desmoplasia

The stromal, or 'desmoplastic', responses seen histologically in primary breast carcinomas can vary from being predominantly cellular (fibroblasts/myofibroblasts) with little collagen to being a dense acellular tissue. The mechanisms underlying the stromal response are complex; paracrine activation of myofibroblasts by growth factors is important but the contribution of cytokines/chemokines should not be ignored. A recent xenograft study has proposed that platelet-derived growth factor (PDGF) is the initiator of the desmoplastic response, but this has not been confirmed by (limited) analyses in vivo. Further studies are required to elaborate the mechanisms of the desmoplastic response, to determine its role in breast cancer progression and whether it is the same for all carcinomas

Culture shapes how we look at faces

Background: Face processing, amongst many basic visual skills, is thought to be invariant across all humans. From as early as 1965, studies of eye movements have consistently revealed a systematic triangular sequence of fixations over the eyes and the mouth, suggesting that faces elicit a universal, biologically-determined information extraction pattern. Methodology/Principal Findings: Here we monitored the eye movements of Western Caucasian and East Asian observers while they learned, recognized, and categorized by race Western Caucasian and East Asian faces. Western Caucasian observers reproduced a scattered triangular pattern of fixations for faces of both races and across tasks. Contrary to intuition, East Asian observers focused more on the central region of the face. Conclusions/Significance: These results demonstrate that face processing can no longer be considered as arising from a universal series of perceptual events. The strategy employed to extract visual information from faces differs across cultures

Multiscale methods for the solution of the Helmholtz and Laplace equations

This paper presents some numerical results about applications of multiscale techniques to boundary integral equations. The numerical schemes developed here are to some extent based on the results of the papers [6]—[10]. Section 2 deals with a short description of the theory of generalized Petrov-Galerkin methods for elliptic periodic pseudodifferential equations in $\mathbb{R}^n$ covering classical Galerkin schemes, collocation, and other methods. A general setting of multiresolution analysis generated by periodized scaling functions as well as a general stability and convergence theory for such a framework is outlined. The key to the stability analysis is a local principle due to one of the authors. Its applicability relies here on a sufficiently general version of a so-called discrete commutator property of wavelet bases (see [6]). These results establish important prerequisites for developing and analysing methods for the fast solution of the resulting linear systems (Section 2.4). The crucial fact which is exploited by these methods is that the stiffness matrices relative to an appropriate wavelet basis can be approximated well by a sparse matrix while the solution to the perturbed problem still exhibits the same asymptotic accuracy as the solution to the full discrete problem. It can be shown (see [7]) that the amount of the overall computational work which is needed to realize a required accuracy is of the order $\mathcal{O}(N(\log N)^b)$, where $N$ is the number of unknowns and $b \geq 0$ is some real number

Elastic response of cross-laminated engineered bamboo panels subjected to in-plane loading

© ICE Publishing: All rights reserved. Novel cross-laminated bamboo panels comprising three and five layers (G-XLam3 and G-XLam5) were tested in compression along the main (0°) and the transverse (90°) directions. Linear variable differential transformer (LVDT) and non-contact three-dimensional digital image correlation (DIC) measuring techniques were used separately to measure deformation in the elastic region, and the elastic moduli, Ep C,0 and Ep C,90, were derived. Mean elastic modulus values obtained using LVDTs exhibited a good match with analytically predicted values. In contrast, the elastic values obtained by the DIC method were considerably higher and presented a considerable scatter of results. For instance, the Ep C,0 for G-XLam3 and G-XLam5 panels were 17·22 and 15·67 GPa, and 14·86 and 12·48 GPa, using the DIC and LVDT methods, respectively. In general, G-XLam panels with a fifth of the cross-sectional thickness and twice the density of analogous cross-laminated timber exhibited an approximately two-fold increase in Ep C,0 and Ep C,90. Overall, this research provides guidelines for the assessment and standardisation of the testing procedures for similar engineered bamboo products using contact and non-contact methods and highlights the potential of using G-XLam panels in stiffness-driven applications and in combination with wood for structural purposes

Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis

BACKGROUND. Tuberculosis (TB) kills more people than any other infection, and new diagnostic tests to identify active cases are required. We aimed to discover and verify novel markers for TB in nondepleted plasma. / METHODS. We applied an optimized quantitative proteomics discovery methodology based on multidimensional and orthogonal liquid chromatographic separation combined with high-resolution mass spectrometry to study nondepleted plasma of 11 patients with active TB compared with 10 healthy controls. Prioritized candidates were verified in independent UK (n = 118) and South African cohorts (n = 203). / RESULTS. We generated the most comprehensive TB plasma proteome to date, profiling 5022 proteins spanning 11 orders-of-magnitude concentration range with diverse biochemical and molecular properties. We analyzed the predominantly low–molecular weight subproteome, identifying 46 proteins with significantly increased and 90 with decreased abundance (peptide FDR ≤ 1%, q ≤ 0.05). Verification was performed for novel candidate biomarkers (CFHR5, ILF2) in 2 independent cohorts. Receiver operating characteristics analyses using a 5-protein panel (CFHR5, LRG1, CRP, LBP, and SAA1) exhibited discriminatory power in distinguishing TB from other respiratory diseases (AUC = 0.81). / CONCLUSION. We report the most comprehensive TB plasma proteome to date, identifying novel markers with verification in 2 independent cohorts, leading to a 5-protein biosignature with potential to improve TB diagnosis. With further development, these biomarkers have potential as a diagnostic triage test. / FUNDING. Colciencias, Medical Research Council, Innovate UK, NIHR, Academy of Medical Sciences, Program for Advanced Research Capacities for AIDS, Wellcome Centre for Infectious Diseases Research

Cells activated for wound repair have the potential to direct collective invasion of an epithelium.

Mechanisms regulating how groups of cells are signaled to move collectively from their original site and invade surrounding matrix are poorly understood. Here we develop a clinically relevant ex vivo injury invasion model to determine whether cells involved in directing wound healing have invasive function and whether they can act as leader cells to direct movement of a wounded epithelium through a three-dimensional (3D) extracellular matrix (ECM) environment. Similar to cancer invasion, we found that the injured cells invade into the ECM as cords, involving heterotypical cell-cell interactions. Mesenchymal cells with properties of activated repair cells that typically locate to a wound edge are present in leader positions at the front of ZO-1-rich invading cords of cells, where they extend vimentin intermediate filament-enriched protrusions into the 3D ECM. Injury-induced invasion depends on both vimentin cytoskeletal function and MMP-2/9 matrix remodeling, because inhibiting either of these suppressed invasion. Potential push and pull forces at the tips of the invading cords were revealed by time-lapse imaging, which showed cells actively extending and retracting protrusions into the ECM. This 3D injury invasion model can be used to investigate mechanisms of leader cell-directed invasion and understand how mechanisms of wound healing are hijacked to cause disease

DRG coding practice: a nationwide hospital survey in Thailand

<p>Abstract</p> <p>Background</p> <p>Diagnosis Related Group (DRG) payment is preferred by healthcare reform in various countries but its implementation in resource-limited countries has not been fully explored.</p> <p>Objectives</p> <p>This study was aimed (1) to compare the characteristics of hospitals in Thailand that were audited with those that were not and (2) to develop a simplified scale to measure hospital coding practice.</p> <p>Methods</p> <p>A questionnaire survey was conducted of 920 hospitals in the Summary and Coding Audit Database (SCAD hospitals, all of which were audited in 2008 because of suspicious reports of possible DRG miscoding); the questionnaire also included 390 non-SCAD hospitals. The questionnaire asked about general demographics of the hospitals, hospital coding structure and process, and also included a set of 63 opinion-oriented items on the current hospital coding practice. Descriptive statistics and exploratory factor analysis (EFA) were used for data analysis.</p> <p>Results</p> <p>SCAD and Non-SCAD hospitals were different in many aspects, especially the number of medical statisticians, experience of medical statisticians and physicians, as well as number of certified coders. Factor analysis revealed a simplified 3-factor, 20-item model to assess hospital coding practice and classify hospital intention.</p> <p>Conclusion</p> <p>Hospital providers should not be assumed capable of producing high quality DRG codes, especially in resource-limited settings.</p

The Role of Individual Variables, Organizational Variables and Moral Intensity Dimensions in Libyan Management Accountants’ Ethical Decision Making

This study investigates the association of a broad set of variables with the ethical decision making of management accountants in Libya. Adopting a cross-sectional methodology, a questionnaire including four different ethical scenarios was used to gather data from 229 participants. For each scenario, ethical decision making was examined in terms of the recognition, judgment and intention stages of Rest’s model. A significant relationship was found between ethical recognition and ethical judgment and also between ethical judgment and ethical intention, but ethical recognition did not significantly predict ethical intention—thus providing support for Rest’s model. Organizational variables, age and educational level yielded few significant results. The lack of significance for codes of ethics might reflect their relative lack of development in Libya, in which case Libyan companies should pay attention to their content and how they are supported, especially in the light of the under-development of the accounting profession in Libya. Few significant results were also found for gender, but where they were found, males showed more ethical characteristics than females. This unusual result reinforces the dangers of gender stereotyping in business. Personal moral philosophy and moral intensity dimensions were generally found to be significant predictors of the three stages of ethical decision making studied. One implication of this is to give more attention to ethics in accounting education, making the connections between accounting practice and (in Libya) Islam. Overall, this study not only adds to the available empirical evidence on factors affecting ethical decision making, notably examining three stages of Rest’s model, but also offers rare insights into the ethical views of practising management accountants and provides a benchmark for future studies of ethical decision making in Muslim majority countries and other parts of the developing world

Short-Course, High-Dose Rifampicin Achieves Wolbachia Depletion Predictive of Curative Outcomes in Preclinical Models of Lymphatic Filariasis and Onchocerciasis

Lymphatic filariasis (LF) and onchocerciasis are priority neglected tropical diseases targeted for elimination. The only safe drug treatment with substantial curative activity against the filarial nematodes responsible for LF (Brugia malayi, Wuchereria bancrofti) or onchocerciasis (Onchocerca volvulus) is doxycycline. The target of doxycycline is the essential endosymbiont, Wolbachia. Four to six weeks doxycycline therapy achieves >90% depletion of Wolbachia in worm tissues leading to blockade of embryogenesis, adult sterility and premature death 18–24 months post-treatment. Long treatment length and contraindications in children and pregnancy are obstacles to implementing doxycycline as a public health strategy. Here we determine, via preclinical infection models of Brugia malayi or Onchocerca ochengi that elevated exposures of orally-administered rifampicin can lead to Wolbachia depletions from filariae more rapidly than those achieved by doxycycline. Dose escalation of rifampicin achieves >90% Wolbachia depletion in time periods of 7 days in B. malayi and 14 days in O. ochengi. Using pharmacokinetic-pharmacodynamic modelling and mouse-human bridging analysis, we conclude that clinically relevant dose elevations of rifampicin, which have recently been determined as safe in humans, could be administered as short courses to filariasis target populations with potential to reduce anti-Wolbachia curative therapy times to between one and two weeks

Health-promoting behaviors and social support of women of reproductive age, and strategies for advancing their health: Protocol for a mixed methods study

<p>Abstract</p> <p>Background</p> <p>Determining the health-promoting behaviors of women during the important period of reproduction provides valuable information for designing appropriate intervention programs for advancing women's health. There is no study on the health-promoting behaviors of women of reproductive age in Iran. Thus, the aim of this study is to explore these health-promoting behaviors for the purpose of developing comprehensive and culturally sensitive health advancement strategies for Iranian women.</p> <p>Methods/Design</p> <p>This study has a sequential explanatory mixed methods design. The follow-up explanation model is used to elaborate the quantitative results by collecting qualitative data from participants who could best assist in elucidating the results. The study is conducted in two sequential phases. The first phase is a population-based cross-sectional survey in which 1350 Iranian women of reproductive age are selected by proportional random multistage cluster sampling of the 22 main municipal sectors of Tehran, Iran. Questionnaires are completed through a face-to-face interview. The second phase is a qualitative study in which participants are selected using purposive sampling in the form of extreme case sampling on the basis of health-promoting behavior scores. The qualitative phase is based on data collected from focus group discussions or individual in-depth interviews. A conventional qualitative content analysis approach is used, and the data are managed with a computer-assisted program. Women's health-promoting strategies are developed using the qualitative and quantitative results, a review of the related literature, and the nominal group technique among experts.</p> <p>Discussion</p> <p>The findings of this mixed methods sequential explanatory study, obtained using a culturally sensitive approach, provide insights into the health behavioral factors that need to be considered if preventive strategies and intervention programs are to be designed to promote women's health in the community.</p