Exploring hypotheses of the actions of TGF-beta 1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis

In vivo and in vitro studies give a paradoxical picture of the actions of the key regulatory factor TGF-beta 1 in epidermal wound healing with it stimulating migration of keratinocytes but also inhibiting their proliferation. To try to reconcile these into an easily visualized 3D model of wound healing amenable for experimentation by cell biologists, a multiscale model of the formation of a 3D skin epithelium was established with TGF-beta 1 literature-derived rule sets and equations embedded within it. At the cellular level, an agent-based bottom-up model that focuses on individual interacting units ( keratinocytes) was used. This was based on literature-derived rules governing keratinocyte behavior and keratinocyte/ECM interactions. The selection of these rule sets is described in detail in this paper. The agent-based model was then linked with a subcellular model of TGF-beta 1 production and its action on keratinocytes simulated with a complex pathway simulator. This multiscale model can be run at a cellular level only or at a combined cellular/subcellular level. It was then initially challenged ( by wounding) to investigate the behavior of keratinocytes in wound healing at the cellular level. To investigate the possible actions of TGF-beta 1, several hypotheses were then explored by deliberately manipulating some of these rule sets at subcellular levels. This exercise readily eliminated some hypotheses and identified a sequence of spatial-temporal actions of TGF-beta 1 for normal successful wound healing in an easy-to-follow 3D model. We suggest this multiscale model offers a valuable, easy-to-visualize aid to our understanding of the actions of this key regulator in wound healing, and provides a model that can now be used to explore pathologies of wound healing

Comparison of outpatient health care utilization among returning women and men Veterans from Afghanistan and Iraq

<p>Abstract</p> <p>Background</p> <p>The number of women serving in the United States military increased during Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF), leading to a subsequent surge in new women Veterans seeking health care services from the Veterans Administration (VA). The objective of this study was to examine gender differences among OEF/OIF Veterans in utilization of VA outpatient health care services.</p> <p>Methods</p> <p>Our retrospective cohort consisted of 1,620 OEF/OIF Veterans (240 women and 1380 men) who enrolled for outpatient healthcare at a single VA facility. We collected demographic data and information on military service and VA utilization from VA electronic medical records. To assess gender differences we used two models: use versus nonuse of services (logistic regression) and intensity of use among users (negative binomial regression).</p> <p>Results</p> <p>In our sample, women were more likely to be younger, single, and non-white than men. Women were more likely to utilize outpatient care services (odds ratio [OR] = 1.47, 95% confidence interval [CI]:1.09, 1.98), but once care was initiated, frequency of visits over time (intensity) did not differ by gender (incident rate ratio [IRR] = 1.07; 95% CI: 0.90, 1.27).</p> <p>Conclusion</p> <p>Recently discharged OEF/OIF women Veterans were more likely to seek VA health care than men Veterans. But the intensity of use was similar between women and men VA care users. As more women use VA health care, prospective studies exploring gender differences in types of services utilized, health outcomes, and factors associated with satisfaction will be required.</p

Climate change and increased risk for the insurance sector: A global perspective and an assessment for the Netherlands.

Climate change is projected to increase the frequency and severity of extreme weather events. As a consequence, economic losses caused by natural catastrophes could increase significantly. This will have considerable consequences for the insurance sector. On the one hand, increased risk from weather extremes requires assessing expected changes in damage and including adequate climate change projections in risk management. On the other hand, climate change can also bring new business opportunities for insurers. This paper gives an overview of the consequences of climate change for the insurance sector and discusses several strategies to cope with and adapt to increased risks. The particular focus is on the Dutch insurance sector, as the Netherlands is extremely vulnerable to climate change, especially with regard to extreme precipitation and flooding. Current risk sharing arrangements for weather risks are examined while potential new business opportunities, adaptation strategies, and public-private partnerships are identified. © The Author(s) 2009

Bayesian probabilistic network modeling from multiple independent replicates

Often protein (or gene) time-course data are collected for multiple replicates. Each replicate generally has sparse data with the number of time points being less than the number of proteins. Usually each replicate is modeled separately. However, here all the information in each of the replicates is used to make a composite inference about signal networks. The composite inference comes from combining well structured Bayesian probabilistic modeling with a multi-faceted Markov Chain Monte Carlo algorithm. Based on simulations which investigate many different types of network interactions and experimental variabilities, the composite examination uncovers many important relationships within the networks. In particular, when the edge's partial correlation between two proteins is at least moderate, then the composite's posterior probability is large

Dual Use of Veterans Health Administration and Indian Health Service: Healthcare Provider and Patient Perspectives

Many American Indian and Alaska Native veterans are eligible for healthcare from Veterans Health Administration (VHA) and from Indian Health Service (IHS). These organizations executed a Memorandum of Understanding in 2003 to share resources, but little was known about how they collaborated to deliver healthcare. To describe dual use from the stakeholders’ perspectives, including incentives that encourage cross-use, which organization’s primary care is “primary,” and the potential problems and opportunities for care coordination across VHA and IHS. VHA healthcare staff, IHS healthcare staff and American Indian and Alaska Native veterans. Focus groups were conducted using a semi-structured guide. A software-assisted text analysis was performed using grounded theory to develop analytic categories. Dual use was driven by variation in institutional resources, leading patients to actively manage health-seeking behaviors and IHS providers to make ad hoc recommendations for veterans to seek care at VHA. IHS was the “primary” primary care for dual users. There was little coordination between VHA and IHS resulting in delays and treatment conflicts, but all stakeholder groups welcomed future collaboration. Fostering closer alignment between VHA and IHS would reduce care fragmentation and improve accountability for patient care

Blood volume measurement with indocyanine green pulse spectrophotometry: dose and site of dye administration

(1) To determine the optimal administration site and dose of indocyanine green (ICG) for blood volume measurement using pulse spectrophotometry, (2) to assess the variation in repeated blood volume measurements for patients after subarachnoid hemorrhage and (3) to evaluate the safety and efficacy of this technique in patients who were treated for an intracranial aneurysm. Four repeated measurements of blood volume (BV) were performed in random order of bolus dose (10 mg or 25 mg ICG) and venous administration site (peripheral or central) in eight patients admitted for treatment of an intracranial aneurysm. Another five patients with subarachnoid hemorrhage underwent three repeated BV measurements with 25 mg ICG at the same administration site to assess the coefficient of variation. The mean +/- SD in BV was 4.38 +/- 0.88 l (n = 25) and 4.69 +/- 1.11 l (n = 26) for 10 mg and 25 mg ICG, respectively. The mean +/- SD in BV was 4.59 +/- 1.15 l (n = 26) and 4.48 +/- 0.86 l (n = 25) for central and peripheral administration, respectively. No significant difference was found. The coefficient of variance of BV measurement with 25 mg of ICG was 7.5% (95% CI: 3-12%). There is no significant difference between intravenous administration of either 10 or 25 mg ICG, and this can be injected through either a peripheral or central venous catheter. The 7.5% coefficient of variation in BV measurements determines the detectable differences using ICG pulse spectrophotometr

The solid-state photo-CIDNP effect

The solid-state photo-CIDNP effect is the occurrence of a non-Boltzmann nuclear spin polarization in rigid samples upon illumination. For solid-state NMR, which can detect this enhanced nuclear polarization as a strong modification of signal intensity, the effect allows for new classes of experiments. Currently, the photo- and spin-chemical machinery of various RCs is studied by photo-CIDNP MAS NMR in detail. Until now, the effect has only been observed at high magnetic fields with 13C and 15N MAS NMR and in natural photosynthetic RC preparations in which blocking of the acceptor leads to cyclic electron transfer. In terms of irreversible thermodynamics, the high-order spin structure of the initial radical pair can be considered as a transient order phenomenon emerging under non-equilibrium conditions and as a first manifestation of order in the photosynthetic process. The solid-state photo-CIDNP effect appears to be an intrinsic property of natural RCs. The conditions of its occurrence seem to be conserved in evolution. The effect may be based on the same fundamental principles as the highly optimized electron transfer. Hence, the effect may allow for guiding artificial photosynthesis