Arterial blood pressure targets in septic shock: is it time to move to an individualized approach?

Xu and colleagues evaluated the impact of increasing mean arterial blood pressure levels through norepinephrine administration on systemic hemodynamics, tissue perfusion, and sublingual microcirculation of septic shock patients with chronic hypertension. The authors concluded that, although increasing arterial blood pressure improved sublingual microcirculation parameters, no concomitant improvement in systemic tissue perfusion indicators was found. Here, we discuss why resuscitation targets may need to be individualized, taking into account the patient's baseline condition, and present directions for future research in this field.

Electrochemical CO2 Reduction - A Critical View on Fundamentals, Materials and Applications

The electrochemical reduction of CO2 has been extensively studied over the past decades. Nevertheless, this topic has been tackled so far only by using a very fundamental approach and mostly by trying to improve kinetics and selectivities toward specific products in half-cell configurations and liquid-based electrolytes. The main drawback of this approach is that, due to the low solubility of CO2 in water, the maximum CO2 reduction current which could be drawn falls in the range of 0.01–0.02 A cm–2. This is at least an order of magnitude lower current density than the requirement to make CO2-electrolysis a technically and economically feasible option for transformation of CO2 into chemical feedstock or fuel thereby closing the CO2 cycle. This work attempts to give a short overview on the status of electrochemical CO2 reduction with respect to challenges at the electrolysis cell as well as at the catalyst level. We will critically discuss possible pathways to increase both operating current density and conversion efficiency in order to close the gap with established energy conversion technologies.

A multi-level stakeholder approach to sustainable land management

Soils provide us with over 90% of all human food, livestock feed, fibre and fuel on Earth. Soils, however, have more than just productive functions. The key challenge in coming years will be to address the diverse and potentially conflicting demands now being made by human societies and other forms of life, while ensuring that future generations have the same potential to use soils and land of comparable quality. In a multi-level stakeholder approach, down-to-earth action will have to be supplemented with measures at various levels, from households to communities, and from national policies to international conventions. Knowledge systems, both indigenous and scientific, and related research and learning processes must play a central role. Ongoing action can be enhanced through a critical assessment of the impact of past achievements, and through better cooperation between people and institutions.

Wright’s Version of Critical Realism

N. T. Wright’s research project “Christian Origins and the Question of God” is characterized by its use of the method of critical realism. Now, “critical realism” is a term that has been used in connection with different epistemo-logical positions because the term has been “constantly reinvented.” It is very easy to make up a term when one wants to distinguish oneself from an assumed naïve approach to reality. As has been observed earlier, the use of a distinct term does not necessarily mean the same if used by another author; the context is important. One has to track literal dependencies to evaluate whether continuity with former uses of a term is intended. That is to say, the term “critical realism” has proven to be equivocal, although this has rarely been noticed . This does not mean that taking such a critical realist stance cannot present a decisive advantage over rather unreflective approaches to whatever sort of reality. Nevertheless, philosophically it can probably only be a start. The purpose of this contribution to this compendium will be to analyze the content claims and the status of N. T. Wright’s critical realism in these regards, with a special emphasis on Paul and the Faithfulness of God, of course.

14-3-3zeta overexpression in multiple human cancers plays a critical role in cancer progression

14-3-3 is a family of highly conserved and ubiquitously expressed proteins in eukaryotic organisms. 14-3-3 isoforms bind in a phospho-serine/threonine-dependent manner to a host of proteins involved in essential cellular processes including cell cycle, signal transduction and apoptosis. We fortuitously discovered 14-3-3 zeta overexpression in many human primary cancers, such as breast, lung, and sarcoma, and in a majority of cancer cell lines. To determine 14-3-3 zeta involvement in breast cancer progression, we used immunohistochemical analysis to examine 14-3-3 zeta expression in human primary invasive breast carcinomas. High 14-3-3 zeta expression was significantly correlated with poor prognosis of breast cancer patients. Increased expression of 14-3-3 zeta was also significantly correlated with elevated PKB/Akt activation in patient samples. Thus, 14-3-3 zeta is a marker of poor prognosis in breast cancers. Furthermore, up-regulation of 14-3-3 zeta enhanced malignant transformation of cancer cells in vitro. ^ To determine the biological significance of 14-3-3 zeta in human cancers, small interfering RNAs (siRNA) were used to specifically block 14-3-3 zeta expression in cancer cells. 14-3-3 zeta siRNA inhibited cellular proliferation by inducing a G1 arrest associated with up-regulation of p27 KIP1 and p21CIP1 cyclin dependent kinase inhibitors. Reduced 14-3-3 zeta inhibited PKB/Akt activation while stimulating the p38 signaling pathway. Silencing 14-3-3 zeta expression also increased stress-induced apoptosis by caspase activation. Notably, 14-3-3 zeta siRNA inhibited transformation related properties of breast cancer cells in vitro and inhibited tumor progression of breast cancer cells in vivo. 14-3-3 zeta may be a key regulatory factor controlling multiple signaling pathways leading to tumor progression. ^ The data indicate 14-3-3 zeta is a major regulator of cell growth and apoptosis and may play a critical role in the development of multiple cancer types. Hence, blocking 14-3-3 zeta may be a promising therapeutic approach for numerous cancers. ^

Can accreditation work as a tool for quality improvement in public health? A critical review

Public health departments play an important role in promoting and preserving the health of communities. The lack of a system to ensure their quality and accountability led to the development of a national voluntary accreditation program by Public Health Accreditation Board (PHAB). The concept that accreditation will lead to quality improvement in public health which will ultimately lead to healthy communities seems intuitive but lacks a robust body of evidence. A critical review of literature was conducted to explore if accreditation can lead to quality improvement in public health. The articles were selected from publically available databases using a specific set of criteria for inclusion, exclusion, and appraisal. To understand the relationship between accreditation and quality improvement, the potential strengths and limitations of accreditation process were evaluated. Recommendations for best practices are suggested so that public health accreditation can yield maximum benefits. A logic model framework to help depict the impact of accreditation on various levels of public health outcomes is also discussed in this thesis. The literature review shows that existing accreditation programs in other industries show limited but encouraging evidence that accreditation will improve quality and strengthen the delivery of public health services. While progress in introducing accreditation in public health can be informed by other accredited industries, the public health field has its own set of challenges. Providing incentives, creating financing strategies, and having a strong leadership will allow greater access to accreditation by all public health departments. The suggested recommendations include that continuous evaluation, public participation, systems approach, clear vision, and dynamic standards should become hallmarks of the accreditation process. Understanding the link between accreditation, quality improvement, and health outcomes will influence the successful adoption and implementation of the public health accreditation program. This review of literature suggests that accreditation is an important step in improving the quality of public health departments and in ultimately improving the health of communities. However, accreditation should be considered in an integrated system of tools and approaches to improve the public health practice. Hence, it is a means to an end - not an end unto itself.^

A critical assessment of the National Institutes of Health Consensus Development Program against the eras which shaped it

This research study offers a critical assessment of NIH's Consensus Development Program (CDP), focusing upon its historical and valuative bases and its institutionalization in response to social and political forces. The analysis encompasses systems-level, as well as interpersonal factors in the adoption of consensus as the mechanism for resolving scientific controversies in clinical practice application. Further, the evolution of the CDP is also considered from an ecological perspective as a reasoned adaptation by NIH to pressures from its supporters and clients for translating biomedical research into medical practice. The assessment examines federal science policy and institutional designs for the inclusion of the public interest and democratic deliberation.^ The study relies on three distinct approaches to social research. Conventional historical methods were utilized in the interpretation of social and political influences across eras on the evolution of the National Institutes of Health and its response to demands for accountability and relevance through its Consensus Development Program. An embedded single-case study was utilized for an empirical examination of the CDP mechanism through five exemplar conferences. Lastly, a sociohistorical approach was taken to the CDP in order to consider its responsiveness to the values of the eras which created and shaped it. An exploration of organizational behavior with considerations for institutional reform as a response to continuing political and social pressure, it is a study of organizational birth, growth, and response to demands from its environment. The study has explanatory import in its attempt to account for the creation, timing, and form of the CDP, relative to political, institutional, and cultural pressures, and predictive import thorough its historical view which provides a basis for informed speculation on the playing out of tensions between extramural and intermural scientists and the current demands for health care reform. ^

Critical determinants of estrogen receptor -mediated agonist activity

Exogenous ligands that bind to the estrogen receptor (ER) exhibit unique pharmacologies distinct from that observed with the endogenous hormone, 17β-estradiol (ED. Differential activity among ER ligands has been observed at the level of receptor binding, promoter interaction and transcriptional activation. Furthermore, xenoestrogens can display tissue-specific agonist activity on the cellular level, functioning as an agonist in one tissue and as an antagonist in another. That the same ligand, functioning through the same receptor, can produce differing agonist responses on the cellular level indicates that there are tissue-specific determinants of agonist activity. In these studies critical molecular determinants of agonist activity were characterized for several cell types. In the normal and neoplastic myometrium a proliferative response was dependent upon activation of AF2 of the ER, functioning as a determinant of agonism in this cell type. Progesterone receptor (PR) ligands transdominantly suppressed ER-mediated transcription and proliferation in uterine leiomyoma cells, indicating that ER/PR cross-talk can modulate agonist activity in a myometrial cell background. In the breast, the agonist response to ER ligands was investigated by employing a functional genomics approach to generate gene expression profiles. Treatment of breast cancer cells with the selective estrogen receptor modulator tamoxifen largely recapitulated the expression profile induced by treatment with the agonist E2, despite the well-characterized antiproliferative effects produced by tamoxifen in this cell type. While the expression of many genes involved in regulating cell cycle progression, including fos, myc, cdc25a, stk15 and cyclin A, were induced by both E2 and tamoxifen in breast cells, treatment with the agonist E2 specifically induced the expression of cyclin D1, fra-1 , and uracil DNA glycosylase. These results suggest that the inability of tamoxifen to transactivate expression of only a few key genes, functioning as cellular gatekeepers, prevent tamoxifen-treated breast cells from entering the cell cycle. Thus, the expression of these agonist-specific marker genes is a potential determinant of agonist activity at the cellular level in the breast. Collectively, studies in the breast and uterine myometrium have identified several mechanisms whereby ER ligands modulate ER-mediated signaling and provide insights into the biology of tissue-specific agonist activity in hormone-responsive tissues. ^

Response of three krill species to hypoxia and warming: An experimental approach to oxygen minimum zones expansion in coastal ecosystems

To understand the adaptation of euphausiid (krill) species to oxygen minimum zones (OMZ), respiratory response and stress experiments combining hypoxia/reoxygenation exposure with warming were conducted. Experimental krill species were obtained from the Antarctic (South Georgia area), the Humboldt Current system (HCS, Chilean coast), and the Northern California Current system (NCCS, Oregon). Euphausia mucronata from the HCS shows oxyconforming or oxygen partial pressure (pO2)-dependent respiration below 80% air saturation (18 kPa). Normoxic subsurface oxygenation in winter posed a "high oxygen stress" for this species. The NCCS krill, Euphausia pacifica, and the Antarctic krill, Euphausia superba maintain respiration rates constant down to low critical pO2 values of 6 kPa (30% air saturation) and 11 kPa (55% air saturation), respectively. Antarctic krill had the lowest antioxidant enzyme activities, but the highest concentrations of the molecular antioxidant glutathione (GSH) and was not affected by 6 h exposure to moderate hypoxia. Temperate krill species had higher SOD (superoxide dismutase) values in winter than in summer, which relate to higher winter metabolic rate (E. pacifica). In all species, antioxidant enzyme activities remained constant during hypoxic exposure at habitat temperature. Warming by 7°C above habitat temperature in summer increased SOD activities and GSH levels in E. mucronata (HCS), but no oxidative damage occurred. In winter, when the NCCS is well mixed and the OMZ is deeper, +4°C of warming combined with hypoxia represents a lethal condition for E. pacifica. In summer, when the OMZ expands upwards (100 m subsurface), antioxidant defences counteracted hypoxia and reoxygenation effects in E. pacifica, but only at mildly elevated temperature (+2°C). In this season, experimental warming by +4°C reduced antioxidant activities and the hypoxia combination again caused mortality of exposed specimens. We conclude that a climate change scenario combining warming and hypoxia represents a serious threat to E. pacifica and, as a consequence, NCCS food webs.

Theory of a Flowchart Approach to Industrial Cluster Policy

A flowchart approach to industrial cluster policy emphasizes the importance ofthe ordering of policy measures. The flow of policy implementation is to establish an industrial zone, to invite an anchor company, and to promote its related companies to invest in the industrial zone. This article delineated "a flowchart approach to industrial cluster policy" by proposing sufficient conditions for forming industrial clusters typical in the manufacturing industry in Asia to enhance regional economic growth. The typical industrial cluster policy was theorized by defining an industrial zone as "quasi-public goods", and it was shown that the policy enhances economic growth under a production function of "increasing returns to scale" of an anchor company. Critical amounts of the production of "scale economies" that are used by the related companies to decide whether or not to invest in clusters were also shown.

Shedding light on the shadow economy : a nighttime light approach

Measuring the shadow economy is inherently difficult, but critical for understanding economic development. Using census data on formal and informal sectors in Cambodia, we document that 96.6% of non-farm establishments do not formally register with the government, and their sales accounted for 76.6% of total sales in 2011. We estimate a relationship between nighttime light and sales across regions separately for formal and informal firms for 2011, and estimate their past sales from changes in nighttime light for 1993-2010. Both formal and informal firms increased their estimated sales, and the share of informal sales increased from 68.8% in 1993 to 76.6% in 2011, suggesting that the informal sector increased quantitatively in both absolute and relative terms throughout the economic development of the Cambodian economy.

The ballast pick-up problem. A theoretical approach and two experimental campaigns

The aim of this contribution is to present a theoretical approach and two experimental campaigns (on wind tunnel and on the track) concerning the research work about the ballast train-induced-wind erosion (BTIWE) phenomenon. When a high speed train overpasses the critical speed, it produces a wind speed close to the track large enough to start the motion of the ballast elements, eventually leading to the rolling of the stones (Kwon and Park, 2006) and, if these stones get enough energy, they can jump and then initiate a saltation-like chain reaction, as found in the saltation processes of soil eolian erosion (Bagnold, 1941). The expelled stones can reach a height which is larger than the lowest parts of the train, striking them (and the track surroundings) producing considerable damage that should be avoided. There is not much published work about this phenomenon, in spite of the great interest that exists due to its relevant applications in increasing the maximum operative train speed. Particularly, the initiation of flight of ballast due to the pass of a high speed train has been studied by Kwon and Park (2006) by performing field and wind tunnel experiments.

On a meaningful integration of web services in data-intensive biomedical environments: The DICODE approach

This paper reports on an innovative approach that aims to reduce information management costs in data-intensive and cognitively-complex biomedical environments. Recognizing the importance of prominent high-performance computing paradigms and large data processing technologies as well as collaboration support systems to remedy data-intensive issues, it adopts a hybrid approach by building on the synergy of these technologies. The proposed approach provides innovative Web-based workbenches that integrate and orchestrate a set of interoperable services that reduce the data-intensiveness and complexity overload at critical decision points to a manageable level, thus permitting stakeholders to be more productive and concentrate on creative activities.