Urinary Biomarkers Indicative of Apoptosis and Acute Kidney Injury in the Critically Ill.

BACKGROUND Apoptosis is a key mechanism involved in ischemic acute kidney injury (AKI), but its role in septic AKI is controversial. Biomarkers indicative of apoptosis could potentially detect developing AKI prior to its clinical diagnosis. METHODS As a part of the multicenter, observational FINNAKI study, we performed a pilot study among critically ill patients who developed AKI (n = 30) matched to critically ill patients without AKI (n = 30). We explored the urine and plasma levels of cytokeratin-18 neoepitope M30 (CK-18 M30), cell-free DNA, and heat shock protein 70 (HSP70) at intensive care unit (ICU) admission and 24h thereafter, before the clinical diagnosis of AKI defined by the Kidney Disease: Improving Global Outcomes -creatinine and urine output criteria. Furthermore, we performed a validation study in 197 consecutive patients in the FINNAKI cohort and analyzed the urine sample at ICU admission for CK-18 M30 levels. RESULTS In the pilot study, the urine or plasma levels of measured biomarkers at ICU admission, at 24h, or their maximum value did not differ significantly between AKI and non-AKI patients. Among 20 AKI patients without severe sepsis, the urine CK-18 M30 levels were significantly higher at 24h (median 116.0, IQR [32.3-233.0] U/L) than among those 20 patients who did not develop AKI (46.0 [0.0-54.0] U/L), P = 0.020. Neither urine cell-free DNA nor HSP70 levels significantly differed between AKI and non-AKI patients regardless of the presence of severe sepsis. In the validation study, urine CK-18 M30 level at ICU admission was not significantly higher among patients developing AKI compared to non-AKI patients regardless of the presence of severe sepsis or CKD. CONCLUSIONS Our findings do not support that apoptosis detected with CK-18 M30 level would be useful in assessing the development of AKI in the critically ill. Urine HSP or cell-free DNA levels did not differ between AKI and non-AKI patients.

Association of oliguria with the development of acute kidney injury in the critically ill

Urine output (UO) criterion may increase the sensitivity of the definition of acute kidney injury (AKI). We determined whether the empirically derived definition for oliguria(<0.5 ml/kg/h) is independently associated with adverse outcome. Data analysis included hourly recorded UO from the prospective, multicenter FINNAKI study conducted in 16 Finnish intensive care units. Confounder-adjusted association of oliguria of different severity and duration primarily with the development of AKI defined by creatinine criterion (Cr-AKI) or renal replacement therapy(RRT) was assessed. Secondarily, we determined the association of oliguria with 90-day mortality. Of the 1966 patients analyzed for the development of AKI, 454 (23.1%) reached this endpoint. Within this AKI cohort, 312 (68.7%)developed Cr-AKI, 21 (4.6%) commenced RRT without Cr-AKI, and 121 (26.7%) commenced RRT with Cr-AKI. Episodes of severe oliguria (<0.1 ml/kg/h) for more than 3 h were independently associated with the development of Cr-AKI or RRT. The shortest periods of consecutive oliguria independently associated with an increased risk for 90-day mortality were 6–12 h of oliguria from 0.3 to <0.5 ml/kg/h, over 6 h of oliguria from 0.1 to <0.3 ml/kg/h, and severe oliguria lasting over 3 h.Thus, our findings underlie the importance of hourly UO measurements.

A feasibility study for the provision of electronic healthcare tools and services in areas of Greece, Cyprus and Italy

Background Through this paper, we present the initial steps for the creation of an integrated platform for the provision of a series of eHealth tools and services to both citizens and travelers in isolated areas of thesoutheast Mediterranean, and on board ships travelling across it. The platform was created through an INTERREG IIIB ARCHIMED project called INTERMED. Methods The support of primary healthcare, home care and the continuous education of physicians are the three major issues that the proposed platform is trying to facilitate. The proposed system is based on state-of-the-art telemedicine systems and is able to provide the following healthcare services: i) Telecollaboration and teleconsultation services between remotely located healthcare providers, ii) telemedicine services in emergencies, iii) home telecare services for "at risk" citizens such as the elderly and patients with chronic diseases, and iv) eLearning services for the continuous training through seminars of both healthcare personnel (physicians, nurses etc) and persons supporting "at risk" citizens. These systems support data transmission over simple phone lines, internet connections, integrated services digital network/digital subscriber lines, satellite links, mobile networks (GPRS/3G), and wireless local area networks. The data corresponds, among others, to voice, vital biosignals, still medical images, video, and data used by eLearning applications. The proposed platform comprises several systems, each supporting different services. These were integrated using a common data storage and exchange scheme in order to achieve system interoperability in terms of software, language and national characteristics. Results The platform has been installed and evaluated in different rural and urban sites in Greece, Cyprus and Italy. The evaluation was mainly related to technical issues and user satisfaction. The selected sites are, among others, rural health centers, ambulances, homes of "at-risk" citizens, and a ferry. Conclusions The results proved the functionality and utilization of the platform in various rural places in Greece, Cyprus and Italy. However, further actions are needed to enable the local healthcare systems and the different population groups to be familiarized with, and use in their everyday lives, mature technological solutions for the provision of healthcare services.

[Integrating psychotherapeutic treatment of severe mental illness: between desirability and clinical practice]

Psychiatric care for severe and persistent mentally ill individuals has considerably changed over the last three decades. Striving for improvement in services provision for these patients has led to the emergence of various specialized community services, suited housing and supported work offers. Moreover, community-based treatment is also offered during acute episodes of mental illness. At the same time a range of evidence-based psychotherapeutic approaches targeting treatment needs of people with severe mental illness were developed in a process independent of the rise of community psychiatry. At present, however, a sufficient level of coordination of psychiatric services and integration of evidence-based psychological treatment into psychiatric care has not been achieved. Thus, these issues represent important steps in the further development.This paper discusses recent developments in psychiatric care of people with severe mental illness and reviews the evidence-based psychotherapy approaches suited to fit the needs of patient-centered integrated care.

GATS and the Regulation of Trade in Services

This collection of essays takes stock of the key challenges that have arisen since the entry into force of the General Agreement on Trade in Services in the mid-1990s and situates them in the context of the WTO's Doha Development Agenda and the proliferation of preferential agreements addressing services today. The multidisciplinary approach provides an opportunity for many of the world's leading experts and a number of new analytical voices to exchange ideas on the future of services trade and regulation. Cosmopolitan approaches to the treatment of labour mobility, the shape of services trade disciplines in the digital age and pro-competitive regulation in air transport are explored with a view to helping readers gain a better understanding of the forces shaping the changes. An essential read for all those concerned with the evolution of the rules-based trading system and its impact on the service economy.

Opportunities and limits of the ecosystem services framework in capturing the cultural dimension of sustainable regional and landscape development in protected areas

With regard to protected areas, the concepts of ecosystem services and the cultural dimension of sustainable development (SD) are increasingly under debate. This contribution analyses the role of cultural aspects within the ecosystem services framework using the Millennium Ecosystem Assessment classification as a reference. The limits of the ecosystem services framework in capturing the cultural dimension are highlighted. Potential ways of strengthening the position of cultural values within this framework are discussed.

Coupled human and natural system dynamics as key to the sustainability of Lake Victoria's ecosystem services

East Africa’s Lake Victoria provides resources and services to millions of people on the lake’s shores and abroad. In particular, the lake’s fisheries are an important source of protein, employment, and international economic connections for the whole region. Nonetheless, stock dynamics are poorly understood and currently unpredictable. Furthermore, fishery dynamics are intricately connected to other supporting services of the lake as well as to lakeshore societies and economies. Much research has been carried out piecemeal on different aspects of Lake Victoria’s system; e.g., societies, biodiversity, fisheries, and eutrophication. However, to disentangle drivers and dynamics of change in this complex system, we need to put these pieces together and analyze the system as a whole. We did so by first building a qualitative model of the lake’s social-ecological system. We then investigated the model system through a qualitative loop analysis, and finally examined effects of changes on the system state and structure. The model and its contextual analysis allowed us to investigate system-wide chain reactions resulting from disturbances. Importantly, we built a tool that can be used to analyze the cascading effects of management options and establish the requirements for their success. We found that high connectedness of the system at the exploitation level, through fisheries having multiple target stocks, can increase the stocks’ vulnerability to exploitation but reduce society’s vulnerability to variability in individual stocks. We describe how there are multiple pathways to any change in the system, which makes it difficult to identify the root cause of changes but also broadens the management toolkit. Also, we illustrate how nutrient enrichment is not a self-regulating process, and that explicit management is necessary to halt or reverse eutrophication. This model is simple and usable to assess system-wide effects of management policies, and can serve as a paving stone for future quantitative analyses of system dynamics at local scales.

Assisted and unassisted suicide in men and women: longitudinal study of the Swiss population.

BackgroundIn Switzerland assisted suicide is legal if no self-interest is involved.AimsTo compare the strength and direction of associations with sociodemographic factors between assisted and unassisted suicides.MethodWe calculated rates and used Cox and logistic regression models in a longitudinal study of the Swiss population.ResultsAnalyses were based on 5 004 403 people, 1301 assisted and 5708 unassisted suicides from 2003 to 2008. The rate of unassisted suicides was higher in men than in women, rates of assisted suicides were similar in men and women. Higher education was positively associated with assisted suicide, but negatively with unassisted. Living alone, having no children and no religious affiliation were associated with higher rates of both.ConclusionsSome situations that indicate greater vulnerability such as living alone were associated with both assisted and unassisted suicide. Among the terminally ill, women were more likely to choose assisted suicide, whereas men died more often by unassisted suicide.

Reflections on the preferential liberalization of services trade

This paper takes stock of the forces that lie behind the recent rise of preferential agreements in services trade. Its initial focus is with a number of distinguishing features of services trade that set it apart from trade in goods and shapes trade liberalization and rule-making approaches in the services field. The paper then documents the nature, modal, and sectoral incidence of the trade and investment preferences spawned by preferential trade agreements (PTAs) in services. It does so with a view to addressing the question of how preferential the preferential treatment of services trade is. Finally, the paper addresses a number of considerations arising from attempts to multilateralize preferential access and rule-making in services trade.

Dysfunction of respiratory muscles in critically ill patients on the intensive care unit.

Muscular weakness and muscle wasting may often be observed in critically ill patients on intensive care units (ICUs) and may present as failure to wean from mechanical ventilation. Importantly, mounting data demonstrate that mechanical ventilation itself may induce progressive dysfunction of the main respiratory muscle, i.e. the diaphragm. The respective condition was termed 'ventilator-induced diaphragmatic dysfunction' (VIDD) and should be distinguished from peripheral muscular weakness as observed in 'ICU-acquired weakness (ICU-AW)'. Interestingly, VIDD and ICU-AW may often be observed in critically ill patients with, e.g. severe sepsis or septic shock, and recent data demonstrate that the pathophysiology of these conditions may overlap. VIDD may mainly be characterized on a histopathological level as disuse muscular atrophy, and data demonstrate increased proteolysis and decreased protein synthesis as important underlying pathomechanisms. However, atrophy alone does not explain the observed loss of muscular force. When, e.g. isolated muscle strips are examined and force is normalized for cross-sectional fibre area, the loss is disproportionally larger than would be expected by atrophy alone. Nevertheless, although the exact molecular pathways for the induction of proteolytic systems remain incompletely understood, data now suggest that VIDD may also be triggered by mechanisms including decreased diaphragmatic blood flow or increased oxidative stress. Here we provide a concise review on the available literature on respiratory muscle weakness and VIDD in the critically ill. Potential underlying pathomechanisms will be discussed before the background of current diagnostic options. Furthermore, we will elucidate and speculate on potential novel future therapeutic avenues.

Reflections on the Preferential Liberalization of Services Trade

This paper takes stock of the forces that lie behind the recent rise of preferential agreements in services trade. Its focuses first on a number of distinguishing features of services trade that sets it apart from trade in goods and shapes trade liberalization and rule-making approaches in the services field. The paper then documents the nature, modal and sectoral incidence of the trade and investment preferences spawned by preferential trade agreements (PTAs) in services. It does so with a view to addressing the question: how “preferential” is the preferential treatment of services trade? Finally, the paper addresses a number of considerations arising from attempts to multilateralize preferential access and rule-making in services trade.