Predicting early complications in patients with spinal gunshot wounds: A multicenter study.

Introduction: There is a wide variation in the clinical presentation of spinal gunshot wounds ranging from isolated minor stable fractures to extremely severe injuries with catastrophic neurological damage. Research question: we aim to analyze the risk factors for early complications and impact of surgical treatment in patients with spinal gunshot wounds. Material and methods: This is a multicentre retrospective case-control study to compare patients with spinal gunshot wounds who had early complications with those who did not. The following matching criteria were used: sex (1:1), injury level (1:1) and age (±5 years). Univariate and multivariate analyses were performed using logistic regression. Results: Results: Among 387 patients, 36.9 % registered early complications, being persistent pain (n = 32; 15 %), sepsis/septic shock (n = 28; 13 %), pneumonia (n = 27; 13 %) and neurogenic bladder (n = 27; 12 %) the most frequently reported. After case-control matched analysis, we obtained 133 patients who suffered early complications (cases) and 133 patients who did not as control group, not differing significantly in sex (p = 1000), age (p = 0,535) and injury level (p = 1000), while the 35 % of complications group required surgical treatment versus 15 % of the non-complication group (p < 0.001). On multivariable analysis, significant predictors of complications were surgical treatment for spinal injury (OR = 3.50, 95 % CI = 1.68-7.30), dirty wound (3.32, 1.50-7.34), GCS ≤8 (3.56, 1.17-10.79), hemodynamic instability (2.29, 1.07-4.88), and multiple bullets (1.97, 1.05-3.67). Discussion and conclusion: Spinal gunshot wounds are associated with a high risk of early complications, especially when spinal surgery is required, and among patients with dirty wound, low level of consciousness, hemodynamic instability, and multiple bullets.

The study of intercalated cells using ex vivo techniques: primary cell culture, cell lines, kidney slices, and organoids.

This review summarizes methods to study kidney intercalated cell (IC) function ex vivo. While important for acid-base homeostasis, IC dysfunction is often not recognized clinically until it becomes severe. The advantage of using ex vivo techniques is that they allow for the differential evaluation of IC function in controlled environments. Although in vitro kidney tubular perfusion is a classical ex vivo technique to study IC, here we concentrate on primary cell cultures, immortalized cell lines, and ex vivo kidney slices. Ex vivo techniques are useful in evaluating IC signaling pathways that allow rapid responses to extracellular changes in pH, CO2, and bicarbonate (HCO3-). However, these methods for IC work can also be challenging, as cell lines that recapitulate IC do not proliferate easily in culture. Moreover, a "pure" IC population in culture does not necessarily replicate its collecting duct (CD) environment, where ICs are surrounded by the more abundant principal cells (PCs). It is reassuring that many findings obtained in ex vivo IC systems signaling have been largely confirmed in vivo. Some of these newly identified signaling pathways reveal that ICs are important for regulating NaCl reabsorption, thus suggesting new frontiers to target antihypertensive treatments. Moreover, recent single-cell characterization studies of kidney epithelial cells revealed a dual developmental origin of IC, as well as the presence of novel CD cell types with certain IC characteristics. These exciting findings present new opportunities for the study of IC ex vivo and will likely rediscover the importance of available tools in this field.NEW & NOTEWORTHY The study of kidney intercalated cells has been limited by current cell culture and kidney tissue isolation techniques. This review is to be used as a reference to select ex vivo techniques to study intercalated cells. We focused on the use of cell lines and kidney slices as potential useful models to study membrane transport proteins. We also review how novel collecting duct organoids may help better elucidate the role of these intriguing cells.

Management of decontamination in chemical accidents: a laboratory model.

Rapid and efficient decontamination of the skin is a major task for emergency rescue services in the event of a chemical accident involving humans. While rinsing the skin with water (and soap) has been the standard procedure, some skepticism has developed in recent years regarding the situational suitability of this method. The efficacy of three different decontamination materials/techniques (Easyderm® cleaning cloth, water-soaked all-purpose sponge, rinsing with water) in removing Capsaicin, Bromadiolone, Paraquat and 2,2'-dichlorodiethylether (DCEE) from porcine skin was compared. Different cleaning motions (wiping, twisting, pressing) with the Easyderm® were evaluated for their effectiveness in removing Capsaicin from porcine skin. Finally, the impact of different exposure times of the skin to Capsaicin on the decontamination process were investigated. Contaminant recovery rates (CRRs) were analysed in the skin and in each decontamination material using high-performance-liquid-chromatography (HPLC; used for Capsaicin, Bromadiolone, Paraquat) or gas chromatography (GC; used for DCEE). Wiping the skin with the amphiphilic Easyderm® was most effective for decontamination of Capsaicin and DCEE, while the water rinsing method gave the best results for removing Paraquat and Bromadiolone. Both wiping with the Easyderm® and rotating the Easyderm® were significantly more effective in cleaning Capsaicin-contaminated skin than pressing the Easyderm® on the contamination area alone. Prolonged exposure times of the porcine skin to Capsaicin were associated with a decrease in efficacy of the following decontamination. Emergency rescue services should have materials available that can remove both hydrophilic and hydrophobic substances from skin. Since not all of our results for comparing different decontamination materials were as distinct as we expected, there are likely several other factors determining the efficacy of skin decontamination in some cases. Time is key; therefore, first responders should try to begin the decontamination process as soon as possible after arriving at the scene.

A novel monoclonal IgG1 antibody specific for Galactose-alpha-1,3-galactose questions alpha-Gal epitope expression by bacteria.

The alpha-Gal epitope (α-Gal) with the determining element galactose-α1,3-galactose can lead to clinically relevant allergic reactions and rejections in xenotransplantation. These immune reactions can develop because humans are devoid of this carbohydrate due to evolutionary loss of the enzyme α1,3-galactosyltransferase (GGTA1). In addition, up to 1% of human IgG antibodies are directed against α-Gal, but the stimulus for the induction of anti-α-Gal antibodies is still unclear. Commensal bacteria have been suggested as a causal factor for this induction as α-Gal binding tools such as lectins were found to stain cultivated bacteria isolated from the intestinal tract. Currently available tools for the detection of the definite α-Gal epitope, however, are cross-reactive, or have limited affinity and, hence, offer restricted possibilities for application. In this study, we describe a novel monoclonal IgG1 antibody (27H8) specific for the α-Gal epitope. The 27H8 antibody was generated by immunization of Ggta1 knockout mice and displays a high affinity towards synthetic and naturally occurring α-Gal in various applications. Using this novel tool, we found that intestinal bacteria reported to be α-Gal positive cannot be stained with 27H8 questioning whether commensal bacteria express the native α-Gal epitope at all.

[Management of COVID-19 mass casualty incidents in nursing and retirement homes]. / Managementstrategie für den Massenanfall von Erkrankten/Infizierten in Alten- und Pflegeheimen im Kontext der COVID-19-Pandemie.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, outbreaks in inpatient care facilities, which grow into a large-scale emergency scenario, are frequently observed. A standardized procedure analogous to algorithms for mass casualty incidents (MCI) is lacking. METHODS: Based on a case report and the literature, the authors present a management strategy for infectious MCI during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and distinguish it from traumatic MCI deployment tactics. RESULTS: This management strategy can be divided into three phases, beginning with the acute emergency response including triage, stabilization of critical patients, and transport of patients requiring hospitalization. Phase 2 involves securing the facility's operational readiness, or housing residents elsewhere in case staff are infected or quarantined to a relevant degree. Phase 3 marks the return to regular operations. DISCUSSION: Phase 1 is based on usual MCI principles, phase 2 on hospital crisis management. Avoiding evacuation of residents to relieve hospitals is an important operational objective. The lack of mission and training experience with such situations, the limited applicability of established triage algorithms, and the need to coordinate a large number of participants pose challenges. CONCLUSION: This strategic model offers a practical, holistic approach to the management of infectious mass casualty scenarios in nursing facilities.

Characterization of New Allergens from the Venom of the European Paper Wasp Polistes dominula.

Discriminating Polistes dominula and Vespula spp. venom allergy is of growing importance worldwide, as systemic reactions to either species' sting can lead to severe outcomes. Administering the correct allergen-specific immunotherapy is therefore a prerequisite to ensure the safety and health of venom-allergic patients. Component-resolved diagnostics of Hymenoptera venom allergy might be improved by adding additional allergens to the diagnostic allergen panel. Therefore, three potential new allergens from P. dominula venom-immune responsive protein 30 (IRP30), vascular endothelial growth factor C (VEGF C) and phospholipase A2 (PLA2)-were cloned, recombinantly produced and biochemically characterized. Sera sIgE titers of Hymenoptera venom-allergic patients were measured in vitro to assess the allergenicity and potential cross-reactivity of the venom proteins. IRP30 and VEGF C were classified as minor allergens, as sensitization rates lay around 20-40%. About 50% of P. dominula venom-allergic patients had measurable sIgE titers directed against PLA2 from P. dominula venom. Interestingly, PLA2 was unable to activate basophils of allergic patients, questioning its role in the context of clinically relevant sensitization. Although the obtained results hint to a questionable benefit of the characterized P. dominula venom proteins for improved diagnosis of venom-allergic patients, they can contribute to a deeper understanding of the molecular mechanisms of Hymenoptera venoms and to the identification of factors that determine the allergenic potential of proteins.

Evaluation of comprehensiveness and reliability of electronic health records concerning resuscitation efforts within academic intensive care units: a retrospective chart analysis.

BACKGROUND: According to the literature, the validity and reliability of medical documentation concerning episodes of cardiopulmonary resuscitation (CPR) is suboptimal. However, little is known about documentation quality of CPR efforts during intensive care unit (ICU) stays in electronic patient data management systems (PDMS). This study analyses the reliability of CPR-related medical documentation within the ICU PDMS. METHODS: In a retrospective chart analysis, PDMS records of three ICUs of a single university hospital were searched over 5 y for CPR check marks. Respective datasets were analyzed concerning data completeness and data consistency by comparing the content of three documentation forms (physicians' log, nurses' log, and CPR incident form), as well as physiological and therapeutic information of individual cases, for missing data and plausibility of CPR starting time and duration. To compare data reliability and completeness, a quantitative measure, the Consentaneity Index (CI), is proposed. RESULTS: One hundred sixty-five datasets were included into the study. In 9% (n = 15) of cases, there was neither information on the time points of CPR initiation nor on CPR duration available in any data source. Data on CPR starting time and duration were available from at least two data sources in individual cases in 54% (n = 90) and 45% (n = 74), respectively. In these cases, the specifications of CPR starting time did differ by a median ± interquartile range of 10.0 ± 18.5 min, CPR duration by 5.0 ± 17.3 min. The CI as a marker of data reliability revealed a low consistency of CPR documentation in most cases, with more favorable results, if the time interval between the CPR episode and the time of documentation was short. CONCLUSIONS: This study reveals relevant proportions of missing and inconsistent data in electronic CPR documentation in the ICU setting. The CI is suggested as a tool for documentation quality analysis and monitoring of improvements.

[The disaster task force medical officer as a pivotal decision maker in the superordinate pandemic hospital capacity management : A field report covering the initial COVID-19 surge in a Bavarian district]. / Der Ärztliche Leiter Führungsgruppe Katastrophenschutz als zentrale Entscheidungsinstanz bei der Steuerung regionaler Krankenhauskapazitäten in der Pandemie : Ein Erfahrungsbericht zur ersten Welle der COVID-19-Pandemie in einem bayerischen Regierungsbezirk.

BACKGROUND AND OBJECTIVE: During the initial phase of the COVID-19 pandemic the government of the state of Bavaria, Germany, declared a state of emergency for its entire territory for the first time in history. Some areas in eastern Bavaria were among the most severely affected communities in Germany, prompting authorities and hospitals to build up capacities for a surge of COVID-19 patients. In some areas, intensive care unit (ICU) capacities were heavily engaged, which occasionally made a redistribution of patients necessary. MATERIAL AND METHODS: For managing COVID-19-related hospital capacities and patient allocation, crisis management squads in Bavaria were expanded by disaster task force medical officers ("Ärztlicher Leiter Führungsgruppe Katastrophenschutz" [MO]) with substantial executive authority. The authors report their experiences as MO concerning the superordinate patient allocation management in the district of Upper Palatinate (Oberpfalz) in eastern Bavaria. RESULTS: By abandoning routine patient care and building up additional ICU resources, surge capacity for the treatment of COVID-19 patients was generated in hospitals. In parts of the Oberpfalz, ICU capacities were almost entirely occupied by patients with corona virus infections, making reallocation to other hospitals within the district and beyond necessary. The MO managed patient pathways in an escalating manner by defining local (within the region of responsibility of a single MO), regional (within the district), and cross-regional (over district borders) reallocation lanes, as needed. When regional or cross-regional reallocation lanes had to be established, an additional management level located at the district government was involved. Within the determined reallocation lanes, emitting and receiving hospitals mutually agreed on any patient transfer without explicitly involving the MO, thereby maintaining the established interhospital routine transfer procedures. The number of patients and available treatment resources at each hospital were monitored with the help of a web-based treatment capacity registry. If indicated, reallocation lanes were dynamically revised according to the present situation. To oppose further virus spreading in nursing homes, the state government prohibited patient allocation to these facilities, which led to considerably longer hospital length of stay of convalescent elderly and/or dependent patients. In parallel to the flattening of the COVID-19 incidence curve, routine hospital patient care could be re-established in a stepwise manner. CONCLUSION: Patient allocation during the state of emergency by the MO sought to keep up routine interhospital reallocation procedures as much as possible, thereby reducing management time and effort. Occasionally, difficulties were observed during patient allocations crossing district borders, if other MO followed different management principles. The nursing home blockade and conflicting financial interests of hospitals posed challenges to the work of the disaster task force medical officers.

Policy and Pandemic: The Changing Practice of Nephrology During the Coronavirus Disease-2019 Outbreak.

The coronavirus (coronavirus disease-2019) pandemic has changed care delivery for patients with end-stage kidney disease. We explore the US healthcare system as it pertains to dialysis care, including existing policies, modifications implemented in response to the coronavirus disease-2019 crisis, and possible next steps for policy makers and nephrologists. This includes policies related to resource management, use of telemedicine, prioritization of dialysis access procedures, expansion of home dialysis modalities, administrative duties, and quality assessment. The government has already established policies that have instated some flexibilities to help providers focus their response to the crisis. However, future policy during and after the coronavirus disease-2019 pandemic can bolster our ability to optimize care for patients with end-stage kidney disease. Key themes in this perspective are the importance of policy flexibility, clear strategies for emergency preparedness, and robust health systems that maximize accessibility and patient autonomy.

Primary mass casualty incident triage: evidence for the benefit of yearly brief re-training from a simulation study.

BACKGROUND: Triage is a mainstay of early mass casualty incident (MCI) management. Standardized triage protocols aim at providing valid and reproducible results and, thus, improve triage quality. To date, there is little data supporting the extent and content of training and re-training on using such triage protocols within the Emergency Medical Services (EMS). The study objective was to assess the decline in triage skills indicating a minimum time interval for re-training. In addition, the effect of a one-hour repeating lesson on triage quality was analyzed. METHODS: A dummy based trial on primary MCI triage with yearly follow-up after initial training using the ASAV algorithm (Amberg-Schwandorf Algorithm for Primary Triage) was undertaken. Triage was assessed concerning accuracy, sensitivity, specificity, over-triage, under-triage, time requirement, and a comprehensive performance measure. A subgroup analysis of professional paramedics was made. RESULTS: Nine hundred ninety triage procedures performed by 51 providers were analyzed. At 1 year after initial training, triage accuracy and overall performance dropped significantly. Professional paramedic's rate of correctly assigned triage categories deteriorated from 84 to 71%, and the overall performance score decreased from 95 to 90 points (maximum = 100). The observed decline in triage performance at 1 year after education made it necessary to conduct re-training. A brief didactic lecture of 45 min duration increased accuracy to 88% and the overall performance measure to 97. CONCLUSIONS: To improve disaster preparedness, triage skills should be refreshed yearly by a brief re-education of all EMS providers.

Quality of inter-hospital transportation in 431 transport survivor patients suffering from acute respiratory distress syndrome referred to specialist centers.

BACKGROUND: The acute respiratory distress syndrome (ARDS) is a life-threatening condition. In special situations, these critically ill patients must be transferred to specialized centers for escalating treatment. The aim of this study was to evaluate the quality of inter-hospital transport (IHT) of ARDS patients. METHODS: We evaluated medical and organizational aspects of structural and procedural quality relating to IHT of patients with ARDS in a prospective nationwide ARDS study. The qualification of emergency staff, the organizational aspects and the occurrence of critical events during transport were analyzed. RESULTS: Out of 1234 ARDS patients, 431 (34.9%) were transported, and 52 of these (12.1%) treated with extracorporeal membrane oxygenation. 63.1% of transferred patients were male, median age was 54 years, and 26.8% of patients were obese. All patients were mechanically ventilated during IHT. Pressure-controlled ventilation was the preferred mode (92.1%). Median duration to organize the IHT was 165 min. Median distance for IHT was 58 km, and median duration of IHT 60 min. Forty-two patient-related and 8 technology-related critical events (11.6%, 50 of 431 patients) were observed. When a critical event occurred, the PaO2/FiO2 ratio before transport was significant lower (68 vs. 80 mmHg, p = 0.017). 69.8% of physicians and 86.7% of paramedics confirmed all transfer qualifications according to requirements of the German faculty guidelines (DIVI). CONCLUSIONS: The transport of critically ill patients is associated with potential risks. In our study the rate of patient- and technology-related critical events was relatively low. A severe ARDS with a PaO2/FiO2 ratio < 70 mmHg seems to be a risk factor for the appearance of critical events during IHT. The majority of transport staff was well qualified. Time span for organization of IHT was relatively short. ECMO is an option to transport patients with a severe ARDS safely to specialized centers. Trial registration NCT02637011 (ClinicalTrials.gov, Registered 15 December 2015, retrospectively registered).

In Vitro Induction of Endothelial Apoptosis of the Post-Hypoxic Blood-Brain Barrier by Isoflurane but Not by Sevoflurane and Midazolam.

BACKGROUND: The effects of anesthetics on the injured brain continue to be the subject of controversial discussion. Since isoflurane has recently been shown to induce apoptosis of cerebral endothelial cells, this study compared different anesthetic compounds regarding their potential to induce cerebro-vascular apoptosis. METHODS: The in vitro model of the blood-brain barrier used in this study consisted of astrocyte-conditioned human umbilical vein endothelial cells (AC-HUVEC) has been used. After 24 h of deep hypoxia and reoxygenation or control treatment, AC-HUVEC were exposed to 0, 0.5, 1.0, or 2.0 times the minimum alveolar concentration of isoflurane or sevoflurane, or 0, 75, 150, or 300 nM of midazolam for 2 h. After 24 h, AC-HUVEC were harvested, and the degree of apoptosis was assessed by means of Western blots for the Bax and Bcl-2 ratio and, for controls and the highest concentration groups, terminal deoxynucleotidyl-mediated dUTP-biotin nick end labeling (TUNEL). RESULTS: Without hypoxic pretreatment, 2.0 MAC of isoflurane slightly increased TUNEL intensity compared to control and sevoflurane, but without any significant changes in the Bax and Bcl-2 ratio. After hypoxic pretreatment, exposure to isoflurane led to a multifold increase in the Bax and Bcl-2 ratio in a dose dependent manner, which was also significantly higher than the ratio observed in the 2 MAC sevoflurane group. TUNEL intensity in the post-hypoxic 2 MAC isoflurane group was increased by a factor of 11 vs. control and by 40 vs. sevoflurane. Sevoflurane and midazolam did not significantly alter these markers of apoptosis, when compared to the control group. CONCLUSIONS: Isoflurane administered after hypoxia elevates markers of apoptosis in endothelial cells transdifferentiated to the cerebro-vascular endothelium. Endothelial apoptosis may be a previously underestimated mechanism of anesthetic neurotoxicity. Administration of high concentrations of isoflurane in experimental settings may have negative effects on the blood-brain barrier.

Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant chemicals.

Diesel exhaust particles (DEPs) are a major component of diesel emissions, responsible for a large portion of their toxicity. In this study, we examined the toxic effects of DEPs on endothelial cells and the role of DEP-induced heme oxygenase-1 (HO-1) expression. Human microvascular endothelial cells (HMECs) were treated with an organic extract of DEPs from an automobile engine (A-DEP) or a forklift engine (F-DEP) for 1 and 4h. ROS generation, cell viability, lactate dehydrogenase leakage, expression of HO-1, inflammatory genes, cell adhesion molecules and unfolded protein respone (UPR) gene were assessed. HO-1 expression and/or activity were inhibited by siRNA or tin protoporphyrin (Sn PPIX) and enhanced by an expression plasmid or cobalt protoporphyrin (CoPPIX). Exposure to 25µg/ml of A-DEP and F-DEP significantly induced ROS production, cellular toxicity and greater levels of inflammatory and cellular adhesion molecules but to a different degree. Inhibition of HO-1 enzymatic activity with SnPPIX and silencing of the HO-1 gene by siRNA enhanced DEP-induced ROS production, further decreased cell viability and increased expression of inflammatory and cell adhesion molecules. On the other hand, overexpression of the HO-1 gene by a pcDNA 3.1D/V5-HO-1 plasmid significantly mitigated ROS production, increased cell survival and decreased the expression of inflammatory genes. HO-1 expression protected HMECs from DEP-induced prooxidative and proinflammatory effects. Modulation of HO-1 expression could potentially serve as a therapeutic target in an attempt to inhibit the cardiovascular effects of ambient PM.

Evaluation of a novel algorithm for primary mass casualty triage by paramedics in a physician manned EMS system: a dummy based trial.

BACKGROUND: The Amberg-Schwandorf Algorithm for Primary Triage (ASAV) is a novel primary triage concept specifically for physician manned emergency medical services (EMS) systems. In this study, we determined the diagnostic reliability and the time requirements of ASAV triage. METHODS: Seven hundred eighty triage runs performed by 76 trained EMS providers of varying professional qualification were included into the study. Patients were simulated using human dummies with written vital signs sheets. Triage results were compared to a standard solution, which was developed in a modified Delphi procedure. Test performance parameters (e.g. sensitivity, specificity, likelihood ratios (LR), under-triage, and over-triage) were calculated. Time measurements comprised the complete triage and tagging process and included the time span for walking to the subsequent patient. Results were compared to those published for mSTaRT. Additionally, a subgroup analysis was performed for employment status (career/volunteer), team qualification, and previous triage training. RESULTS: For red patients, ASAV sensitivity was 87%, specificity 91%, positive LR 9.7, negative LR 0.139, over-triage 6%, and under-triage 10%. There were no significant differences related to mSTaRT. Per patient, ASAV triage required a mean of 35.4 sec (75th percentile 46 sec, 90th percentile 58 sec). Volunteers needed slightly more time to perform triage than EMS professionals. Previous mSTaRT training of the provider reduced under-triage significantly. There were significant differences in time requirements for triage depending on the expected triage category. CONCLUSIONS: The ASAV is a specific concept for primary triage in physician governed EMS systems. It may detect red patients reliably. The test performance criteria are comparable to that of mSTaRT, whereas ASAV triage might be accomplished slightly faster. From the data, there was no evidence for a clinically significant reliability difference between typical staffing of mobile intensive care units, patient transport ambulances, or disaster response volunteers. Up to now, there is no clinical validation of either triage concept. Therefore, reality based evaluation studies are needed.

Development towards sustainability: how to judge past and proposed policies?

Most countries have, at least since the 1992 United Nations summit in RIO, adopted some vague "sustainable development" policies. The goals of such policies are to combine economic growth with social development, while protecting our fragile planetary life support system. The scientific data about the state of our planet, presented at the 2012 (Rio+20) summit, documented that today's human family lives even less sustainably than it did in 1992. The data indicate furthermore that the environmental impacts from our current economic activities are so large, that we are approaching situations where potentially controllable regional problems can easily lead to uncontrollable global disasters. Despite these obvious failures, our political global leaders and their institutions are continuing the same "sustainable development" policies, which are now supplemented by equally vague ideas about future "green economies". Assuming that (1) the majority of the human family, once adequately informed, wants to achieve a "sustainable way of life" and (2) that the "development towards sustainability" roadmap will be based on scientific principles, one must begin with unambiguous and quantifiable definitions of these goals. As will be demonstrated, the well known scientific method to define abstract and complex issues by their negation, satisfies these requirements. Following this new approach, it also becomes possible to decide if proposed and actual policy changes will make our way of life less unsustainable, and thus move us potentially into the direction of sustainability. Furthermore, if potentially dangerous tipping points are to be avoided, the transition roadmap must include some minimal speed requirements. Combining the negation method and the time evolution of that remaining natural capital in different domains, the transition speed for a "development towards sustainability" can be quantified at local, regional and global scales. The presented ideas allow us to measure the rate of natural capital depletion and the rate of restoration that will be required if humanity is to avoid reaching a sustainable future by a collapse transition. Unfortunately, the existence of quantifiable methods and tools in no way guarantees that they will be used in changing the direction of our journey.

The end of cheap uranium.

Historic data from many countries demonstrate that on average no more than 50-70% of the uranium in a deposit could be mined. An analysis of more recent data from Canada and Australia leads to a mining model with an average deposit extraction lifetime of 10±2 years. This simple model provides an accurate description of the extractable amount of uranium for the recent mining operations. Using this model for all larger existing and planned uranium mines up to 2030, a global uranium mining peak of at most 58±4 ktons around the year 2015 is obtained. Thereafter we predict that uranium mine production will decline to at most 54±5 ktons by 2025 and, with the decline steepening, to at most 41±5 ktons around 2030. This amount will not be sufficient to fuel the existing and planned nuclear power plants during the next 10-20 years. In fact, we find that it will be difficult to avoid supply shortages even under a slow 1%/year worldwide nuclear energy phase-out scenario up to 2025. We thus suggest that a worldwide nuclear energy phase-out is in order. If such a slow global phase-out is not voluntarily effected, the end of the present cheap uranium supply situation will be unavoidable. The result will be that some countries will simply be unable to afford sufficient uranium fuel at that point, which implies involuntary and perhaps chaotic nuclear phase-outs in those countries involving brownouts, blackouts, and worse.

Neurovascular protection by targeting early blood-brain barrier disruption with neurotrophic factors after ischemia-reperfusion in rats*.

The 'new penumbra' concept imbues the transition between injury and repair at the neurovascular unit with profound implications for selecting the appropriate type and timing of neuroprotective interventions. In this conceptual study, we investigated the protective effects of pigment epithelium-derived factor (PEDF) and compared them with the properties of epidermal growth factor (EGF) in a rat model of ischemia-reperfusion injury. We initiated a delayed intervention 3 hours after reperfusion using equimolar amounts of PEDF and EGF. These agents were then administered intravenously for 4 hours following reperfusion after 1 hour of focal ischemia. Magnetic resonance imaging indices were characterized, and imaging was performed at multiple time points post reperfusion. PEDF and EGF reduced lesion volumes at all time points as observed on T2-weighted images (T2-LVs). In addition PEDF selectively attenuated lesion volume expansion at 48 hours after reperfusion and persistently modulated blood-brain barrier (BBB) permeability at all time points. Intervention with peptides is suspected to cause edema formation at distant regions. The observed T2-LV reduction and BBB modulation by these trophic factors is probably mediated through a number of diverse mechanisms. A thorough evaluation of neurotrophins is still necessary to determine their time-dependent contributions against injury and their modulatory effects on repair after stroke.

Isoflurane induces endothelial apoptosis of the post-hypoxic blood-brain barrier in a transdifferentiated human umbilical vein endothelial cell model.

Isoflurane is a popular volatile anesthetic agent used in humans as well as in experimental animal research. In previous animal studies of the blood-brain barrier (BBB), observations towards an increased permeability after exposure to isoflurane are reported. In this study we investigated the effect of a 2-hour isoflurane exposure on apoptosis of the cerebral endothelium following 24 hours of hypoxia in an in vitro BBB model using astrocyte-conditioned human umbilical vein endothelial cells (AC-HUVECs). Apoptosis of AC-HUVECs was investigated using light microscopy of the native culture for morphological changes, Western blot (WB) analysis of Bax and Bcl-2, and a TUNEL assay. Treatment of AC-HUVECs with isoflurane resulted in severe cellular morphological changes and a significant dose-dependent increase in DNA fragmentation, which was observed during the TUNEL assay analysis. WB analysis confirmed increases in pro-apoptotic Bax levels at 4 hours and 24 hours and decreases in anti-apoptotic Bcl-2 in a dose-dependent manner compared with the control group. These negative effects of isoflurane on the BBB after a hypoxic challenge need to be taken into account not only in experimental stroke research, but possibly also in clinical practice.

Comprehensive small animal imaging strategies on a clinical 3 T dedicated head MR-scanner; adapted methods and sequence protocols in CNS pathologies.

BACKGROUND: Small animal models of human diseases are an indispensable aspect of pre-clinical research. Being dynamic, most pathologies demand extensive longitudinal monitoring to understand disease mechanisms, drug efficacy and side effects. These considerations often demand the concomitant development of monitoring systems with sufficient temporal and spatial resolution. METHODOLOGY AND RESULTS: This study attempts to configure and optimize a clinical 3 Tesla magnetic resonance scanner to facilitate imaging of small animal central nervous system pathologies. The hardware of the scanner was complemented by a custom-built, 4-channel phased array coil system. Extensive modification of standard sequence protocols was carried out based on tissue relaxometric calculations. Proton density differences between the gray and white matter of the rodent spinal cord along with transverse relaxation due to magnetic susceptibility differences at the cortex and striatum of both rats and mice demonstrated statistically significant differences. The employed parallel imaging reconstruction algorithms had distinct properties dependent on the sequence type and in the presence of the contrast agent. The attempt to morphologically phenotype a normal healthy rat brain in multiple planes delineated a number of anatomical regions, and all the clinically relevant sequels following acute cerebral ischemia could be adequately characterized. Changes in blood-brain-barrier permeability following ischemia-reperfusion were also apparent at a later time. Typical characteristics of intra-cerebral haemorrhage at acute and chronic stages were also visualized up to one month. Two models of rodent spinal cord injury were adequately characterized and closely mimicked the results of histological studies. In the employed rodent animal handling system a mouse model of glioblastoma was also studied with unequivocal results. CONCLUSIONS: The implemented customizations including extensive sequence protocol modifications resulted in images of high diagnostic quality. These results prove that lack of dedicated animal scanners shouldn't discourage conventional small animal imaging studies.