Bilateral posterior ischaemic optic neuropathy after severe diabetic ketoacidosis, cardiopulmonary resuscitation and respiratory failure

A 44-year-old male European with type I diabetes mellitus fell into diabetic ketoacidosis. In the emergency room, he developed an episode of asystole and respiratory failure requiring one cycle of cardiopulmonary resuscitation and extracorporeal membrane oxygenation (ECMO). Waking up 7 days later, he presented a bilateral complete loss of vision. Ophthalmological examination including funduscopy on days 1 and 10, after extubation, showed bilateral large round pupils non-reactive to light and a normal fundus. Neuroimaging studies, including MRI and MRA of the brain, were all within normal limits. A lumbar puncture and comprehensive serological testing excluded an infectious or rheumatic cause. An empirical high-dose intravenous steroid treatment administered for 5 days had no effect on his vision. His eye examination at 1.5 months follow-up showed a normal fundus except for progressive bilateral optic nerve disc pallor, which pointed towards the diagnosis of a posterior ischaemic optic neuropathy.

A comparison of Markov and generalized linear models of hospital mortality

This paper reports a comparison of three modeling strategies for the analysis of hospital mortality in a sample of general medicine inpatients in a Department of Veterans Affairs medical center. Logistic regression, a Markov chain model, and longitudinal logistic regression were evaluated on predictive performance as measured by the c-index and on accuracy of expected numbers of deaths compared to observed. The logistic regression used patient information collected at admission; the Markov model was comprised of two absorbing states for discharge and death and three transient states reflecting increasing severity of illness as measured by laboratory data collected during the hospital stay; longitudinal regression employed Generalized Estimating Equations (GEE) to model covariance structure for the repeated binary outcome. Results showed that the logistic regression predicted hospital mortality as well as the alternative methods but was limited in scope of application. The Markov chain provides insights into how day to day changes of illness severity lead to discharge or death. The longitudinal logistic regression showed that increasing illness trajectory is associated with hospital mortality. The conclusion is reached that for standard applications in modeling hospital mortality, logistic regression is adequate, but for new challenges facing health services research today, alternative methods are equally predictive, practical, and can provide new insights. ^

Third degree atrioventricular block and accelerated idioventricular rhythm associated with a heart base chemodectoma in a syncopal Rottweiler.

A 7-year-old male intact Rottweiler was presented with a 1-week history of lethargy, anorexia, vomiting and multiple syncopal events. The results of the clinical examination and electrocardiography were consistent with a third degree atrioventricular block and an intermittent accelerated idioventricular rhythm. Haematology, serum biochemistry, serology for Borrelia burgdorferi, blood culture, total T4, thoracic radiography and echocardiography did not reveal the cause of the arrhythmia. Response to medical treatment with isoproterenol was poor. Pacemaker placement was declined by the owners and the dog was euthanized at their request. Histopathological examination of the heart revealed a chemodectoma at the base of the heart. There was no neoplastic infiltration of the conduction tissue. Potential mechanisms explaining the association of the arrhythmias and the tumour, such as vagal stimulation and neuroendocrine factors are discussed.

Pitfalls and premature failure of the Freedom SOLO stentless valve.

OBJECTIVES This study reports a series of pitfalls, premature failures and explantations of the third-generation Freedom SOLO (FS) bovine pericardial stentless valve. METHODS A total of 149 patients underwent aortic valve replacement using the FS. Follow-up was 100% complete with an average observation time of 5.5 ± 2.3 years (maximum 8.7 years) and a total of 825 patient-years. Following intraoperative documentation, all explanted valve prostheses underwent histological examination. RESULTS Freedom from structural valve deterioration (SVD) at 5, 6, 7, 8 and 9 years was 92, 88, 80, 70 and 62%, respectively. Fourteen prostheses required explantation due to valve-independent dysfunction (n = 5; i.e. thrombus formation, oversizing, aortic dilatation, endocarditis and suture dehiscence) or valve-dependent failure (acute leaflet tears, n = 4 and severe stenosis, n = 5). Thus, freedom from explantation at 5, 6, 7, 8 and 9 years was 95, 94, 91, 81 and 72%, respectively. An acute vertical tear along the non-coronary/right coronary commissure to the base occurred at a mean of 6.0 years (range 4.3-7.3 years) and affected size 25 and 27 prostheses exclusively. Four FS required explantation after a mean of 7.5 years (range 7.0-8.3 years) due to severe functional stenosis and gross calcification that included the entire aortic root. CONCLUSIONS The FS stentless valve is safe to implant and shows satisfying mid-term results in our single institution experience. Freedom from SVD and explantation decreased markedly after only 6-7 years, so that patients with FS require close observation and follow-up. Exact sizing, symmetric positioning and observing patient limitations are crucial for optimal outcome.

Postnatal Notch1 activation induces T‑cell malignancy in conditional and inducible mouse models

The Notch1 signaling pathway is essential for hematopoietic development. However, the effects of postnatal activation of Notch1 signaling on hematopoietic system is not yet fully understood. We previously generated ZEG‑IC‑Notch1 transgenic mice that have a floxed β‑geo/stop signal between a CMV promoter and intracellular domain of Notch1 (IC‑Notch1). Constitutively active IC‑Notch1 is silent until the introduction of Cre recombinase. In this study, endothelial/hematopoietic specific expression of IC‑Notch1 in double transgenic ZEG‑IC‑Notch1/Tie2‑Cre embryos induced embryonic lethality at E9.5 with defects in vascular system but not in hematopoietic system. Inducible IC‑Notch1 expression in adult mice was achieved by using tetracycline regulated Cre system. The ZEG‑IC‑Notch1/Tie2‑tTA/tet‑O‑Cre triple transgenic mice survived embryonic development when maintained on tetracycline. Post‑natal withdrawal of tetracycline induced expression of IC‑Notch1 transgene in hematopoietic cells of adult mice. The triple transgenic mice displayed extensive T‑cell infiltration in multiple organs and T‑cell malignancy of lymph nodes. In addition, the protein levels of p53 and alternative reading frame (ARF) were decreased in lymphoma‑like neoplasms from the triple transgenic mice while their mRNA expression remained unchanged, suggesting that IC‑Notch1 might repress ARF‑p53 pathway by a post‑transcriptional mechanism. This study demonstrated that activation of constitutive Notch1 signaling after embryonic development alters adult hematopoiesis and induces T‑cell malignancy.

A regional climate palaeosimulation for Europe in the period 1500–1990 – Part 2: Shortcomings and strengths of models and reconstructions

This study compares gridded European seasonal series of surface air temperature (SAT) and precipitation (PRE) reconstructions with a regional climate simulation over the period 1500–1990. The area is analysed separately for nine subareas that represent the majority of the climate diversity in the European sector. In their spatial structure, an overall good agreement is found between the reconstructed and simulated climate features across Europe, supporting consistency in both products. Systematic biases between both data sets can be explained by a priori known deficiencies in the simulation. Simulations and reconstructions, however, largely differ in the temporal evolution of past climate for European subregions. In particular, the simulated anomalies during the Maunder and Dalton minima show stronger response to changes in the external forcings than recorded in the reconstructions. Although this disagreement is to some extent expected given the prominent role of internal variability in the evolution of regional temperature and precipitation, a certain degree of agreement is a priori expected in variables directly affected by external forcings. In this sense, the inability of the model to reproduce a warm period similar to that recorded for the winters during the first decades of the 18th century in the reconstructions is indicative of fundamental limitations in the simulation that preclude reproducing exceptionally anomalous conditions. Despite these limitations, the simulated climate is a physically consistent data set, which can be used as a benchmark to analyse the consistency and limitations of gridded reconstructions of different variables. A comparison of the leading modes of SAT and PRE variability indicates that reconstructions are too simplistic, especially for precipitation, which is associated with the linear statistical techniques used to generate the reconstructions. The analysis of the co-variability between sea level pressure (SLP) and SAT and PRE in the simulation yields a result which resembles the canonical co-variability recorded in the observations for the 20th century. However, the same analysis for reconstructions exhibits anomalously low correlations, which points towards a lack of dynamical consistency between independent reconstructions.

Mutation of the ER retention receptor KDELR1 leads to cell-intrinsic lymphopenia and a failure to control chronic viral infection

Endoplasmic reticulum (ER)-resident proteins are continually retrieved from the Golgi and returned to the ER by Lys-Asp-Glu-Leu (KDEL) receptors, which bind to an eponymous tetrapeptide motif at their substrate's C terminus. Mice and humans possess three paralogous KDEL receptors, but little is known about their functional redundancy, or if their mutation can be physiologically tolerated. Here, we present a recessive mouse missense allele of the prototypical mammalian KDEL receptor, KDEL ER protein retention receptor 1 (KDELR1). Kdelr1 homozygous mutants were mildly lymphopenic, as were mice with a CRISPR/Cas9-engineered frameshift allele. Lymphopenia was cell intrinsic and, in the case of T cells, was associated with reduced expression of the T-cell receptor (TCR) and increased expression of CD44, and could be partially corrected by an MHC class I-restricted TCR transgene. Antiviral immunity was also compromised, with Kdelr1 mutant mice unable to clear an otherwise self-limiting viral infection. These data reveal a nonredundant cellular function for KDELR1, upon which lymphocytes distinctly depend.

Pitfalls and premature failure of the Freedom SOLO stentless valve

Gebiet: Chirurgie Abstract: Objectives This study reports a series of pitfalls, premature failures and explantations of the third generation Freedom SOLO bovine pericardial stentless valve. – – Methods 149 patients underwent aortic valve replacement (AVR) using the FS. Follow-up was 100% complete with an average observation time of 5.5±2.3 years (max. 8.7 years) and a total of 825 patient years. Following intraoperative documentation, all explanted valve prostheses underwent histological examination. – – Results Freedom from structural valve deterioration (SVD) at 5, 6, 7, 8 and 9 years was 92%, 88%, 80% and 70% and 62%, respectively. 14 prostheses required explantation due to valve-independent dysfunction (n=5, i.e. thrombus formation, oversizing, aortic dilatation, endocarditis and suture dehiscence) or valve-dependent failure (acute leaflet tears, n=4, severe stenosis, n=5). Thus freedom from explantation at 5, 6, 7, 8 and 9 years was 95%, 94%, 91% and 81% and 72%, respectively. An acute vertical tear along the non-coronary/right-coronary commissure to the base occurred at a mean of 6.0 years [range 4.3?7.3 years] and affected size 25 and 27 prostheses exclusively. Four FS required explantation after a mean of 7.5 years [range 7.0?8.3 years] due to severe functional stenosis and gross calcification that included the entire aortic root. – – Conclusions The Freedom SOLO stentless valve is safe to implant and shows satisfying mid-term results in our single institution experience. Freedom from SVD and explantation decreased markedly after only 6 ? 7 years, so that patients with FS require close observation and follow-up. Exact sizing, symmetric positioning and observing patient limitations are crucial for optimal outcome.

Comparison of compliance and immune response of drug users on the standard and accelerated hepatitis B vaccine schedules - Houston, Texas

Despite the availability of hepatitis B vaccine for over two decades, drug users and other high-risk adult populations have experienced low vaccine coverage. Poor compliance has limited efforts to reduce transmission of hepatitis B infection in this population. Evidence suggests that immunological response in drug users is impaired compared to the general population, both in terms of lower seroprotection rates and antibodies levels.^ The current study investigated the effectiveness of the multi-dose hepatitis B vaccine and compared the effect of the standard and accelerated vaccine schedules in a not-in-treatment, drug-using adult population in the city of Houston, USA.^ A population of drug-users from two communities in Houston, susceptible to hepatitis B, was sampled by outreach workers and referral methodology. Subjects were randomized either to the standard hepatitis vaccine schedule (0, 1-, 6-month) or to an accelerated schedule (0, 1-, 2-month). Antibody levels were detected through laboratory analyses at various time-points. The participants were followed for two years and seroconversion rates were calculated to determine immune response.^ A four percent difference in the overall compliance rate was observed between the standard (73%) and accelerated schedules (77%). Logistic regression analyses showed that drug users living on the streets were twice as likely to not complete all three vaccine doses (p=0.028), and current speedball use was also associated with non-completion (p=0.002). Completion of all three vaccinations in the multivariate analysis was also correlated with older age. Drug users on the accelerated schedule were 26% more likely to achieve completion, although this factor was marginally significant (p=0.085).^ Cumulative adequate protective response was gained by 65% of the HBV susceptible subgroup by 12-months and was identical for both the standard and accelerated schedules. Excess protective response (>=100 mIU/mL) occurred with greater frequency at the later period for the standard schedule (36% at 12-months compared to 14% at six months), while the greater proportion of excess protective response for the accelerated schedule occurred earlier (34% at 6 months compared to 18% at 12-months). Seroconversion at the adequate protective response level of 10 mIU/mL was reached by the accelerated schedule group at a quicker rate (62% vs. 49%), and with a higher mean titer (104.8 vs. 64.3 mIU/mL), when measured at six months. Multivariate analyses indicated a 63% increased risk of non-response for older age and confirmed the existence of an accelerating decline in immune response to vaccination manifesting after 40 years (p=0.001). Injecting more than daily was also highly associated with the risk of non-response (p=0.016).^ The substantial increase in the seroprotection rate at six months may be worth the trade-off against the faster antibody titer decrease and is recommended for enhancing compliance and seroconversion. Utilization of the accelerated schedule with the primary objective of increasing compliance and seroconversion rates during the six months after the first dose may confer early protective immunity and reduce the HBV vulnerability of drug users who continue, or have recently initiated, increased high risk drug use and sexual behaviors.^

Innnovation and new business models for the regional development: travel and transportation

Regional development could present different strategies: •Relocation of industry clusters •Foreign Direct Investment attraction •Innovation based on new business models The Regional Government of Madrid (3rd largest GDP in the EU) selected strategic industries to compete & innovate: •Travel & Transportation •Aerospace •Nanotech. & •Biotech. •ICTs. •Energy

Seismic Hazard and Risk in Central America

1999 Seismic Hazard In Guatemala 2001 Post-Event Mision 2006 Resis Ii Project Norad 2007 Workshop Seismic Hazard 2010 Book Amenaza Sísmica En América Central 2011 Cooperation Haití, República Dominicana, Puerto Rico

Seismic Hazard and Ground Motion Characterization at the Itoiz Dam (Northern Spain).

This paper presents a new hazard-consistent ground motion characterization of the Itoiz dam site, located in Northern Spain. Firstly, we propose a methodology with different approximation levels to the expected ground motion at the dam site. Secondly, we apply this methodology taking into account the particular characteristics of the site and of the dam. Hazard calculations were performed following the Probabilistic Seismic Hazard Assessment method using a logic tree, which accounts for different seismic source zonings and different ground-motion attenuation relationships. The study was done in terms of peak ground acceleration and several spectral accelerations of periods coinciding with the fundamental vibration periods of the dam. In order to estimate these ground motions we consider two different dam conditions: when the dam is empty (T = 0.1 s) and when it is filled with water to its maximum capacity (T = 0.22 s). Additionally, seismic hazard analysis is done for two return periods: 975 years, related to the project earthquake, and 4,975 years, identified with an extreme event. Soil conditions were also taken into account at the site of the dam. Through the proposed methodology we deal with different forms of characterizing ground motion at the study site. In a first step, we obtain the uniform hazard response spectra for the two return periods. In a second step, a disaggregation analysis is done in order to obtain the controlling earthquakes that can affect the dam. Subsequently, we characterize the ground motion at the dam site in terms of specific response spectra for target motions defined by the expected values SA (T) of T = 0.1 and 0.22 s for the return periods of 975 and 4,975 years, respectively. Finally, synthetic acceleration time histories for earthquake events matching the controlling parameters are generated using the discrete wave-number method and subsequently analyzed. Because of the short relative distances between the controlling earthquakes and the dam site we considered finite sources in these computations. We conclude that directivity effects should be taken into account as an important variable in this kind of studies for ground motion characteristics.