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Summary: The domestic cat (Felis silvestris catus) is a valued companion animal throughout the world. Over 60 different cat breeds are accepted for competition by the cat fancy registries in different countries. Genetic markers, including short tandem repeats and SNPs, are available to evaluate and manage levels of inbreeding and genetic diversity, population and breed structure relationships, and individual identification for forensic and registration purposes. The International Society of Animal Genetics (ISAG) hosts the Applied Genetics in Companion Animals Workshop, which supports the standardization of genetic marker panels and genotyping for the identification of cats via comparison testing. SNP panels have been in development for many species, including the domestic cat. An ISAG approved core panel of SNPs for use in cat identification and parentage analyses is presented. SNPs (n = 121) were evaluated by different university‐based and commercial laboratories using 20 DNA samples as part of the ISAG comparison testing procedures. Different SNP genotyping technologies were examined, including DNA arrays, genotyping‐by‐sequencing and mass spectroscopy, to select a robust and efficient panel of 101 SNPs as the ISAG core panel for cats. The SNPs are distributed across all chromosomes including two on the X chromosome and an XY pseudo‐autosomal sexing marker (zinc‐finger XY; ZFXY). A population study demonstrated that the markers have an average polymorphic information content of 0.354 and a power of exclusion greater than 0.9999. The SNP panel should keep testing affordable while also allowing for the development of additional panels to monitor health, phenotypic traits, hybrid cats and highly inbred cats. [ABSTRACT FROM AUTHOR]

Abstract: A mathematical model based on a generalized Maxwell-Stefan equation has been developed to describe multicomponent ion and water transport inside a cation-exchange membrane. This model has been validated using experimental data and has been used to predict concentration profiles, membrane potential drop, and transport numbers of ions and water for the chlor-alkali process at increased current densities. Several improvements have been made to previously developed Maxwell-Stefan models. In our model, the generalized Maxwell-Stefan equation is written in terms of concentration instead of mole fraction and the fixed group (membrane) concentration is assumed to be constant. We have adapted the Augmented matrix method using the built-in partial differential equation parabolic elliptic (pdepe) solver in Matlab®, and both the concentration and the electrical potential gradients have been solved simultaneously. The boundary conditions are determined with the Donnan equilibrium at the membrane-solution interface. We have also employed semi-empirical correlations to define the Maxwell-Stefan diffusivities inside the membrane. For the bulk diffusivities, we applied the correlations for the concentrated solution instead of the values at infinite dilution. With the diffusivities presented in this work, the model shows a better fit to the experimental data than with previously reported fitted diffusivities. Prediction of the sodium transport number and water transport number is generally good, whereas the deviations with regard to membrane potential might also be related to issues with the experimental data. The model predicts an increase in both sodium and water transport numbers at increased current density operation of chlor-alkali production.Graphical abstract: [ABSTRACT FROM AUTHOR]

A brain MRI revealed multiple linear and punctiform T2 hyperintense white matter lesions with subtle enhancement on T1-weighted post-gadolinium MRI (Fig. In Susac's syndrome, brain MRI shows multiple white matter high-intensity lesions on T2-weighted images. According to the proposed criteria for Susac's syndrome, our patient can be classified as probable Susac's syndrome, since no lesions were present in the corpus callosum [[11]]. Our case report shows that Susac's syndrome can occur as a rare neurological irAE and illustrates the difficulties to discern this syndrome from LM. [Extracted from the article]

This experiment was designed to study if liquid conservation buffer used in the novel Tissue Sampling Technology (TST) from Allflex can be used for Illumina BeadChip genotyping. Ear punches were collected from 6 bovine samples, using both the Tissue Sampling Unit (TSU) as well as the Total Tagger Universal (TTU) collection system. The stability of the liquid conservation buffer was tested by genotyping samples on Illumina BeadChips, incubated at 0, 3, 15, 24, 48, 72, 168, 336, 720 h after sample collection. Additionally, a replenishment study was designed to test how often the liquid conservation buffer could be completely replenished before a significant call rate drop could be observed. Results from the stability study showed an average call rate of 0.993 for samples collected with the TSU system and 0.953 for samples collected with the TTU system, both exceeding the inclusion threshold call rate of 0.85. As an additional control, the identity of the individual animals was confirmed using the International Society of Animal Genetics (ISAG) recommended SNP panel. The replenishment study revealed a slight drop in the sample call rate after replenishing the conservation buffer for the fourth time for the TSU as well as the TTU samples. In routine analysis, this application allows for multiple experiments to be performed on the liquid conservation buffer, while maintaining the tissue samples for future use. The data collected in this study shows that the liquid conservation buffer used in the TST system can be used for Illumina BeadChip genotyping applications. [ABSTRACT FROM AUTHOR]

Objective: To examine whether successful coronary reperfusion after thrombolytic treatment in patients with confirmed acute myocardial infarction can be diagnosed from the plasma marker fatty acid binding protein (FABP), for either acute clinical decision making or retrospective purposes.Design: Retrospective substudy of the GUSTO trial.Setting: 10 hospitals in four European countries.Patients: 115 patients were treated with thrombolytic agents within six hours after the onset of acute myocardial infarction. Patency of the infarct related artery was determined by angiography within 120 minutes of the start of thrombolysis.Main Outcome Measures: First hour rate of increase in plasma FABP concentration after thrombolytic treatment, compared with increase in plasma myoglobin concentration and creatine kinase isoenzyme MB (CK-MB) activity. Infarct size was estimated from the cumulative release of the enzyme alpha hydroxybutyrate dehydrogenase in plasma during 72 hours, or from the sum of ST segment elevations on admission. Logistic regression analyses were performed to construct predictive models for patency.Results: Complete reperfusion (TIMI 3) occurred in 50 patients, partial reperfusion (TIMI 2) in 36, and no reperfusion (TIMI 0+1) in 29. Receiver operating characteristic (ROC) curve analyses showed that the best performance of FABP was obtained when TIMI scores 2 and 3 were grouped and compared with TIMI score 0+1. The performance of FABP as a reperfusion marker was improved by combining it with alpha hydroxybutyrate dehydrogenase infarct size, but not with an early surrogate of infarct size (ST segment elevation on admission). In combination with infarct size FABP performed as well as myoglobin (areas under the ROC curve 0.868 and 0.857, respectively) and better than CK-MB (area = 0.796). At optimum cut off levels, positive predictive values were 97% for FABP, 95% for myoglobin, and 89% for CK-MB (without infarct size, 87%, 88%, and 87%, respectively), and negative predictive values were 55%, 52%, and 50%, respectively (without infarct size, 44%, 42%, and 34%).Conclusions: FABP and myoglobin perform equally well as reperfusion markers, and successful reperfusion can be assessed, with positive predictive values of 87% and 88%, or even 97% and 95% when infarct size is also taken into account. However, identification of non-reperfused patients remains a problem, as negative predictive values will generally remain below 70%. [ABSTRACT FROM AUTHOR]

Abstract: Connectivity and network analysis in neuroscience has been applied to multiple spatial scales, but the links between these different scales have rarely been investigated. In tumor-related epilepsy, altered network topology is related to behavior, but the molecular basis of these observations is unknown. We elucidate the associations between microscopic features of brain tumors, local network topology, and functional patient status. We hypothesize that expression of proteins related to tumor-related epilepsy is directly correlated with network characteristics of the tumor area. Glioma patients underwent magnetoencephalography, and functional network topology of the tumor area was used to predict tissue protein expression patterns of tumor tissue collected during neurosurgery. Protein expression and network topology were interdependent; in particular between-module connectivity was selectively associated with two epilepsy-related proteins. Total number of seizures was related to both the role of the tumor area in the functional network and to protein expression. Importantly, classification of protein expression was predicted by between-module connectivity with up to 100% accuracy. Thus, network topology may serve as an intermediate level between molecular features of tumor tissue and symptomatology in brain tumor patients, and can potentially be used as a non-invasive marker for microscopic tissue characteristics. [Copyright &y& Elsevier]

Motivation: Many enzymes are not absolutely specific, or even promiscuous: they can catalyze transformations of more compounds than the traditional ones as listed in, e.g. KEGG. This information is currently only available in databases, such as the BRENDA enzyme activity database. In this article, we propose to model enzyme aspecificity by predicting whether an input compound is likely to be transformed by a certain enzyme. Such a predictor has many applications, for example, to complete reconstructed metabolic networks, to aid in metabolic engineering or to help identify unknown peaks in mass spectra. [ABSTRACT FROM PUBLISHER]

The article discusses the study which aims to provide evidence on the effectiveness and tolerability of switching between biologics treatment for psoriasis. The study analysed and compared data of patients' characteristics who switched between biologics either successfully treated or not. Results of the study show that unsatisfactory results with one biologic do not predict the response to another biologic.

Background: Relatives who are bereaved by suicide likely consult their GP when they feel the need for professional help. GPs may play a key role in establishing who is at risk for adverse consequences of the loss as they are familiar with relatives' possible psychiatric vulnerabilities. The availability of evidence-based services for relatives of suicide victims is limited. Successful implementation of services needs analysis of key factors considered critical in the achievement of changes. We investigated GPs' management of help requests of relatives bereaved by suicide and examined determinants of GPs willingness to refer for evidence-based follow-up care.Methods: A cross-sectional survey among 488 GPs in the northern part of The Netherlands.Results: A 44% response was achieved (n = 214) during the last 3 years, 38 (18%) were exposed to suicide, 21 (10%) to help requests without being exposed to suicide and 52 (24%) to both suicide and help requests. Out of 106 requests, 69 (65%) were handled by the GP; 60 (57%) were either directly or additionally referred, principally for mental health care. Suicide exposure and female gender were associated with the doctor's perception that follow-up care following a loss through suicide is useful. The perception that help is useful increased the likelihood of GPs' referral for evidence-based follow-up care.Conclusions: GPs support the availability of evidence-based follow-up care for relatives of suicide victims. To modify GPs' key role in referring relatives for it, GPs should be well informed of its usefulness and to whom. [ABSTRACT FROM AUTHOR]

Contents The final stages of cervical ripening and parturition resemble an inflammatory process. Although the role of cytokines in both spontaneous and experimentally induced parturitions has been described in several small laboratory animals and humans, the involvement of pro-inflammatory and regulatory cytokines in physiologic parturition in cows has not been determined. In this study, the cytokine expression profiles were assessed in bovine cervical tissue at several stages of pregnancy and at parturition. Serial biopsy samples of the cervix were obtained from 10 cows on day 185 and day 275 of pregnancy (which was on average 5.4 days before parturition) and at parturition. Messenger RNA expression levels of interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)α were determined using real-time polymerase chain reaction and the number of neutrophils and eosinophils was estimated by Luna and Sirius Red staining. At parturition, IL-8 expression had increased 430-fold (p < 0.001) when compared with that of the day 185 of pregnancy, large numbers of neutrophils had invaded the cervix while eosinophils remained scarce, IL-1β had increased eightfold (p < 0.05) and IL-6 had not changed significantly. Additionally, IL-10 was increased by 10-fold (p < 0.001) and TNFα decreased by 57% (p < 0.05) when compared with that of the day 185 of pregnancy. The large increase in expression of IL-8, enabling the influx of neutrophils, is indicative of its important role in the final stage of cervical ripening and at parturition. As previous studies have shown that neutrophils excrete matrix metalloproteinases (MMP), this might contribute to softening of the cervix. In contrast, the only slightly increased levels of IL-1, steady concentrations of IL-6 and decreased TNFα, the potential consequences of increased IL-10 expression, indicate that final cervical of cows in ripening at term parturition is an inflammatory process influenced by regulatory cytokines. [ABSTRACT FROM AUTHOR]

Abstract: The importance of macrostructural white matter changes, including white matter lesions and atrophy, in intact brain functioning is increasingly being recognized. Diffusion tensor imaging (DTI) enables measurement of the microstructural integrity of white matter. Loss of white matter integrity in aging has been reported, but whether this is inherent to the aging process itself or results from specific white matter pathology is unknown. In 832 persons aged 60 years and older from the population-based Rotterdam Study, we measured fractional anisotropy (FA) and directional diffusivities in normal-appearing white matter using DTI. All subjects'' DTI measures were projected onto a common white matter skeleton to enable robust voxelwise comparison. With increasing age, multiple regions showed significant decreases in FA or increases in axial or radial diffusivity in normal-appearing white matter. However, nearly all of these regional changes were explained by either white matter atrophy or by white matter lesions; each of which related to changes in distinct brain regions. These results indicate that loss of white matter integrity in aging is primarily explained by atrophy and lesion formation and not by the aging process itself. Furthermore, white matter atrophy and white matter lesion formation relate to loss of integrity in distinct brain regions, indicating the two processes are pathophysiologically different. [Copyright &y& Elsevier]

Background Etanercept and efalizumab recently became available and reimbursed for routine use in severe psoriasis in the Netherlands. The criteria for reimbursement are Psoriasis Area and Severity Index (PASI) ≥ 10 (or Skindex-29 ≥ 35 if PASI ≥ 8 and < 10) and ineffectiveness of ultraviolet (UV) B/psoralen plus UVA, methotrexate and ciclosporin, or a contraindication to or serious side-effect(s) during these treatments. Objectives We hypothesized: (i) that efficacy would be lower than that obtained in published phase II and III studies because (a) resistance to all conventional therapies as a reimbursement condition would select for more resistant cases and (b) inclusion would be more restricted to severe cases (higher PASI), and (ii) that efficacy would be lower in obese patients due to the possible role of adipose tissue in tumour necrosis factor (TNF)- α homeostasis. Methods We treated 50 patients (38 men, 12 women; mean PASI 15·8) with etanercept 25 mg or 50 mg twice weekly and evaluated in a retrospective analysis the efficacy and safety in comparison with data from published trials. Additionally, we related the clinical effect to the body mass index (BMI), for adipose tissue is thought to have a possible role in TNF- α homeostasis. Results Based on the literature, 30% and 49% of the patients treated with etanercept 25 mg and 50 mg twice weekly, respectively, should have achieved 75% or more improvement in PASI compared with baseline (PASI 75), and 10% and 21%, respectively, should have achieved 90% or more improvement (PASI 90). Our data showed that 21% in the 2 × 25 mg group and 23% in the 2 × 50 mg group achieved PASI 75. PASI 90 was only attained in 7% of patients treated with 2 × 25 mg and 6% of those treated with 2 × 50 mg. Contrary to our hypothesis, the mean initial PASI was comparable with the mean PASI mentioned in the phase II and III clinical trials. Although fatigue is not identified as a side-effect of etanercept, 10% of our patients reported fatigue as an adverse event during etanercept treatment. High BMI, indicating overweight or obesity, was found both in patients with little efficacy and in patients achieving PASI 75 or better. Conclusions Use of etanercept in real practice gives impressive results, but these are generally less favourable than those published in clinical trial reports. This is probably due to the stringent conditions for reimbursement, which select for more treatment-resistant patients. Fatigue as a possible side-effect of etanercept should also be an issue for further investigation. Finally, the BMI does not seem to influence the patients’ response to etanercept, although further investigations would be needed to confirm this. [ABSTRACT FROM AUTHOR]

Chronic dysfunction after complicated grief is not rare and emphasizes the need to identify bereaved individuals at risk. Three months following bereavement, self-reported psychiatric and general health of 153 relatives of 74 suicides was worse than of 70 relatives of 39 natural deaths. Moreover, the felt need for professional help was higher among the former, even after adjustment for expectedness of death, sociodemographic differences, and relatives'/spouses' neuroticism. This suggests that suicide-bereaved individuals may constitute a high-risk group of mourners in need of targeted postvention. [ABSTRACT FROM AUTHOR]

Understanding of the physical backgrounds is essential for good engineering practice with respect to liquefaction of sandy soils around and beneath marine structures. Several types of liquefaction can be distinguished. The corresponding physical phenomena are briefly described. Among them are: compressibility of soil skeleton, dilation, contraction, elastic versus plastic deformation, interaction between pore water and soil skeleton, compressibility of pore water, monotonic versus cyclic response, instantaneous versus residual liquefaction, drainage and pre-shearing. In each particular case just a limited number of these phenomena is relevant and needs to be modeled. A survey of typical cases is presented and the relevant phenomena are discussed. Most will be elaborated on in other papers appearing in this issue. This paper may help to discover the relationship between the different papers. [ABSTRACT FROM AUTHOR]

The foundation of a vertical breakwater or offshore gravity platform may fail due to wave loading. The question is discussed whether liquefaction phenomena in a sandy subsoil, such as the generation of residual excess pore pressures and cyclic mobility, may significantly contribute to such failure. Theory, descriptions of prototype failure cases, and several scale tests are analyzed. It is concluded that the most spectacular failure type “liquefaction flow failure” is only possible in the case of a subsoil of very loose sand or silt combined with a low drainage potential, e.g., by the presence of a clay layer or large structure dimensions. Three other potential failure types are more likely in other cases: stepwise liquefaction failure, stepwise failure, and wobble failure. Their relevance increases with decreasing relative density and decreasing drainage potential. Brief recommendations for assessment of each failure type are presented. [ABSTRACT FROM AUTHOR]

Joint function is described by biomechanical parameters like range of motion (ROM), stiffness, laxity and stability. However, these terms are frequently used ambiguously. Due to the lack in standardisation, it is difficult to compare results of examinations. A literature survey is performed and an inventory is made about the definitions used for the terms. The final definition for ROM is the range of translation and rotation through which a joint may be actively or passively moved in a certain direction. Joint stiffness describes the resistance of the joint to imposed relative movement between two joint surfaces. Laxity is the normal amount of motion that results from passive forces or moments and stability is the ability to control positions or movements of joints. [ABSTRACT FROM AUTHOR]

Experiments have been performed to determine the path of entry into and exit from the phosphorescent triplet state T[sub 0] of quinoxaline in a durene host. First of all the decay of phosphorescence after flash excitation was followed at 4.2 and 1.34°K. It was found that for both perdeutero- and perhydroquinoxaline the lifetime is shortened by a factor of about three when the temperature is lowered from 4.2 to 1.34°K. At 1.34°K relaxation between the spin components (i.e. re-orientation of the triplet spin angular momentum) is slow relative to the decay, and the observed reduction in lifetime indicates that entry into and exit from T[sub 0] are through the same spin component. Similar decay experiments were then carried out at 1.34°K in a 10 kG magnetic field or in a somewhat weaker field so chosen that the effect of microwave saturation of one of the E.S.R. transitions between the components could be observed. From the results it follows that on intersystem crossing the molecules enter the manifold T[sub 0] through the top zero-field component and thus initially have their spins aligned. Decay departs almost exclusively from the same component, even in the case of perhydroquinoxaline, where at least 45 per cent of it must be radiationless. The decay route agrees with out-of-plane polarization of phosphorescence for the free molecule. Finally, spin alignment on intersystem crossing is discussed from the theoretical point of view. It appears that the phenomenon is clear-cut only in molecules such as those of the aza-aromatics, where strong spin-orbit coupling of the atomic type occurs betwen ππ and nπ states. [ABSTRACT FROM AUTHOR]

Analyzes the photometric monitoring of eta Carinae, pulsating luminous blue variable (LBV). Mechanism of LBV pulsation; Stability of pulsation period in 20 years; Evidence of secondary periods in eta Carinae.

Presents a letter to the editor about the occurrence of dermatitis during efalizumab treatment in patients with psoriasis vulgaris.

A letter to the editor is presented in response to the article "DRESS syndrome caused by efalizumab."

The purpose of this study was to evaluate the influence of psychiatric symptoms and illness status on the health-related quality of life (HRQOL) of outpatients with Type I and Type II diabetes mellitus. Using a two-stage design, all patients were assessed by two measures of quality of life (Diabetes Quality of Life Measure; Medical Outcome Study Health Survey) and a psychiatric symptoms checklist (SCL-90-R). Patients scoring 63 or greater on the global severity index of the SCL-90-R and 30% below this cutoff were then evaluated using the Structured Clinical Interview for the DSM-III-R (SCID). Quality of life in both Type I and Type II diabetes was influenced by the level of current psychiatric symptoms and presence of co-morbid psychiatric disorder, after controlling for number of diabetic complications (e.g. effect of lifetime psychiatric illness on diabetes-related HRQOL; F=46.8; df=3, 135; p < 0.005). These effects were found consistently across specific domains. Both recent and past psychiatric disorders influenced HRQOL. Separate analyses comparing patients with and without depression showed similar effects. No interaction effects between diabetes type, number of complications, and psychiatric status were found in analyses. Finally, increased severity of psychiatric symptoms was correlated with decreased HRQOL in patients without current, recent, or past psychiatric diagnosis. This study shows the consistent, independent contribution of psychiatric symptoms and illness to the HRQOL of patients with a co-existing medical illness. Thus, psychiatric interventions addressing common conditions, such as depression, could improve the HRQOL of patients without changing medical status. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Ravelli A, Jager K, de Groot M, Erwich J, Rijninks-van Driel G, Tromp M, Eskes M, Abu-Hanna A, Mol B. Travel time from home to hospital and adverse perinatal outcomes in women at term in the Netherlands. BJOG 2011;118:457-465. To study the effect of travel time, at the start or during labour, from home to hospital on mortality and adverse outcomes in pregnant women at term in primary and secondary care. Population-based cohort study from 2000 up to and including 2006. The Netherlands Perinatal Registry. A total of 751 926 singleton term hospital births. We assessed the impact of travel time by car, calculated from the postal code of the woman's residence to the 99 maternity units, on neonatal outcome. Logistic regression modelling with adjustments for gestational age, maternal age, parity, ethnicity, socio-economic status, urbanisation, tertiary care centres and volume of the hospital was used. Mortality (intrapartum, and early and late neonatal mortality) and adverse neonatal outcomes (mortality, Apgar <4 and/or admission to a neonatal intensive care unit). The mortality was 1.5 per 1000 births, and adverse outcomes occurred in 6.0 per 1000 births. There was a positive relationship between longer travel time (≥20 minutes) and total mortality (OR 1.17, 95% CI 1.002-1.36), neonatal mortality within 24 hours (OR 1.51, 95% CI 1.13-2.02) and with adverse outcomes (OR 1.27, 95% CI 1.17-1.38). In addition to travel time, both delivery at 37 weeks of gestation (OR 2.23, 95% CI 1.81-2.73) or 41 weeks of gestation (OR 1.52, 95% CI 1.29-1.80) increased the risk of mortality. A travel time from home to hospital of 20 minutes or more by car is associated with an increased risk of mortality and adverse outcomes in women at term in the Netherlands. These findings should be considered in plans for the centralisation of obstetric care. [ABSTRACT FROM AUTHOR]

Results of large-scale model experiments in a wave flume are discussed. These experiments are concerned with the study of the generation of transient or instantaneous and residual pore pressure in a seabed beneath a caisson breakwater subjected to both pulsating and breaking wave loads. The simulated seabed and drainage conditions correspond to those encountered in a loose sand bed with thin clay or silt layers. Even under such unfavorable conditions total liquefaction due to residual pore pressures could not occur during the experiments. It is shown that the residual pore pressure is essentially generated by the caisson motions due to breaking wave loads and that they are closely related to residual soil deformations, which may lead to the failure of the breakwater. [ABSTRACT FROM AUTHOR]

Objective: Depression is common among patients with diabetes, but its relationship to glycemic control has not been systematically reviewed. Our objective was to determine whether depression is associated with poor glycemic control.Research Design and Methods: Medline and PsycINFO databases and published reference lists were used to identify studies that measured the association of depression with glycemic control. Meta-analytic procedures were used to convert the findings to a common metric, calculate effect sizes (ESs), and statistically analyze the collective data.Results: A total of 24 studies satisfied the inclusion and exclusion criteria for the meta-analysis. Depression was significantly associated with hyperglycemia (Z = 5.4, P < 0.0001). The standardized ES was in the small-to-moderate range (0.17) and was consistent, as the 95% CI was narrow (0.13-0.21). The ES was similar in studies of either type 1 or type 2 diabetes (ES 0.19 vs. 0.16) and larger when standardized interviews and diagnostic criteria rather than self-report questionnaires were used to assess depression (ES 0.28 vs. 0.15).Conclusions: Depression is associated with hyperglycemia in patients with type 1 or type 2 diabetes. Additional studies are needed to establish the directional nature of this relationship and to determine the effects of depression treatment on glycemic control and the long-term course of diabetes. [ABSTRACT FROM AUTHOR]

BACKGROUND: A single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia. METHODS: In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months. RESULTS: Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P = 0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group B) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome. CONCLUSIONS: The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects. (Funded by Novartis and others; RACE ClinicalTrials.gov number, NCT02099747; EudraCT number, 2014-000363-40.). [ABSTRACT FROM AUTHOR]

Introduction: Current guidelines advocate empirical antibiotic treatment (EAT) in haematological patients with febrile neutropenia. However, the optimal duration of EAT is unknown. In 2011, we have introduced a protocol, promoting discontinuation of carbapenems as EAT after 3 days in most patients and discouraging the standard use of vancomycin. This study assesses the effect of introducing this protocol on carbapenem and vancomycin use in high-risk haematological patients and its safety. Methods: A retrospective before-after study was performed comparing a cohort from 2007 to 2011 (period I, before restrictive EAT use) with a cohort from 2011 to 2014 (period II, restrictive EAT use). Neutropenic episodes related to chemotherapy or stem cell transplantation (SCT) in patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) were analysed. The primary outcome was the use of carbapenems and vancomycin as EAT during neutropenia, expressed as days of therapy (DOT)/100 neutropenic days and analysed with interrupted time series (ITS). Also the use of other antibiotics was analysed. Safety measurements included 30-day mortality, ICU admittance within 30 days after start of EAT and positive blood cultures with carbapenem-susceptible microorganisms. Results: Three hundred sixty-two neutropenic episodes with a median duration of 18 days were analysed, involving 201 patients. ITS analysis showed decreased carbapenem use with a step change of − 16.1 DOT/100 neutropenic days (95% CI − 26.77 to − 1.39) and an overall reduction of 21.6% (8.7 DOT/100 neutropenic days). Vancomycin use decreased with a step change of − 13.7 DOT/100 neutropenic days (95% CI − 23.75 to − 3.0) and an overall reduction of 54.7% (14.6 DOT/100 neutropenic days). The use of all antibiotics combined decreased from 155.6 to 138 DOT/100 neutropenic days, a reduction of 11.3%. No deaths directly related to early discontinuation of EAT were identified, also no notable difference in ICU-admission (9/116 in period I, 9/152 in period II) and positive blood cultures (4/116 in period I, 2/152 in period II) was detected. Conclusion: The introduction of a protocol promoting restrictive use of EAT resulted in reduction of carbapenem and vancomycin use and appears to be safe in AML or high-risk MDS patients with febrile neutropenia during chemotherapy or SCT. [ABSTRACT FROM AUTHOR]

A 52-year-old previously healthy man was admitted to the hospital with haematuria, painful micturition and fever. Laboratory investigation showed the presence of a haemolytic uraemic syndrome (HUS), characterized by haemolysis, renal insufficiency and mental disturbances. A urinary tract infection caused by a verotoxin-producing E. coli other than O157:H7 was diagnosed. Treatment of this infection resulted in his complete recovery from the illness. Both the search for a focus outside the gastrointestinal tract and the search for verotoxin genes by specific polymerase chain reaction can be crucial in a patient with HUS without preceding diarrhoea. [ABSTRACT FROM AUTHOR]

The article focuses on the first-line treatment of patients with Idiopathic aplastic anemia (AA). Topics discussed include effectiveness of of antithymocyte globul in the treatment of aplastic anemia and mentions treatment options for AA by allogeneic hematopoietic cell transplantation and immunosuppressive therapy with cyclosporin A.

A zero-gap spinning disc membrane electrochemical reactor (SDMER) is presented for the intensification of the chlor-alkali process at high current densities up to 20 kA/m 2 . Two configurations of the SDMER, namely rotor-stator (RS) and thin-film (TF), are investigated and compared with a conventional parallel plate (PP) cell. The cell voltage as a function of current density is virtually identical for both SDMER configurations, and lower when compared to PP cell. The effect of the rotational speed on the cell voltage shows a decrease of 0.9 V at 6 kA/m 2 when the rotational speed is increased from 40 to 60 rad/s. The estimated membrane permselectivity, increases with increasing current density to values between 0.95 and 0.98. The intensification of the chlor-alkali process was successful with the SDMER by obtaining an approximately three times higher production compared to the PP cell when increasing the current density from 6 kA/m 2 to 20 kA/m 2 . [ABSTRACT FROM AUTHOR]

Abstract: The efficacy of azacitidine has been demonstrated in acute myeloid leukemia (AML) patients with 20–30% bone marrow (BM) blasts, but limited data is available on patients with ≥30% blasts. We analyzed 55 newly diagnosed AML patients, treated with azacitidine. The overall response rate was 42%. Median overall survival (OS) was 12.3 months. We confirmed poor-risk cytogenetics, therapy-related AML, performance score ≥2, and white blood cell count ≥15×109/L as independent adverse predictors for OS. The BM blast percentage, however, had no impact on OS (P =0.55). In conclusion, administration of azacitidine is effective in AML patients with 20–30% and >30% BM blasts. [Copyright &y& Elsevier]

Purpose: Advanced radiotherapy treatments require appropriate quality assurance (QA) to verify 3D dose distributions. Moreover, increase in patient numbers demand efficient QA-methods. In this study, a time efficient method that combines model-based QA and measurement-based QA was developed; i.e., the hybrid-QA. The purpose of this study was to determine the reliability of the model-based QA and to evaluate time efficiency of the hybrid-QA method. Methods: Accuracy of the model-based QA was determined by comparison of COMPASS calculated dose with Monte Carlo calculations for heterogeneous media. In total, 330 intensity modulated radiation therapy (IMRT) treatment plans were evaluated based on the mean gamma index (GI) with criteria of 3%/3mm and classification of PASS (GI ≤ 0.4), EVAL (0.4 < GI > 0.6), and FAIL (GI ≥ 0.6). Agreement between model-based QA and measurement-based QA was determined for 48 treatment plans, and linac stability was verified for 15 months. Finally, time efficiency improvement of the hybrid-QA was quantified for four representative treatment plans. Results: COMPASS calculated dose was in agreement with Monte Carlo dose, with a maximum error of 3.2% in heterogeneous media with high density (2.4 g/cm3). Hybrid-QA results for IMRT treatment plans showed an excellent PASS rate of 98% for all cases. Model-based QA was in agreement with measurement-based QA, as shown by a minimal difference in GI of 0.03 ± 0.08. Linac stability was high with an average GI of 0.28 ± 0.04. The hybrid-QA method resulted in a time efficiency improvement of 15 min per treatment plan QA compared to measurement-based QA. Conclusions: The hybrid-QA method is adequate for efficient and accurate 3D dose verification. It combines time efficiency of model-based QA with reliability of measurement-based QA and is suitable for implementation within any radiotherapy department. [ABSTRACT FROM AUTHOR]

An abstract is offered of a research paper on Klebsiella pneumoniae in the Netherlands by C. Hattink and colleagues, presented at the International Conference on Prevention & Infection Control (ICPIC 2011) held in Geneva, Switzerland on June 29-July 2, 2011.

Background: Both epilepsy patients and brain tumor patients show altered functional connectivity and less optimal brain network topology when compared to healthy controls, particularly in the theta band. Furthermore, the duration and characteristics of epilepsy may also influence functional interactions in brain networks. However, the specific features of connectivity and networks in tumor-related epilepsy have not been investigated yet. We hypothesize that epilepsy characteristics are related to (theta band) connectivity and network architecture in operated glioma patients suffering from epileptic seizures. Included patients participated in a clinical study investigating the effect of levetiracetam monotherapy on seizure frequency in glioma patients, and were assessed at two time points: directly after neurosurgery (t1), and six months later (t2). At these time points, magnetoencephalography (MEG) was recorded and information regarding clinical status and epilepsy history was collected. Functional connectivity was calculated in six frequency bands, as were a number of network measures such as normalized clustering coefficient and path length.Results: At the two time points, MEG registrations were performed in respectively 17 and 12 patients. No changes in connectivity or network topology occurred over time. Increased theta band connectivity at t1 and t2 was related to a higher total number of seizures. Furthermore, higher number of seizures was related to a less optimal, more random brain network topology. Other factors were not significantly related to functional connectivity or network topology.Conclusions: These results indicate that (pathologically) increased theta band connectivity is related to a higher number of epileptic seizures in brain tumor patients, suggesting that theta band connectivity changes are a hallmark of tumor-related epilepsy. Furthermore, a more random brain network topology is related to greater vulnerability to seizures. Thus, functional connectivity and brain network architecture may prove to be important parameters of tumor-related epilepsy. [ABSTRACT FROM AUTHOR]

Abstract: Hippocampal atrophy on MRI and changes in diffusion tensor imaging (DTI) measures of the hippocampus have been reported in patients with Alzheimer''s disease. We examined the association between hippocampal volumes, DTI measures of the hippocampus and memory performance in 892 non-demented persons (age≥55years) across different age groups. Hippocampal volume was segmented on 3D volumetric MRI scans. The segmentations were co-registered to mean diffusivity (MD) and fractional anisotropy (FA) maps to yield mean hippocampal MD and FA measurements. Higher MD of the hippocampus was associated with impaired verbal memory performance. In all persons ≥55years, a higher MD of the hippocampus was associated with a worse memory performance. Hippocampal volumes were very weakly positively associated with delayed recall and only in persons >65years. FA of the hippocampus was not associated with memory performance. Follow-up studies will be needed to determine whether higher MD of hippocampus at younger ages could be an earlier marker of incident Alzheimer''s disease than hippocampal volume. [Copyright &y& Elsevier]

To assess experiences related to antidepressant use reported to an internet-based medicine reporting system and to compare the nature of the side effects reported by patients with those reported by health care professionals (HCPs). All reports submitted from May 2004 to May 2005 to an internet-based medicine reporting system in The Netherlands related to the use of antidepressants were analysed. Spontaneous reports of adverse drug reactions on antidepressants from HCPs received by The Netherlands Pharmacovigilance Centre Lareb from May 2004 to May 2005 were included for comparison. Of the 2232 individuals who submitted a report to the internet-based medicine reporting system, 258 submitted a report on antidepressants. Of these, 92 individuals (36%) reported on effectiveness, 40 (16%) of whom reported on ineffectiveness, and 217 (84%) submitted a report on side effects, with 202 (78%) reporting a total of 630 side effects that were experienced as negative. Fourteen individuals (5%) reported a practical issue and four (2%) reported a reimbursement issue. Of all 630 side effects reported, 48% resulted in the patient discontinuing the antidepressant therapy; of these 29% did not inform their HCP. Of all the side effects reported, 52% were perceived as “very negative”. In comparison to the side effects reported by HCPs, patients more often reported apathy, excessive sweating, ineffectiveness, somnolence, insomnia, sexual problems and weight increase. Patients report the ineffectiveness and side effects of antidepressant therapy as negative and leading to discontinuation of the therapy. Patients and HCPs differ in the nature of the reported side effects. Patient experiences should be included in the evaluation of antidepressant treatment in clinical practice. [ABSTRACT FROM AUTHOR]

The survival of microencapsulated islet grafts is limited, even if capsular overgrowth is restricted to a small percentage of the capsules. In search of processes other than overgrowth contributing to graft failure, we have studied the islets in non-overgrown capsules at several time points after allotransplantation in the rat. All recipients of islet allografts became normoglycemic. Grafts were retrieved at 4 and 8 weeks after implantation and at 15.3 +/- 2.3 weeks postimplant, 2 weeks after the mean time period at which graft failure occurred. Overgrowth of capsules was complete within 4 weeks postimplant, and it was usually restricted to <10% of the capsules. During the first 4 weeks of implantation, 40% of the initial number of islets was lost. Thereafter, we observed a decrease in function rather than in numbers of islets, as illustrated by a decline in the ex vivo glucose-induced insulin response. At 4 and 8 weeks postimplant, beta-cell replication was 10-fold higher in encapsulated islets than in islets in the normal pancreas, but these high replication rates were insufficient to prevent a progressive increase in the percentage of nonviable tissue in the islets. Necrosis and not apoptosis proved to be the major cause of cell death in the islets. The necrosis mainly occurred in the center of the islets, which indicates insufficient nutrition as a major causative factor. Our study demonstrates that not only capsular overgrowth but also an imbalance between beta-cell birth and beta-cell death contributes to the failure of encapsulated islet grafts. Our observations indicate that we should focus on finding or creating a transplantation site that, more than the unmodified peritoneal cavity, permits for close contact between the blood and the encapsulated islet tissue. [ABSTRACT FROM AUTHOR]