Messias : drei Dichtungen

Mei͏̈r Wiener

Jüdisches Leben : den Oppenheim'schen Bildern aus dem altjüdischen Familienleben nachgedichtet

von Rosa Meyer, geb. Jacob

Polymorphisms in the vitamin D receptor and their associations with risk of schizophrenia and selected anthropometric measures

The association between vitamin D levels and skeletal growth has long been recognized. However, exposure to low levels of vitamin D during early life is also known to alter brain development, and is a candidate risk factor for schizophrenia. This study examines the association between four polymorphisms in the vitamin D receptor (VDR) and 1) risk of schizophrenia, and 2) three anthropometric variables (height, head size, and head shape). Four single-nucleotide polymorphisms (SNPs; rs10735810/FokI, rsl544410/BsmI, rs7975232/ApaI, and rs731236/TaqI) in the VDR gene were genotyped in 179 individuals with schizophrenia and 189 healthy controls. No significant associations were detected between any of the four VDR SNPs and risk of schizophrenia. Patients were slightly but significantly shorter compared to controls. Of the four SNPs, only rs10735810/FokI was associated with any of the anthropometric measures: the M4 isoform of this SNP was significantly associated with larger head size (P = 0.002). In light of the evidence demonstrating a role for vitamin D during brain development, the association between polymorphisms in VDR and brain development warrants closer scrutiny.

A D-optimal designed population pharmacokinetic study of itraconazole capsules and solution in adults with cystic fibrosis

Background: Oral itraconazole (ITRA) is used for the treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis (CF) because of its antifungal activity against Aspergillus species. ITRA has an active hydroxy-metabolite (OH-ITRA) which has similar antifungal activity. ITRA is a highly lipophilic drug which is available in two different oral formulations, a capsule and an oral solution. It is reported that the oral solution has a 60% higher relative bioavailability. The influence of altered gastric physiology associated with CF on the pharmacokinetics (PK) of ITRA and its metabolite has not been previously evaluated. Objectives: 1) To estimate the population (pop) PK parameters for ITRA and its active metabolite OH-ITRA including relative bioavailability of the parent after administration of the parent by both capsule and solution and 2) to assess the performance of the optimal design. Methods: The study was a cross-over design in which 30 patients received the capsule on the first occasion and 3 days later the solution formulation. The design was constrained to have a maximum of 4 blood samples per occasion for estimation of the popPK of both ITRA and OH-ITRA. The sampling times for the population model were optimized previously using POPT v.2.0.[1] POPT is a series of applications that run under MATLAB and provide an evaluation of the information matrix for a nonlinear mixed effects model given a particular design. In addition it can be used to optimize the design based on evaluation of the determinant of the information matrix. The model details for the design were based on prior information obtained from the literature, which suggested that ITRA may have either linear or non-linear elimination. The optimal sampling times were evaluated to provide information for both competing models for the parent and metabolite and for both capsule and solution simultaneously. Blood samples were assayed by validated HPLC.[2] PopPK modelling was performed using FOCE with interaction under NONMEM, version 5 (level 1.1; GloboMax LLC, Hanover, MD, USA). The PK of ITRA and OH‑ITRA was modelled simultaneously using ADVAN 5. Subsequently three methods were assessed for modelling concentrations less than the LOD (limit of detection). These methods (corresponding to methods 5, 6 & 4 from Beal[3], respectively) were (a) where all values less than LOD were assigned to half of LOD, (b) where the closest missing value that is less than LOD was assigned to half the LOD and all previous (if during absorption) or subsequent (if during elimination) missing samples were deleted, and (c) where the contribution of the expectation of each missing concentration to the likelihood is estimated. The LOD was 0.04 mg/L. The final model evaluation was performed via bootstrap with re-sampling and a visual predictive check. The optimal design and the sampling windows of the study were evaluated for execution errors and for agreement between the observed and predicted standard errors. Dosing regimens were simulated for the capsules and the oral solution to assess their ability to achieve ITRA target trough concentration (Cmin,ss of 0.5-2 mg/L) or a combined Cmin,ss for ITRA and OH-ITRA above 1.5mg/L. Results and Discussion: A total of 241 blood samples were collected and analysed, 94% of them were taken within the defined optimal sampling windows, of which 31% where taken within 5 min of the exact optimal times. Forty six per cent of the ITRA values and 28% of the OH-ITRA values were below LOD. The entire profile after administration of the capsule for five patients was below LOD and therefore the data from this occasion was omitted from estimation. A 2-compartment model with 1st order absorption and elimination best described ITRA PK, with 1st order metabolism of the parent to OH-ITRA. For ITRA the clearance (ClItra/F) was 31.5 L/h; apparent volumes of central and peripheral compartments were 56.7 L and 2090 L, respectively. Absorption rate constants for capsule (kacap) and solution (kasol) were 0.0315 h-1 and 0.125 h-1, respectively. Comparative bioavailability of the capsule was 0.82. There was no evidence of nonlinearity in the popPK of ITRA. No screened covariate significantly improved the fit to the data. The results of the parameter estimates from the final model were comparable between the different methods for accounting for missing data, (M4,5,6)[3] and provided similar parameter estimates. The prospective application of an optimal design was found to be successful. Due to the sampling windows, most of the samples could be collected within the daily hospital routine, but still at times that were near optimal for estimating the popPK parameters. The final model was one of the potential competing models considered in the original design. The asymptotic standard errors provided by NONMEM for the final model and empirical values from bootstrap were similar in magnitude to those predicted from the Fisher Information matrix associated with the D-optimal design. Simulations from the final model showed that the current dosing regimen of 200 mg twice daily (bd) would provide a target Cmin,ss (0.5-2 mg/L) for only 35% of patients when administered as the solution and 31% when administered as capsules. The optimal dosing schedule was 500mg bd for both formulations. The target success for this dosing regimen was 87% for the solution with an NNT=4 compared to capsules. This means, for every 4 patients treated with the solution one additional patient will achieve a target success compared to capsule but at an additional cost of AUD $220 per day. The therapeutic target however is still doubtful and potential risks of these dosing schedules need to be assessed on an individual basis. Conclusion: A model was developed which described the popPK of ITRA and its main active metabolite OH-ITRA in adult CF after administration of both capsule and solution. The relative bioavailability of ITRA from the capsule was 82% that of the solution, but considerably more variable. To incorporate missing data, using the simple Beal method 5 (using half LOD for all samples below LOD) provided comparable results to the more complex but theoretically better Beal method 4 (integration method). The optimal sparse design performed well for estimation of model parameters and provided a good fit to the data.

Annotated record of the detailed examination of Mn deposits from the Snellius II - Cruise 4 stations in the vicinity of the island of Misool, Eastern Indonesia

The chemical analyses of ferromanganese encrustations found on the seabed west of Misool, eastern Indonesia, indicate that these deposits formed in a way different from that of world-wide occurring manganese nodules. Ferromanganese coated pebbles and fragments that were found in the deeper parts of the study area probably originate from nearby ridges. The ferromanganese crust on the upper part of a dolomite fragment of ?30 kg is likely to be formed by hydrogenous processes, whereas that from the lower part seems to be formed by diagenetic processes mainly. These assumptions are supported by pore-water data from two box cores taken in the same area. The manganese and iron profiles versus depth in these cores indicate a high flux of these metals to the uppermost sediment layer, and possibly into the overlying bottom water. Factor analysis for the principal components of the microprobe analytical results of the mainly hydrogenous ferromanganese crust demonstrates a strong correlation of manganese with the trace metals, of iron with phosphorus and an antipathetic relationship between iron and manganese. Similar results have also been reported for abyssal manganese nodules in the world oceans. Factor analysis for the principal components of the analytical data obtained for the diagenetic ferromanganese crust results in a clear dolomite (Ca/Mg) dilution factor only.

Stomach content records for pelagic fish (herring, mackerel, blue whiting, albacore and bluefin tuna) in the northeast Atlantic

Fish stomach content records extracted from the DAPSTOM 4.5 database (held at the UK Centre for Environment, Fisheries and Aquaculture Science - CEFAS). Data collated as part of the EU Euro-Basin project and specifically concerning herring (Clupea harengus), mackerel (Scomber scombrus), blue whiting (Micromesistius poutassou), albacore (Thunnus alalunga) and bluefin tuna (Thunnus thynnus). The data set consist of 20720 records - collected throughout the northeast Atlantic, between 1906 and 2011 - mostly during routine fisheries monitoring research cruises.

Determinação do estado fundamental de compostos antiferromagnéticos da série Tb(1-x)Y(x)RhIn(5): aproximação teórico experimental

We present the results of electrical resistivity, magnetic susceptibility, specific heat and x-ray absorption spectroscopy measurements in Tb1−xYxRhIn5 (x = 0.00, 0.15, 0.4.0, 0.50 e 0.70) single crystals. Tb1−xYxRhIn5 is an antiferromagnetic AFM compound with ordering temperature TN ≈ 46 K, the higher TN within the RRhIn5 serie (R : rare earth). We evaluate the physical properties evolution and the supression of the AFM state considering doping and Crystalline Electric Field (CEF) effects on magnetic exchange interaction between Tb3+ magnetic ions. CEF acts like a perturbation potential, breaking the (2J + 1) multiplet s degeneracy. Also, we studied linear-polarization-dependent soft x-ray absorption at Tb M4 and M5 edges to validate X-ray Absorption Spectroscopy as a complementary technique in determining the rare earth CEF ground state. Samples were grown by the indium excess flux and the experimental data (magnetic susceptibility and specific heat) were adjusted with a mean field model that takes account magnetic exchange interaction between first neighbors and CEF effects. XAS experiments were carried on Total Electron Yield mode at Laborat´onio Nacional de Luz S´ıncrotron, Campinas. We measured X-ray absorption at Tb M4,5 edges with incident polarized X-ray beam parallel and perpendicular to c-axis (E || c e E ⊥ c). The mean field model simulates the mean behavior of the whole system and, due to many independent parameters, gives a non unique CEF scheme. XAS is site- and elemental- specific technique and gained the scientific community s attention as complementary technique in determining CEF ground state in rare earth based compounds. In this work we wil discuss the non conclusive results of XAS technique in TbRhIn5 compounds.

A crença sobre a morte e o coping religioso-espiritual em pacientes internados com doenças crônicas

The human being is understood as an integral being, complex, which has multiple dimensions: social, biological, psychological, anthropological, spiritual and others. As its biological dimension, the man presents the possibility of physical illness, which means that the body requires care. The sick away from humans in health and safety conditions, approaching them directly from the finitude and vulnerability condition, leading us to contact the major uncertainties of life: suffering of disease and death. Religiosity and spirituality are important coping strategy for human when faced with borderline situations. When people turn to religion to cope with stress is the religious and spiritual coping. The objective of this research was to evaluate the relationship between the views on death and the religious-spiritual coping in patients with chronic diseases hospitalized. The study included ten patients hospitalized for chronic disease complications Medical Clinic Unit of a public hospital in the city of Uberlândia/MG. two psychological scales were used: Scale Religious-Spiritual Coping Brief (CRE-Brief Scale) and Scale Brief Diverse Perspectives of Death and a structured interview (audiogravada) on the subject of death and religious and spiritual coping. The results indicated that 80% of the sample (N = 8) consisted of patients hospitalized due to chronic diseases, while 20% accounted for patients with AIDS complications. Analyzing the results of scale CRE-Brief, it emphasizes the use of strategies of religious and spiritual coping by participants as compared to CRE Total, all study participants had average or high scores for this index, with a low utilization CRE negative and average utilization CRE Positive. Regarding views on death, the results obtained by the Different Perspectives Quick Scale on Death suggest that this sample agrees with the view death as something that is part of the natural cycle of life (M8 - Death as a natural end) and features the prospect of death as uncertainty, mystery and ignorance (M4 - death as Unknown). The correlations between the measures the factors and items of CRE-Bref and dimensions of Short scales on different perspectives of Death notes the prevalence of correlations of M4 dimensions - Death as unknown and M8 - Death as a natural order to the creditor scale soon. In the interview analysis revealed a positive influence of religion/ spirituality on health, from the perspective of the respondent, highlighting the protection promoted by religion. It also noticed the use of prayer as a coping strategy of hospitalization and illness. Regarding the interview about the topic of death, there was a predominance of issues related to "afterlife", "unknown" and "abandonment", which are associated with the visions of death and mystery and death as a natural end. In the interviews there belief clues about death as a terrifying mystery connected, so the unknown and the feeling of fear on the same. The experience of illness can therefore be considered as a source of vulnerability, since it is present personal perception of danger (external) - own illness and possible death, especially in those patients undergoing ICU - and where control is insufficient for the sense of security, since the hospital providing care to the patient are delegated to third parties and patients assume a passive role. This fact is important and relevant to health professionals who deal daily with patients hospitalized for chronic diseases, since the recourse to religion and spirituality as a coping strategy that psychic movement was not constituted in a form of negative distance or even denial of health condition. On the contrary, it refers to a movement in search of comfort and security provided by the religion and spirituality.

Geochemistry of sheeted dike complex minerals of ODP Hole 140-504B

Diabases were recovered during Legs 137 and 140 at Hole 504B from depths between 1621.5 and 2000.4 meters below seafloor in the lower sheeted dike complex. The samples contain multiple generations of millimetric to centimetric veins. The orientation of the measured veins suggests that two main vein sets exist: one characterized by shallow dipping and the other by random trend. Thermal contraction during rock cooling is considered the main mechanism responsible for fracture formation. Vein infill is related to the circulation of hydrothermal fluids near the spreading axis. Some veins are surrounded by millimeter-sized alteration halos due to fluid percolation from the fractures through the host rock. Vein-filling minerals are essentially amphibole, chlorite, and zeolites. Amphibole composition is controlled by the microstructural site of the rock. Actinolite is the main amphibole occurring in the veins and also in the groundmass away from the halos. In the alteration halos, amphibole shows composition of actinolitic hornblende and Mg-hornblende. Late-stage tension gashes and interstitial spaces in some amphibole-bearing veins are filled with zeolites, suggesting that the veins likely suffered multiple opening stages that record the cooling history of the circulating fluids. Evidence of deformation recorded by the recovered samples seems to be restricted to veins that clearly represent elements of weakness of the rock. On the basis of vein geometry and microstructure we infer structural interpretations for the formation mechanism and for deformation of veins.

Macroscopic Quantum Resonators (MAQRO): 2015 update

Do the laws of quantum physics still hold for macroscopic objects - this is at the heart of Schrödinger’s cat paradox - or do gravitation or yet unknown effects set a limit for massive particles? What is the fundamental relation between quantum physics and gravity? Ground-based experiments addressing these questions may soon face limitations due to limited free-fall times and the quality of vacuum and microgravity. The proposed mission Macroscopic Quantum Resonators (MAQRO) may overcome these limitations and allow addressing such fundamental questions. MAQRO harnesses recent developments in quantum optomechanics, high-mass matter-wave interferometry as well as state-of-the-art space technology to push macroscopic quantum experiments towards their ultimate performance limits and to open new horizons for applying quantum technology in space. The main scientific goal is to probe the vastly unexplored ‘quantum-classical’ transition for increasingly massive objects, testing the predictions of quantum theory for objects in a size and mass regime unachievable in ground-based experiments. The hardware will largely be based on available space technology. Here, we present the MAQRO proposal submitted in response to the 4th Cosmic Vision call for a medium-sized mission (M4) in 2014 of the European Space Agency (ESA) with a possible launch in 2025, and we review the progress with respect to the original MAQRO proposal for the 3rd Cosmic Vision call for a medium-sized mission (M3) in 2010. In particular, the updated proposal overcomes several critical issues of the original proposal by relying on established experimental techniques from high-mass matter-wave interferometry and by introducing novel ideas for particle loading and manipulation. Moreover, the mission design was improved to better fulfill the stringent environmental requirements for macroscopic quantum experiments.

TRPV2 Channels Contribute to Stretch-Activated Cation Currents and Myogenic Constriction in Retinal Arterioles

Purpose: Activation of the transient receptor potential channels, TRPC6, TRPM4, and TRPP1 (PKD2), has been shown to contribute to the myogenic constriction of cerebral arteries. In the present study we sought to determine the potential role of various mechanosensitive TRP channels to myogenic signaling in arterioles of the rat retina.

Methods: Rat retinal arterioles were isolated for RT-PCR, Fura-2 Ca2+ microfluorimetry, patch-clamp electrophysiology, and pressure myography studies. In some experiments, confocal immunolabeling of wholemount preparations was used to examine the localization of specific mechanosensitive TRP channels in retinal vascular smooth muscle cells (VSMCs).

Results: Reverse transcription-polymerase chain reaction analysis demonstrated mRNA expression for TRPC1, M7, V1, V2, V4, and P1, but not TRPC6 or M4, in isolated retinal arterioles. Immunolabeling revealed plasma membrane, cytosolic and nuclear expression of TRPC1, M7, V1, V2, V4, and P1 in retinal VSMCs. Hypoosmotic stretch-induced Ca2+ influx in retinal VSMCs was reversed by the TRPV2 inhibitor tranilast and the nonselective TRPP1/V2 antagonist amiloride. Inhibitors of TRPC1, M7, V1, and V4 had no effect. Hypoosmotic stretch-activated cation currents were similar in Na+ and Cs+ containing solutions suggesting no contribution by TRPP1 channels. Direct plasma membrane stretch triggered cation current activity that was blocked by tranilast and specific TRPV2 pore-blocking antibodies and mimicked by the TRPV2 activator, Δ9-tetrahydrocannabinol. Preincubation of retinal arterioles with TRPV2 blocking antibodies prevented the development of myogenic tone.

Conclusions: Our results suggest that retinal VSMCs express a range of mechanosensitive TRP channels, but only TRPV2 appears to contribute to myogenic signaling in this vascular bed.

Os estilos de liderança nas organizações não governamentais da região metropolitana de Belém

This study aimed to analyze the leadership style adopted by managers of nongovernmental organizations in the metropolitan region of Belem on the theory of Hersey and Blanchard. This theory is called situational leadership ranks E1, E2, E3, E4 and the styles of leadership and maturity in parallel classes M1, M2, M3 and M4. This study examined the relationship of leadership styles with the maturity of work, identified the relationship of leadership styles as related to psychological maturity and job maturity and psychological maturity. The main objectives were to analyze and relate leadership styles with the maturity of the leaders and understand the phenomenon of leadership from the self-perception of those who lead the organizations studied. To achieve the objectives we used a questionnaire already validated the theory of situational leadership and applied in 320 non-governmental organizations in the metropolitan region of Belem The methodology was quantitative, descriptive and exploratory. The analysis was by descriptive statistics and inferential statistics for univariate and bivariate form, applying the chi-square, the V Crammer and Spearman correlation. The data analysis shows safety, attested to the frequencies, and average margin of error and after application of the tests it was found that a relationship between the leadership style of work with the maturity and psychological maturity. The managers of nongovernmental organizations practicing various styles of leadership and focus on the quadrant of high maturity. It was diagnosed when the manager uses only one style of leadership was the predominance of E3 "share or support", which represents 24% of the sample. As uses two styles of leadership is the predominance of E3 and E2, which represents 76%. So the managers of nongovernmental organizations in the metropolitan region of Belem, practicing a style of leadership support, sharing ideas for decision making using a democratic style

Os estilos de liderança nas organizações não governamentais da região metropolitana de Belém

This study aimed to analyze the leadership style adopted by managers of nongovernmental organizations in the metropolitan region of Belem on the theory of Hersey and Blanchard. This theory is called situational leadership ranks E1, E2, E3, E4 and the styles of leadership and maturity in parallel classes M1, M2, M3 and M4. This study examined the relationship of leadership styles with the maturity of work, identified the relationship of leadership styles as related to psychological maturity and job maturity and psychological maturity. The main objectives were to analyze and relate leadership styles with the maturity of the leaders and understand the phenomenon of leadership from the self-perception of those who lead the organizations studied. To achieve the objectives we used a questionnaire already validated the theory of situational leadership and applied in 320 non-governmental organizations in the metropolitan region of Belem The methodology was quantitative, descriptive and exploratory. The analysis was by descriptive statistics and inferential statistics for univariate and bivariate form, applying the chi-square, the V Crammer and Spearman correlation. The data analysis shows safety, attested to the frequencies, and average margin of error and after application of the tests it was found that a relationship between the leadership style of work with the maturity and psychological maturity. The managers of nongovernmental organizations practicing various styles of leadership and focus on the quadrant of high maturity. It was diagnosed when the manager uses only one style of leadership was the predominance of E3 "share or support", which represents 24% of the sample. As uses two styles of leadership is the predominance of E3 and E2, which represents 76%. So the managers of nongovernmental organizations in the metropolitan region of Belem, practicing a style of leadership support, sharing ideas for decision making using a democratic style