[Guideline-adherent psychiatric psychotherapeutic treatment of bipolar disorders : Which resources are needed?] / Leitliniengerechte psychiatrisch-psychotherapeutische Behandlung bei bipolaren Störungen : Welche Ressourcen werden dafür benötigt?

In this article the guideline-adherent psychiatric psychotherapeutic treatment of patients with bipolar disorders is outlined and the required resources are estimated. Based on the core recommendations of the S3 guidelines for diagnostics and treatment of bipolar disorders published in 2012, inpatient treatment needs in hours per week and per patient are determined for both manic and bipolar depressive episodes. The resulting staffing requirements are estimated on this basis. In summary, for guideline-adherent inpatient psychiatric psychotherapeutic treatment the additional needs regarding the physician/psychotherapeutic domain add up to 44 min per patient and week during a manic episode and 88 min for patients with bipolar depression when compared to current psychiatry staffing regulations.

[Suicidal ideation of prisoners : Influence of duration of imprisonment, personality traits and disorders]. / Suizidalität von Inhaftierten : Einfluss von Haftdauer, Persönlichkeitsauffälligkeiten und Persönlichkeitsstörungen.

BACKGROUND: Although in recent years many efforts have been made in suicide prevention, suicidal ideation in prison is still a major problem. The present study is part of a project being carried out in Saxony, Germany on the investigation and prevention of suicide in prisons. OBJECTIVE: The aim of this study was to determine whether the duration of imprisonment, personality traits and personality disorders have an influence on the suicidal ideation of prisoners. MATERIAL AND METHODS: In this study 113 volunteers among prisoners from 6 prisons in Saxony participated in a structured interview and filled out several questionnaires on sociodemographic details, personality using the personality style and disorder inventory (PSSI) and the assessment of DSM-IV personality disorders (ADP-IV) questionnaire as well as attitudes towards suicide using the questionnaire on stressful social experiences (FBS) and the Viennese instrument for suicidality on correctional institutions (VISCI). RESULTS: Significant correlations were found between personality traits and personality disorders and suicidal ideation and suicide attempts. A positive correlation was also found between personality disorders and scores in the VISCI. High scores in the PSSI were correlated with all aspects of suicidal ideation; however, length of time spent in prison and total duration of imprisonment appeared to have little impact on suicide parameters and were only correlated with the self-declared current suicidal ideation. DISCUSSION: Although there were some limitations, this study could confirm data in the literature that personality disorders are associated with an increased risk of suicidal ideation in prisoners. The lack of association of suicidal thoughts as measured in this study with the total time spent in prison and duration of imprisonment is in contradiction to the results of other studies and warrants further investigation.

A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer.

BACKGROUND: Masitinib is a selective oral tyrosine-kinase inhibitor. The efficacy and safety of masitinib combined with gemcitabine was compared against single-agent gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Patients with inoperable, chemotherapy-naïve, PDAC were randomized (1 : 1) to receive gemcitabine (1000 mg/m(2)) in combination with either masitinib (9 mg/kg/day) or a placebo. The primary endpoint was overall survival (OS) in the modified intent-to-treat population. Secondary OS analyses aimed to characterize subgroups with poor survival while receiving single-agent gemcitabine with subsequent evaluation of masitinib therapeutic benefit. These prospectively declared subgroups were based on pharmacogenomic data or a baseline characteristic. RESULTS: Three hundred and fifty-three patients were randomly assigned to receive either masitinib plus gemcitabine (N = 175) or placebo plus gemcitabine (N = 178). Median OS was similar between treatment-arms for the overall population, at respectively, 7.7 and 7.1 months, with a hazard ratio (HR) of 0.89 (95% CI [0.70; 1.13]. Secondary analyses identified two subgroups having a significantly poor survival rate when receiving single-agent gemcitabine; one defined by an overexpression of acyl-CoA oxidase-1 (ACOX1) in blood, and another via a baseline pain intensity threshold (VAS > 20 mm). These subgroups represent a critical unmet medical need as evidenced from median OS of 5.5 months in patients receiving single-agent gemcitabine, and comprise an estimated 63% of patients. A significant treatment effect was observed in these subgroups for masitinib with median OS of 11.7 months in the 'ACOX1' subgroup [HR = 0.23 (0.10; 0.51), P = 0.001], and 8.0 months in the 'pain' subgroup [HR = 0.62 (0.43; 0.89), P = 0.012]. Despite an increased toxicity of the combination as compared with single-agent gemcitabine, side-effects remained manageable. CONCLUSIONS: The present data warrant initiation of a confirmatory study that may support the use of masitinib plus gemcitabine for treatment of PDAC patients with overexpression of ACOX1 or baseline pain (VAS > 20mm). Masitinib's effect in these subgroups is also supported by biological plausibility and evidence of internal clinical validation. TRIAL REGISTRATION: ClinicalTrials.gov:NCT00789633.

Control of morphology and crystal purity of InP nanowires by variation of phosphine flux during selective area MOMBE.

We present experimental results showing how the growth rate, morphology and crystal structure of Au-catalyzed InP nanowires (NWs) fabricated by selective area metal organic molecular beam epitaxy can be tuned by the growth parameters: temperature and phosphine flux. The InP NWs with 20-65 nm diameters are grown at temperatures of 420 and 480 °C with the PH3 flow varying from 1 to 9 sccm. The NW tapering is suppressed at a higher temperature, while pure wurtzite crystal structure is preferred at higher phosphine flows. Therefore, by combining high temperature and high phosphine flux, we are able to fabricate non-tapered and stacking fault-free InP NWs with the quality that other methods rarely achieve. We also develop a model for NW growth and crystal structure which explains fairly well the observed experimental tendencies.

Shadowing and mask opening effects during selective-area vapor-liquid-solid growth of InP nanowires by metalorganic molecular beam epitaxy.

Indium phosphide nanowires were grown by metalorganic molecular beam epitaxy using the selective-area vapor-liquid-solid method. We show experimentally and theoretically that the size of the annular opening around the nanowire has a major impact on nanowire growth rate. In addition, we observed a considerable reduction of the growth rate in dense two-dimensional arrays, in agreement with a calculation of the shadowing of the scattered precursors. Due to the impact of these effects on growth, they should be considered during selective-area vapor-liquid-solid nanowire epitaxy.

Evaluation of the local temperature of conductive filaments in resistive switching materials.

The resistive switching effect in metal oxides and other dielectric materials is among the leading future non-volatile memory technologies. Resistive switching is widely ascribed to the formation and rupture of conductive filaments in the oxide, which are generated by temperature-enhanced nano-scale ion migration or other thermal effects. In spite of the central role of the local filament temperature on the switching effect, as well as on the conduction and reliability physics, no measurement methods of the filament temperature are yet available. In this work, we report on a method for evaluating the conducting filament temperature, using a metal-insulator-semiconductor bipolar transistor structure. The filament temperature is obtained by analyzing the thermal excitation rate of electrons from the filament Fermi level into the conduction band of a p-type semiconductor electrode. Measurements were carried out to obtain the conductive filament temperature in hafnia at varying ambient temperatures in the range of 3-300 K. Significant Joule heating of the filament was observed across the entire measured ambient temperature range. The extracted temperatures provide physical insight into the resistive switching effect.

No correlation between lithium serum levels and psychopathological features during the euthymic interval of patients with recurrent affective disorder.

INTRODUCTION: The aim of this prospective study was to investigate the influence of lithium serum levels on subclinical psychopathological features during the euthymic interval in patients with an affective disorder. METHODS: The study included 54 patients with a recurrent affective disorder undergoing a continuous prophylactic lithium treatment (31 unipolar, 23 bipolar). The observation period lasted for 2 years and included 332 visits. Visits consisted of a detailed interview, a continuous measurement of lithium levels and the collection of validated scales including HAMD, YMRS, CGI, VAMS and the SCL-90R. Several correlations between lithium serum levels and different psychopathological features during the euthymic interval were calculated on an individual patient basis and on a group basis to reveal generally occurring correlations. RESULTS: No generally occurring significant correlations between lithium serum levels and specific psychopathological features were found. Only on a single patient level, 32 significant correlations between lithium level and specific psychopathological features were found, partly indicating a negative and partly indicating a positive influence of higher lithium levels on psychopathological symptoms. Nevertheless, in the group analyses no significant correlations were found. DISCUSSION: Higher lithium levels were not associated with an improved psychopathological status, but they were not associated with a worse status (due to a higher burden of side effects) either. According to the literature there is currently no strong evidence to treat patients with a higher lithium level. It is recommended to start with a lower level and to continue with individual adjustments in accordance to prophylactic efficacy and tolerability.

Evolution of germline TP53 variant classification in children with cancer.

Li-Fraumeni syndrome, caused by germline pathogenic variants in TP53, results in susceptibility to multiple cancers. Variants of uncertain significance (VUS) and reclassification of variants over time pose management concerns given improved survival with cancer surveillance for LFS patients. We describe the experience of TP53 variant reclassification at a pediatric cancer center. METHODS: We reviewed medical records (2010-2019) of 756 patients seen in Texas Children's Cancer Genetics Clinic. We noted initial TP53 classification and any reclassifications. We then classified TP53 variants following ClinGen TP53 variant curation expert panel recommendations using data from ClinVar, medical literature and IARC database. RESULTS: Of 234 patients tested for TP53, 27 (11.5%) reports contained pathogenic/likely pathogenic (P/LP) variants and 7 (3)% contained VUS. By January 2022, 4 of 6 unique VUS and 2 of 16 unique P/LP variants changed interpretations in ClinVar. Reinterpretation of these 4 VUS in ClinVar matched clinical decision at the time of initial report. Applying TP53 VCEP specifications classified 3 VUS to P/LP/benign, and one pathogenic variant to likely benign. CONCLUSIONS: Planned review of variant significance is essential, especially for patients with high probability of LFS.

Comparative analysis of antibody responses to outer surface protein (Osp)A and OspC in dogs vaccinated with Lyme disease vaccines.

Lyme disease (LD), the most common tick-borne disease of canines and humans in N. America, is caused by the spirochete Borreliella burgdorferi. Subunit and bacterin vaccines are available for the prevention of LD in dogs. LD bacterin vaccines, which are comprised of cell lysates of two strains of B. burgdorferi, contain over 1000 different proteins and cellular constituents. In contrast, subunit vaccines are defined in composition and consist of either outer surface protein (Osp)A or OspA and an OspC chimeritope. In this study, we comparatively assessed antibody responses to OspA and OspC induced by vaccination with all canine bacterin and subunit LD vaccines that are commercially available in North America. Dogs were administered a two-dose series of the vaccine to which they were assigned (3 weeks apart): Subunit-AC, Subunit-A, Bacterin-1, and Bacterin-2. Antibody titers to OspA and OspC were determined by ELISA and the ability of each vaccine to elicit antibodies that recognize diverse OspC proteins (referred to as OspC types) assessed by immunoblot. While all of the vaccines elicited similar OspA antibody responses, only Subunit-AC triggered a robust and broadly cross-reactive antibody response to divergent OspC proteins. The data presented within provide new information regarding vaccination-induced antibody responses to key tick and mammalian phase antigens by both subunit and bacterin LD canine vaccine formulations.

Comparison of Eimeria species distribution and salinomycin resistance in commercial broiler operations utilizing different coccidiosis control strategies.

The purpose of the present study was to evaluate the species composition and salinomycin sensitivity of Eimeria oocysts isolated from commercial broiler farms that differed by means of coccidiosis control (anticoccidial drugs [ACD] vs. live oocyst vaccines [VAC]). A comparison of Eimeria species composition and salinomycin sensitivity was also made before and after a producer switched from salinomycin to live oocyst vaccines. In general, no significant difference was observed in the concentration of Eimeria spp. oocysts in litter from VAC-utilizing farms compared to litter from ACD-utilizing farms. Application of PCR-based methods to detect coccidia found that Eimeria species distribution in litter from VAC operations more closely resembled the species composition in the live oocyst vaccines. Drug sensitivity testing found that Eimeria oocysts from VAC operations displayed greater salinomycin sensitivity as measured by weight gain and feed conversion efficiency compared to oocysts from ACD farms. These findings provide additional evidence for the usefulness of live oocyst vaccines to restore ionophore sensitivity in poultry operations that contain an ionophore-resistant population of Eimeria spp. oocysts.

Overbank Sedimentation in the Delaware River Valley during the Last 6000 Years.

A thick sequence of floodplain sediments has accumulated in the Delaware River Valley by the process of overbank deposition. Textures in the sediments indicate that the sequence contains no point-bar deposits and is unbroken by periods of erosion. Fourteen radiocarbon dates show that deposition began at least 6000 years ago and has continued to the present. Because the Delaware River shifts its position laterally at a very slow rate, overbank deposition becomes dominant in the construction of its floodplain.

Viable Eimeria oocysts in poultry house litter at the time of chick placement.

The purpose of this study was to determine if Eimeria oocysts recovered from litter at the time of chick placement in commercial broiler houses contained oocysts that were infectious for chickens. Over 100 litter samples were collected from 30 poultry farms representing a total of 60 different broiler houses with 9 houses sampled more than once over 1.5 yr. The samples were collected just before the placement of newly hatched chicks and after an anticoccidial drug (ACD) or Eimeria vaccine (VAC) program, and processed for counting oocysts followed by Eimeria species determination using ITS1 PCR. Broiler chicks were inoculated with recovered Eimeria oocysts to determine if the litter oocysts were viable and capable of causing patent infection. At placement, E. maxima (Emax) oocysts were detected in 70 of 75 houses after ACD program and 46 of 47 houses after VAC program. Eimeria acervulina, E. praecox, and/or E. tenella (Eapt) were detected in 75 of 75 houses after ACD program and 47 of 47 houses after VAC program. Viability testing revealed that 33.0% of broiler houses contained viable Emax oocysts, while 46.9% contained viable Eapt oocysts. During VAC programs, the concentration of Emax oocysts at placement and the total number of Emax oocysts shed by chickens in viability studies showed a very strong correlation (r = 0.83). Likewise, during ACD programs, the concentration of Eapt oocysts at placement and the total number of Eapt oocysts shed by chickens in the viability study showed a strong correlation (r = 0.62). In general, Eimeria oocyst levels at placement and number of viable oocysts shed by chickens in the viability study were similar among houses on the same farm. However, the number of Eimeria oocysts shed in the viability studies was considerably less than expected based on the number of oocysts given. These data suggest that nearly 100% of all poultry houses contain Emax and Eapt oocysts at placement with 30 to 50% of the houses containing viable Eimeria oocysts, thus possibly representing a source of the protozoa to newly hatched chicks.

Synthesis and secretion of an atriopeptin-like protein in rat kidney cell culture.

The synthesis and secretion of an atriopeptin(AP)-like prohormone (AP126ir) has been demonstrated in rat neonatal renal cell cultures. AP126ir could be detected in the cellular extract and the medium from cultured kidney cells of neonatal and adult rats using an enzyme immunoassay specific for cardiac AP prohormone. On reverse-phase high-performance liquid chromatography, the AP obtained from the extract and the medium comigrated with cardiac AP prohormone. Incubation of the renal AP in the medium with thrombin resulted in the generation of a single low molecular mass peak which migrated with the cardiac carboxy-terminal 28-amino acid AP. Neonatal kidney cells pulsed with [35S]methionine secreted radiolabeled AP126ir, which was detected by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis chromatography. Incubation of neonatal kidney cell cultures with the protein synthesis inhibitor cycloheximide resulted in a significant decrease in both the cellular and media AP. No decrease in cellular and media AP was detected when neonatal atrial cultures were treated with cycloheximide. These data demonstrate the de novo synthesis of an AP prohormone-like protein in neonatal rat kidney cultures. Furthermore, unlike the atria, kidney cells appear to secrete AP solely by constitutive means. In primary adult rat kidney cultures, most of AP126ir was detected in the cortical tubule fraction demonstrating that these cells secrete AP126ir in the adult rat kidney. We hypothesize that the renal AP may be important as an autocrine or paracrine regulator of renal function.

Calibration model of a dual gain flat panel detector for 2D and 3D x-ray imaging.

The continuing research and further development in flat panel detector technology have led to its integration into more and more medical x-ray systems for two-dimensional (2D) and three-dimensional (3D) imaging, such as fixed or mobile C arms. Besides the obvious advantages of flat panel detectors, like the slim design and the resulting optimum accessibility to the patient, their success is primarily a product of the image quality that can be achieved. The benefits in the physical and performance-related features as opposed to conventional image intensifier systems, (e.g., distortion-free reproduction of imaging information or almost linear signal response over a large dynamic range) can be fully exploited, however, only if the raw detector images are correctly calibrated and postprocessed. Previous procedures for processing raw data contain idealizations that, in the real world, lead to artifacts or losses in image quality. Thus, for example, temperature dependencies or changes in beam geometry, as can occur with mobile C arm systems, have not been taken into account up to this time. Additionally, adverse characteristics such as image lag or aging effects have to be compensated to attain the best possible image quality. In this article a procedure is presented that takes into account the important dependencies of the individual pixel sensitivity of flat panel detectors used in 2D or 3D imaging and simultaneously minimizes the work required for an extensive recalibration. It is suitable for conventional detectors with only one gain mode as well as for the detectors specially developed for 3D imaging with dual gain read-out technology.

In vivo imaging of zebrafish reveals differences in the spinal networks for escape and swimming movements.

Most studies of spinal interneurons in vertebrate motor circuits have focused on the activity of interneurons in a single motor behavior. As a result, relatively little is known about the extent to which particular classes of spinal interneurons participate in different behaviors. Similarities between the morphology and connections of interneurons activated in swimming and escape movements in different fish and amphibians led to the hypothesis that spinal interneurons might be shared by these behaviors. To test this hypothesis, we took advantage of the optical transparency of zebrafish larvae and developed a new preparation in which we could use confocal calcium imaging to monitor the activity of individual identified interneurons noninvasively, while we simultaneously filmed the movements of the fish with a high-speed digital camera. With this approach, we could directly examine the involvement of individual interneurons in different motor behaviors. Our work revealed unexpected differences in the interneurons activated in swimming and escape behaviors. The observations lead to predictions of different behavioral roles for particular classes of spinal interneurons that can eventually be tested directly in zebrafish by using laser ablations or mutant lines with interneuronal deficits.

Functional assessment of the Fontan operation: combined M-mode, two-dimensional and Doppler echocardiographic studies.

Combined M-mode, two-dimensional and Doppler echocardiographic studies were used to assess the postoperative status of 33 patients who had undergone the modified Fontan procedure. Twenty-four patients had surgical repair with use of a simple direct right atrium to pulmonary artery anastomosis. The remaining patients had repair with use of a prosthesis or associated Glenn shunt. Twenty-seven patients were studied early in the postoperative period (2 months or less) and the remaining patients were studied up to 6 years postoperatively. A total of 36 examinations were performed. Of the 33 patients, 13 had tricuspid atresia, 12 had double inlet left ventricle with hypoplastic right ventricular outlet chamber and 8 had complex lesions with atrioventricular canal, double outlet right ventricle or a hypoplastic ventricle. Postoperative assessment by M-mode and two-dimensional echocardiography demonstrated normal or mildly reduced ventricular function (ejection fraction greater than 40%) in 22 patients. In 24 patients, a "normal" flow pattern was observed in the pulmonary artery by pulsed Doppler echocardiography, with predominant diastolic flow and accentuation by atrial systole somewhat similar to the venous flow pattern observed in the superior vena cava. "Abnormal" flow patterns (disorganized systolic flow, absence of atrial waves and little or no increase with inspiration) were observed in nine patients with reduced ventricular function or residual shunt. Continuous wave Doppler study also demonstrated mild dynamic subaortic obstruction in two patients. Combined pulsed and continuous wave studies showed atrioventricular valve insufficiency in 10 patients. Follow-up studies revealed a satisfactory clinical course in most patients. Three patients died approximately 4 to 8 months after their Fontan operation.

Functional single ventricle: cardiorespiratory response to exercise.

The cardiorespiratory response to exercise was measured in 27 children with functional single ventricle. All 27 patients had a significant reduction in exercise time, work performed, maximal exercise heart rate, maximal oxygen uptake and systemic arterial blood oxygen saturation. The reduction in exercise performance increased with increasing age of the patients. All patients ventilated excessively at rest and during exercise. This study documented the precise level of exercise intolerance in patients with functional single ventricle. The progressive deterioration in exercise performance with increasing patient age may lend credence to the concept that operation for physiologic correction of functional single ventricle should be considered during or before adolescence.

Detection of the insulating gap and conductive filament growth direction in resistive memories.

Filament growth is a key aspect in the operation of bipolar resistive random access memory (RRAM) devices, yet there are conflicting reports in the literature on the direction of growth of conductive filaments in valence change RRAM devices. We report here that an insulating gap between the filament and the semiconductor electrode can be detected by the metal-insulator-semiconductor bipolar transistor structure, and thus provide information on the filament growth direction. Using this technique, we show how voltage polarity and electrode chemistry control the filament growth direction during electro-forming. The experimental results and the nature of a gap between the filament and an electrode are discussed in light of possible models of filament formation.

Regulation of insulin-like growth factor I (IGF-I) gene expression in brain of transgenic mice expressing an IGF-I-luciferase fusion gene.

Insulin-like growth factor I (IGF-I) plays an important role in the development and function of the central nervous system (CNS). Little is known, however, about the factors and mechanisms involved in regulation of CNS IGF-I gene expression. To facilitate our goal to define mechanisms of IGF-I gene regulation in the CNS, we generated several lines of transgenic (Tg) mice that express firefly luciferase (LUC) under control of a 11.3-kb fragment from the 5' region of the rat IGF-I gene. Consistent with expression of the native IGF-I gene in murine brain, expression of the transgene predominated in neurons and astrocytes and used promoter 1, the major IGF-I promoter in the CNS and in most tissues. Transgene messenger RNA and protein expression rapidly increased after birth and peaked at postnatal (P) day 4 in all brain regions studied. LUC activities in all regions then gradually decreased to 0.5-4% of their peak values at P31, except for the olfactory bulb, which maintained about one third of its maximal activity. Compared with littermate controls, administration of dexamethasone decreased LUC activity and transgenic IGF-I messenger RNA abundance, whereas GH significantly increased the expression of the transgene. Addition of GH to cultured fetal brain cells from Tg mice for 12 h also increased LUC activity in a dose-dependent manner (77-388%). These results show that this IGF-I promoter transgene is expressed in a fashion similar to the endogenous IGF-I gene, and thus indicates that the transgene contains cis-elements essential for developmental, GH, and glucocorticoid regulation of IGF-I gene expression in the CNS. These Tg mice should serve as an useful model to study mechanisms of IGF-I gene regulation in the brain.

A confocal study of spinal interneurons in living larval zebrafish.

We used confocal microscopy to examine the morphology of spinal interneurons in living larval zebrafish with the aim of providing a morphological foundation for generating functional hypotheses. Interneurons were retrogradely labeled by injections of fluorescent dextrans into the spinal cord, and the three-dimensional morphology of living cells was reconstructed from confocal optical sections through the transparent fish. At least eight types of interneurons are present in the spinal cord of larval zebrafish; four of these are described here for the first time. The newly discovered cell types include classes of commissural neurons with axons that ascend, descend, and bifurcate in the contralateral spinal cord. Our reexamination of previously described cell types revealed functionally relevant features of their morphology, such as undescribed commissural axons, as well as the relationships between the trajectories of the axons of interneurons and the descending Mauthner axons. In addition to describing neurons, we surveyed their morphology at multiple positions along the spinal cord and found longitudinal changes in their distribution and sizes. For example, some cell types increase in size from rostral to caudal, whereas others decrease. Our observations lead to predictions of the roles of some of these interneurons in motor circuits. These predictions can be tested with the combination of functional imaging, single-cell ablation, and genetic approaches that make zebrafish a powerful model system for studying neuronal circuits.