Supporting family dementia caregivers: testing the efficacy of dementia care management on multifaceted caregivers' burden.

OBJECTIVES: Current research suggests that dementia care management (DCM) can decrease burden and associated health impairments of caregivers. The objective of this secondary analysis is to investigate the impact of DCM on multifaceted caregivers' burden dimensions by differentiating between objective and subjective burden. METHODS: A sample of n = 317 dyads of caregivers and community-dwelling people with dementia (PwD) participated in a general practitioner-based, cluster-randomized intervention trial (Identifier:NCT01401582) with two arms and comprehensive data assessment at baseline and 12-month follow-up. Data provided by the caregiver included an inventory with 88 items in 20 different dimensions. RESULTS: Caregivers in the intervention 'DCM' group showed decreased caregiver burden, especially in caregivers' objective burden due to caring (i.e. emotional support), caregivers' subjective burden due to behavior change (i.e. cognition, aggression and resistance, depression, late symptoms) and caregivers' subjective burden due to perceived conflicts between needs and responsibilities to care (i.e. financial losses) compared to caregivers in the control 'care as usual' group, which showed significant increased caregiver burden after 12 months. CONCLUSION: Our findings support evidence for the effectiveness of DCM to lower family dementia caregivers' burden in multifaceted dimensions.

Impact of Everolimus and Low-Dose Cyclosporin on Cytomegalovirus Replication and Disease in Pediatric Renal Transplantation.

In order to investigate the hypothesis that the mammalian target of rapamycin inhibitor everolimus (EVR) shows anticytomegalovirus (CMV) activity in pediatric patients, we analyzed the impact of EVR-based immunosuppressive therapy on CMV replication and disease in a large cohort (n = 301) of pediatric kidney allograft recipients. The EVR cohort (n = 59), who also received low-dose cyclosporin, was compared with a control cohort (n = 242), who was administered standard-dose cyclosporin or tacrolimus and an antimetabolite, mostly mycophenolate mofetil (91.7%). Multivariate analysis revealed an 83% lower risk of CMV replication in the EVR cohort than in the control cohort (p = 0.005). In CMV high-risk (donor+/recipient-) patients (n = 88), the EVR-based regimen was associated with a significantly lower rate of CMV disease (0% vs. 14.3%, p = 0.046) than the standard regimen. In patients who had received chemoprophylaxis with (val-)ganciclovir (n = 63), the CMV-free survival rates at 1 year and 3 years posttransplant (100%) were significantly (p = 0.015) higher in the EVR cohort (n = 15) than in the control cohort (n = 48; 1 year, 75.0%; 3 years, 63.3%). Our data suggest that in pediatric patients at high risk of CMV, an EVR-based immunosuppressive regimen is associated with a lower risk of CMV disease than a standard-dose calcineurin inhibitor-based regimen.

Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study.

BACKGROUND: Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1 expression. We conducted a large study evaluating FOLR1 expression with survival in different histological types of OvCa. METHODS: Tissue microarrays composed of tumour samples from 2801 patients in the Ovarian Tumour Tissue Analysis (OTTA) consortium were assessed for FOLR1 expression by centralised immunohistochemistry. We estimated associations for overall (OS) and progression-free (PFS) survival using adjusted Cox regression models. High-grade serous ovarian carcinomas (HGSC) from The Cancer Genome Atlas (TCGA) were evaluated independently for association between FOLR1 mRNA upregulation and survival. RESULTS: FOLR1 expression ranged from 76% in HGSC to 11% in mucinous carcinomas in OTTA. For HGSC, the association between FOLR1 expression and OS changed significantly during the years following diagnosis in OTTA (Pinteraction=0.01, N=1422) and TCGA (Pinteraction=0.01, N=485). In OTTA, particularly for FIGO stage I/II tumours, patients with FOLR1-positive HGSC showed increased OS during the first 2 years only (hazard ratio=0.44, 95% confidence interval=0.20-0.96) and patients with FOLR1-positive clear cell carcinomas (CCC) showed decreased PFS independent of follow-up time (HR=1.89, 95% CI=1.10-3.25, N=259). In TCGA, FOLR1 mRNA upregulation in HGSC was also associated with increased OS during the first 2 years following diagnosis irrespective of tumour stage (HR: 0.48, 95% CI: 0.25-0.94). CONCLUSIONS: FOLR1-positive HGSC tumours were associated with an increased OS in the first 2 years following diagnosis. Patients with FOLR1-negative, poor prognosis HGSC would be unlikely to benefit from anti-FOLR1 therapies. In contrast, a decreased PFS interval was observed for FOLR1-positive CCC. The clinical efficacy of FOLR1-targeted interventions should therefore be evaluated according to histology, stage and time following diagnosis.

Malignant peritoneal mesothelioma in a 16-year-old girl: presentation of a rare disease.

Malignant peritoneal mesothelioma is extremely rarely seen in young patients.A 16 year-old girl presented with appendicitis-like acute abdominal pain. Intra-operatively, multiple confluent peritoneal nodules were seen on the entire greater omentum and in the pelvis infiltrating the uterus and both ovaries. Biopsies were obtained and interpreted as serous ovarian carcinoma. Radical surgical resection and hyperthermic intraperitoneal chemotherapy -(HIPEC) with carboplatin was performed and followed by 2 cycles of carboplatin/paclitaxel. Histological reevaluation showed characteristic features of epithelioid peritoneal mesothelioma and ruled out serous ovarian cancer. Therapy was continued with 6 cycles of pemetrexed/cisplatin.3 months after end of chemotherapy vital tumor tissue was found in the recess behind the liver, which could be resected completely. The patient is currently disease-free 17 months after initial diagnosis.Malignant peritoneal mesothelioma in young female patients might be under-recognized and possibly misdiagnosed as ovarian serous carcinoma in some cases. International and interdisciplinary cooperation is necessary in order to provide evidence based guidelines for diagnosis and treatment in the future.

The era of centers: the influence of establishing specialized centers on patients' choice of hospital.

PURPOSE: It is considered that establishing accredited specialized centers can serve as a marketing tool. This study investigated whether accredited specialized centers influence patients' choice of hospital. METHODS: A total of 2,389 patients was included in a questionnaire survey: 468 at the Department of Gynecology, 745 at the certified University Breast Center of Franconia, 1,000 at the University Perinatal Center of Franconia and 176 for whom classification details were lacking. RESULTS: Among the oncological patients, physicians in private practice played an important role in the choice of hospital (58.4 vs. 25.7%; P < 0.001; OR 4.058). Among obstetric patients, the primary factors were recommendations from family [odds ratio (OR) 0.495], friends (OR 0.218), and previous personal experience of the hospital (OR 0.695). For oncological patients, treatment quality (OR 2.693), availability of a center (OR 1.785), and certification (OR 3.939) were comparatively more important. For obstetric patients, friendliness (OR 0.409) and attractive accommodation (OR 0.153) were more important. CONCLUSIONS: Physicians are the most important source of recommendations for oncological patients. From the marketing point of view, intensive involvement of local private-practice physicians is necessary. The availability of certified perinatal centers does not currently play any part in patients' choice of hospital.

Rewetting does not return drained fen peatlands to their old selves.

Peatlands have been drained for land use for a long time and on a large scale, turning them from carbon and nutrient sinks into respective sources, diminishing water regulation capacity, causing surface height loss and destroying biodiversity. Over the last decades, drained peatlands have been rewetted for biodiversity restoration and, as it strongly decreases greenhouse gas emissions, also for climate protection. We quantify restoration success by comparing 320 rewetted fen peatland sites to 243 near-natural peatland sites of similar origin across temperate Europe, all set into perspective by 10k additional European fen vegetation plots. Results imply that rewetting of drained fen peatlands induces the establishment of tall, graminoid wetland plants (helophytisation) and long-lasting differences to pre-drainage biodiversity (vegetation), ecosystem functioning (geochemistry, hydrology), and land cover characteristics (spectral temporal metrics). The Paris Agreement entails the rewetting of 500,000 km2 of drained peatlands worldwide until 2050-2070. A better understanding of the resulting locally novel ecosystems is required to improve planning and implementation of peatland rewetting and subsequent management.

Demagnetization of magnetically shielded rooms.

Magnetically shielded rooms for specific high resolution physiological measurements exploiting the magnetic field, e.g., of the brain (dc-magnetoencephalography), low-field NMR, or magnetic marker monitoring, need to be reproducibly demagnetized to achieve reliable measurement conditions. We propose a theoretical, experimental, and instrumental base whereupon the parameters which affect the quality of the demagnetization process are described and how they have to be handled. It is demonstrated how conventional demagnetization equipment could be improved to achieve reproducible conditions. The interrelations between the residual field and the variability at the end of the demagnetization process are explained on the basis of the physics of ferromagnetism and our theoretical predictions are evaluated experimentally.

Nonspectral modes and how to find them in the Ornstein-Uhlenbeck process with white µ-stable noise.

We consider the Ornstein-Uhlenbeck process with a broad initial probability distribution (Lévy distribution), which exhibits so-called nonspectral modes. The relaxation rate of such modes differs from those determined from the parameters of the corresponding Fokker-Plank equation. The first nonspectral mode is shown to govern the relaxation process and allows for estimation of the initial distribution's Lévy index. A method based on continuous wavelet transformation is proposed to extract both (spectral and nonspectral) relaxation rates from a stochastic data sample.

Gestational and Non-gestational Trophoblastic Disease. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry No. 032/049, December 2015).

Purpose: The aim was to establish an official interdisciplinary guideline, published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). The guideline was developed for use in German-speaking countries. In addition to the Germany Society of Gynecology and Obstetrics, the guideline has also been approved by the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). The aim was to standardize diagnostic procedures and the management of gestational and non-gestational trophoblastic disease in accordance with the principles of evidence-based medicine, drawing on the current literature and the experience of the colleagues involved in compiling the guideline. Methods: This s2k guideline represents the consensus of a representative panel of experts with a range of different professional backgrounds commissioned by the DGGG. Following a review of the international literature and international guidelines on trophoblastic tumors, a structural consensus was achieved in a formalized, multi-step procedure. This was done using uniform definitions, objective assessments, and standardized management protocols. Recommendations: The recommendations of the guideline cover the epidemiology, classification and staging of trophoblastic tumors; the measurement of human chorionic gonadotropin (hCG) levels in serum, and the diagnosis, management, and follow-up of villous trophoblastic tumors (e.g., partial mole, hydatidiform mole, invasive mole) and non-villous trophoblastic tumors (placental site nodule, exaggerated placental site, placental site tumor, epitheloid trophoblastic tumor, and choriocarcinoma).

Molecular basis of glycoalkaloid induced membrane disruption.

In this study the interaction between the glycoalkaloids alpha-chaconine, alpha-solanine and alpha-tomatine and sterols in model membranes was analysed systematically using techniques like membrane leakage, binding experiments, detergent extraction, electron microscopy, NMR and molecular modelling. The most important properties for sterols to interact with glycoalkaloids turned out to be a planer ring structure and a 3 beta-OH group, whereas for alpha-chaconine the 5-6 double bond and the 10-methyl group were also of importance. The importance of sugar-sugar interactions was illustrated by the high synergistic effect between alpha-chaconine and alpha-solanine, the leakage enhancing effect of glycolipids, and the almost complete loss of activity after deleting one or more mono-saccharides from the glycoalkaloids. The formed complexes which were resistant against detergent extraction existed of glycoalkaloid/sterol in a 1:1 ratio and formed tubular structures (alpha-chaconine) with an inner monolayer of phospholipids, whereas with alpha-tomatine also spherical structures were formed. Based on the results a molecular model for glycoalkaloid induced membrane disruption is presented.

Barriers to providing diabetes care in community health centers.

OBJECTIVE: We aimed to identify barriers to improving care for individuals with diabetes in community health centers. These findings are important because many such patients, as in most other practice settings, receive care that does not meet evidence-based standards. RESEARCH DESIGN AND METHODS: In 42 Midwestern health centers, we surveyed 389 health providers and administrators about the barriers they faced delivering diabetes care. We report on home blood glucose monitoring, HbA1c tests, dilated eye examinations, foot examinations, diet, and exercise, all of which are a subset of the larger clinical practice recommendations of the American Diabetes Association (ADA). RESULTS: Among the 279 (72%) respondents, providers perceived that patients were significantly less likely than providers to believe that key processes of care were important (overall mean on 30-point scale: providers 26.8, patients 18.2, P = 0.0001). Providers were more confident in their ability to instruct patients on diet and exercise than on their ability to help them make changes in these areas. Ratings of the importance of access to care and finances as barriers varied widely; however, >25% of the providers and administrators agreed that significant barriers included affordability of home blood glucose monitoring, HbA1c testing, dilated eye examination, and special diets; nonproximity of ophthalmologist; forgetting to order eye examinations and to examine patients' feet; time required to teach home blood glucose monitoring; and language or cultural barriers. CONCLUSIONS: Providers in health centers indicate a need to enhance behavioral change in diabetic patients. In addition, better health care delivery systems and reforms that improve the affordability, accessibility, and efficiency of care are also likely to help health centers meet ADA standards of care.

Erratum: Sarcoma of the Uterus. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015/074, August 2015).

[This corrects the article DOI: 10.1055/s-0035-1558120.].

Sarcoma of the Uterus. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015/074, August 2015).

Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Due to their rarity and their heterogeneous histopathology uterine sarcomas remain challenging tumors to manage and need a multidisciplinary approach. To our knowledge so far there is no evidence-based guideline on the appropiate management of these heterogeneous tumors. Methods: This S2k-guideline is the work of an representative committee of experts from a variety of different professions who were commissioned by the DGGG to carry out a systematic literature review of uterine sarcoma. Members of the participating scientific societies developed a structured consensus in a formal procedure. Recommendations: 1. The incidence and histopathologic classification of uterine sarcoma. 2. The clinical manifestations, diagnosis and staging of uterine sarcoma. 3. The management of leiomyosarcoma. 4. The management of endometrial stromal sarcoma and undifferentiated uterine sarcoma. 5. The management of adenosarcoma as well as carcinosarcomas. 6. The management of morcellated uterine sarcoma.

Impedance analyser module for EIT and spectroscopy using undersampling.

In this paper we present the concept, the design and the test procedure for a DSP-based high-precision and high-performance wide-band (up to 10 MHz) bioimpedance analyser module for application in EIT or bioimpedance spectroscopy. The module implements a digital concept with appropriate signal conditioning hardware for voltage and current measurement, early signal digitization and subsequent digital signal processing in order to calculate the components of impedance (or admittance). At low frequencies, the module utilizes the conventional direct conversion method, whereas at high frequencies the undersampling technique is used. The advantages of the described system are the following: (a) the frequency range is extended to higher frequencies, (b) the number of data sampled per time interval is significantly reduced, and (c) the current consumption and the costs of the ADCs can be significantly reduced. The validation procedure is performed by comparing the measured and theoretical values of the magnitude and the phase of the impedance for a commonly used tissue model. The module offers an accuracy of better than 0.012% for the magnitude of impedance and better than 0.02 degrees for the phase.

Low-temperature scanning electron microscopy in fungus-nematode interaction.

A comparative study has been made of different preparation techniques used for the scanning electron microscope (SEM), with regard to their application to fungus-nematode interaction. The preparation of frozen-hydrated specimens of both healthy and Arthrobotrys-oligospora-infected second-stage larvae of the root-knot nematode (Meloidogyne sp.) is described, and the results are compared with those obtained by critical point-drying and freeze-drying. In all cases the frozen-hydrated specimens consistently showed the best preservation.

[A multichannel device for the noninvasive analysis of the state and function of organs and tissues]. / Multikanalsystem zur nichtinvasiven Funktions- und Zustandsanalyse von Organen und Gewebe.

The subject of this paper is to present a technical description of a high-performance, modular research device, designed and constructed with the aim of enabling the non-invasive investigation of the passive electrical properties of biological tissue in the frequency range 1 kHz-1 MHz. The modular hardware- and software of the device makes the system highly flexible when it comes to applying a wide range of methods for the non-invasive analysis of the state and function of biological tissues and evaluating them in a clinical setting. Furthermore, the concept also makes it possible to combine the modules in new ways for new applications, to accommodate future developments in bio-impedance research.

[A method for improving measuring accuracy in multi-channel impedance spectroscopy (MIS)]. / Methode zur Verbesserung der Messgenauigkeit bei der Multikanal-Impedanz-Spektroskopie (MIS).

The use of impedance spectroscopy as a diagnostic tool for the investigation of biological objects involves the consideration of numerous parameters impacting on measuring accuracy. This paper describes a calibration method for multichannel instruments that reduces the non-inconsiderable influence of frequency response variations between the channels, thus significantly increasing measuring accuracy. The method is tested in a recently developed, high-resolution, multi-channel bio-impedance analyser. Reduction of the measuring error is demonstrated, and the magnitude and phase resolution is quantified. The advantage of this method lies in its applicability to existing systems. Furthermore, an additional calibration impedance is not needed.

Quantitative evaluation of the performance of different electrical tomography devices.

Two widely used electrical tomography systems, the Sheffield Mark I and the DAS-01P, were quantitatively evaluated and compared to the newly developed Goe-MF system. The performance was quantified using a hardware phantom which closely matches the real input and transfer impedances of the human thorax and allows measurements equivalent to different states of lung inflation. Our results demonstrate that adequate averaging is necessary for noise reduction for the Mark I and especially for the DAS-01P system to get meaningful results even in visualizing maximal respiratory manoeuvres. The Goe-MF system showed a notably improved signal-to-noise ratio which allows also dynamic measurements at low levels of lung volume changes, e.g., in intensive care lung injury patients.

Technique for the direct measurement of DC-like magnetic biosignals demonstrated by the cold reflex of the abdomen.

Very low frequency dc-like signals, such as the cold reflex, could only be measured up to now by moving the subject repeatedly, up to the magnetic detector. PTB's novel magnetically shielded room BMSR 2, together with a low noise 16 channel SQUID magnetometer, allow the recording of dc-like signals without moving the subject; these are direct measurements. The total observed magnetic drifts are limited by 1/f-noise and external disturbances to a value below 6 pT/h. The measurement is continuous in time, therefore provides frequency resolution from dc to several kHz. This allows us to also observe the changing pattern between two different static magnetic states. As an example, the measurement of the cold reflex of the abdomen is shown and discussed. Not only the expected cold reflex, but other periodic and spontaneous signals from the human body can be seen with this method.

Spatial distribution of cardiac magnetic vector fields acquired from 3120 SQUID positions.

An extended measurement of the magnetic vector field of the human heart is presented. It is acquired by sequential recordings, shifting a 16 SQUID vector magnetometer across 195 positions over a healthy subject's thorax. The magnetocardiographic (MCG) signals were synchronized using a simultaneously measured ECG channel. The registration of the field extends over a volume of 1000 mm x 600 mm x 420 mm sampled at 3120 SQUID positions. We present diagrams of the vector amplitude of selected points in 6 planes at increasing distances from the frontal thorax. Each plane contains 76 vector points. Additionally, we measured the vector field at 126 points lateral to the chest. At the edge points of the measurement volume, the absolute value of the magnetic vector signal amplitude exceeds 0.3 pT in all measurement points. The dataset provides an excellent base to study dedicated MCG detection or rejection methods. Examples where rejection of the heart signal is necessary are magnetoencephalography, magnetoneurography and fetal MCG. The knowledge of the spatio-temporal distribution of the magnetic vector field of the heart supports the development and comparison of multi-SQUID systems and will be used to create new MCG interpretation and representation algorithms.