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This article, published in the journal Neuropediatrics, explores the differences between prepubertal and (post)pubertal children with multiple sclerosis (MS) in terms of clinical, laboratory, and imaging features. The study included 248 MS patients from various European pediatric hospitals who were diagnosed before the age of 18. The results showed that prepubertal children had an equal distribution of MS between sexes, while postpubertal children had a higher prevalence in females. Prepubertal children also had more relapses in the first two years and a different range of MRI features compared to (post)pubertal children. Overall, the findings suggest both similarities and differences between the two age groups in terms of MS characteristics. [Extracted from the article]

This article, published in the journal Neuropediatrics, explores the clinical course and final diagnosis of Acute Disseminated Encephalomyelitis (ADEM) without MOG antibodies. ADEM is a rare inflammatory disorder of the central nervous system (CNS), and MOG antibodies are found in 50% of children with ADEM. The study collected data from 40 children with MOG-negative ADEM and found that in 72.5% of cases, the diagnosis remained ADEM at the last follow-up. However, in 27.5% of cases, the diagnosis was revised to conditions such as multiple sclerosis (MS), glioblastoma, CNS vasculitis, leukoencephalopathy, and autoimmune encephalitis. The study highlights the importance of considering alternative diagnoses in cases of MOG-negative ADEM. [Extracted from the article]

This article, published in the journal Neuropediatrics, discusses the use of A20 (TNFAIP3) as a potential biomarker to distinguish relapse from remission in pediatric patients with monophasic MOGAD (MOG-IgG-associated disorders). MOGAD is a type of acquired demyelinating syndrome associated with antibodies against myelin oligodendrocyte glycoprotein. The study found that A20 levels were significantly lower during clinical events compared to remission in monophasic MOGAD patients. However, there was no significant difference in A20 levels between clinical events and remission in multiphasic MOGAD patients. The authors suggest that further research is needed to investigate the diagnostic, prognostic, and therapeutic implications of A20 in pediatric MOGAD patients. [Extracted from the article]

This article, published in the journal Neuropediatrics, examines the significance of intrathecal IgM synthesis and the MRZ reaction in pediatric multiple sclerosis (MS). The study included 75 children with MS and analyzed their clinical presentation, MR imaging, and cerebrospinal fluid analysis. The results showed that intrathecal IgM synthesis and a positive MRZ reaction were present in a significant portion of the children, but they were not associated with markers of disease progression such as the presence of spinal cord lesions, total lesion load, and relapse rate. This suggests that these features may not be predictive of a poor prognosis in pediatric MS. [Extracted from the article]

Hepatocellular carcinoma is a leading cause of cancer-related death in many parts of the world. Traditional treatment options are not always effective. During the promising minimally invasive electroporation-based therapies, biological cell membranes are exposed to an external, sufficiently high, pulsed electric field which creates so-called nanopores into the lipid bilayer of the cell membrane. These pores can either be permanent (irreversible electroporation (IRE)), leading to apoptosis, or repairable (reversible electroporation (RE)), with continued cell function. In tumor therapy, RE is used to increase the diffusion of a chemotherapeutic drug during electrochemotherapy. For both IRE and RE, the success of the treatment is dependent on application of the appropriate electric field. Therefore, this study aims to define the pulse parameters and thresholds for IRE and RE on hepatocellular carcinoma (HepG2) cells in-vitro. In a custom-made in-vitro setup, HepG2 cell viability (0, 5, 10, and 15 min), and the peak temperature were measured after electroporation with the different IRE and RE pulsing protocols, to determine the most successful settings for IRE and RE. A CAM/PI flow cytometric assay was performed to confirm cell permeabilization for the RE pulsing protocols with the highest cell viability. The results indicated that an IRE pulsing protocol (70 pulses, 100 µ s pulse length, and 100 ms interval) with an electric field strength of 4000 V/cm was needed as threshold for almost complete cell death of HepG2 cells. A RE pulsing protocol (8 pulses, 100 µ s pulse length, and 1000 ms interval) with an electric field strength of 1000 V/cm was needed as threshold for viable and permeabilized HepG2 cells. The low peak temperatures (max 30.1°C for IRE, max 23.1°C for RE) within this study indicated that the reduction in HepG2 cell viability was caused by the applied electric field and was not a result of Joule heating. [ABSTRACT FROM AUTHOR]

Background: A further increase in renewable energy supply is needed to substitute fossil fuels and combat climate change. Each energy source and respective technologies have specific techno-economic and environmental characteristics as well as social implications. This paper presents a comprehensive approach for prospective sustainability assessment of energy technologies developed within the Helmholtz Initiative "Energy System 2050" (ES2050). Methods: The "ES2050 approach" comprises environmental, economic, and social assessment. It includes established life cycle based economic and environmental indicators, and social indicators derived from a normative concept of sustainable development. The elaborated social indicators, i.e. patent growth rate, acceptance, and domestic value added, address three different socio-technical areas, i.e. innovation (patents), public perception (acceptance), and public welfare (value added). Results: The implementation of the "ES2050 approach" is presented exemplarily and different sustainability indicators and respective results are discussed based on three emerging technologies and corresponding case studies: (1) synthetic biofuels for mobility; (2) hydrogen from wind power for mobility; and (3) batteries for stationary energy storage. For synthetic biofuel, the environmental advantages over fossil gasoline are most apparent for the impact categories Climate Change and Ionizing Radiation—human health. Domestic value added accounts for 66% for synthetic biofuel compared to 13% for fossil gasoline. All hydrogen supply options can be considered to become near to economic competitiveness with fossil fuels in the long term. Survey participants regard Explosion Hazard as the most pressing concern about hydrogen fuel stations. For Li-ion batteries, the results for patent growth rate indicate that they enter their maturity phase. Conclusions: The "ES2050 approach" enables a consistent prospective sustainability assessment of (emerging) energy technologies, supporting technology developers, decision-makers in politics, industry, and society with knowledge for further evaluation, steering, and governance. The approach presented is considered rather a starting point than a blueprint for the comprehensive assessment of renewable energy technologies though, especially for the suggested social indicators, their significance and their embedding in context scenarios for prospective assessments. [ABSTRACT FROM AUTHOR]

Reducing greenhouse gas (GHG) emissions in the transport sector is one of the biggest challenges in the German energy transition. Furthermore, sustainable development does not stop with reducing GHG emissions. Other environmental, social and economic aspects should not be neglected. Thus, here a comprehensive sustainability assessment for passenger vehicles is conducted for 2020 and 2050. The discussed options are an internal combustion engine vehicle (ICEV) fuelled with synthetic biofuel and fossil gasoline, a battery electric vehicle (BEV) with electricity from wind power and electricity mix Germany and a fuel cell electric vehicle (FCEV) with hydrogen from wind power. The life cycle-based assessment entails 13 environmental indicators, one economic and one social indicator. For integrated consideration of the different indicators, the MCDA method Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) is chosen. For the assessment, a consistent assessment framework, i.e. background scenario and system boundaries, and a detailed modelling of vehicle production, fuel supply and vehicle use are the cornerstones. The BEV with wind power is the most sustainable option in 2020 as well as in 2050. While in 2020, the second rank is taken by the ICEV with synthetic biofuel from straw and the last rank by the FCEV, in 2050 the FCEV is the runner-up. With the help of MCDA, transparent and structured guidance for decision makers in terms of sustainability assessment of motorized transport options is provided. [ABSTRACT FROM AUTHOR]

To strengthen the economic pillar in sustainability assessment, the indicator 'domestic value added' is introduced. It aims at comparing established and less developed technologies regarding their prospective value added in a country. This is done by classifying a technology's value added to the developed categories: domestic, potential domestic and non-domestic. Within this paper, two methods for assessing this indicator are introduced focussing on their applicability in a sustainability assessment context. Both methods are tested on a case study comparing two alternative drivetrain technologies for the passenger car sector (battery and fuel cell electric vehicle) to the conventionally used internal combustion engine. The first method is life cycle cost-based whereas the second is based on Input Output analysis. If a life cycle cost assessment is already available for the technology under assessment, the easier to implement life cycle cost-based approach is recommended, as the results are similar to the more complex Input Output-based approach. From the 'domestic value added' perspective, the battery electric vehicle is already more advantageous than the conventional internal combustion engine over the lifecycle. Fuel cell electric vehicles have the highest potential to increase their 'domestic value added' share in the future. This paper broadens the economic pillar in sustainability assessment by introducing a new indicator 'domestic value added' and giving practical information on how to prospectively assess it for existing and less developed technologies or innovations. [ABSTRACT FROM AUTHOR]

Objective: Brain atrophy has the potential to become a biomarker for severity of radiation-induced side-effects. Particularly brain tumour patients can show great MRI signal changes over time caused by e.g. oedema, tumour progress or necrosis. The goal of this study was to investigate if such changes affect the segmentation accuracy of normal appearing brain and thus influence longitudinal volumetric measurements. Materials and methods: T1-weighted MR images of 52 glioblastoma patients with unilateral tumours acquired before and three months after the end of radio(chemo)therapy were analysed. GM and WM volumes in the contralateral hemisphere were compared between segmenting the whole brain (full) and the contralateral hemisphere only (cl) with SPM and FSL. Relative GM and WM volumes were compared using paired t tests and correlated with the corresponding mean dose in GM and WM, respectively. Results: Mean GM atrophy was significantly higher for full segmentation compared to cl segmentation when using SPM (mean ± std: ΔVGM,full = − 3.1% ± 3.7%, ΔVGM,cl = − 1.6% ± 2.7%; p < 0.001, d = 0.62). GM atrophy was significantly correlated with the mean GM dose with the SPM cl segmentation (r = − 0.4, p = 0.004), FSL full segmentation (r = − 0.4, p = 0.004) and FSL cl segmentation (r = -0.35, p = 0.012) but not with the SPM full segmentation (r = − 0.23, p = 0.1). Conclusions: For accurate normal tissue volume measurements in brain tumour patients using SPM, abnormal tissue needs to be masked prior to segmentation, however, this is not necessary when using FSL. [ABSTRACT FROM AUTHOR]

Copyright of Pädiatrie & Pädologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: The purpose of our study was to evaluate the outcome of selective pelvic arterial embolisation (PAE) in women with severe postpartum hemorrhage (PPH).Methods: We performed a retrospective, controlled, single-center cohort study. A total of 16 consecutive women with PPH who underwent therapeutic PAE were included. As historical control group, we included 22 women with similar severity of PPH who were managed without PAE. Outcome measures included necessity of surgical interventions such as postpartum hysterectomy and laparotomy after vaginal delivery, the amount of red blood cell transfusions, and hematologic findings after the procedure.Results: PAE was successful in stopping PPH and preserving the uterus in all 16 women in the study group. No woman in the PAE group required a postpartum hysterectomy, whereas postpartum hysterectomy was unavoidable in two women in the control group. Laparotomy after vaginal delivery was necessary in two women of the group without embolisation. Hematologic parameters after the treatment were better in the PAE group than in the control group, although these differences were only in part statistically significant. There were no unwarranted effects of PAE identifiable in the study group.Conclusion: This is the first controlled study assessing the efficacy of PAE for the treatment of PPH. Our data suggest that PAE is effective for the treatment of severe PPH. In view of the lack of complications and unwarranted effects, clinical use of PAE in severe PPH seems justified, particularly in view of the life-threatening condition and the potential to preserve fertility in affected patients. Further evidence from well-designed prospective randomized-controlled trials would be nevertheless desirable in the future. [ABSTRACT FROM AUTHOR]

Collisions of excited 113Cd(5 3P1) atoms with various molecular gases (N2, H2, D2, CO, CO2, CH4, C2H6, C2H4, O2) have been investigated using atomic fluorescence spectroscopy. By selective excitation of a hyperfine structure level with a pulsed dye laser and studying the time dependence of the fluorescence signals as a function of the buffer gas density the cross sections for quenching, fine structure transfer, and hyperfine structure transfer could be obtained. For N2 molecules the collisions can be described by a decoupling model as has been shown previously for the noble gases as collision partners. [ABSTRACT FROM AUTHOR]

With the introduction of automatic vehicle guidance (AV), mixed traffic scenarios between automatically and manually guided vehicles are to be expected, at least during a transitions phase. To ensure the safety of motor vehicle transportation, it will be essential to develop a cooperative relationship between human drivers and AV. Research in this area is currently being done to gain insight into the manner of human drivers’ decisions to transfer the same behaviours to automatic vehicle guidance. A lot of research is being done to prepare for the introduction of AV, but there is still a lack of information on how individual road users make decisions in cooperative decisions. Currently, there is no study that has tried to understand the decision-making process with the help of an online-survey. For that reason, a questionnaire study on cooperative traffic situations (N = 281) was carried out, which was analysed with the Natural Decision Making approach. By means of the NDM approach and the use of the recognition module, links between planned action and the expected action between road users were identified. Furthermore, it was possible to categorize individual communication signals into offensive or defensive signals and thus make predictions about the intention of the driver. These findings can be used to derive design recommendations for automatic vehicle guidance in cooperative situations. [ABSTRACT FROM AUTHOR]

Member states of the United Nations (UN) agree that its development system needs substantial reform given its fragmentation and outdated structures, as well as new demands from the 2030 Agenda. Yet, a recent two-year reform process yielded no substantial reform decisions. Why did member states fail to endorse the necessary reforms despite almost unanimous recognition of the need for change? This paper describes member states’ conflicting positions on reforming the UN and analyses their failure to delegate authority to the UN development system. North and South, donors and recipients, are locked in a struggle for power and control, maximising bilateral influence at the expense of the benefits of multilateral cooperation. The paper contributes to the pool of UN studies, adding a decidedly political perspective of the reform process. It is based on diplomatic statements, negotiation drafts and interviews with UN diplomats. [ABSTRACT FROM AUTHOR]

Summary: Tick‐borne diseases are considered a major hindrance to the health and productive performance of cattle in Bangladesh. To elucidate the epidemiology of tick‐borne pathogens (TBPs) in local cattle, a cross‐sectional study was performed in the 12 subdistricts (Upazilas) of Mymensingh district in Bangladesh. Blood samples and ticks were collected from 384 clinically healthy cattle kept by 135 farmers from 96 randomly selected villages. DNA extracted from the blood samples was subsequently screened by polymerase chain reaction (PCR) and a Reverse Line Blot (RLB) hybridization assay using an in‐house prepared chemiluminescence solution for the presence of Anaplasma, Ehrlichia, Rickettsia, Babesia and Theileria spp. A total of 2,287 ticks were collected from 232 infested cattle (60.4%, 232/384) and identified morphologically as Rhipicephalus (Boophilus) microplus (n = 1,432, 62.6%) and Haemaphysalis bispinosa (n = 855; 37.4%). The RLB results demonstrated that the majority of the cattle (62.2%) were infected with at least one TBP. Theileria orientalis infections were most common (212/384, 55.2%) followed by infections with Anaplasma bovis (137/384, 35.67%), Anaplasma marginale (16/384, 4.17%), Babesia bigemina (4/384, 1.04%) and Babesia bovis (2/384, 0.52%). A previously uncharacterized Anaplasma sp. (Anaplasma sp. Mymensingh) and Babesia sp. (Babesia sp. Mymensingh), which are genetically closely related to Anaplasma platys and B. bigemina, were detected in 50 of 384 (13.0%) and 1 of 384 (0.3%) of the blood samples, respectively. Key risk factors for the occurrence of T. orientalis, A. marginale and Anaplasma sp. Mymensingh were identified. In conclusion, this study revealed that cattle in Mymensingh district are mainly infested with R. microplus and H. bispinosa ticks and may carry multiple TBPs. In addition, two previously uncharacterized pathogens were detected in the bovine blood samples. The pathogenicity of these species remains to be determined. [ABSTRACT FROM AUTHOR]

In this work, we present a new numerical framework for the efficient solution of the time-harmonic elastic wave equation at multiple frequencies. We show that multiple frequencies (and multiple right-hand sides) can be incorporated when the discretized problem is written as a matrix equation. This matrix equation can be solved efficiently using the preconditioned IDR( s) method. We present an efficient and robust way to apply a single preconditioner using MSSS matrix computations. For 3D problems, we present a memory-efficient implementation that exploits the solution of a sequence of 2D problems. Realistic examples in two and three spatial dimensions demonstrate the performance of the new algorithm. [ABSTRACT FROM AUTHOR]

Background: In early-stage non-small cell lung cancer (NSCLC) without affected lymph nodes detected at staging, surgical resection is still the mainstay of treatment. However, in patients with metastatic mediastinal lymph nodes (pN2) or non-radically resected primary tumors (R1/R2), postoperative radiotherapy (possibly combined with chemotherapy) is indicated. So far, investigations about time factors affecting postoperative radiotherapy have only examined the waiting time defined as interval between surgery and start of radiotherapy, but not the overall treatment time (OTT) itself. Conversely, results from trials on primary radio(chemo)therapy in NSCLC show that longer OTT correlates with significantly worse local tumor control and overall survival rates. This time factor of primary radio(chemo)therapy is thought to mainly be based on repopulation of surviving tumor cells between irradiation fractions. It remains to be elucidated if such an effect also occurs when patients with NSCLC are treated with postoperative radiotherapy after surgery (and chemotherapy). Our own retrospective data suggest an advantage of shorter OTT also for postoperative radiotherapy in this patient group.Methods/design: This is a multicenter, prospective randomized trial investigating whether an accelerated course of postoperative radiotherapy with photons or protons (7 fractions per week, 2 Gy fractions) improves locoregional tumor control in NSCLC patients in comparison to conventional fractionation (5 fractions per week, 2 Gy fractions). Target volumes and total radiation doses will be stratified in both treatment arms based on individual risk factors.Discussion: For the primary endpoint of the study we postulate an increase in local tumor control from 70% to 85% after 36 months. Secondary endpoints are overall survival of patients; local recurrence-free and distant metastases-free survival after 36 months; acute and late toxicity and quality of life for both treatment methods.Trial Registration: ClinicalTrials.gov, NCT02189967 . Registered on 22 May 2014. [ABSTRACT FROM AUTHOR]

Objectives Primary familial brain calcification ( PFBC) is a rare neurological disease often inherited as a dominant trait. Mutations in four genes ( SLC20A2, PDGFB, PDGFRB, and XPR1) have been reported in patients with PFBC. Of these, point mutations or small deletions in SLC20A2 are most common. Thus far, only one large deletion covering entire SLC20A2 and several smaller, exonic deletions of SLC20A2 have been reported. The aim of this study was to identify the causative gene defect in a Finnish PFBC family with three affected patients. Materials and methods A Finnish family with three PFBC patients and five unaffected subjects was studied. Sanger sequencing was used to exclude mutations in the coding and splice site regions of SLC20A2, PDGFRB, and PDGFB. Whole-exome ( WES) and whole-genome sequencing ( WGS) were performed to identify the causative mutation. A SNP array was used in segregation analysis. Results Copy number analysis of the WGS data revealed a heterozygous deletion of ~578 kb on chromosome 8. The deletion removes the 5′ UTR region, the noncoding exon 1 and the putative promoter region of SLC20A2 as well as the coding regions of six other genes. Conclusions Our results support haploinsufficiency of SLC20A2 as a pathogenetic mechanism in PFBC. Analysis of copy number variations ( CNVs) is emerging as a crucial step in the molecular genetic diagnostics of PFBC, and it should not be limited to coding regions, as causative variants may reside in the noncoding parts of known disease-associated genes. [ABSTRACT FROM AUTHOR]

Batteries are considered as one of the key flexibility options for future energy storage systems. However, their production is cost- and greenhouse-gas intensive and efforts are made to decrease their price and carbon footprint. We combine life-cycle assessment, Monte-Carlo simulation, and size optimization to determine life-cycle costs and carbon emissions of different battery technologies in stationary applications, which are then compared by calculating a single score. Cycle life is determined as a key factor for cost and CO2 emissions. This is not only due to the required battery replacements but also due to oversizing needed for battery types with low cycle lives to reduce degradation effects. Most Li-ion but also the NaNiCl batteries show a good performance in all assessed applications whereas lead-acid batteries fall behind due to low cycle life and low internal efficiency. For redox-flow batteries, a high dependence on the desired application field is pointed out. [ABSTRACT FROM AUTHOR]

The semaphorins constitute a large family of secreted and membrane-associated proteins that regulate many developmental processes, including neural circuit assembly, bone formation and angiogenesis. Recently, bi-allelic loss-of-function variants in SEMA3A (semaphorin 3A) were identified in a single patient with a particular pattern of multiple congenital anomalies ( MCA). Using homozygosity mapping combined with exome sequencing, we identified a homozygous SEMA3A variant causing a premature stop codon in an 8 year old boy with the same pattern of MCA. The phenotype of these patients is characterized by postnatal short stature, skeletal anomalies of the thorax, a minor congenital heart or vascular defect, camptodactyly, micropenis, and variable additional anomalies. Motor development is delayed in both patients, and intellectual development is delayed in one patient. Our observation of a second case supports the notion that bi-allelic mutations in SEMA3A cause an autosomal recessive type of syndromic short stature. [ABSTRACT FROM AUTHOR]

Palatine (PT) and mandibular torus (MT) have long been of interest to dental researchers and anthropologists, but their aetiology remains unresolved. Some combination of genetic and environmental factors influences their expression, but the relative role of each remains contentious. Previous research has shown that the Greenlandic Norse exhibit exceptionally high frequencies and pronounced expressions of PT and MT. In this regard, they are significantly different from genetically related medieval Scandinavian populations, so environmental factors have to be considered. An earlier study that estimated stable carbon and nitrogen isotope compositions for a Greenlandic Norse sample makes it possible to compare directly PT and MT expression with the relative degree of marine protein intake. For comparative purposes, parallel observations were made on a Greenlandic Inuit sample. Some researchers suggest the intake of marine resources could impact bone development, including torus expression, but our analysis found no significant correlation between PT or MT expression and δ13C and δ15N values in the Norse. In the Inuit, PT expression also showed no relationship to stable isotope compositions. MT size in the Inuit did, however, show a significant inverse relationship with δ13C and δ15N values. As MT size goes up, stable isotope compositions go down. Compared with contemporary European populations, the Greenlandic Norse show very positive isotope compositions, but the Inuit, with their high protein-high fat diet, show significantly higher δ13C and δ15N values than the Norse. It is unclear how this relates to the contrasting findings for MT size and stable isotope values. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Copyright of Trauma und Berufskrankheit is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction Assessment of practical skills in undergraduate dental education has difficulties, including a lack of transparency/objectivity in student evaluations. This prospective study investigated whether agreement between student- and faculty-based assessments increased when students were trained to use the assessment criteria. Materials and methods Assessment criteria were available for 6 tasks in the Phantom course of Conservative Dentistry: Class II cavity preparation, composite restoration, gold and ceramic partial crown preparation, trepanation and access cavity preparation, and root canal filling. Forty-two students were allocated to three different assessment training groups. Students' self-assessments of practical tests were compared with instructors' assessments, depending on training intensity and task type (Pearson's rho, ANOVA, Tukey's post hoc test, Kruskal-Wallis test). Students/instructors were questioned regarding benefits/drawbacks of the criteria. Results Student self-assessments showed either consent (24.2%), overestimation (31%) or underestimation (44.8%). Gender differences were negligible. Regarding passing/failing grades, more intensive training yielded significantly increased agreement only for preparation of gold partial crowns (rho = +0.313, P = 0.044). Ratings exhibited significant differences amongst tasks ( P = 0.002), for example, trepanation assessment had significantly lower differences than gold or ceramic preparation assessments. These discrepancies decreased with increased training. Students consistently reported benefitting most from learning the criteria for gold preparations, followed by composite and ceramic preparations. They also reported that learning the criteria was beneficial for knowledge transfer/feedback. Instructors rated the criteria as helpful for task evaluation and feedback efficiency. Conclusions Pre-defined assessment criteria may increase consistency between student self-assessment and instructor assessment depending on the task, improving transparency and feedback in dental education. [ABSTRACT FROM AUTHOR]

In 2012, a new Ehlers-Danlos ( ED) variant, characterized by severe progressive kyphoscoliosis, neonatal myopathy and hearing loss, with normal urinary lysylpyridinoline to hydroxylysylpyridinoline ratio and most often a recurrent homozygous mutation in the FKBP14 gene, was reported. Because one of the major affected tissues in ED syndrome is the skin, recognition of the cutaneous features of this newly recognized EDS variant is important. We describe the cutaneous phenotype of an adolescent girl harbouring the recurrent homozygous FKBP14 mutation. Distinctive features included molluscoid pseudotumours and multiple isolated comedones. Molluscoid pseudotumours are a characteristic finding in patients with the classic ED variant, but are rarely reported in other variants. We discuss the cutaneous phenotype of FKBP14-deficient EDS and compare it with other kyphoscoliotic variants. [ABSTRACT FROM AUTHOR]

Background and Purpose: Hypoxia and reoxygenation are important determinants of outcome after radiotherapy. HIF-1α is a key molecule involved in cellular response to hypoxia. HIF-1α expression levels have been shown to change after irradiation. The objective of the present study was to explore the prognostic value of HIF-1α expression during fractionated irradiation.Materials and Methods: Six human squamous cell carcinoma models xenografted in nude mice were analysed. Tumours were excised after 3, 5 and 10 fractions. HIF-1α expression was quantified by western blot. For comparative analysis, previously published data on local tumour control data and pimonidazole hypoxic fraction was used.Results: HIF-1α expression in untreated tumours exhibited intertumoural heterogeneity and did not correlate with pimonidazole hypoxic fraction. During fractionated irradiation the majority of tumour models exhibited a decrease in HIF-1α expression, whereas in UT-SCC-5 no change was observed. Neither kinetics nor expression levels during fractionated irradiation correlated with local tumour control.Conclusion: Our data do not support the use of HIF-1α determined during treatment as a biomarker to predict outcome after fractionated irradiation. [ABSTRACT FROM AUTHOR]

Purpose: Anti-EGFR antibody cetuximab (C225) is used in combination with radiotherapy of head and neck squamous cell carcinoma (HNSCC) patients. We investigated whether conjugation of cetuximab with trans-cyclohexyl-diethylene-triamine-pentaacetic acid (CHX-A″-DTPA) and radiolabeling with (90)Yttrium affect the molecular and cellular function of cetuximab and improve its combined effect with external-beam irradiation (EBI).Methods: The following cell lines were used: HNSCC UT5, SAS, FaDu, as well as A43, Chinese hamster ovary cells (CHO), and human skin fibroblast HSF7. Binding affinity and kinetics, specificity, retention, and the combination of (90)Y-cetuximab with EBI were evaluated.Results: Control cetuximab and CHX-A″-DTPA-cetuximab blocked the proliferation activity of UT5 cells. In combination with EBI, CHX-A″-DTPA-cetuximab increased the radiosensitivity of UT5 to a similar degree as control cetuximab did. In contrast, in SAS and HSF7 cells neither proliferation nor radiosensitivity was affected by either of the antibodies. Binding [(90)Y]Y-CHX-A″-DTPA-cetuximab ((90)Y-cetuximab) to EGFR in HNSCC cells occurred time dependently with a maximum binding at 24 h. Retention of (90)Y-cetuximab was similar in both HNSCC cell lines; 24 h after treatment, approximately 90% of bound activity remained in the cell layer. Competition assays, using cell membranes in the absence of an internalized fraction of cetuximab, showed that the cetuximab affinity is not lost as a result of conjugation with CHX-A″-DTPA. Cetuximab and CHX-A″-DTPA-cetuximab blocked EGF-induced Y1068 phosphorylation of EGFR. The lack of an effect of cetuximab on EGF-induced Akt and ERK1/2 phosphorylation and the inhibition of irradiation (IR)-induced Akt and ERK1/2 phosphorylation by cetuximab were not affected by DTPA conjugation. (90)Y-cetuximab in combination with EBI resulted in a pronounced inhibition of colony formation of HNSCC cells.Conclusions: Conjugation of CHX-A″-DTPA to cetuximab does not alter the cellular and biological function of cetuximab. (90)Y-labeling of cetuximab in combination with EBI may improve radiotherapy outcome. [ABSTRACT FROM AUTHOR]

Objective: To evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP) as a diagnostic and prognostic marker for systolic heart failure in the general population.Design: Study participants, randomly selected to be representative of the background population, filled in a heart failure questionnaire and underwent pulse and blood pressure measurements, electrocardiography, echocardiography, and blood sampling and were followed up for a median (range) period of 805 (60-1171) days.Setting: Participants were recruited from four randomly selected general practitioners and were examined in a Copenhagen university hospital.Patients: 382 women and 290 men in four age groups (50-59 (n = 174); 60-69 (n = 204); 70-79 (n = 174); > or = 80 years (n = 120)).Main Outcome Measures: Value of NT-proBNP in evaluating patients with symptoms of heart failure and impaired left ventricular (LV) systolic function; prognostic value of NT-proBNP for mortality and hospital admissions.Results: In 38 (5.6%) participants LV ejection fraction (LVEF) was < or = 40%. NT-proBNP identified patients with symptoms of heart failure and LVEF < or = 40% with a sensitivity of 0.92, a specificity of 0.86, positive and negative predictive values of 0.11 and 1.00, and area under the curve of 0.94. NT-proBNP was the strongest independent predictor of mortality (hazard ratio (HR) = 5.70, p < 0.0001), hospital admissions for heart failure (HR = 13.83, p < 0.0001), and other cardiac admissions (HR = 3.69, p < 0.0001). Mortality (26 v 6, p = 0.0003), heart failure admissions (18 v 2, p = 0.0002), and admissions for other cardiac causes (44 v 13, p < 0.0001) were significantly higher in patients with NT-proBNP above the study median (32.5 pmol/l).Conclusions: Measurement of NT-proBNP may be useful as a screening tool for systolic heart failure in the general population. [ABSTRACT FROM AUTHOR]

Background and Purpose: 4-Methyl-N-methylcathinone (mephedrone) is a synthetic stimulant that acts as a substrate-type releaser at transporters for dopamine (DAT), noradrenaline (NET) and 5-HT (SERT). Upon systemic administration, mephedrone is metabolized to several phase I compounds: the N-demethylated metabolite, 4-methylcathinone (nor-mephedrone); the ring-hydroxylated metabolite, 4-hydroxytolylmephedrone (4-OH-mephedrone); and the reduced keto-metabolite, dihydromephedrone.Experimental Approach: We used in vitro assays to compare the effects of mephedrone and synthetically prepared metabolites on transporter-mediated uptake and release in HEK293 cells expressing human monoamine transporters and in rat brain synaptosomes. In vivo microdialysis was employed to examine the effects of i.v. metabolite injection (1 and 3 mg·kg(-1) ) on extracellular dopamine and 5-HT levels in rat nucleus accumbens.Key Results: In cells expressing transporters, mephedrone and its metabolites inhibited uptake, although dihydromephedrone was weak overall. In cells and synaptosomes, nor-mephedrone and 4-OH-mephedrone served as transportable substrates, inducing release via monoamine transporters. When administered to rats, mephedrone and nor-mephedrone produced elevations in extracellular dopamine and 5-HT, whereas 4-OH-mephedrone did not. Mephedrone and nor-mephedrone, but not 4-OH-mephedrone, induced locomotor activity.Conclusions and Implications: Our results demonstrate that phase I metabolites of mephedrone are transporter substrates (i.e. releasers) at DAT, NET and SERT, but dihydromephedrone is weak in this regard. When administered in vivo, nor-mephedrone increases extracellular dopamine and 5-HT in the brain whereas 4-OH-mephedrone does not, suggesting the latter metabolite does not penetrate the blood-brain barrier. Future studies should examine the pharmacokinetics of nor-mephedrone to determine its possible contribution to the in vivo effects produced by mephedrone. [ABSTRACT FROM AUTHOR]

Purpose: To compare a dedicated simulation model for hypoxia PET against tumor microsections stained for different parameters of the tumor microenvironment. The model can readily be adapted to a variety of conditions, such as different human head and neck squamous cell carcinoma (HNSCC) xenograft tumors. Methods: Nine different HNSCC tumor models were transplanted subcutaneously into nude mice. Tumors were excised and immunoflourescently labeled with pimonidazole, Hoechst 33342, and CD31, providing information on hypoxia, perfusion, and vessel distribution, respectively. Hoechst and CD31 images were used to generate maps of perfused blood vessels on which tissue oxygenation and the accumulation of the hypoxia tracer FMISO were mathematically simulated. The model includes a Michaelis-Menten relation to describe the oxygen consumption inside tissue. The maximum oxygen consumption rate M0 was chosen as the parameter for a tumor-specific optimization as it strongly influences tracer distribution. M0 was optimized on each tumor slice to reach optimum correlations between FMISO concentration 4 h postinjection and pimonidazole staining intensity. Results: After optimization, high pixel-based correlations up to R² = 0.85 were found for individual tissue sections. Experimental pimonidazole images and FMISO simulations showed good visual agreement, confirming the validity of the approach. Median correlations per tumor model varied significantly (p < 0.05), with R² ranging from 0.20 to 0.54. The optimum maximum oxygen consumption rate M0 differed significantly (p < 0.05) between tumor models, ranging from 2.4 to 5.2 mm Hg/s. Conclusions: It is feasible to simulate FMISO distributions that match the pimonidazole retention patterns observed in vivo. Good agreement was obtained for multiple tumor models by optimizing the oxygen consumption rate, M0, whose optimum value differed significantly between tumor models. [ABSTRACT FROM AUTHOR]

Background CADASIL is an inherited systemic small vessel disease, the affected status of brain vessels leading to subcortical vascular dementia. The defective gene is NOTCH3 in which over 230 different pathogenic mutations have been identified. The clinical course of CADASIL is highly variable even within families. Previous studies have shown that additional genetic factors modify the phenotype. Aims and methods Altogether, 134 Finnish CADASIL patients with p.Arg133Cys mutation were analysed for possible associations between the apolipoprotein E ( APOE) genotype, angiotensinogen ( AGT) p.Met268Thr polymorphism or neutral p.Ala202Ala NOTCH3 polymorphism and earlier first-ever stroke or migraine. Results We found no association between the APOE genotypes, AGT polymorphism, NOTCH3 polymorphism and earlier first-ever stroke or migraine. Conclusions The APOE, AGT and NOTCH3 polymorphism did not modify the onset of strokes or migraine in our CADASIL sample, which is one of the largest mutationally homogenous CADASIL populations published to date. International collaboration, pooled analyses and genomewide approaches are warranted to identify the genetic factors that modify the highly variable CADASIL phenotype. [ABSTRACT FROM AUTHOR]

An adequate information basis is important for designing and evaluating policy measures to reach international climate goals. Current energy statistics are primarily based on the UN's International Recommendations for Energy Statistics (IRES). We have examined changes in the energy system and how they can be depicted in energy balances, using IRES methodology as the benchmark. We have found that the increasing variety in energy generation through prosumers cannot be illustrated currently. In the manufacturing industries, state-of-the-art balancing limits the depiction of autoproducers' output other than electricity and heat. Their numbers will increase due to hydrogen demand for decarbonisation, among others. In efforts to inform necessary decision-making regarding decarbonisation, an additional focus must also be set on the representation of energy services in demand. Including useful energy categories allows the development of specific useful energy demands, enabling application-driven technology and energy carrier deployment. To remedy the identified shortcomings, the Sectoral Gross Energy Balance Border enables the identification of involved economic units (e.g. manufacturing industry sectors, households, services and energy industries). It features a sector-interrelated approach, in which energy flows follow the physical location of energy operation. Thereby, energy balances can illustrate the multiple transformations in the energy system and better inform policymaking. • Current international energy balancing is challenged by the developments of the energy transition. • The introduction of a novel energy balance border can remedy this issue. • Energy generation, transformation and demand are visualised by involved economic unit. • Application in an analysis of a fully decarbonised case study of Austria. [ABSTRACT FROM AUTHOR]

One zebu bull of 365 kg live weight was treated along the back line with 36 mL of fipronil as a pour-on formulation. Long-lasting mortalities of Glossina palpalis gambiensis were recorded despite exposure to sunlight and regular rinsing with 50 L of water during the following 5 months. Significantly higher mortalities were still observed even 140, 170 and 190 days after treatment following their triple releases or triple feeding of caged tsetse on the treated bull. Mortalities of 70, 80 and 44 %, respectively, were recorded after 15 days of observation. This contrasted with the mortalities of control flies that were released in the presence of the untreated bull or fed in cages on the animal, amounting to 20 and twice 10 % after 170 and 190 days. The feeding successes of the released or caged flies were higher than 95 % and did not differ between control and experimental groups, indicating no repulsive or irritant effects of fipronil. The findings of this study are discussed, particularly in view of the potential of fipronil as an effective means for tsetse control. [ABSTRACT FROM AUTHOR]

The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed. [ABSTRACT FROM AUTHOR]

Background and Purpose Methcathinone ( MCAT) is a potent monoamine releaser and parent compound to emerging drugs of abuse including mephedrone (4- CH3 MCAT), the para-methyl analogue of MCAT. This study examined quantitative structure-activity relationships ( QSAR) for MCAT and six para-substituted MCAT analogues on (a) in vitro potency to promote monoamine release via dopamine and serotonin transporters ( DAT and SERT, respectively), and (b) in vivo modulation of intracranial self-stimulation ( ICSS), a behavioural procedure used to evaluate abuse potential. Neurochemical and behavioural effects were correlated with steric ( Es), electronic ( σp) and lipophilic ( πp) parameters of the para substituents. Experimental Approach For neurochemical studies, drug effects on monoamine release through DAT and SERT were evaluated in rat brain synaptosomes. For behavioural studies, drug effects were tested in male Sprague- Dawley rats implanted with electrodes targeting the medial forebrain bundle and trained to lever-press for electrical brain stimulation. Key Results MCAT and all six para-substituted analogues increased monoamine release via DAT and SERT and dose- and time-dependently modulated ICSS. In vitro selectivity for DAT versus SERT correlated with in vivo efficacy to produce abuse-related ICSS facilitation. In addition, the Es values of the para substituents correlated with both selectivity for DAT versus SERT and magnitude of ICSS facilitation. Conclusions and Implications Selectivity for DAT versus SERT in vitro is a key determinant of abuse-related ICSS facilitation by these MCAT analogues, and steric aspects of the para substituent of the MCAT scaffold (indicated by Es) are key determinants of this selectivity. [ABSTRACT FROM AUTHOR]

Background and Purpose There is growing concern over the abuse of certain psychostimulant methcathinone ( MCAT) analogues. This study extends an initial quantitative structure-activity relationship ( QSAR) investigation that demonstrated important steric considerations of seven 4- (or para-)substituted analogues of MCAT. Specifically, the steric character ( Taft's steric ES) of the 4-position substituent affected in vitro potency to induce monoamine release via dopamine and 5-HT transporters ( DAT and SERT) and in vivo modulation of intracranial self-stimulation ( ICSS). Here, we have assessed the effects of other steric properties of the 4-position substituents. Experimental Approach Definitive steric parameters that more explicitly focus on the volume, width and length of the MCAT 4-position substituents were assessed. In addition, homology models of human DAT and human SERT based upon the crystallized D rosophila DAT were constructed and docking studies were performed, followed by hydropathic interaction ( HINT) analysis of the docking results. Key Results The potency of seven MCAT analogues at DAT was negatively correlated with the volume and maximal width of their 4-position substituents, whereas potency at SERT increased as substituent volume and length increased. SERT/ DAT selectivity, as well as abuse-related drug effects in the ICSS procedure, also correlated with the same parameters. Docking solutions offered a means of visualizing these findings. Conclusions and Implications These results suggest that steric aspects of the 4-position substituents of MCAT analogues are key determinants of their action and selectivity, and that the hydrophobic nature of these substituents is involved in their potency at SERT. [ABSTRACT FROM AUTHOR]

Background Myelin oligodendrocyte glycoprotein (MOG) antibodies have been recently described in children with acute disseminating encephalomyelitis (ADEM), but the clinical and neuroradiological characterisation of this subgroup is lacking Objective To compare the clinical and neuroradiological features of paediatric ADEM with and without MOG antibodies. Methods Clinical course, cerebrospinal fluid (CSF)-, MRI studies, outcome and MOG status of 33 paediatric ADEM prospectively studied were reviewed. Results MOG antibodies (median 1:2560; range 1:160-1:20 480) were detected in 19 children with ADEM. The majority of children showed a decline of serum MOG-IgG titres over time. Children wit h MOG antibodies did not differ in their age at presentation, sex ratio, the presence of oligoclonal bands, clinical symptoms or initial severity, apart from a higher CSF cell count (p=0.038), compared with children without MOG antibodies. In addition, further relapsing demyelinating episodes associated with MOG antibodies were observed only in children with MOG antibodies. All 19 children with MOG antibodies had a uniform MRI pattern, characterised by large, hazy and bilateral lesions and the absence of atypical MRI features (eg, mainly small lesions, well-defined lesions), which was significantly different compared to that of children without MOG antibodies (p=0.003; and p=0.032, respectively). In addition, children with MOG antibodies had involvement of more anatomical areas (p=0.035) including the myelon characterised by a longitudinally extensive transverse myelitis (p=0.003), more often a complete resolution of lesions (p=0.036) and a better outcome (p=0.038). Conclusions Patients with ADEM with MOG antibodies in our cohort had a uniform MRI characterised by large, bilateral and widespread lesions with an increased frequency of longitudinal extensive transverse myelitis and a favourable clinical outcome in contrast to children lacking MOG antibodies. [ABSTRACT FROM AUTHOR]

Serotonin and oxytocin influence aggressive and anxiety-like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesized that oxytocin acts on raphe neurons to influence serotonergically mediated anxiety-like, aggressive and parental care behaviors. We eliminated expression of the oxytocin receptor in raphe neurons by crossing mice expressing Cre recombinase under control of the serotonin transporter promoter (Slc6a4) with our conditional oxytocin receptor knockout line. The knockout mice generated by this cross are normal across a range of behavioral measures: there are no effects for either sex on locomotion in an open-field, olfactory habituation/dishabituation or, surprisingly, anxiety-like behaviors in the elevated O and plus mazes. There was a profound deficit in male aggression: only one of 11 raphe oxytocin receptor knockouts showed any aggressive behavior, compared to 8 of 11 wildtypes. In contrast, female knockouts displayed no deficits in maternal behavior or aggression. Our results show that oxytocin, via its effects on raphe neurons, is a key regulator of resident-intruder aggression in males but not maternal aggression. Furthermore, this reduction in male aggression is quite different from the effects reported previously after forebrain or total elimination of oxytocin receptors. Finally, we conclude that when constitutively eliminated, oxytocin receptors expressed by serotonin cells do not contribute to baseline anxiety-like behaviors or maternal care. [ABSTRACT FROM AUTHOR]