Special electronic devices which contain boundary-scan facilities that are compatible with the IEEE Standard 1149.1 and which were originally developed to facilitate the test of electronic equipment ...during board production offer also an excellent tool for permanent control of even large electronic systems. Here the control of a part of the electronics of a complex High-Energy Physics experiment is described.
We report on the growth chemistry and properties of nanocrystalline Si:H (nc-Si:H) films and devices grown using three different growth techniques ECR plasma, VHF plasma and hot wire. It is found ...that the films grown using ECR plasma deposition are predominantly oriented, whereas the orientation depends upon pressure, growth rate and ion bombardment in films grown using VHF plasma. Remote hot wire grown films also show both and orientations. It is also found that all the films are stressed, with both compressive and tensile stress being present in the same film. The stress depends upon the grain size. Stress can explain the shift in Raman peak from its nominal value of 520 cm/sup -1/. Devices with good minority carrier diffusion lengths can be fabricated in both and materials. Electron mobilities are in the range of 0.5-1.0 cm/sup 2//Vs.
Patients with prognathism and retrognathism show extensive morphologic changes after orthognathic surgery. The inability of muscles to adapt adequately might be one reason for observed relapses. The ...aim of this prospective study was to analyze the regulation of functional genes after surgery and changes in myosin heavy chain (MyHC) isoform expression, a potential molecular marker profile for inadequate muscle adaptation. 29 adult patients with prognathic and retrognathic mandibles were involved. A total of 232 muscle biopsies were taken from both masseter muscles presurgically and 6 months later. The mRNA expression of “mechano growth factor” (MGF), myostatin, and 3 MyHC isoforms were quantified by real-time polymerase chain reaction. The MGF mRNA was significantly up-regulated ( P < .005), whereas myostatin mRNA showed no significant regulation. There was a shift in MyHC isoform expression. The MyHC-I mRNA was decreased ( P < .005), whereas MyHC-IIa mRNA was increased ( P < .005). The coherence of increased MGF expression and MyHC isoform shift 6 months after orthognatic surgery indicates an adequate muscle adaptation and higher mastication activity.
Several recent developments in linear accelerator-based radiation therapy (RT) such as fast multileaf collimators, accelerated intensity modulation paradigms like volumeric modulated arc therapy and ...flattening filter-free (FFF) high-dose-rate therapy have dramatically shortened the duration of treatment fractions. Deliverable photon dose distributions have approached physical complexity limits as a consequence of precise dose calculation algorithms and online 3-dimensional image guided patient positioning (image guided RT). Simultaneously, beam quality and treatment speed have continuously been improved in particle beam therapy, especially for scanned particle beams. Applying complex treatment plans with steep dose gradients requires strategies to mitigate and compensate for motion effects in general, particularly breathing motion. Intrafractional breathing-related motion results in uncertainties in dose delivery and thus in target coverage. As a consequence, generous margins have been used, which, in turn, increases exposure to organs at risk. Particle therapy, particularly with scanned beams, poses additional problems such as interplay effects and range uncertainties. Among advanced strategies to compensate breathing motion such as beam gating and tracking, deep inspiration breath hold (DIBH) gating is particularly advantageous in several respects, not only for hypofractionated, high single-dose stereotactic body RT of lung, liver, and upper abdominal lesions but also for normofractionated treatment of thoracic tumors such as lung cancer, mediastinal lymphomas, and breast cancer. This review provides an in-depth discussion of the rationale and technical implementation of DIBH gating for hypofractionated and normofractionated RT of intrathoracic and upper abdominal tumors in photon and proton RT.
The World Health Organization's strategy toward healthy aging fosters person-centered integrated care sustained by eHealth systems. However, there is a need for standardized frameworks or platforms ...accommodating and interconnecting multiple of these systems while ensuring secure, relevant, fair, trust-based data sharing and use. The H2020 project GATEKEEPER aims to implement and test an open-source, European, standard-based, interoperable, and secure framework serving broad populations of aging citizens with heterogeneous health needs.
We aim to describe the rationale for the selection of an optimal group of settings for the multinational large-scale piloting of the GATEKEEPER platform.
The selection of implementation sites and reference use cases (RUCs) was based on the adoption of a double stratification pyramid reflecting the overall health of target populations and the intensity of proposed interventions; the identification of a principles guiding implementation site selection; and the elaboration of guidelines for RUC selection, ensuring clinical relevance and scientific excellence while covering the whole spectrum of citizen complexities and intervention intensities.
Seven European countries were selected, covering Europe's geographical and socioeconomic heterogeneity: Cyprus, Germany, Greece, Italy, Poland, Spain, and the United Kingdom. These were complemented by the following 3 Asian pilots: Hong Kong, Singapore, and Taiwan. Implementation sites consisted of local ecosystems, including health care organizations and partners from industry, civil society, academia, and government, prioritizing the highly rated European Innovation Partnership on Active and Healthy Aging reference sites. RUCs covered the whole spectrum of chronic diseases, citizen complexities, and intervention intensities while privileging clinical relevance and scientific rigor. These included lifestyle-related early detection and interventions, using artificial intelligence-based digital coaches to promote healthy lifestyle and delay the onset or worsening of chronic diseases in healthy citizens; chronic obstructive pulmonary disease and heart failure decompensations management, proposing integrated care management based on advanced wearable monitoring and machine learning (ML) to predict decompensations; management of glycemic status in diabetes mellitus, based on beat to beat monitoring and short-term ML-based prediction of glycemic dynamics; treatment decision support systems for Parkinson disease, continuously monitoring motor and nonmotor complications to trigger enhanced treatment strategies; primary and secondary stroke prevention, using a coaching app and educational simulations with virtual and augmented reality; management of multimorbid older patients or patients with cancer, exploring novel chronic care models based on digital coaching, and advanced monitoring and ML; high blood pressure management, with ML-based predictions based on different intensities of monitoring through self-managed apps; and COVID-19 management, with integrated management tools limiting physical contact among actors.
This paper provides a methodology for selecting adequate settings for the large-scale piloting of eHealth frameworks and exemplifies with the decisions taken in GATEKEEPER the current views of the WHO and European Commission while moving forward toward a European Data Space.
Summary
Background
Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous group of rare Mendelian skin disorders characterized by cornification and differentiation defects of ...keratinocytes. Mutations in nine genes including PNPLA1 are known to cause nonsyndromic forms of ARCI. To date, only 10 distinct pathogenic mutations in PNPLA1 have been reported.
Objectives
To identify new causative PNPLA1 mutations.
Methods
We screened genetically unresolved cases, including our ARCI collection, comprising more than 700 families. Screening for mutations was performed either by direct Sanger sequencing or in combination with a multigene panel, followed by sequence and mutation analysis.
Results
Here we report on 16 novel mutations present in patients from 17 families. While all previously reported mutations and most of our novel mutations are located within the core patatin domain, we report five novel PNPLA1 mutations that are downstream of this domain. Thus, as recently described for PNPLA2, we hypothesize that a region larger than the core domain is required for full enzymatic activity of PNPLA1 in human skin barrier formation.
Conclusions
We estimate the frequency of PNPLA1 mutations among patients with ARCI to be around 3%. Most of our patients were born as collodion babies and showed a relatively mild ichthyosis phenotype. In four unrelated patients we observed a cyclic scaling course, which seems to be a potential phenotypic variation in a small percentage of patients with PNPLA1 mutations. The variability of the clinical manifestations and the lack of typical clinical features are specific for patients with PNPLA1 mutations, and emphasize the importance of DNA sequencing for differential diagnosis of ARCIs.
What's already known about this topic?
Only five reports with 10 distinct PNPLA1 mutations causing autosomal recessive congenital ichthyosis (ARCI) have been described.
Relatively little is known about the type and localization of mutations in PNPLA1 that cause ARCI.
What does this study add?
This is the first comprehensive series of PNPLA1 mutations, from 18 patients with autosomal recessive congenital ichthyosis.
The results of this study provide important conclusions about the localization of disease‐causing mutations in PNPLA1 and the resulting phenotype, including clinical variations.
What is the translational message?
Multigene panels and knowledge about causative PNPLA1 mutations will lead to progress in deciphering the function of PNPLA1.
This might facilitate diagnosis and provide a basis for novel therapeutic strategies in patients with PNPLA1 mutations.
Respond to this article
Linked Comment: Uitto et al. Br J Dermatol 2017; 177:342–343
Plain language summary available online
This prospective multicentre phase II study characterises the toxicity and activity of first-line capecitabine and oxaliplatin combination therapy (CAPOX) in advanced biliary system adenocarcinomas. ...Patients received oxaliplatin (130 mg m(-2), day 1) plus capecitabine (1000 mg m(-2) b.i.d., days 1-14) every 3 weeks. Patients were stratified prospectively into two groups based on location of the primary (gallbladder carcinoma (GBC) or extrahepatic cholangiocarcinoma (ECC) versus intrahepatic mass-forming type cholangiocarcinoma (ICC)). Sixty-five patients were evaluable. The response rate in 47 patients with GBC/ECC was 27% (4% complete responses), and in 23 patients (49%) stable disease (SD) was encountered. In 18 patients with ICC, we observed no objective responses, but 6 patients (33%) had SD. Median survival was 12.8 months (95% CI, 10.0-15.6) for patients with GBC or ECC (GBC: 8.2 months; 95% CI, 4.3-11.7; ECC: 16.8 months; 95% CI, 12.7-20.5), and 5.2 months (95% CI, 0.6-9.8) for ICC patients. In both cohorts, therapy was well tolerated. The most common grade 3-4 toxicity was peripheral sensory neuropathy (11 patients). Our data suggest that the CAPOX regimen is a well-tolerated and active treatment option for advanced ECC and GBC but might produce poorer results for ICC.
PDF
