Background Molecular data of histologically classified oligodendrogliomas are available offering the possibility to stratify these human brain tumors into clinically relevant molecular subtypes. Methods Gene copy number, mutation, and expression data of 193 histologically classified oligodendrogliomas from The Cancer Genome Atlas (TCGA) were analyzed by well-established computational approaches (unsupervised clustering, statistical testing, network inference). Results We applied hierarchical clustering to tumor gene copy number profiles and revealed three molecular subgroups within histologically classified oligodendrogliomas. We further screened these subgroups for molecular glioma markers (1p/19q co-deletion, IDH mutation, gain of chromosome 7 and loss of chromosome 10) and found that our subgroups largely resemble known molecular glioma subtypes. We excluded glioblastoma-like tumors (7a10d subgroup) and derived a gene expression signature distinguishing histologically classified oligodendrogliomas with concurrent 1p/19q co-deletion and IDH mutation (1p/19q subgroup) from those with predominant IDH mutation alone (IDHme subgroup). Interestingly, many signature genes were part of signaling pathways involved in the regulation of cell proliferation, differentiation, migration, and cell-cell contacts. We further learned a gene regulatory network associated with the gene expression signature revealing novel putative major regulators with functions in cytoskeleton remodeling (e.g. APBB1IP, VAV1, ARPC1B), apoptosis (CCNL2, CREB3L1), and neural development (e.g. MYTIL, SCRT1, MEF2C) potentially contributing to the manifestation of differences between both subgroups. Moreover, we revealed characteristic expression differences of several HOX and SOX transcription factors suggesting the activity of different glioma stemness programs in both subgroups. Conclusions We show that gene copy number profiles alone are sufficient to derive molecular subgroups of histologically classified oligodendrogliomas that are well-embedded into general glioma classification schemes. Moreover, our revealed novel putative major regulators and characteristic stemness signatures indicate that different developmental programs might be active in these subgroups, providing a basis for future studies.

Background Polypharmacy is often prescribed for bipolar disorder, yet medication non-adherence remains a serious problem. This study investigated the regularity in the daily dosage taken of mood stabilizers and second generation antipsychotics. Methods Daily self-reported data on medications taken and mood were available from 241 patients with a diagnosis of bipolar disorder who received treatment as usual. Patients who took the same mood stabilizer or second generation antipsychotic for ≥ 100 days were included. Approximate entropy was used to determine serial regularity in daily dosage taken. Generalized estimating equations were used to estimate if demographic or clinical variables were associated with regularity. Results There were 422 analysis periods available from the 241 patients. Patients took drugs on 84.4% of days. Considerable irregularity was found, mostly due to single-day omissions and dosage changes. Drug holidays (missing 3 or more consecutive days) were found in 35.8% of the analysis periods. Irregularity was associated with an increasing total number of psychotropic drugs taken (p = 0.009), the pill burden (p = 0.026), and the percent of days depressed (p = 0.049). Conclusion Despite low missing percent of days, daily drug dosage may be irregular primarily due to single day omissions and dosage changes. Drug holidays are common. Physicians should expect to see partial adherence in clinical practice, especially with complex drug regimens. Daily dosage irregularity may impact the continuity of drug action, contribute to individual variation in treatment response, and needs further study.

Cloud computing has a significant impact on information and communication technology (ICT) and is one of the most important technological drivers of the digitalization of enterprises. However, due to the increasing dissemination of cloud services and the growing number of cloud service providers (CSPs), the uncertainty and risks for user companies in adopting cloud services have also increased. In this paper, we address those aspects from the perspective of the CSPs. We identified relevant literature and studies and conducted interviews with business experts from 16 German CSPs. In our results, we present current customer requirements and barriers to using cloud services from a provider’s viewpoint and identify the actions of and obstacles for CSPs in meeting the needs and constraints of the customers. Finally, we identify current and future challenges for CSPs in dealing with customer requirements and barriers by addressing their root causes. One of the main challenges from the CSPs’ perspective is addressing customers appropriately and building relationships of trust. This also “forces” changes in the sales processes. In this process, the essential challenges can be identified as an increase in complexity and a simultaneous simplification of specific sales activities. Therefore, the necessity arises for the continuous support of business relationships through value-adding and additional services. However, this results in another challenge for the CSPs – Namely, to find the right balance between standardization and meeting customer-specific requirements. In our paper, we show that the perspective of the CSPs is rarely discussed in the literature. Nevertheless, understanding the perceptions of the providers and their actions and measures is essential for future research activities in the field of cloud service selection. Comparing the customers’ perspectives and viewpoints with the CSPs’ actions will enhance the development of a holistic selection approach for future cloud projects. Therefore, our paper’s contribution to research is also the identification of this missing integration.

The subject of this splitted article is the commissioning of a new application that may be part of a processing machine. At the example of the intermittent transport of small sized goods, for example, chocolate bars, ideas for increasing the maximum machine performance are discussed. Therefore, optimal process motion profiles are synthesised with the help of a computer simulation. In the first part of the paper, the modelling of the process was shown. This second part focusses on implementing the simulated motion approaches on an experimental test rig, whereby the new motion approach is compared to the conventional approach. Hence, the increasing of the performance can be proven. Eventually, possibilities for an online process control are observed which are necessary to prevent unstable process conditions.

Even though deficits in inhibitory control and conflict monitoring are well-known in ADHD, factors that further modulate these functions remain to be elucidated. One factor that may be of considerable importance is how inhibitory control is modulated by multisensory information processing. We examined the influence of concurrent auditory conflicting or redundant information on visually triggered response inhibition processes in adolescent ADHD patients and healthy controls. We combined high-density event-related potential (ERP) recordings with source localization to delineate the functional neuroanatomical basis of the involved neurophysiological processes. In comparison to controls, response inhibition (RI) processes in ADHD were compromised in conflicting conditions, but showed no differences to controls when redundant or no concurrent auditory information was presented. These effects were reflected by modulations at the response selection stage (P3 ERP) in the medial frontal gyrus (BA32), but not at the attentional selection (P1, N1 ERPs) or resource allocation level (P2 ERP). Conflicting information during RI exerts its influences in adolescent ADHD via response selection mechanisms, but not via attentional selection. It is not the mere presence of concurrent information, but the presence of conflicting information during RI that may destabilize goal shielding processes in medial frontal cortical regions, by means of increasing the automaticity of response tendencies. The occurring RI deficits might relate to the increased impulsivity in adolescent ADHD and a corresponding vulnerability to react to an increased automaticity of pre-potent response tendencies. ADHD patients show a bias to a specific content of information which can modulate inhibitory control.

Background Creutzfeldt–Jakob disease is a rare and rapidly fatal neurodegenerative disease. Since clinicians may see only very few cases during their professional career, it is important to be familiar with the clinical presentation and progression, to perform appropriate investigations, and allow for quick diagnosis. Case presentation A 73-year-old British Caucasian woman presented with acute confusion of 2 weeks’ duration on a background of low mood following a recent bereavement. Her symptoms included behavioral change, visual hallucinations, vertigo, and recent falls. She was mildly confused, with left-sided hyperreflexia, a wide-based gait, and intention tremor in her left upper limb. Initial blood tests, computed tomography, and magnetic resonance imaging of her brain showed no significant abnormality. Following admission, she had rapid cognitive decline and developed florid and progressive neurological signs; a diagnosis of prion disease was suspected. A lumbar puncture was performed; cerebrospinal fluid was positive for 14–3-3 protein, real-time quaking-induced conversion, and raised levels of s-100b proteins were detected. An electroencephalogram showed bilateral periodic triphasic waves on a slow background. The diagnosis of probable Creutzfeldt–Jakob disease was made. Conclusions This case report highlights key features in the initial presentation and clinical development of a rare but invariably rapidly progressive and fatal disease. It emphasizes the importance of considering a unifying diagnosis for multifaceted clinical presentations. Although it is very rare, Creutzfeldt–Jakob disease should be considered a diagnosis for a mixed neuropsychiatric presentation, particularly with rapid progressive cognitive decline and development of neurological signs. However, to avoid overlooking early signal change on magnetic resonance imaging, it is important to take diffusion-weighted magnetic resonance imaging for all patients with neuropsychological symptoms. Importantly, early diagnosis also ensures the arrangement of suitable contamination control measures to minimize the risk of infection to health care professionals and other patients.

The past years have seen an incredible increase in the quality and success rates of treatments in pediatric medicine. One of the resulting major challenges refers to the management of primary or secondary residual executive function deficits in affected children. These deficits lead to problems in the ability to acquire, understand, and apply abstract and complex knowledge and to plan, direct, and control actions. Executive functions deficits are important to consider because they are highly predictive of functioning in social and academic aspects of daily life. We argue that current clinical practice does not sufficiently account for the complex cognitive processes in this population. This is because widely applied pharmacological interventions only rarely account for the complexity of the underlying neuronal mechanisms and do not fit well into possibly powerful “individualized medicine” approaches. Novel treatment approaches targeting deficits in executive functions in seriously ill children could focus on neuronal oscillations, as these have some specific relations to different aspects of executive function. Importantly, such treatment approaches can be individually tailored to the individuals’ deficits and can be transferred into home-treatment or e-health solutions. These approaches are easy-to-use, can be easily integrated into daily life, and are becoming increasingly cost-effective.

The code observable of global navigation satellite systems (GNSS) is influenced by group delay variations (GDV) of transmitter and receiver antennas. For the Global Positioning System (GPS), the variations can sum up to 1 m in the ionosphere-free linear combination and thus can significantly affect precise code applications. The contribution of the GPS transmitters can amount to 0.8 m peak-to-peak over the entire nadir angle range. To verify the assumption of their time-invariance, we determined daily individual satellite GDV for GPS transmitter antennas over a period of more than two years. Dual-frequency observations of globally distributed reference stations and their multipath combination form the basis for our analysis. The resulting GPS GDV are stable on the level of a few centimeters for C1, P2, and for the ionosphere-free linear combination. Our study reveals that the inconsistencies of the GDV of space vehicle number (SVN) 55 with respect to earlier studies are not caused by temporal instabilities, but are rather related to receiver properties.

Background There are a few epidemiological studies that (1) link increased ambient air pollution (AP) with an increase in lung cancer incidence rates and (2) investigate whether residing in green spaces could be protective against cancer. However, it is completely unclear whether other forms of cancer are also affected by AP and if residential green spaces could lower cancer incidence rates in general. Therefore, the objective was to estimate whether AP and green space are associated with several cancer types. Methods The analysis was based on routine health care data from around 1.9 million people from Saxony who were free of cancer in 2008 and 2009. Incident cancer cases (2010–2014) of mouth and throat, skin (non-melanoma skin cancer - NMSC), prostate, breast, and colorectum were defined as: (1) one inpatient diagnosis, or (2) two outpatient diagnoses in two different quarters within one year and a specific treatment or death within two quarters after the diagnosis. Exposures, derived from freely available 3rd party data, included particulate matter with aerodynamic diameter of less than 10 μm (PM10) and nitrogen dioxide (N02) as well as green space (Normalized Difference Vegetation Index - NDVI). Associations between air pollutants, green space, and cancer incidence were assessed by multilevel Poisson models. Age, sex, physician contacts, short- and long-term unemployment, population density, and having an alcohol-related disorder were considered as potential confounders. Results Three thousand one hundred seven people developed mouth and throat cancer, 33,178 NMSC, 9611 prostate cancer, 9577 breast cancer, and 11,975 colorectal cancer during the follow-up period (2010–2014). An increase in PM10 of 10 μg/m3 was associated with a 53% increase in relative risk (RR) of mouth and throat cancer and a 52% increase in RR of NMSC. Prostate and breast cancer were modestly associated with PM10 with an increase in RR of 23 and 19%, respectively. The associations with N02 were in the same direction as PM10 but the effect estimates were much lower (7–24%). A 10% increase in NDVI was most protective of mouth and throat cancer (− 11% RR) and of NMSC (− 16% RR). Colorectal cancer was not affected by any of the exposures. Conclusions In addition to the studies carried out so far, this study was able to provide evidence that higher ambient AP levels increase the risk of mouth and throat cancer as well as of NMSC and that a higher residential green space level might have a protective effect for NMSC in areas with low to moderate UV intensity. Nevertheless, we cannot rule out residual confounding by socioeconomic or smoking status.

Time and circumstances for the disappearance of Neanderthals and its relationship with the advent of Modern Humans are not yet sufficiently resolved, especially in case of the Iberian Peninsula. Reconstructing palaeoenvironmental conditions during the last glacial period is crucial to clarifying whether climate deteriorations or competition and contacts with Modern Humans played the pivotal role in driving Neanderthals to extinction. A high-resolution loess record from the Upper Tagus Basin in central Spain demonstrates that the Neanderthal abandonment of inner Iberian territories 42 kyr ago coincided with the evolvement of hostile environmental conditions, while archaeological evidence testifies that this desertion took place regardless of modern humans’ activities. According to stratigraphic findings and stable isotope analyses, this period corresponded to the driest environmental conditions of the last glacial apart from an even drier period linked to Heinrich Stadial 3. Our results show that during Marine Isotope Stages (MIS) 4 and 2 climate deteriorations in interior Iberia temporally coincided with northern hemisphere cold periods (Heinrich stadials). Solely during the middle MIS 3, in a period surrounding 42 kyr ago, this relation seems not straightforward, which may demonstrate the complexity of terrestrial climate conditions during glacial periods.