Supporting the Development of Cyber-Physical Systems with Natural Language Processing: A Report

Software has become the driving force for innovations in any technical system that observes the environment with different sensors and influence it by controlling a number of actuators; nowadays called Cyber-Physical System (CPS). The development of such systems is inherently inter-disciplinary and often contains a number of independent subsystems. Due to this diversity, the majority of development information is expressed in natural language artifacts of all kinds. In this paper, we report on recent results that our group has developed to support engineers of CPSs in working with the large amount of information expressed in natural language. We cover the topics of automatic knowledge extraction, expert systems, and automatic requirements classification. Furthermore, we envision that natural language processing will be a key component to connect requirements with simulation models and to explain tool-based decisions. We see both areas as promising for supporting engineers of CPSs in the future

Is 24/7 remote patient management in heart failure necessary? Results of the telemedical emergency service used in the TIM‐HF and in the TIM‐HF2 trials

Aims: Telemedical emergency services for heart failure (HF) patients are usually provided during business hours. However, many emergencies occur outside of business hours. This study evaluates if a 24/7 telemedical emergency service is needed for the remote management of high-risk HF patients. Methods: and results The study included 1119 patients merged from the TIM-HF and TIM-HF2 trials [age 69 +/- 11, 73% male, left ventricular ejection fraction 37% +/- 13, 557 New York Heart Association (NYHA) II/562 NYHA III]. Patients received a 24/7 physician-guided emergency service provided by the telemedical centre (TMC) in addition to remote management within business hours. During emergency calls, patient status, symptoms, electronic patient record, and instant telemonitoring data were evaluated by the TMC physician. Following diagnosis, patients were referred for hospital admission or instructed to stay at home. Apart from the TMC, patients could place a call to the public emergency service at any time. Seven hundred sixty-eight emergency calls were placed over 1383 patient years (0.56 calls/patient year). Five hundred twenty-six calls (69%) occurred outside business hours. There were 146 (19%) emergency calls for worsening HF, 297 (39%) other cardiovascular, and 325 (42%) non-cardiac causes, with a similar pattern inside and outside business hours. Of the 1119 patients, 417 (37%) placed at least one emergency call. Patients with NYHA Class III, higher N-terminal prohormone of brain natriuretic peptide (>1.400 pg/mL) levels, ischaemic aetiology of HF, implanted defibrillator, and impaired renal function had a higher probability of placing emergency calls. During study follow-up, patients who made an emergency call had a higher all-cause mortality (22% vs. 11%, P = 0.007 in TIM-HF; 16% vs. 4%, P < 0.001 in TIM-HF2) and more unplanned hospitalizations (324 vs. 162, P < 0.001 in TIM-HF; 545 vs. 180, P < 0.001 in TIM-HF2). Of the total 1,211 unplanned hospital admissions, 492 (41%) were initiated by a patient emergency call. Three hundred seventy-nine calls (49%) were placed to the TMC, whereas 389 calls (51%) were made to the public emergency service. Three hundred twenty-six (84%) of the calls to the public emergency service resulted in acute hospitalizations. The TMC initiated 202 (53%) hospital admissions; 177 (47%) patients were advised to stay at home. All patients that remained at home were alive during a prespecified safety period of 7 days post-call. Diagnoses made by the TMC physician were confirmed in 83% of cases by the hospital. Conclusion: A telemedical emergency service for high-risk HF patients is safe and should operate 24/7 to reduce unplanned hospitalizations. Emergency calls could be considered as a marker for higher morbidity and mortality

Mix it - cograzing with cattle reduces broiler losses and increases broiler range use

Pasture access allows broilers to perform a wide range of behaviors and is a prerequisite in organic poultry production, but exposes broilers to various potential hazards including predators. Co-grazing broilers with cattle can reduce land use and could offer protection from avian predation. Thus, we aimed to assess the effects of co-grazing on broiler losses, range use, performance, contact dermatitis and broilers’ manipulation of cow pats. To this end, across 5 replicates we compared each a treatment group of 54 to 61 broilers co-grazing with 10 young cattle and a similar sized control group of broilers on a pasture which had been grazed by cattle 2 weeks prior. Broilers had pasture access during civil daylight and were locked in the coop overnight. Continuous video recordings of the pastures were used to identify the cause when broilers were missing or found dead. On 2 days per week in 4 replicates, broiler distribution in the pasture and maintenance behaviour (i.e. foraging, standing, lying, locomotion) were observed directly using instantaneous scan sampling. Based on the broilers’ distance to the coop we calculated a group Ranging Distance Index (RDI). Cow pats were assessed weekly and contact dermatitis was scored before slaughter. Broilers in the treatment groups ranged further (p = 0.003) and higher percentages of birds tended to be outside (p = 0.09) compared to the control groups. Broiler losses due to predatory birds were consistently lower in treatment (median, range: 1, 0 to 3) than in control groups (3, 2 to 5, p = 0.025). Live weight before slaughter was slightly higher (p = 0.035) in treatment groups than in control groups. Feed conversion ratio (p = 0.174), maintenance behaviors and prevalence of contact dermatitis were not affected. No manipulation of cow pats by broilers was found or observed. Overall, co-grazing with cattle positively affected broiler range use, losses due to avian predation and weight gain

Over-Expression of LEDGF/p75 in HEp-2 Cells Enhances Autoimmune IgG Response in Patients with Benign Prostatic Hyperplasia : A Novel Diagnostic Approach with Therapeutic Consequence?

Lens epithelium-derived growth factor splice variant of 75 kDa (LEDGF/p75) is an autoantigen over-expressed in solid tumors and acts as a stress-related transcriptional co-activator. Participation of autoimmune responses in the pathophysiology of benign prostatic hyperplasia (PBH) and a corresponding immunosuppressive therapy by TNFalpha antagonists has been recently suggested. Thus, autoAb testing could aid in the diagnosis of BPH patients profiting from such therapy. We generated CRISPR/Cas9 modified HEp-2 LEDGF knock-out (KO) and HEp-2 LEDGF/p75 over-expressing (OE) cells and examined IgG autoantibody reactivity to LEDGF/p75 in patients with prostate cancer (PCa, n = 89), bladder cancer (BCa, n = 116), benign prostatic hyperplasia (BPH, n = 103), and blood donors (BD, n = 60) by indirect immunofluorescence assay (IFA). Surprisingly, we could not detect elevated binding of autoAbs against LEDGF/p75 in cancer patients, but autoAb reactivity to LEDGF/p75 OE cells in about 50% of patients with BPH was unexpectedly significantly increased. Furthermore, a line immunoassay enabling the detection of 18 different autoAbs revealed a significantly increased occurrence of anti-dsDNA autoAbs in 34% of BPH patients in contrast to tumor patients and BD. This finding was confirmed by anti-mitochondrial (mDNA) autoAb detection with the Crithidia luciliae immunofluorescence test, which also showed a significantly higher prevalence (34%) of anti-mDNA autoAbs in BPH. In summary, our study provided further evidence for the occurrence of autoimmune responses in BPH. Furthermore, LEDGF/p75 over-expression renders HEp-2 cells more autoantigenic and an ideal target for autoAb analysis in BPH with a potential therapy consequence

Sommergrundlinien 2012

Die deutsche Wirtschaft wird im Prognosezeitraum deutlich schwächer wachsen als in den vergangenen zwei Jahren. Nach drei Prozent 2011 dürfte die Produktion in diesem Jahr nur noch um ein Prozent zunehmen, 2013 werden es knapp zwei Prozent sein. Die Expansion in Deutschland ist in erster Linie durch die binnenwirtschaftliche Dynamik getrieben. Erst ab der Jahreswende dürften auch die Exporte wieder stärker zulegen. Die zunächst schwächere Konjunktur wird vorübergehend wohl auch zu einem Rückgang der Beschäftigung führen; die Arbeitslosenquote bleibt mit knapp sieben Prozent in diesem und im nächsten Jahr in jahresdurchschnittlicher Betrachtung aber stabil

Influence of biological sex, age and smoking on Graves’ orbitopathy – a ten-year tertiary referral center analysis

PurposeSeverity of Graves’ orbitopathy (GO) shows wide individual differences. For optimal treatment, it is important to be able to predict the natural course of the disease as accurate as possible to counteract with anti-inflammatory and surgical treatment. Therefore, we aimed to further elucidate the impact of sex, age and smoking on GO.MethodsWe collected the clinical and demographic data of all patients of our tertiary referral center from January 2008 till December 2018 and analyzed it with descriptive statistics. Only patients with a complete data set were included in the further analysis. Odds ratio’s for moderate-to-severe and sight-threatening GO in relation to age, sex and smoking were calculated by means of multivariate logistic regression models.ResultsWe evaluated the data of 4260 patient with GO and complete data sets. Most of these were women (83%). There were no significant differences between male and female patients regarding smoking habits and thyroid treatment. Men were significantly older at initial manifestation of TED (51.8 vs. 49.9y, p&lt;0.01) and showed significant more often severe stages (61% vs. 53%, p&lt;0.0001). Therefore, they needed significantly more intense treatment with steroids, irradiation, orbital decompression and muscle surgery. In multivariate logistic regression analyses age (OR 0.97, 95% CI:0.97-0.98, p&lt;0.0001), male sex (OR 1.64, 95% CI:1.38-1.9, p&lt;0.0001), smoking (OR 1.19, 95% CI:1.04-1.36, p=0.01), Grave’s disease (OR 1.55, 95% CI:1.26-1.90, p&lt;0.0001) and history of radioiodine treatment (RAI) (OR 2.44, 95% CI:2.10-2.86, p&lt;0.0001) showed an significant association with severe stages of GO.DiscussionOur retrospective analysis showed once more that women are more often afflicted by GO. In contrast, men seem to be more severely afflicted and in need of anti-inflammatory and surgical treatments. This might be due to a different approach to the health system and resilience to GO specific symptoms, as well as previously described worse thyroid control. Estrogen mediated effects might also play a role as in other autoimmune diseases and should be subject of further trials. Besides the biological sex, smoking could again be confirmed as serious risk factor for severe GO. Of note, RAI was associated with more severe stages of GO, which should be subject to further investigation

Round-Robin test for the histological diagnosis of acute colonic Graft-versus-Host disease validating established histological criteria and grading systems

Histomorpholgy is one of the mainstays of acute Graft-versus-host disease (GvHD) diagnosis. However, concerns about reproducibility and the most appropriate grading system question its usefulness. Our aim was to assess histomorphological parameters and previously reported grading systems for GvHD regarding reproducibility and validity. Moreover, we propose that sum scores, derived by combining separately scored morphological parameters into a total score, might provide a simplified but equally effective means to grade GvHD. A total of 123 colon biopsies were assessed across four pathologists for intestinal GvHD using a Round-Robin test and results were correlated with clinical findings. Interobserver reproducibility was high for histological parameters that were evaluated as indicators of acute GvHD. Published grading systems were moderately reproducible (ICC 0.679–0.769) while simplified sum scores, in comparison, showed better interrater reliability (ICC 0.818–0.896). All grading systems and sum scores were associated with clinical signs of GvHD and in part with therapy response and survival. However, they were not able to stratify patients according to the clinical severity of GvHD. In a hot-spot analysis 1 crypt apoptotic body (CAB) in 10 crypts was a reasonable cut-off value for minimal diagnostic criteria of GvHD. In conclusion, histology can contribute to the diagnosis of GvHD and is reproducible. Published grading systems are able to reflect clinical findings as are simplified sum scores, which showed improved reproducibility and might be easier to handle as they are based on adding up histological parameters rather than transferring histological findings into a separate grading system. Sum scores will have to be further tested in a prospective setting.Open Access funding enabled and organized by Projekt DEAL.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Wilhelm Sander-Stiftung http://dx.doi.org/10.13039/100008672Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum ErlangenFriedrich-Alexander-Universität Erlangen-Nürnberg (1041

Lack of astrocytes hinders parenchymal oligodendrocyte precursor cells from reaching a myelinating state in osmolyte-induced demyelination

Demyelinated lesions in human pons observed after osmotic shifts in serum have been referred to as central pontine myelinolysis (CPM). Astrocytic damage, which is prominent in neuroinflammatory diseases like neuromyelitis optica (NMO) and multiple sclerosis (MS), is considered the primary event during formation of CPM lesions. Although more data on the effects of astrocyte-derived factors on oligodendrocyte precursor cells (OPCs) and remyelination are emerging, still little is known about remyelination of lesions with primary astrocytic loss. In autopsy tissue from patients with CPM as well as in an experimental model, we were able to characterize OPC activation and differentiation. Injections of the thymidine-analogue BrdU traced the maturation of OPCs activated in early astrocyte-depleted lesions. We observed rapid activation of the parenchymal NG2+ OPC reservoir in experimental astrocyte-depleted demyelinated lesions, leading to extensive OPC proliferation. One week after lesion initiation, most parenchyma-derived OPCs expressed breast carcinoma amplified sequence-1 (BCAS1), indicating the transition into a pre-myelinating state. Cells derived from this early parenchymal response often presented a dysfunctional morphology with condensed cytoplasm and few extending processes, and were only sparsely detected among myelin-producing or mature oligodendrocytes. Correspondingly, early stages of human CPM lesions also showed reduced astrocyte numbers and non-myelinating BCAS1+ oligodendrocytes with dysfunctional morphology. In the rat model, neural stem cells (NSCs) located in the subventricular zone (SVZ) were activated while the lesion was already partially repopulated with OPCs, giving rise to nestin+ progenitors that generated oligodendroglial lineage cells in the lesion, which was successively repopulated with astrocytes and remyelinated. These nestin+ stem cell-derived progenitors were absent in human CPM cases, which may have contributed to the inefficient lesion repair. The present study points to the importance of astrocyte-oligodendrocyte interactions for remyelination, highlighting the necessity to further determine the impact of astrocyte dysfunction on remyelination inefficiency in demyelinating disorders including MS

Introducing a nationwide registry: the Swiss study on aneurysmal subarachnoid haemorrhage (Swiss SOS)

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is a haemorrhagic form of stroke and occurs in a younger population compared with ischaemic stroke or intracerebral haemorrhage. It accounts for a large proportion of productive life-years lost to stroke. Its surgical and medical treatment represents a multidisciplinary effort. Due to the complexity of the disease, the management remains difficult to standardise and quality of care is accordingly difficult to assess. Objective: To create a registry to assess management parameters of patients treated for aSAH in Switzerland. Methods: A cohort study was initiated with the aim to record characteristics of patients admitted with aSAH, starting January 1st 2009. Ethical committee approval was obtained or is pending from the institutional review boards of all centres. In the study period, seven Swiss hospitals (five university [U], two non-university medical centres) harbouring a neurosurgery department, an intensive care unit and an interventional neuroradiology team so far agreed to participate in the registry (Aarau, Basel [U], Bern [U], Geneva [U], Lausanne [U], St. Gallen, Zürich [U]). Demographic and clinical parameters are entered into a common database. Discussion: This database will soon provide (1) a nationwide assessment of the current standard of care and (2) the outcomes for patients suffering from aSAH in Switzerland. Based on data from this registry, we can conduct cohort comparisons or design diagnostic or therapeutic studies on a national level. Moreover, a standardised registration system will allow healthcare providers to assess the quality of car