Robot-Aided Fabrication of Materially Efficient Complex Concrete Assemblies

This paper presents a novel approach for the materially efficient production of doubly-curved Expanded Polystyrene (EPS) form-work for insitu concrete construction and a novel application of a patented Glass Reinforced Concrete (GRC) technology. Research objectives focus on the development of complex form-work generation and concrete application via advanced computational and robotic methods. While it is viable to produce form-work with complex geometries with advanced digital and robotic fabrication tools, a key consideration area is the reduction of form-work waste material. The research agenda explores methods of associating architectural, spatial, and structural criteria with a material-informed holistic approach. The digital and physical investigations are founded on Robotic Hot-Wire Cutting (RHWC). The geometrical and physical principles of RHWC are transformed into design inputs, whereby digital and physical tests inform each other simultaneously. Correlations are set between form-work waste optimization with the geometrical freedom and constraints of hot-wire cutting via computational methods

Association of CHA2DS2-VASc score with successful recanalization in acute ischemic stroke patients undergoing endovascular thrombectomy

Introduction: The CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease and sex) score is a simple risk stratification algorithm to estimate stroke/thromboembolic risk in patients with non-valvular atrial fibrillation (AF). Higher pre-stroke CHA2DS2-VASc score is known to be associated with greater stroke severity and poorer outcomes. AF patients generally have higher CHA2DS2-VASc scores than non-AF patients. The Modified Thrombolysis in Cerebral Infarction (mTICI) score is the most widely used grading system to assess the result of recanalizing therapies in acute ischemic stroke (AIS). mTICI 2c and mTICI 3 are conventionally accepted as successful recanalization. Aim: We investigated whether pre-stroke CHA2DS2-VASc score is associated with mTICI recanalization score in AIS patients with and without AF undergoing percutaneous thrombectomy. Material and methods: One hundred fifty-nine patients with the diagnosis of AIS who were admitted within 6 h from symptom onset were included in the study (mean age: 65.7 ±12.9). All subjects underwent endovascular treatment. CHA2DS2-VASc scores of the participants were calculated. Subjects were grouped according to mTICI scores achieved after endovascular treatment. mTICI 2c and mTICI 3 were accepted as successful recanalization. Results: Successful reperfusion was observed in 130 (81.8%) of all patients who underwent endovascular treatment (mTICI flow ≥ 2c) and first-pass reperfusion was observed in 107 (67.3%) patients. When the patients with successful (mTICI flow ≥ 2c) and unsuccessful (mTICI flow ≤ 2b) reperfusion were divided into groups, no significant difference was observed between the patients in terms of comorbidities such as AF, hypertension, hyperlipidemia, coronary artery disease and cerebrovascular accident history. Patients with unsuccessful reperfusion were older than patients with successful reperfusion (71.4 ±11.2 vs. 64.5 ±13.01, p = 0.006), with a higher CHA2DS2-VASc score (4.1 ±1.5 vs. 3.04 ±1.6, p = 0.002). In addition, the duration of the procedure was longer in the unsuccessful reperfusion group (92.4 ±27.2 min vs. 65.0 ±25.1 min, p < 0.001). CHA2DS2-VASc score significantly correlated with successful recanalization (correlation coefficient; 0.243, p = 0.002). Multivariate logistic regression analysis revealed that only CHA2DS2-VASc score (OR = 1.43, 95% CI: 1.09-1.87, p = 0.006) and procedure time (OR = 1.03, 95% CI: 1.01-1.05, p < 0.001) were independent predictors of successful reperfusion. The receiver-operating characteristic (ROC) curve was used to determine the cut-off value for the CHA2DS2-VASc score that best predicts successful reperfusion. The optimal threshold was 3.5, with a sensitivity of 58.6% and specificity of 59.2% (area under the curve (AUC): 0.669, p = 0.005). Conclusions: For the first time in the literature, we investigated and demonstrated that pre-stroke CHA2DS2-VASc score was associated with success of recanalization as assessed with mTICI 2c and mTICI 3 in a cohort of AIS patients regardless of AF presence who underwent endovascular treatment. Our findings deserve to be tested with large scale long term studies

Prevalence and burden of headache in children and adolescents in Austria - a nationwide study in a representative sample of pupils aged 10-18 years

Background Headache disorders are highly prevalent worldwide, but not so well investigated in children and adolescents as in adults: few studies have included representative nationwide samples. No data exist for Austria until now. In a representative sample of children and adolescents in Austria, we estimated the prevalence and attributable burden of headache disorders, including the new diagnostic category of “undifferentiated headache” (UdH) defined as mild headache lasting less than 1 hour. Methods Within the context of a broader national mental health survey, children and adolescents aged 10–18 years were recruited from purposively selected schools. Mediated self-completed questionnaires included sociodemographic enquiry (gender, age, socioeconomic status, family constellation, residence [urban or rural] and migration background). Prevalence and attributable burden of all headache, UdH, migraine (definite plus probable), tension-type headache (TTH: definite plus probable) and headache on ≥15 days/month (H15+) were assessed using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents. Health-related quality of life (HrQoL) was assessed using the KIDSCREEN questionnaire. Results Of 7643 selected pupils, 3386 (44.3%) completed the questionnaires. The 1-year prevalence of headache was 75.7%, increasing with age and higher in girls (82.1%) than in boys (67.7%; p < 0.001). UdH, migraine, TTH and H15+ were reported by 26.1%, 24.2%, 21.6% and 3.0% of participants. Attributable burden was high, with 42% of those with headache experiencing restrictions in daily activities. Medication use (50% overall) was highest in H15+ (67%) and still considerable in UdH (29%). HrQoL was reduced for all headache types except UdH. Participants in single parent or patchwork families had a higher probability of migraine (respectively, OR 1.5, p < 0.001; OR 1.5, p < 0.01). Participants with a migration background had a lower probability of TTH (OR 0.7, p < 0.01). Conclusions Headache disorders are both very common and highly burdensome in children and adolescents in Austria. This study contributes to the global atlas of headache disorders in these age groups, and corroborates and adds knowledge of the new yet common and important diagnostic category of UdH. The findings call for action in national and international health policies, and for further epidemiological research

Extending the definition of modularity to directed graphs with overlapping communities

Complex networks topologies present interesting and surprising properties, such as community structures, which can be exploited to optimize communication, to find new efficient and context-aware routing algorithms or simply to understand the dynamics and meaning of relationships among nodes. Complex networks are gaining more and more importance as a reference model and are a powerful interpretation tool for many different kinds of natural, biological and social networks, where directed relationships and contextual belonging of nodes to many different communities is a matter of fact. This paper starts from the definition of modularity function, given by M. Newman to evaluate the goodness of network community decompositions, and extends it to the more general case of directed graphs with overlapping community structures. Interesting properties of the proposed extension are discussed, a method for finding overlapping communities is proposed and results of its application to benchmark case-studies are reported. We also propose a new dataset which could be used as a reference benchmark for overlapping community structures identification.Comment: 22 pages, 11 figure

Activity Dependent Protein Degradation Is Critical for the Formation and Stability of Fear Memory in the Amygdala

Protein degradation through the ubiquitin-proteasome system [UPS] plays a critical role in some forms of synaptic plasticity. However, its role in memory formation in the amygdala, a site critical for the formation of fear memories, currently remains unknown. Here we provide the first evidence that protein degradation through the UPS is critically engaged at amygdala synapses during memory formation and retrieval. Fear conditioning results in NMDA-dependent increases in degradation-specific polyubiquitination in the amygdala, targeting proteins involved in translational control and synaptic structure and blocking the degradation of these proteins significantly impairs long-term memory. Furthermore, retrieval of fear memory results in a second wave of NMDA-dependent polyubiquitination that targets proteins involved in translational silencing and synaptic structure and is critical for memory updating following recall. These results indicate that UPS-mediated protein degradation is a major regulator of synaptic plasticity necessary for the formation and stability of long-term memories at amygdala synapses

Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy

Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ΔΨm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control

The pharmacological regulation of cellular mitophagy

Small molecules are pharmacological tools of considerable value for dissecting complex biological processes and identifying potential therapeutic interventions. Recently, the cellular quality-control process of mitophagy has attracted considerable research interest; however, the limited availability of suitable chemical probes has restricted our understanding of the molecular mechanisms involved. Current approaches to initiate mitophagy include acute dissipation of the mitochondrial membrane potential (ΔΨm) by mitochondrial uncouplers (for example, FCCP/CCCP) and the use of antimycin A and oligomycin to impair respiration. Both approaches impair mitochondrial homeostasis and therefore limit the scope for dissection of subtle, bioenergy-related regulatory phenomena. Recently, novel mitophagy activators acting independently of the respiration collapse have been reported, offering new opportunities to understand the process and potential for therapeutic exploitation. We have summarized the current status of mitophagy modulators and analyzed the available chemical tools, commenting on their advantages, limitations and current applications

Primary tracheal adenocystic carcinoma and tracheal tumors during pregnancy

Cancer complicates approximately 0.1% of all pregnancies. Primary tracheal carcinoma is one of very rarely seen tumors and the rate of its being seen makes up approximately % 0.2 of all tumors of respiratory tract. The patient, 28 years old, who has 28-weeks-pregnant, was diagnosed with primary tracheal adenocystic carcinoma. Patient was made operation as thoracotomy and tracheal tumor was removed at the 28th week of pregnancy. Patient was delivered with sectio abdominale at the 39th week of pregnancy. Primary tracheal adenocystic carcinoma is very rarely seen tumors and it is the first tracheal ACC with pregnancy case in literature to have been detected and surgically treated during pregnancy. We discussed primary tracheal adenocystic carcinoma and tracheal tumors during pregnancy with literature

<i>mito</i>-QC illuminates mitophagy and mitochondrial architecture <i>in vivo</i>

Autophagic turnover of mitochondria, termed mitophagy, is proposed to be an essential quality-control (QC) mechanism of pathophysiological relevance in mammals. However, if and how mitophagy proceeds within specific cellular subtypes in vivo remains unclear, largely because of a lack of tractable tools and models. To address this, we have developed “mito-QC,” a transgenic mouse with a pH-sensitive fluorescent mitochondrial signal. This allows the assessment of mitophagy and mitochondrial architecture in vivo. Using confocal microscopy, we demonstrate that mito-QC is compatible with classical and contemporary techniques in histochemistry and allows unambiguous in vivo detection of mitophagy and mitochondrial morphology at single-cell resolution within multiple organ systems. Strikingly, our model uncovers highly enriched and differential zones of mitophagy in the developing heart and within specific cells of the adult kidney. mito-QC is an experimentally advantageous tool of broad relevance to cell biology researchers within both discovery-based and translational research communities

Long-term results of radiotherapy for periarthritis of the shoulder: a retrospective evaluation

<p>Abstract</p> <p>Background</p> <p>To evaluate retrospectively the results of radiotherapy for periarthritis of the shoulder</p> <p>Methods</p> <p>In 1983–2004, 141 patients were treated, all had attended at least one follow-up examination. 19% had had pain for several weeks, 66% for months and 14% for years. Shoulder motility was impaired in 137/140 patients. Nearly all patients had taken oral analgesics, 81% had undergone physiotherapy, five patients had been operated on, and six had been irradiated. Radiotherapy was applied using regular anterior-posterior opposing portals and Co-60 gamma rays or 4 MV photons. 89% of the patients received a total dose of 6 Gy (dose/fraction of 1 Gy twice weekly, the others had total doses ranging from 4 to 8 Gy. The patients and the referring doctors were given written questionnaires in order to obtain long-term results. The mean duration of follow-up was 6.9 years [0–20 years].</p> <p>Results</p> <p>During the first follow-up examination at the end of radiotherapy 56% of the patients reported pain relief and improvement of motility. After in median 4.5 months the values were 69 and 89%, after 3.9 years 73% and 73%, respectively. There were virtually no side effects. In the questionnaires, 69% of the patients reported pain relief directly after radiotherapy, 31% up to 12 weeks after radiotherapy. 56% of the patients stated that pain relief had lasted for "years", in further 12% at least for "months".</p> <p>Conclusion</p> <p>Low-dose radiotherapy for periarthropathy of the shoulder was highly effective and yielded long-lasting improvement of pain and motility without side effects.</p