Designing of passive residential buildings – case study

This paper describes the process of designing the passive residential buildings. The analysis is carried out on the basis of the Mannheim project, created as an entry for the Isover competition – Multi-Comfort House. Particular steps of the design process are analyzed for meeting the requirements of passive standard building. The specific solutions adopted in the Mannheim project are presented as an example

Bioinspired bola-type peptide dendrimers inhibit proliferation and invasiveness of glioblastoma cells in a manner dependent on their structure and amphipathic properties

(1) Background: Natural peptides supporting the innate immune system studied at the functional and mechanistic level are a rich source of innovative compounds for application in human therapy. Increasing evidence indicates that apart from antimicrobial activity, some of them exhibit selective cytotoxicity towards tumor cells. Their cationic, amphipathic structure enables interactions with the negatively-charged membranes of microbial or malignant cells. It can be modeled in 3D by application of dendrimer chemistry. (2) Methods: Here we presented design principles, synthesis and bioactivity of branched peptides constructed from ornithine (Orn) assembled as proline (Pro)- or histidine (His)-rich dendrons and dendrimers of the bola structure. The impact of the structure and amphipathic properties of dendrons/dendrimers on two glioblastoma cell lines U87 and T98G was studied with the application of proliferation, apoptosis and cell migration assays. Cell morphology/cytoskeleton architecture was visualized by immunofluorescence microscopy. (3) Results: Dimerization of dendrons into bola dendrimers enhanced their bioactivity. Pro- and His-functionalized bola dendrimers displayed cytostatic activity, even though differences in the responsiveness of U87 and T98G cells to these compounds indicate that their bioactivity depends not only on multiple positive charge and amphipathic structure but also on cellular phenotype. (4) Conclusion: Ornithine dendrons/dendrimers represent a group of promising anti-tumor agents and the potential tools to study interrelations between drug bioactivity, its chemical properties and tumor cells’ phenotype

Combining Transarterial Radioembolization (TARE) and CT-Guided High-Dose-Rate Interstitial Brachytherapy (CT-HDRBT): A Retrospective Analysis of Advanced Primary and Secondary Liver Tumor Treatment

Purpose: Treatment of patients with primary and secondary liver tumors remains challenging. This study analyzes the efficacy and safety of transarterial radioembolization (TARE) combined with CT-guided high-dose-rate interstitial brachytherapy (CT-HDRBT) for the treatment of primary and secondary liver tumors. Patients and Methods: A total of 77 patients (30 female) with various liver malignancies were treated. Primary endpoints were median overall survival (OS) and time to untreatable progression (TTUP). Additionally, subgroup analyses were performed in consideration of diagnosis and procedure sequence. Median OS and TTUP prediction were estimated using Kaplan-Meier analysis and hazard ratios (HR) were calculated using a multivariate Cox proportional hazard model. Results: A total of 115 CT-HDRBT and 96 TARE procedures were performed with Purpose: Treatment of patients with primary and secondary liver tumors remains challenging. This study analyzes the efficacy and safety of transarterial radioembolization (TARE) combined with CT-guided high-dose-rate interstitial brachytherapy (CT-HDRBT) for the treatment of primary and secondary liver tumors. Patients and methods: A total of 77 patients (30 female) with various liver malignancies were treated. Primary endpoints were median overall survival (OS) and time to untreatable progression (TTUP). Additionally, subgroup analyses were performed in consideration of diagnosis and procedure sequence. Median OS and TTUP prediction were estimated using Kaplan-Meier analysis and hazard ratios (HR) were calculated using a multivariate Cox proportional hazard model. Results: A total of 115 CT-HDRBT and 96 TARE procedures were performed with no significant complications recorded. Median OS and TTUP were 29.8 (95% CI 18.1-41.4) and 23.8 (95% CI 9.6-37.9) months. Median OS for hepatocellular carcinoma (HCC)-, cholangiocarcinoma carcinoma (CCA) and colorectal cancer (CRC) patients was 29.8, 29.6 and 34.4 months. Patients starting with TARE had a median OS of 26.0 (95% CI 14.5-37.5) compared to 33.7 (95% CI 21.6-45.8) months for patients starting with CT-HDRBT. Hazard ratio of 1.094 per month was shown for patients starting with CT-HDRBT. Conclusion: Combining TARE and CT-HDRBT is effective and safe for the treatment of advanced stage primary and secondary liver tumors. Our data indicate that early TARE during the disease progression may have a positive effect on survival.no significant complications recorded. Median OS and TTUP were 29.8 (95% CI 18.1-41.4) and 23.8 (95% CI 9.6-37.9) months. Median OS for hepatocellular carcinoma (HCC)-, cholangiocarcinoma carcinoma (CCA) and colorectal cancer (CRC) patients was 29.8, 29.6 and 34.4 months. Patients starting with TARE had a median OS of 26.0 (95% CI 14.5-37.5) compared to 33.7 (95% CI 21.6-45.8) months for patients starting with CT-HDRBT. Hazard ratio of 1.094 per month was shown for patients starting with CT-HDRBT. Conclusion: Combining TARE and CT-HDRBT is effective and safe for the treatment of advanced stage primary and secondary liver tumors. Our data indicate that early TARE during the disease progression may have a positive effect on survival

Enabling the freight traffic controller for collaborative multi-drop urban logistics: practical and theoretical challenges

There is increasing interest in how horizontal collaboration between parcel carriers might help alleviate problems associated with last-mile logistics in congested urban centers. Through a detailed review of the literature on parcel logistics pertaining to collaboration, along with practical insights from carriers operating in the United Kingdom, this paper examines the challenges that will be faced in optimizing multicarrier, multidrop collection, and delivery schedules. A “freight traffic controller” (FTC) concept is proposed. The FTC would be a trusted third party, assigned to equitably manage the work allocation between collaborating carriers and the passage of vehicles over the last mile when joint benefits to the parties could be achieved. Creating this FTC concept required a combinatorial optimization approach for evaluation of the many combinations of hub locations, network configuration, and routing options for vehicle or walking to find the true value of each potential collaboration. At the same time, the traffic, social, and environmental impacts of these activities had to be considered. Cooperative game theory is a way to investigate the formation of collaborations (or coalitions), and the analysis used in this study identified a significant shortfall in current applications of this theory to last-mile parcel logistics. Application of theory to urban freight logistics has, thus far, failed to account for critical concerns including (a) the mismatch of vehicle parking locations relative to actual delivery addresses; (b) the combination of deliveries with collections, requests for the latter often being received in real time during the round; and (c) the variability in travel times and route options attributable to traffic and road network conditions

Effect of Methotrexate in the Treatment of Distal Interphalangeal Joint Extensor Tendon Enthesopathy in Patients with Nail Psoriasis

To assess the effect of methotrexate on the development of distal interphalangeal joint extensor tendon enthesopathy in psoriasis, thirty-two people aged 34 to 57 years with nail psoriasis and distal interphalangeal joint extensor tendon enthesopathy (19 patients with Ps (psoriasis) and 13 with PsA (psoriatic arthritis) were started on methotrexate at 15 to 25 mg/week and the treatment was continued for 6 months). A total of 319 nails were examined. After six months of treatment, the thicknesses of the nail plate, nail bed and nail matrix were found to decrease in both groups of patients. Methotrexate treatment resulted in a decrease in the joint extensor tendon thickness only in patients with Ps (0.94 ± 0.05 vs. 0.96 ± 0.04, p < 0.001), where the tendon thickness after treatment correlated with the matrix thickness (r = 0.337, p = 0.018) and with the bed thickness (r = 0.299, p = 0.039). Methotrexate treatment resulted in a decrease in the extensor tendon thickness only in patients with Ps but not in PsA. The findings of this study may suggest the effectiveness of systemic treatment of nail psoriasis in patients without arthritis and the use of US nail examinations in Ps and PsA patients in morphological change assessment and response to treatment

Ultrasound Assessment of Changes in Nails in Psoriasis and Psoriatic Arthritis

Aim of the Study. The aim of the study was to conduct an ultrasound (US) assessment of changes in fingernails in psoriatic patients with nail involvement. Material. A total of 69 patients with psoriatic changes in nails participated in the study, including 38 patients with psoriasis (Ps) and 31 with psoriatic arthritis (PsA) and 30 people in the control group. A total of 988 nails were examined. Results. The thickness of the nail plate, nail bed, and matrix as shown in an ultrasound examination increased with the mNAPSI index (r=0.328, p=0.021; r=0.219, p=0.036; and r=0.422, p=0.011, respectively). The thickness of nail plate, bed, and matrix in patients with onycholysis and hyperkeratosis-type changes (concomitant or present separately) was significantly greater than when only pitting-type changes occurred (p=0.007, p=0.035, and p=0.023, respectively). An examination of nails with only pitting-type changes showed an increase in the matrix thickness compared to the control group (p=0.018). The focal hyperechoic involvement of the dorsal plate (80%) was the change most often observed in an US examination in Ps patients, whereas loosening of the borders of the ventral plate was most often observed in PsA patients. The thickness of nail bed in PsA patients increased with the duration of arthritis (r=0.399, p=0.022) and was correlated with the number of swollen digits (r=0.278, p=0.041). Conclusions. The findings of this study may indicate an association of an inflammation in the nail bed with PsA development. Apart from a direct assessment of the described morphological changes of nails, a US examination could prove useful in an assessment of intensity of a local inflammation as a prognostic factor for PsA development

Combining Transarterial Radioembolization (TARE) and CT-Guided High-Dose-Rate Interstitial Brachytherapy (CT-HDRBT): A Retrospective Analysis of Advanced Primary and Secondary Liver Tumor Treatment

Purpose: Treatment of patients with primary and secondary liver tumors remains challenging. This study analyzes the efficacy and safety of transarterial radioembolization (TARE) combined with CT-guided high-dose-rate interstitial brachytherapy (CT-HDRBT) for the treatment of primary and secondary liver tumors. Patients and Methods: A total of 77 patients (30 female) with various liver malignancies were treated. Primary endpoints were median overall survival (OS) and time to untreatable progression (TTUP). Additionally, subgroup analyses were performed in consideration of diagnosis and procedure sequence. Median OS and TTUP prediction were estimated using Kaplan–Meier analysis and hazard ratios (HR) were calculated using a multivariate Cox proportional hazard model. Results: A total of 115 CT-HDRBT and 96 TARE procedures were performed with no significant complications recorded. Median OS and TTUP were 29.8 (95% CI 18.1–41.4) and 23.8 (95% CI 9.6–37.9) months. Median OS for hepatocellular carcinoma (HCC)-, cholangiocarcinoma carcinoma (CCA) and colorectal cancer (CRC) patients was 29.8, 29.6 and 34.4 months. Patients starting with TARE had a median OS of 26.0 (95% CI 14.5–37.5) compared to 33.7 (95% CI 21.6–45.8) months for patients starting with CT-HDRBT. Hazard ratio of 1.094 per month was shown for patients starting with CT-HDRBT. Conclusion: Combining TARE and CT-HDRBT is effective and safe for the treatment of advanced stage primary and secondary liver tumors. Our data indicate that early TARE during the disease progression may have a positive effect on survival

Absence of an Orphan Mitochondrial Protein, C19orf12, Causes a Distinct Clinical Subtype of Neurodegeneration with Brain Iron Accumulation

The disease classification neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of progressive neurodegenerative disorders characterized by brain iron deposits in the basal ganglia. For about half of the cases, the molecular basis is currently unknown. We used homozygosity mapping followed by candidate gene sequencing to identify a homozygous 11 bp deletion in the orphan gene C19orf12. Mutation screening of 23 ideopathic NBIA index cases revealed two mutated alleles in 18 of them, and one loss-of-function mutation is the most prevalent. We also identified compound heterozygous missense mutations in a case initially diagnosed with Parkinson disease at age 49. Psychiatric signs, optic atrophy, and motor axonal neuropathy were common findings. Compared to the most prevalent NBIA subtype, pantothenate kinase associated neurodegeneration (PKAN), individuals with two C19orf12 mutations were older at age of onset and the disease progressed more slowly. A polyclonal antibody against the predicted membrane spanning protein showed a mitochondrial localization. A histopathological examination in a single autopsy case detected Lewy bodies, tangles, spheroids, and tau pathology. The mitochondrial localization together with the immunohistopathological findings suggests a pathomechanistic overlap with common forms of neurodegenerative disorders

Current state-of-the-art and gaps in platform trials: 10 things you should know, insights from EU-PEARL

Summary: Platform trials bring the promise of making clinical research more efficient and more patient centric. While their use has become more widespread, including their prominent role during the COVID-19 pandemic response, broader adoption of platform trials has been limited by the lack of experience and tools to navigate the critical upfront planning required to launch such collaborative studies. The European Union-Patient-cEntric clinicAl tRial pLatform (EU-PEARL) initiative has produced new methodologies to expand the use of platform trials with an overarching infrastructure and services embedded into Integrated Research Platforms (IRPs), in collaboration with patient representatives and through consultation with U.S. Food and Drug Administration and European Medicines Agency stakeholders. In this narrative review, we discuss the outlook for platform trials in Europe, including challenges related to infrastructure, design, adaptations, data sharing and regulation. Documents derived from the EU-PEARL project, alongside a literature search including PubMed and relevant grey literature (e.g., guidance from regulatory agencies and health technology agencies) were used as sources for a multi-stage collaborative process through which the 10 more important points based on lessons drawn from the EU-PEARL project were developed and summarised as guidance for the setup of platform trials. We conclude that early involvement of critical stakeholder such as regulatory agencies or patients are critical steps in the implementation and later acceptance of platform trials. Addressing these gaps will be critical for attaining the full potential of platform trials for patients. Funding: Innovative Medicines Initiative 2 Joint Undertaking with support from the European Union’s Horizon 2020 research and innovation programme and EFPIA