An Interaction form Generation Tool: EduDesign

AbstractThis paper investigates contributions of customized and simplified generative design tools on the development of novice architects‟ abilities of accelerating their interactions with digital tools and adapting new digital design processes with them. For this purpose, a plugin, called as EduDesign and including various form generations and instructional practices based basic design education, have been developed by scripts of 3D software. Its potentials tested and enriched by different student groups experiences in KBU and ITU. According to the obtained results, positive and negative influences of the plugin are evaluated

Contrastive Representation Learning for Acoustic Parameter Estimation

A study is presented in which a contrastive learning approach is used to extract low-dimensional representations of the acoustic environment from single-channel, reverberant speech signals. Convolution of room impulse responses (RIRs) with anechoic source signals is leveraged as a data augmentation technique that offers considerable flexibility in the design of the upstream task. We evaluate the embeddings across three different downstream tasks, which include the regression of acoustic parameters reverberation time RT60 and clarity index C50, and the classification into small and large rooms. We demonstrate that the learned representations generalize well to unseen data and perform similarly to a fully-supervised baseline.Comment: Accepted for ICASSP 2023, Camera-ready versio

Comparing Venous Reconstructions and Antimicrobial Graft Reconstructions in Mycotic Abdominal Aortic Aneurysms and Aortic Graft Infections

Background: The perioperative mortality and morbidity rates of surgical repair of mycotic abdominal aortic aneurysms and aortic graft infections are high, and the appropriate treatment is debated. This retrospective study compared venous and antimicrobial prosthetic aortic graft reconstructions. Methods: All patients of the Northwest Clinics and St. Antonius Hospital who were treated for mycotic abdominal aortic aneurysms or aortic graft infections between January 1, 2008, and January 1, 2018, were analyzed. Exclusion criterion was treatment other than venous or antimicrobial reconstructions. Primary end points were 30-day complications and mortality rates and 3-year overall survival. Secondary end points were reintervention-free survival, persistent infection and reinfection rates, and hospital length of stay. Results: Fifty-one patients met the inclusion criteria, of whom 32 underwent venous reconstructions and 19 antimicrobial prosthetic aortic graft reconstructions. Baseline characteristics did not differ significantly between these groups, except for duration of surgical repair, which was longer in the venous group. The 30-day and 1-year mortality rates, reinfection rates, complication rates, and hospital length of stay did not significantly differ between the groups. The 3-year overall survival was 77% for venous reconstruction compared with 66% for antimicrobial reconstruction (P = 0.781). The 30-day reintervention rate was 19% for the venous group compared with 42% for the prosthetic group (P = 0.071). Reintervention-free survival at 3 years was 46% for the venous group compared with 52% for the prosthetic group (P = 0.615). Conclusions: Venous reconstruction tends to have better 3-year overall survival and lower 30-day reintervention rates compared with antimicrobial prosthetic graft reconstruction in patients with mycotic abdominal aortic aneurysms or abdominal aortic graft infections. In the acute setting, antimicrobial prosthetic graft reconstruction is a valuable solution due to the shorter operation time and similar 30-day mortality and complication rates

Development of a Prediction Model for the Occurrence of Stenosis or Occlusion after Percutaneous Deep Venous Arterialization

Percutaneous deep venous arterialization (pDVA) is a promising treatment option in patients with chronic limb-threatening ischemia. Stenosis and occlusions, which are the Achilles' heel of every revascularization procedure, can be treated when detected early. However, frequent monitoring after pDVA is required because when stenosis or occlusions develop is unknown. Therefore, patients currently need to visit the hospital every 2 weeks for surveillance, which can be burdensome. Accordingly, we aimed to develop a model that can predict future stenosis or occlusions in patients after pDVA to be able to create tailor-made follow-up protocols. The data set included 343 peak systolic velocity and 335 volume flow measurements of 23 patients. A stenosis or occlusion developed in 17 patients, and 6 patients remained lesion-free. A statistically significant increase in the risk of stenosis or occlusion was found when duplex ultrasound values decreased 20% within 1 month. The prediction model was also able to estimate a patient-specific risk of future stenosis or occlusions. This is promising for the possibility of reducing the frequency of follow-up visits for low-risk patients and increasing the frequency for high-risk patients. These observations are the starting point for individual surveillance programs in post-pDVA patients. Future studies with a larger cohort are necessary for validation of this model

Long-term prevalence of post-traumatic stress disorder symptoms in patients after secondary peritonitis

INTRODUCTION: The aim of this study was to determine the long-term prevalence of post-traumatic stress disorder (PTSD) symptomology in patients following secondary peritonitis and to determine whether the prevalence of PTSD-related symptoms differed between patients admitted to the intensive care unit (ICU) and patients admitted only to the surgical ward. METHOD: A retrospective cohort of consecutive patients treated for secondary peritonitis was sent a postal survey containing a self-report questionnaire, namely the Post-traumatic Stress Syndrome 10-question inventory (PTSS-10). From a database of 278 patients undergoing surgery for secondary peritonitis between 1994 and 2000, 131 patients were long-term survivors (follow-up period at least four years) and were eligible for inclusion in our study, conducted at a tertiary referral hospital in Amsterdam, The Netherlands. RESULTS: The response rate was 86%, yielding a cohort of 100 patients; 61% of these patients had been admitted to the ICU. PTSD-related symptoms were found in 24% (95% confidence interval 17% to 33%) of patients when a PTSS-10 score of 35 was chosen as the cutoff, whereas the prevalence of PTSD symptomology when borderline patients scoring 27 points or more were included was 38% (95% confidence interval 29% to 48%). In a multivariate analyses controlling for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, number of relaparotomies and length of hospital stay, the likelihood of ICU-admitted patients having PTSD symptomology was 4.3 times higher (95% confidence interval 1.11 to 16.5) than patients not admitted to the ICU, using a PTSS-10 score cutoff of 35 or greater. Older patients and males were less likely to report PTSD symptoms. CONCLUSION: Nearly a quarter of patients receiving surgical treatment for secondary peritonitis developed PTSD symptoms. Patients admitted to the ICU were at significantly greater risk for having PTSD symptoms after adjusting for baseline differences, in particular ag

Nicotine Normalizes Intracellular Subunit Stoichiometry of Nicotinic Receptors Carrying Mutations Linked to Autosomal Dominant Nocturnal Frontal Lobe Epilepsy

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is linked with high penetrance to several distinct nicotinic receptor (nAChR) mutations. We studied (α4)_3(2β)_2 versus (α4)_2(β2)_3 subunit stoichiometry for five channel-lining M2 domain mutations: S247F, S252L, 776ins3 in α4, V287L, and V287M in β2. α4 and β2 subunits were constructed with all possible combinations of mutant and wild-type (WT) M2 regions, of cyan and yellow fluorescent protein, and of fluorescent and nonfluorescent M3-M4 loops. Sixteen fluorescent subunit combinations were expressed in N2a cells. Forster resonance energy transfer (FRET) was analyzed by donor recovery after acceptor photobleaching and by pixel-by-pixel sensitized emission, with confirmation by fluorescence intensity ratios. Because FRET efficiency is much greater for adjacent than for nonadjacent subunits and the α4 and β2 subunits occupy specific positions in nAChR pentamers, observed FRET efficiencies from (α4)_3(β2)_2 carrying fluorescent α4 subunits were significantly higher than for (α4)_2(β2)_3; the converse was found for fluorescent 2 subunits. All tested ADNFLE mutants produced 10 to 20% increments in the percentage of intracellular (α4)_3(β2)_2 receptors compared with WT subunits. In contrast, 24- to 48-h nicotine (1 µM) exposure increased the proportion of (α4)_2(β2)_3 in WT receptors and also returned subunit stoichiometry to WT levels for α4S248F and β2V287L nAChRs. These observations may be relevant to the decreased seizure frequency in patients with ADNFLE who use tobacco products or nicotine patches. Fluorescence-based investigations of nAChR subunit stoichiometry may provide efficient drug discovery methods for nicotine addiction or for other disorders that result from dysregulated nAChRs

Repeatability, and Intra-Observer and Interobserver Agreement of Two Dimensional Perfusion Angiography in Patients with Chronic Limb Threatening Ischaemia

Objective. Two dimensional (2D) perfusion angiography is a method that provides quantitative foot perfusion information from standard digital subtraction angiography acquisitions. The aim of this study was to test the reliability of this method in patients with chronic limb threatening ischaemia (CLTI) by investigating repeatability, and intra-observer and interobserver agreement. Methods: Twenty patients with CLTI and a below the knee endovascular revascularisation were included in a prospective clinical study. Prior to treatment two perfusion angiography runs were acquired with a five minute interval without performing an intervention. In these recordings, regions of interest were selected and time density curves and perfusion parameters were determined. To investigate intra-observer agreement one observer performed five measurements on the same acquisition for each patient. To investigate interobserver agreement three observers performed measurements on the same acquisition for each patient. Results were presented in Bland-Altman plots and as the intraclass correlation coefficient per parameter. Results: Two patients were excluded from repeatability analyses because of major motion artefacts. Repeatability analyses of the 18 remaining patients showed excellent correlation for every parameter (> .96). Intra-observer and interobserver agreement for all 20 patients were excellent for all parameters (1.00). Conclusion: Repeatability and intra-observer and interobserver agreement of 2D perfusion angiography in patients with CLTI were found to be excellent. It is therefore a reliable tool when used according to the standardised methods described in this study

Optimized Inhibitors of MDM2 via an Attempted Protein-Templated Reductive Amination

Innovative and efficient hit-identification techniques are required to accelerate drug discovery. Protein-templated fragment ligations represent a promising strategy in early drug discovery, enabling the target to assemble and select its binders from a pool of building blocks. Development of new protein-templated reactions to access a larger structural diversity and expansion of the variety of targets to demonstrate the scope of the technique are of prime interest for medicinal chemists. Herein, we present our attempts to use a protein-templated reductive amination to target protein-protein interactions (PPIs), a challenging class of drug targets. We address a flexible pocket, which is difficult to achieve by structure-based drug design. After careful analysis we did not find one of the possible products in the kinetic target-guided synthesis (KTGS) approach, however subsequent synthesis and biochemical evaluation of each library member demonstrated that all the obtained molecules inhibit MDM2. The most potent library member (Ki=0.095 μm) identified is almost as active as Nutlin-3, a potent inhibitor of the p53-MDM2 PPI