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Modular projects can be of higher quality, a safer, faster and more predictable construction process, and less environmental nuisance compared to a traditional on-site project. High-rise projects seem to be particularly suitable for modular building methods, however there are still some process-related barriers. Research so far has not focused on collaboration forms for modular high-rise projects. This paper examines which collaboration form fits best for a modular high-rise project by conducting an international case study research. From the case studies it is debatable whether the current PDMs meet the need for modular concepts; modular buildings will benefit more from a long-term collaboration with fixed partnerships. This requires a complete different approach to the construction industry. Until then, the best match should be sought by matching the customer profile to the PDM characteristics. The most suitable PDM is dependent on the client profile that can be determined by 17 selection criteria.

Dual compartment suppositories are being developed to prevent HIV and other sexually transmitted infections. Such products, for use in the rectum, the vagina, or both, could have a significant public health impact by decreasing global incidence of these diseases. In this study, 16 women each used two rheologically distinct suppositories in their vagina and rectum. User Sensory Perception and Experience (USPE) scales assessed sensory experiences during sexual activity to understand whether, and how, women perceive formulation properties in the vagina and rectum. Qualitative data from individual in-depth interviews captured women's descriptions and comparisons of the experiences. Significant differences and large Cohen's d effect sizes between vaginal and rectal experiences of suppository-A were found for three scales: Application (APP): Product Awareness, SEX: Initial Penetration; and SEX: Effortful. Qualitative data provided user experience details that credibly align with these score differences. Near significant differences and large effect sizes were found for two additional scales: SEX: Perceived Wetness with suppository-A and SEX: Messiness with suppository-B. In addition, other scale scores showed medium-to-large effect sizes that correspond to hypothesized sensations associated with biophysical properties of the suppositories. Statistical significance combined with large effect sizes and qualitative data accurately represent the hypothesized perceptibility of suppository properties and identifies performance characteristics relevant to acceptability and adherence; together these data provide discernment of factors that can guide the development of dual compartment products. The Clinical Trial Registration number: NCT02744261.

Historical antecedents of pharmaceutical sciences are sound on product orientation based on (analytical) chemistry, drug delivery and basic pharmacology. Over the last decades we have seen a transition towards a stronger disease orientation. This raises questions on whether, how and to what extent unmet medical need (UMN) is important in priority setting, funding and impact in pharmaceutical sciences. An online survey in 2020 collected perspectives of internationally recognised pharmaceutical scientists (N = 92), mainly from academia and industry, on drivers and influencing factors in pharmaceutical sciences. The study offers a unique global perspective, demonstrating a solid command of the global needs in pharmaceutical sciences. The survey revealed that UMN is currently seen as one of the three most important drivers, also in addition to emerging trends in science and opportunities driven by collaboration. There are expectations that UMN's impact becomes more influential. This was consistent for both industry and academic respondents. The majority of respondents also indicated that anticipated lessons learned from COVID-19 will strengthen the impact of UMN on science and leadership. This is important as prioritisation of research towards UMN can address the clinical needs where needed the most.

Mobile malware are malicious programs that target mobile devices. They are an increasing problem, as seen in the rise of detected mobile malware samples per year. The number of active smartphone users is expected to grow, stressing the importance of research on the detection of mobile malware. Detection methods for mobile malware exist but are still limited. In this paper, we provide an overview of the performance of machine learning (ML) techniques to detect malware on Android, without using privileged access. The ML-classifiers use device information such as the CPU usage, battery usage, and memory usage for the detection of 10 subtypes of Mobile Trojans on the Android Operating System (OS). We use a real-life dataset containing device and malware data from 47 users for a year (2016). We examine which features, i.e. aspects, of a device, are most important to monitor to detect (subtypes of) Mobile Trojans. The focus of this paper is on dynamic hardware features. Using these dynamic features we apply state-of-the-art machine learning classifiers: Random Forest, K-Nearest Neighbour, and AdaBoost. We show classification results on different feature sets, making a distinction between global device features, and specific app features. None of the measured feature sets require privileged access. Our results show that the Random Forest classifier performs best as a general malware classifier: across 10 subtypes of Mobile Trojans, it achieves an F1 score of 0.73 with a False Positive Rate (FPR) of 0.009 and a False Negative Rate (FNR) of 0.380. The Random Forest, K-Nearest Neighbours, and AdaBoost classifiers achieve F1 scores above 0.72, an FPR below 0.02 and, an FNR below 0.33, when trained separately to detect each subtype of Mobile Trojans., Comment: 14 pages content, 22 pages total, to be published in ACM DTRAP (currently in last revision phase)

Agricultural land abandonment and its impacts on landscape features have been a, striking characteristic of many European rural areas over the last decades. Although, previous research identified drivers and environmental impacts of abandonment, few, described the post-agricultural abandonment trajectories. However, examining the, driving forces leading to different post-agricultural abandonment trajectories is key to, understand how alternative uses of these lands can be developed to address the, environmental, economic, and social challenges faced in these areas. This paper, reviews the literature of the different trajectories observed after agricultural, abandonment and the related drivers and processes. Based on the literature evidence, we proposed a novel categorisation of different abandonment trajectories, with their, drivers and landscape outcomes. In most reported cases, lands transitioned towards, semi-natural landscapes and few returned to different agricultural uses after, abandonment. The most common driving force of the landscape trajectory was the, absence of land management where secondary succession processes led to seminatural, landscapes. Quality and state of these landscapes were variable. Alternative, trajectories were essentially driven by institutional and socio-economic drivers within, biophysical constraints and opportunities for (re-)afforestation, re-farming, and multifunctional, uses of the land after abandonment. While abandoned lands can bring, opportunities to respond to biodiversity and other environmental policy goals, the, evidence across case studies suggests that adequate resources with institutional and, socio-economic incentives are required to stimulate favourable development, mitigate, potential trade-offs, and support land management.

Recently, increasing evidence suggests that neuroinflammation may be a critical factor in the development of Parkinson's disease (PD) in addition to the ratio of acetylcholine/dopamine because dopaminergic neurons are particularly vulnerable to inflammatory attack. In this study, we investigated whether botulinum neurotoxin A (BoNT-A) was effective for the treatment of PD through its anti-neuroinflammatory effects and the modulation of acetylcholine and dopamine release. We found that BoNT-A ameliorated MPTP and 6-OHDA-induced PD progression, reduced acetylcholine release, levels of IL-1β, IL-6 and TNF-α as well as GFAP expression, but enhanced dopamine release and tyrosine hydroxylase expression. These results indicated that BoNT-A had beneficial effects on MPTP or 6-OHDA-induced PD-like behavior impairments via its anti-neuroinflammation properties, recovering dopamine, and reducing acetylcholine release.

OBJECTIVETo evaluate outcomes of dogs with parathyroid carcinoma (PTC) treated by surgical excision and to describe the incidence of postoperative hypocalcemia, degree of hypocalcemia, duration of hospitalization, duration of calcium supplementation, and survival timeANIMALS100 client-owned dogs with PTC admitted to academic, referral veterinary institutions.PROCEDURESIn a retrospective multi-institutional study, medical records of dogs undergoing surgical excision of PTC between 2010 to 2019 were reviewed. Signalment, relevant medical history, clinical signs, clinicopathologic testing, imaging, surgical findings, intraoperative complications, histologic examination, and survival time were recorded.RESULTS100 dogs with PTC were included, and 96 dogs had clinical or incidental hypercalcemia. Common clinical signs included polyuria (44%), polydipsia (43%), hind limb paresis (22%), lethargy (21%), and hyporexia (20%). Cervical ultrasonography detected a parathyroid nodule in 91 of 91 dogs, with a single nodule in 70.3% (64/91), 2 nodules in 25.3% (23/91), and ≥ 3 nodules in 4 (4/91)% of dogs. Hypercalcemia resolved in 89 of 96 dogs within 7 days after surgery. Thirty-four percent of dogs developed hypocalcemia, on the basis of individual analyzer ranges, within 1 week after surgery. One dog had metastatic PTC to the prescapular lymph node, and 3 dogs were euthanized for refractory postoperative hypocalcemia. Estimated 1-, 2-, and 3-year survival rates were 84%, 65%, and 51% respectively, with a median survival time of 2 years.CONCLUSIONS AND CLINICAL RELEVANCEExcision of PTC results in resolution of hypercalcemia and excellent long-term tumor control. Surgical excision of PTC is recommended because of resolution of hypercalcemia and a good long-term prognosis. Future prospective studies and long-term follow-up are needed to further assess primary tumor recurrence, metastasis, and incidence of postoperative hypocalcemia.

Background Despite the invention of various non-invasive bioengineering tools, skin-type analysis has largely been based on subjective assessments. However, advancements in the functional cosmetic industry and artificial intelligence-assisted dermatology are creating a greater demand for an objective skin-type classification system. Objectives To propose an objective skin-type classification system solely based on non-invasive, bioengineering devices; provide reference values applicable to the Korean population; and compare our reference values with those of published studies. Methods Biophysical parameter measurements were obtained from the 2018 International Skin Characteristics Data Bank Project conducted by the Foundation of Korea Cosmetic Industry Institute. The participants were 434 healthy South Korean adults. Each participant was assessed using eight bioengineering devices (Tewameter® , pH-meter® , Corneometer® , Sebumeter® , Cutometer® , Spectrophotometer® , PRIMOS® lite, and Janus® ). The measurements were divided into tertiles to determine reference points. Results Our objective skin-type classification consists of five main categories (sensitivity, hydration, oiliness, elasticity, and skin tone) and five corresponding subcategories (erythema, roughness, pores, wrinkles, and pigmentation, respectively). Each skin type was assigned based on the reference point of the biophysical parameter, which was established as the tertile value associated with 'unfavourable' skin characteristics. Individuals were categorized as having sensitive skin when the TEWL scores were over 18.0 g/m2 /h or the pH was over 5.45; dehydrated skin when the corneometric value measured below 47.17 A.U.; oily skin when the sebumetric value exceeded 70 μg/cm2 ; and loose skin when the cutometric R2 value was below 0.68 E/mm. Conclusions This study is the first to provide a comprehensive skin-type classification system based solely on non-invasive biophysical parameters. As measurement data accumulate, the reference points will progress to become more accurate, and they will be subdivided according to gender, age, and ethnic group. Therefore, our classification system serves as a basis for artificial intelligence-based skin-type analysis.

Background: The maturation and patency of permanent vascular access are critical in patients requiring hemodialysis. Although numerus trials have been attempted to achieve permanently patent vascular access, little have been noticeable. Cilostazol, a phosphodiesterase-3 inhibitor, has been shown to be effective in peripheral arterial disease including vascular injury-induced intimal hyperplasia. We therefore aimed to determine the effect of cilostazol on the patency and maturation of permanent vascular access. Methods: This single-center, retrospective study included 194 patients who underwent arteriovenous fistula surgery to compare vascular complications between the cilostazol (n = 107) and control (n = 87) groups. Results: The rate of vascular complications was lower in the cilostazol group than in the control group (36.4% vs. 51.7%; p = 0.033), including maturation failure (2.8% vs. 11.5%; p = 0.016). The rate of reoperation due to vascular injury after hemodialysis initiation following fistula maturation was also significantly lower in the cilostazol group than in the control group (7.5% vs. 28.7%; p

INTRODUCTION: Depression is a prevalent condition for which screening rates remain low and disparities in screening exist. This study examines the impacts of a medical assistant screening protocol on the rates of depression screening, overall and by sociodemographic groups, in a primary care setting. METHODS: Between September 2016 and August 2018, a quasi-experimental study of adult primary care visits was conducted at an urban academic clinic to ascertain the change in the rates of completion of the Patient Health Questionnaire-2 after the implementation of a medical assistant protocol (intervention) versus that of physician-only screening (control arm). Analyses were conducted between April 2019 and April 2020 and used interrupted time-series models with generalized estimating equations. RESULTS: A total of 45,157 visits by 21,377 unique patients were included. Overall, screening increased from 18% (physician-only screening) to 57% (medical assistant protocol) (p

Introduction Retrospective studies suggest that a rapid initiation of treatment results in a better prognosis for patients in the emergency department. There could be a difference between the actual medication administration time and the documented time in the electronic health record. In this study, the difference between the observed medication administration time and documentation time was investigated. Patient and nurse characteristics were also tested for associations with observed time differences. Methods In this prospective study, emergency nurses were followed by observers for a total of 3 months. Patient inclusion was divided over 2 time periods. The difference in the observed medication administration time and the corresponding electronic health record documentation time was measured. The association between patient/nurse characteristics and the difference in medication administration and documentation time was tested with a Spearman correlation or biserial correlation test. Results In 34 observed patients, the median difference in administration and documentation time was 6.0 minutes (interquartile range 2.0-16.0). In 9 (26.5%) patients, the actual time of medication administration differed more than 15 minutes with the electronic health record documentation time. High temperature, lower saturation, oxygen-dependency, and high Modified Early Warning Score were all correlated with an increasing difference between administration and documentation times. Discussion A difference between administration and documentation times of medication in the emergency department may be common, especially for more acute patients. This could bias, in part, previously reported time-to-treatment measurements from retrospective research designs, which should be kept in mind when outcomes of retrospective time-to-treatment studies are evaluated.

Objective To determine if patients who receive tramadol are as likely to develop persistent usage compared to other opioids after urologic surgery and procedures. Methods We identified adults 18 to 64 years old who underwent a urologic procedure in the years 2014 to 2017 using the Truven MarketScan database and subsequently filled an opioid prescription within two weeks of discharge. Patients were excluded if they had any previous opioid prescriptions in the year before surgery. A multivariate logistic regression model was constructed to estimate influence of type of opioid on discharge and various comorbidities on persistent use to determine if persistent use was related to the choice of discharge opioid. We also compared these rates to a 1:3 comorbidities matched, non-surgical cohort of patients from the general population. Results Overall, 115,687 patients were included. After 1 year, 14.8% of the urologic surgery cohort had persistent opioid usage compared to 10.8% in the opioid naive matched non-surgical cohort (OR = 1.37; 95% CI 1.35-1.39). Discharge with tramadol was associated with a higher odd of persistent usage compared to class II opioids controlling for type of urologic surgery, age, gender, and pain related comorbidities (OR = 1.23 95% CI 1.13-1.35). The odds of persistent usage varied slightly by type of urologic procedure, but all were higher than matched non-surgical cohort. Conclusion Patients developed persistent opiate usage after urologic surgery compared to a comorbidity matched non-surgical cohort. In this model, tramadol specifically was associated with higher odds of novel persistent opioid usage compared to other opioids. Urologists should not consider tramadol to be a safer choice with regard to developing persistent usage and consider prospective validation of these results.

Background: Data are scarce on immunogenicity of COVID-19 vaccines in patients with autoimmune diseases, who are often treated with immunosuppressive drugs. We aimed to investigate the effect of different immunosuppressive drugs on antibody development after COVID-19 vaccination in patients with autoimmune diseases. Methods: In this study, we used serum samples collected from patients with autoimmune diseases and healthy controls who were included in two ongoing prospective cohort studies in the Netherlands. Participants were eligible for inclusion in this substudy if they had been vaccinated with any COVID-19 vaccine via the Dutch national vaccine programme, which at the time was prioritising vaccination of older individuals. Samples were collected after the first or second COVID-19 vaccination. No serial samples were collected. Seroconversion rates and IgG antibody titres against the receptor-binding domain of the SARS-CoV-2 spike protein were measured. Logistic and linear regression analyses were used to investigate the association between medication use at the time of vaccination and at least until sampling, seroconversion rates, and IgG antibody titres. The studies from which data were collected are registered on the Netherlands Trial Register, Trial ID NL8513, and ClinicalTrials.org, NCT04498286.Findings: Between April 26, 2020, and March 1, 2021, 3682 patients with rheumatic diseases, 546 patients with multiple sclerosis, and 1147 healthy controls were recruited to participate in the two prospective cohort studies. Samples were collected from patients with autoimmune diseases (n=632) and healthy controls (n=289) after their first (507 patients and 239 controls) or second (125 patients and 50 controls) COVID-19 vaccination. The mean age of both patients and controls was 63 years (SD 11), and 423 (67%) of 632 patients with autoimmune diseases and 195 (67%) of 289 controls were female. Among participants without previous SARS-CoV-2 infection, seroconversion after first vaccination were significantly lower in patients than in controls (210 [49%] of 432 patients vs 154 [73%] of 210 controls; adjusted odds ratio 0·33 [95% CI 0·23-0·48]; pInterpretation: Our data suggest that seroconversion after a first COVID-19 vaccination is delayed in older patients on specific immunosuppressive drugs, but that second or repeated exposure to SARS-CoV-2, either via infection or vaccination, improves humoral immunity in patients treated with immunosuppressive drugs. Therefore, delayed second dosing of COVID-19 vaccines should be avoided in patients receiving immunosuppressive drugs. Future studies that include younger patients need to be done to confirm the generalisability of our results.FUNDING: ZonMw, Reade Foundation, and MS Center Amsterdam.

Objective Advances in surface-based morphometric methods have allowed researchers to separate cortical volume into cortical thickness (CTh) and surface area (SA). Although CTh alterations in major depressive disorder (MDD) have been observed in numerous studies, few studies have described significant SA alterations. Our study aimed to measure patients’ SAs and to compare it with their CTh to examine whether SA exhibits alteration patterns that differ from those of CTh in drug-naïve patients with MDD.Methods A total of 71 drug-naïve MDD patients and 111 healthy controls underwent structural magnetic resonance imaging, and SA and CTh were analyzed between the groups.Results We found a smaller SA in the left superior occipital gyrus (L-SOG) in drug-naïve patients with MDD. In the CTh analysis, the bilateral fusiform gyrus, left middle occipital gyrus, left temporal superior gyrus, and right posterior cingulate showed thinner cortices in patients with MDD, while the CTh of the bilateral SOG, right straight gyrus, right posterior cingulate, and left lingual gyrus were increased.Conclusion Compared with the bilateral occipito-temporal changes in CTh, SA alterations in patients with MDD were confined to the L-SOG. These findings may improve our understanding of the neurobiological mechanisms of SA alteration in relation to MDD.

Background : Major depressive disorder (MDD) is one of the most prevalent mental disorders during adolescence, and early diagnosis and treatment are important. We aimed to characterize the microstructure of the brain in medication-naive adolescents with first-episode MDD. Methods : Patients with MDD (N = 31) and healthy controls (N = 27) participated in this study and severity of depressive symptoms, duration of untreated depressive episode, demographic data, and diffuse tensor imaging data were collected. A comparative analysis of patients and healthy controls was performed, and the effect of medication on the brain`s integrity was investigated through comparison before and after 3 months of treatment in the patient group. Tract-based spatial statistics was used for diffusion tensor image analysis. Results : In the patient group, functional anisotropy (FA) values were significantly higher at the genu of the corpus callosum, body of the corpus callosum, and right anterior corona radiata than in healthy controls. After 3 months of treatment, FA values were significantly decreased in the left anterior limb of the internal capsule, left posterior limb of the internal capsule, and left superior longitudinal fasciculus. Limitations : The sample size is relatively small and 3-month treatment period was relatively short. Conclusion : FA values of patients with MDD were increased compared to healthy controls and decreased after treatment. These results suggested that pharmacological treatments in the early stages of MDD might restore the brain`s integrity.

Background: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. Methods: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin

Knowledge regarding the etiology and prognosis for canine megaesophagus (ME) is currently limited to small case series that may now be out of date in light of recent advances in the understanding of neurological syndromes and the availability of advanced diagnostic testing. Ninety-nine dogs diagnosed with nonstructural ME were included. Congenital idiopathic ME was present in 10 cases, with complete resolution of clinical signs in a single case. Eighty-nine cases were considered acquired, with most cases being either idiopathic (42.7%) or associated with myasthenia gravis (38.2%). Idiopathic cases represented a smaller percentage of acquired ME than previously reported. Death or euthanasia directly related to ME occurred in almost 50% of acquired cases, whereas clinical signs persisted in ∼20% of cases and resolved in 30% of cases. A diagnosis of an underlying etiology, in particular myasthenia gravis, was associated with a better outcome in acquired ME. ME continues to be a challenging condition to manage, with a guarded-to-poor prognosis, particularly when an underlying etiology is not identified. Thorough diagnostic testing for an underlying neurological disorder is important in cases with ME as this may allow institution of appropriate treatment and the potential for a better prognosis.

Contains fulltext : 248362.pdf (Publisher’s version ) (Open Access) INTRODUCTION: One-quarter of the relapses in children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) occur very early (within 18 months, before completion of treatment), and prognosis in these patients is worse compared to cases that relapse after treatment has ended. METHODS: In this study, we performed a genomic analysis of diagnosis-relapse pairs of 12 children who relapsed very early, followed by a deep-sequencing validation of all identified mutations. In addition, we included one case with a good initial treatment response and on-treatment relapse at the end of upfront therapy. RESULTS: We observed a dynamic clonal evolution in all cases, with relapse almost exclusively originating from a subclone at diagnosis. We identified several driver mutations that may have influenced the outgrowth of a minor clone at diagnosis to become the major clone at relapse. For example, a minimal residual disease (MRD)-based standard-risk patient with ETV6-RUNX1-positive leukemia developed a relapse from a TP53-mutated subclone after loss of the wildtype allele. Furthermore, two patients with TCF3-PBX1-positive leukemia that developed a very early relapse carried E1099K WHSC1 mutations at diagnosis, a hotspot mutation that was recurrently encountered in other very early TCF3-PBX1-positive leukemia relapses as well. In addition to alterations in known relapse drivers, we found two cases with truncating mutations in the cohesin gene RAD21. CONCLUSION: Comprehensive genomic characterization of diagnosis-relapse pairs shows that very early relapses in BCP-ALL frequently arise from minor subclones at diagnosis. A detailed understanding of the therapeutic pressure driving these events may aid the development of improved therapies.

Background: The impact of warm ischemia time (WIT) on renal functional recovery remains controversial. We examined the length of WIT >30 min. on the long-term renal function following on-clamp partial nephrectomy (PN). Methods: Data from 23 centers for patients undergoing on-clamp PN between 2000 and 2018 were analyzed. We included patients with two kidneys, single tumor, cT1, minimum 1-year followup, and preoperative eGFR ≥60 ml/min/1.73m2. Patients were divided into two groups according to WIT length: group Ⅰ "WIT ≤30 min." and group Ⅱ "WIT >30 min.". A propensity-score matched analysis (1:1 match) was performed to eliminate potential confounding factors between groups. We compared eGFR values, eGFR (%) preservation, eGFR decline, events of chronic kidney disease (CKD) upgrading, and CKD-free progression rates between both groups. Cox regression analysis evaluated WIT impact on upgrading of CKD stages. Results: The primary cohort consisted of 3526 patients: group Ⅰ (n=2868) and group Ⅱ (n=658). After matching the final cohort consisted of 344 patients in each group. At last followup, there were no significant differences in median eGFR values at 1, 3, 5, and 10 years (P>0.05) between the matched groups. In addition, the median eGFR (%) preservation and absolute eGFR change were similar (89% in group Ⅰ vs. 87% in group Ⅱ, p=0.638) and (-10 in group Ⅰ vs. -11 in group Ⅱ, p=0.577), respectively. The 5 years new-onset CKD-free progression rates were comparable in the non-matched groups (79% in group Ⅰ vs. 81% in group Ⅱ, log-rank, p=0.763) and the matched groups (78.8% in group Ⅰ vs. 76.3% in group Ⅱ, log-rank, p=0.905). Univariable Cox regression analysis showed that WIT >30 min. was not a predictor of overall CKD upgrading (HR:0.953, 95%CI 0.829-1.094, p=0.764) nor upgrading into CKD stage ≥Ⅲ (HR:0.972, 95%CI 0.805-1.173, p=0.764). Retrospective design is a limitation of our study. Conclusions: Our analysis based on a large multicenter international cohort study suggests that WIT length during PN has no effect on the long-term renal function outcomes in patients having two kidneys and preoperative eGFR ≥60 ml/min/1.73m2.

Research into organic light emitters employing multiple resonance-induced thermally activated delayed fluorescence (MR-TADF) materials is presently attracting a great deal of attention due to the potential for efficient deep-blue emission. However, the origins and mechanisms of successful TADF are unclear, as many MR-TADF materials do not show TADF behaviour in solution, but only as particular pure solids. Here, an investigation into a well-known MR-TADF material, DABNA-1, together with other new MR materials (9H-quinolino[3,2,1-kl]phenothiazin-9-one (QPO) and 9H-quinolino-[3,2,1-kl]-phenothiazin-9-one 5,5-dioxide (QP3O)), yields new insights regarding the origin of TADF. Although a material system may support the concept of MR, inefficiency in both forward and reverse intersystem crossings forbids TADF unless a suitable host material allows an exciplex-like host–emitter interaction that boosts TADF. This boosted-TADF mechanism can be generalized to any fluorescence dye that lacks TADF in the photoluminescence measurement but has a thermally accessible S1–T1 energy gap, opening the way to high-performance organic light-emitting diodes. This study reveals the importance of host–guest interactions for effective multiple-resonance thermally activated delayed fluorescence in organic light emitters.

Atypical psychological symptoms frequently occur in early-onset Alzheimer’s disease (EOAD), which makes it difficult to differentiate it from other psychiatric disorders. We report the case of a 28-year-old woman with EOAD, carrying a presenilin-1 mutation (S170P), who was initially misdiagnosed with schizophrenia because of prominent psychiatric symptoms in the first 1–2 years of the disease. Amyloid-β positron emission tomography (PET) showed remarkably high tracer uptake in the striatum and thalamus. Tau PET showed widespread cortical uptake and relatively low uptake in the subcortical and medial temporal regions. Our case advocates for considering EOAD diagnosis for young patients with psychiatric and atypical cognitive symptoms.

Aim: To gain insight into the education about substandard and falsified (SF) medical products. Method: A digital survey was sent to 173 different schools of pharmacy around the world. Results: The response rate was 32% (55 responses, 37 countries). Most schools taught about SF medical products as a stand-alone course or as part of another course or module (67%), whereas 33% did not teach about the subject. The main focus of teaching was on detection (21%) and prevention (21%) of SF medical products, while reporting was taught the least (12%), indicating a knowledge gap in that area. A key barrier to introducing a new course that could close the gaps was insufficient time in pharmacy curriculum (n=33; 60%), while availability of ready-to-adopt course materials was considered as a helpful enabler. Conclusion: These insights can improve the understanding on what is already being taught on SF medical products, where the gaps are and inform the curriculum needed globally.

Video capsule endoscopy (VCE) has become the accepted evaluation of choice for patients with suspected small bowel bleeding. Our aim was to evaluate the impact of early as compared to delayed inpatient VCE on post-index hospitalization readmission rates. We performed a retrospective study using medical claims from the IBM® Marketscan® Commercial Database from January 1, 2004, through September 30, 2018, including adult patients that underwent an inpatient VCE. Early VCE was defined as occurring on days 0, 1, or 2 of the index hospitalizations, whereas delayed VCE was performed on days 3–7. Propensity matching was performed to create an analytic cohort, and outcomes were assessed using logistic regression. Following propensity score matching, 607 patients undergoing early VCE were matched 1:1 with 607 patients undergoing delayed VCE. The median patient age was 65 (IQR: 56–78) years, and 560 (37.9%) of the included patients were female. The mean time to VCE was 1.6 (± 0.6) days for the early VCE group and 4.0 (± 1.2) days from admission for delayed VCE. In unadjusted comparisons, we found no significant difference between early VCE and delayed VCE with respect to 90-day all-cause readmission (18.6% vs. 17.0%, P = 0.5) or 90-day rebleeding risk (10.5% vs. 8.7%, P = 0.331). Patients undergoing an early VCE had a shorter hospital LOS and less total hospitalization charges. Early as compared to delayed inpatient VCE was associated with a reduction in index hospitalization resource utilization. No differences were found with respect to reductions in readmissions or rebleeding events.

Background: The present study investigated the association between two domains of physical activity (occupational physical activity [OPA] and leisure-time physical activity [LTPA]) and sleep duration. Methods: We investigated 3,421 paid workers from the Korea National Health and Nutrition Examination Survey, 2014–2015. Sleep duration was categorized into three categories (short for less than 5 h, optimal for 5–9 h, and long for more than 9 h). OPA and LTPA were defined in terms of answers to relevant questions. Odds ratios were calculated for sleep duration according to each physical activity domain using multinomial logistic regression models. Results: There were 464 subjects (13.6%) who showed short sleep duration, and 169 subjects (4.9%) who showed long sleep duration. Prevalence of OPA and LTPA was higher in male workers than in female workers (for OPA: 3.67% and 1.76%, respectively, p = 0.0108; for LTPA: 16.14% and 6.07%, respectively, p

Contains fulltext : 238920.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Hyperemesis gravidarum (HG) complicates 1% of pregnancies and has a major impact on maternal quality of life and well-being. We know very little about HG's long-term impact after an affected pregnancy, including recurrence rates in future pregnancies, which is essential information for women considering subsequent pregnancies. In this study, we aimed to prospectively measure the recurrence rate of HG and the number of postponed and terminated subsequent pregnancies due to HG. We also aimed to evaluate if there were predictive factors that could identify women at increased risk for HG recurrence, and postponing and terminating subsequent pregnancies. MATERIAL AND METHODS: We conducted a prospective cohort study. A total of 215 women admitted for HG to public hospitals in the Netherlands were enrolled in the original MOTHER randomized controlled trial and associated observational cohort. Seventy-three women were included in this follow-up study. Data were collected through an online questionnaire. Recurrent HG was defined as vomiting symptoms accompanied by any of the following: multiple medication use, weight loss, admission, tube feeding or if nausea and vomiting symptoms were severe enough to affect life and/or work. Outcome measures were recurrence, postponing, and termination rates due to HG. Univariable logistic regression analysis was used to identify predictive factors associated with HG recurrence, and postponing and terminating subsequent pregnancies. RESULTS: Thirty-five women (48%) became pregnant again of whom 40% had postponed their pregnancy due to HG. HG recurred in 89% of pregnancies. One woman terminated and eight women (23%) considered terminating their pregnancy because of recurrent HG. Twenty-four out of 38 women did not get pregnant again because of HG in the past. Univariable logistic regression analysis identifying possible predictive factors found that having a western background was associated with having weight loss due to recurrent HG in subsequent pregnancies (odds ratio 12.9, 95% CI 1.3-130.5, p = 0.03). CONCLUSIONS: High rates of HG recurrence and a high number of postponed pregnancies due to HG were observed. Women can be informed of a high chance of recurrence to enable informed family planning.

Objective Although bipolar II disorder (BD II) is not simply a mitigated form of bipolar I disorder (BD I), their neurobiological differences have not been elucidated. The present study aimed to explore cortical thickness (CT) and surface area (SA) in patients with BD I and BD II and healthy controls (HCs) to investigate the shared and unique neurobiological mechanisms of BD subtypes.Methods We enrolled 30 and 44 patients with BD I and BD II, respectively, and 100 HCs. We evaluated CT and SA using FreeSurfer and estimated differences in CT and SA among the three groups (BD I vs. BD II vs. HC). We adjusted for age, sex, educational level, and intracranial volume as confounding factors.Results We found widespread cortical thinning in the bilateral frontal, temporal, and occipital regions; cingulate gyrus; and insula in patients with BD. Alterations in SA, including increased SA of the pars triangularis and decreased SA of the insula, were noted in patients with BD. Overall, we found BD II patients demonstrated decreased SA in the right long insula compared to BD I patients.Conclusion Our results suggest that decreased SA in the right long insula is crucial for differentiating BD subtypes.

Retrospective descriptive study. To summarize epidemiologic data on nontraumatic spinal cord injury (NTSCI) for the last 30 years and compare these findings to data from individuals with traumatic spinal cord injury (TSCI). National Rehabilitation Center affiliated with the Ministry of Health and Welfare in Korea. The medical records of 948 individuals with NTSCIs were retrospectively reviewed. Three groups were created based on onset period (1990–1999, 2000–2009, 2010–2019) and six groups based on age (≤15, 16–30, 31–45, 46–60, 61–75, and ≥76 years). Pearson’s chi-square and analysis of variance tests were used for statistical analysis. The male-to-female ratio was 1.30:1 for NTSCI individuals and 3.47:1 for TSCI individuals. The mean age (standard deviation [SD]) at the time of injury increased from 38.7 (SD = 18.1) years in the 1990s to 55.5 (SD = 16.6) years in the 2010s (F = 44.597, p ≤ 0.001). Vertebral column degenerative disorder was the primary cause of injury in 28.9% of the cases, and the most common neurologic level was T12-L2. Paraplegia occurred in 74.6% of cases, and tetraplegia in 25.4% of cases. The proportion of NTSCI individuals increased from 11.2% to 29.3% during the observation period. The proportion of NTSCI among total spinal cord injuries has increased in Korea over the last 30 years (1990–2019). Compared to individuals with TSCI, those with NTSCI had a higher age at onset, with different male-to-female ratios. Our study is the most comprehensive investigation of NTSCI in Korea, and our findings can inform research directions and medical guidelines.

Patients with severe asthma have unmet clinical needs for effective and safe therapies. One possibility may be mesenchymal stem cell (MSC) therapy, which can improve asthma in murine models. However, it remains unclear how MSCs exert their beneficial effects in asthma. Here, we examined the effect of human umbilical cord blood-derived MSCs (hUC-MSC) on two mouse models of severe asthma, namely, Alternaria alternata-induced and house dust mite (HDM)/diesel exhaust particle (DEP)-induced asthma. hUC-MSC treatment attenuated lung type 2 (Th2 and type 2 innate lymphoid cell) inflammation in both models. However, these effects were only observed with particular treatment routes and timings. In vitro co-culture showed that hUC-MSC directly downregulated the interleukin (IL)-5 and IL-13 production of differentiated mouse Th2 cells and peripheral blood mononuclear cells from asthma patients. Thus, these results showed that hUC-MSC treatment can ameliorate asthma by suppressing the asthmogenic cytokine production of effector cells. However, the successful clinical application of MSCs in the future is likely to require careful optimization of the route, dosage, and timing.

Firms face a greater risk of lawsuits for overstated rather than understated earnings or net assets, suggesting conservatism can reduce firms' expected legal costs. Because managers with legal expertise are more likely than other managers to recognize the legal benefits of conservatism, this study examines whether legal expertise among members of senior management promotes greater conservatism. Consistent with this prediction, we find that firms with a general counsel (GC) in senior management (our proxy for legal expertise) report more conservatively. We also find that GC firms recalibrate their conservatism levels in response to changes in the legal environment—their conservatism choices are more responsive to litigation against peer firms and to two judicial rulings that affected the litigation risk for firms located in the Ninth Circuit. Overall, our findings suggest that populating senior management with legal experts affects the extent to which a firm's level of conservatism incorporates legal risks. Data Availability: Data are available from public sources identified in the text. JEL Classifications: K40; M41.

Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype with rapid growth, high rates of metastasis, recurrence and drug resistance, and diverse molecular and histological heterogeneity. Patient-derived xenografts (PDXs) provide a translational tool and physiologically relevant system to evaluate tumor biology of rare subtypes. Here, we provide an in-depth comprehensive characterization of a new PDX model for MBC, TU-BcX-4IC. TU-BcX-4IC is a clinically aggressive tumor exhibiting rapid growth in vivo, spontaneous metastases, and elevated levels of cell-free DNA and circulating tumor cell DNA. Relative chemosensitivity of primary cells derived from TU-BcX-4IC was performed using the National Cancer Institute (NCI) oncology drug set, crystal violet staining, and cytotoxic live/dead immunofluorescence stains in adherent and organoid culture conditions. We employed novel spheroid/organoid incubation methods (Pu·MA system) to demonstrate that TU-BcX-4IC is resistant to paclitaxel. An innovative physiologically relevant system using human adipose tissue was used to evaluate presence of cancer stem cell-like populations ex vivo. Tissue decellularization, cryogenic-scanning electron microscopy imaging and rheometry revealed consistent matrix architecture and stiffness were consistent despite serial transplantation. Matrix-associated gene pathways were essentially unchanged with serial passages, as determined by qPCR and RNA sequencing, suggesting utility of decellularized PDXs for in vitro screens. We determined type V collagen to be present throughout all serial passage of TU-BcX-4IC tumor, suggesting it is required for tumor maintenance and is a potential viable target for MBC. In this study we introduce an innovative and translational model system to study cell–matrix interactions in rare cancer types using higher passage PDX tissue.

Educated and skilled women are active change agents. This paper focuses on informal hospitality education as a tool for social change and empowerment for severely marginalized Nepalese women. Studied over 18 months, a small group of women cooking for a boutique local and international tourist market in Kathmandu participated in cookery skills training. The Australian educator/researchers focused on the educational experience to uptake and retention of cookery skills and technical language. As a result of the educational intervention, changes in personal attributes and perceptions of inherent sociocultural gender roles/caste emerged. Participation in the cookery skills training program contributed partially as a catalyst that improved confidence, communication skills and exposed to the women pathways toward self-sustainability, emancipation and empowerment within an often-hostile working environment for women from severely disadvantaged backgrounds in Nepal.

Background: Elevated plasma homocysteine has been found to be associated with an increased risk of osteoporosis, especially hip and vertebral fractures. The plasma concentration of homocysteine is dependent on the activities of several B vitamin-dependent enzymes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and cystathionine β-synthase (CBS). Objectives: We investigated whether genetic variants in some of the genes involved in 1 carbon metabolism modify the association of B vitamin-related measures with bone mineral density (BMD) and strength. Methods: We measured several B vitamins and biomarkers in participants of the Framingham Offspring Study, and performed analyses of methylmalonic acid (MMA) continuously and

Purpose The purpose of this study is to reflect upon the ramifications of two decades of Lean Six Sigma implementations in Dutch healthcare institutions in the light of the current COVID-19 pandemic. Design/methodology/approach The authors provide an evaluation of the impact that Lean Six Sigma implementations have had on the ability of Dutch healthcare institutions to respond adequately to healthcare needs during the COVID-19 crisis. Findings Process improvement in healthcare has had a tendency to cut capacity and flexibility which are needed to deal with excessive demand shocks, such as during a pandemic. The main reason for this failure seems to be an overly strong focus on cost reduction instigated by Lean Six Sigma during stable times. Research limitations/implications Besides the research method being an inferential procedure, the research focuses on the Netherlands and so the generalizability might be limited. However, using Lean Six Sigma to improve healthcare processes has found broad acceptance, so the implications may well carry over to other countries. Practical implications The authors call for a more comprehensive approach of process improvement within healthcare that takes flexibility and buffering in anticipation of excess variability and disruption into greater account. Therefore, this study provides a new perspective on how and to which aim Lean Six Sigma should be applied in healthcare. Originality/value An assessment is given of the impact of Lean Six Sigma implementations on the ability to respond to the COVID-19 crisis. This is done by identifying the focus points of improvement projects and considering the impact on the resilience of healthcare operations.

People with mental health disorders face elevated risk of metabolic syndrome (MetS), which increases the risk of serious health problems and premature mortality. Obesity is prevalent among those ho...

Although deep learning has achieved a milestone in forecasting the El Nino-Southern Oscillation (ENSO), the current models are insufficient to simulate diverse characteristics of the ENSO, which depends on the calendar season. Consequently, a model was generated for specific seasons which indicates these models did not consider physical constraints between different target seasons and forecast lead times, thereby leading to arbitrary fluctuations in the predicted time series. To overcome this problem and account for ENSO seasonality, we developed an all-season convolutional neural network (A_CNN) model. The correlation skill of the ENSO index was particularly improved for forecasts of the boreal spring, which is the most challenging season to predict. Moreover, activation map values indicated a clear time evolution with increasing forecast lead time. The study findings reveal the comprehensive role of various climate precursors of ENSO events that act differently over time, thus indicating the potential of the A_CNN model as a diagnostic tool.

In a democracy, political advertising should offer truthful information so voters can make informed decisions about candidates. Given changes in political advertising (digital media, regulations), ...

Extraprostatic extension (EPE) is a factor in determining pT3a stage in prostate cancer. However, the only distinction in EPE is whether it is focal or non-focal, causing diagnostic and prognostic ambiguity. We substaged pT3a malignancies using classification of EPE to improve personalized prognostication. We evaluated 465 radical prostatectomy specimens with a digital image analyzer by measuring the number, radial distance and two-dimensional square area of the EPE. The most significant cut-off value was proposed as an algorithm for the pT3a substaging system to predict biochemical recurrence (BCR). A combination of the radial distance and the number of EPEs predicted BCR the most effectively. The optimal cut-off criteria were 0.75 mm and 2 mm in radial distance and multifocal EPE (hazard ratio: 2.526, C-index 0.656). The pT3a was subdivided into pT3a1, 2 mm and any number of EPEs or 0.75–2 mm and ≥ 2 EPEs. This combined tier was highly significant in the prediction of BCR-free survival. The combination of radial distance and number of EPEs could be used to subdivide pT3a prostate cancer and may aid in the prediction of BCR.

Creating scalable, high performance PDE-based simulations requires a suitable combination of discretizations, differential operators, preconditioners and solvers. The required combination changes with the application and with the available hardware, yet software development time is a severely limited resource for most scientists and engineers. Here we demonstrate that generating simulation code from a high-level Python interface provides an effective mechanism for creating high performance simulations from very few lines of user code. We demonstrate that moving from one supercomputer to another can require significant algorithmic changes to achieve scalable performance, but that the code generation approach enables these algorithmic changes to be achieved with minimal development effort.

Garlic is one of the most important crops used as condiments in Ethiopian. However, its productivity of garlic is less than half the world average. Lack of productive varieties and improved agronomic practices, as well as diseases and insect pests are the major causes of low productivity. The objective of the present study was to investigate an adaptive performance of some introduced garlic genotypes of Korean varieties in Ethiopia. The thirteen garlic genotypes were imported from the National Institute of Horticulture and Herbal Sciences (NIHHS), Rural Development Administration, Republic of Korea. The genotypes were tested for adaptation at Debre Zeit and Kulumsa agricultural research centers. Among the thirteen genotypes tested, only three genotypes Namdo, Daeseo, and Wangyo 57022 formed bulbs, while the remaining ten genotypes did not form bulbs despite the long growth period (179 days) taken to mature. The three genotypes had bigger bulbs and fewer but bigger cloves compared to the local varieties such as G-94-1/94, G-104-1/94, and Holeta local. A follow up replicated trial comparing Namdo with three local varieties was undertaken at Kulumsa. The replicated trial also showed that Namdo had better yield than the three local varieties. Moreover, it produced bigger bulbs and cloves than all the local varieties, which eases household and industrial processing of cloves. Therefore, verification of Namdo for production in Ethiopia could provide a better option for processing garlic.