Enhancing Validity and Reliability Through Feedback-Driven Exploration: A Study in the Context of Conjoint Analysis

This study proposes a research design for the enhancement of validity and reliability in conjoint analysis research. For this purpose, we are applying the concept of feedback-driven exploration to conjoint analysis and assess the proposed research design concerning its benefits and limitations in respect of validity and reliability of results. The article is of interest for the field of preference elicitation through stated preference methods, and for model validation in transdisciplinary research. By applying the principle of feedback-driven exploration, we allow for feedback loops between researchers, industry experts and survey participants in order to strengthen both validity and reliability. A multi-case study of the agricultural markets in Switzerland illustrates the functioning of the proposed research design. We find that feedback-driven exploration significantly increases validity and reliability by enhancing methodological rigor and implementing an error-correcting mechanism. Additionally, a better understanding of the underlying decision processes is supported by the design due to increased interaction between researchers, industry experts and market participant

Post-acute COVID-19 syndrome. Incidence and risk factors: A Mediterranean cohort study

Objectives: This study aims to analyze the incidence of Post-acute COVID-19 syndrome (PCS) and its components, and to evaluate the acute infection phase associated risk factors.Methods: A prospective cohort study of adult patients who had recovered from COVID-19 (27th February to 29th April 2020) confirmed by PCR or subsequent seroconversion, with a systematic assessment 10-14 weeks after disease onset. PCS was defined as the persistence of at least one clinically relevant symptom, or abnormalities in spirometry or chest radiology. Outcome predictors were analyzed by multiple logistic regression (OR; 95%CI).Results: Two hundred seventy seven patients recovered from mild (34.3%) or severe (65.7%) forms of SARS-CoV-2 infection were evaluated 77 days (IQR 72-85) after disease onset. PCS was detected in 141 patients (50.9%; 95%CI 45.0-56.7%). Symptoms were mostly mild. Alterations in spirometry were noted in 25/269 (9.3%), while in radiographs in 51/277 (18.9%). No baseline clinical features behaved as independent predictors of PCS development.Conclusions: A Post-acute COVID-19 syndrome was detected in a half of COVID19 survivors. Radiological and spirometric changes were mild and observed in less than 25% of patients. No baseline clinical features behaved as independent predictors of Post-acute COVID-19 syndrome development

Mirror gait retraining for the treatment of patellofemoral pain in female runners.

BACKGROUND: Abnormal hip mechanics are often implicated in female runners with patellofemoral pain. We sought to evaluate a simple gait retraining technique, using a full-length mirror, in female runners with patellofemoral pain and abnormal hip mechanics. Transfer of the new motor skill to the untrained tasks of single leg squat and step descent was also evaluated. METHODS: Ten female runners with patellofemoral pain completed 8 sessions of mirror and verbal feedback on their lower extremity alignment during treadmill running. During the last 4 sessions, mirror and verbal feedback were progressively removed. Hip mechanics were assessed during running gait, a single leg squat and a step descent, both pre- and post-retraining. Subjects returned to their normal running routines and analyses were repeated at 1-month and 3-month post-retraining. Data were analyzed via repeated measures analysis of variance. FINDINGS: Subjects reduced peaks of hip adduction, contralateral pelvic drop, and hip abduction moment during running (P<0.05, effect size=0.69-2.91). Skill transfer to single leg squatting and step descent was noted (P<0.05, effect size=0.91-1.35). At 1 and 3 months post retraining, most mechanics were maintained in the absence of continued feedback. Subjects reported improvements in pain and function (P<0.05, effect size=3.81-7.61) and maintained through 3 months post retraining. INTERPRETATION: Mirror gait retraining was effective in improving mechanics and measures of pain and function. Skill transfer to the untrained tasks of squatting and step descent indicated that a higher level of motor learning had occurred. Extended follow-up is needed to determine the long term efficacy of this treatment

Onlinehandel und Raumentwicklung - Neue Urbanität für alte Zentren!

Die Digitalisierung unserer Gesellschaft bedeutet für den Einzelhandel und unsere Städte einen tiefgreifenden Umbruch. Viele Menschen nutzen das Internet inzwischen regelmäßig für ihren Einkauf. Weiterhin hohe Wachstumsraten sprechen für eine anhaltende Dynamik bei der Verbreitung auch in Deutschland. Die veränderten Einkaufsgewohnheiten gehen mit einer Umsatzverlagerung vom stationären Handel in den Onlinehandel einher und verändern die Nutzungsstrukturen in den Stadtzentren. Dies wirft bezüglich der Raumentwicklung vielfältige Fragen auf. Die AG "Onlinehandel und Raumentwicklung" - ein ehrenamtlich arbeitendes, zeitlich befristetes, inter- und transdisziplinäres Gremium der Landesarbeitsgemeinschaft Nordrhein-Westfalen der Akademie für Raumentwicklung in der Leibniz-Gemeinschaft (ARL) - hat diese Fragen aufgegriffen und diskutiert.With the expansion of online trading, retail trade development has reached a new level in the process of ongoing structural change. Multi-channel concepts that combine offline and online retail are becoming increasingly important. In the course of digitalisation, "hybrid" types of enterprises that show significant differences from traditional retail stores are emerging. For providers unable to find answers to the challenges associated with this change, it will become more and more difficult to maintain their market position. The retail structures are changing - and that is changing our cities. In many town centres, the declining demand for retail space is already clearly visible today. The spatial effects depend on the specific situation at the respective location. The basic tendency is to expect a thinning out and polarisation of the urban centre systems: A few town centres with a special experiential character will assert themselves as retail locations and will be able to further distinguish themselves, in other locations the task of local supply will move into the focus in the future, and some town centres will lose their supply function. But even or especially in a digital world: Town centres are not a obsolescent model! On the contrary, the current developments can be the starting line for multifunctional locations to emerge that exude appeal for people and stay generally attractive. Fresh thinking and active engagement are needed to make this vision come true

Nuclear-Targeted Deleted in Liver Cancer 1 (DLC1) Is Less Efficient in Exerting Its Tumor Suppressive Activity Both In Vitro and In Vivo

BACKGROUND: Deleted in liver cancer 1 (DLC1) serves as an important RhoGTPase activating protein (RhoGAP) protein that terminates active RhoA signaling in human cancers. Increasing evidence has demonstrated that the tumor suppressive activity of DLC1 depends not only on RhoGAP activity, but also relies on proper focal adhesion localization through its interaction with tensin family proteins. Recently, there are reports showing that DLC1 can also be found in the nucleus; however, the existence and the relative tumor suppressive activity of nuclear DLC1 have never been clearly addressed. METHODOLOGY AND PRINCIPAL FINDINGS: We herein provide new evidence that DLC1 protein, which predominantly associated with focal adhesions and localized in cytosol, dynamically shuttled between cytoplasm and nucleus. Treatment of cells with nuclear export blocker, Leptomycin B (LMB), retained DLC1 in the nucleus. To understand the nuclear entry of DLC1, we identified amino acids 600-700 of DLC1 as a novel region that is important for its nuclear localization. The tumor suppressive activity of nuclear DLC1 was directly assessed by employing a nuclear localization signal (NLS) fusion variant of DLC1 (NLS-DLC1) with preferential nuclear localization. In SMMC-7721 HCC cells, expression of NLS-DLC1 failed to suppress colony formation and actin stress fiber formation in vitro. The abrogated tumor suppressive activity of nuclear DLC1 was demonstrated for the first time in vivo by subcutaneously injecting p53(-/-) RasV12 hepatoblasts with stable NLS-DLC1 expression in nude mice. The injected hepatoblasts with NLS-DLC1 expression effectively formed tumors when compared with the non-nuclear targeted DLC1. CONCLUSIONS/SIGNIFICANCE: Our study identified a novel region responsible for the nuclear entry of DLC1 and demonstrated the functional difference of DLC1 in different cellular compartments both in vitro and in vivo

Excimer formation by steric twisting in carbazole and triphenylamine-based host materials

This paper presents a detailed spectroscopic investigation of luminescence properties of 4,4′-Bis(N-carbazolyl)-1,1′-biphenyl (CBP) and N,N,N’,N’-tetraphenylbenzidine (TAD) in solutions and neat films. These compounds are compared to their derivatives CDBP and TDAD that contain methyl groups in the 2 and 2’ position of the biphenyl core. We find that whereas steric twisting in CDBP and TDAD leads to a high triplet energy of about 3.0 and 3.1 eV, respectively, these compounds also tend to form triplet excimers in a neat film, in contrast to CBP and TAD. By comparison with N-phenylcarbazole (NPC) and triphenylamine (TPA), on which these compounds are based, as well as with the rigid spiro analogs to CBP and TAD we show that the reduced excimer formation in CBP and TAD can be attributed to a localization of the excitation onto the central biphenyl part of the molecule.We acknowledge support from the Federal Ministry of Education and Research (BMBF) through the project ‘Trip-Q’, the German Science Foundation (DFG) through the Research and Training Group GRK 1640 and the UK Engineering and Physical Sciences Research Council (grant number EP/G060738/1).This is the final published version. It first appeared at http://pubs.acs.org/doi/abs/10.1021/jp512772j

Genetic variants for head size share genes and pathways with cancer

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.</p

Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits

Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but their biological interpretation often remains unclear. Most of these variants overlap with expression QTLs, indicating their potential involvement in regulation of gene expression. Here, we propose a transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) that uses multiple SNPs as instruments and multiple gene expression traits as exposures, simultaneously. Applied to 43 human phenotypes, it uncovers 3,913 putatively causal gene-trait associations, 36% of which have no genome-wide significant SNP nearby in previous GWAS. Using independent association summary statistics, we find that the majority of these loci were missed by GWAS due to power issues. Noteworthy among these links is educational attainment-associated BSCL2, known to carry mutations leading to a Mendelian form of encephalopathy. We also find pleiotropic causal effects suggestive of mechanistic connections. TWMR better accounts for pleiotropy and has the potential to identify biological mechanisms underlying complex traits

Refining Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Genetic Loci by Integrating Summary Data From Genome-wide Association, Gene Expression, and DNA Methylation Studies

Background: Recent genome-wide association studies (GWASs) identified the first genetic loci associated with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). The next step is to use these results to increase our understanding of the biological mechanisms involved. Most of the identified variants likely influence gene regulation. The aim of the current study is to shed light on the mechanisms underlying the genetic signals and prioritize genes by integrating GWAS results with gene expression and DNA methylation (DNAm) levels. Methods: We applied summary-data–based Mendelian randomization to integrate ADHD and ASD GWAS data with fetal brain expression and methylation quantitative trait loci, given the early onset of these disorders. We also analyzed expression and methylation quantitative trait loci datasets of adult brain and blood, as these provide increased statistical power. We subsequently used summary-data–based Mendelian randomization to investigate if the same variant influences both DNAm and gene expression levels. Results: We identified multiple gene expression and DNAm levels in fetal brain at chromosomes 1 and 17 that were associated with ADHD and ASD, respectively, through pleiotropy at shared genetic variants. The analyses in brain and blood showed additional associated gene expression and DNAm levels at the same and additional loci, likely because of increased statistical power. Several of the associated genes have not been identified in ADHD and ASD GWASs before. Conclusions: Our findings identified the genetic variants associated with ADHD and ASD that likely act through gene regulation. This facilitates prioritization of candidate genes for functional follow-up studies