Characterizing multiple sclerosis disease progression using a combined structural and functional connectivity metric.

Purpose: A combined resting state functional connectivity MRI (fcMRI) and diffusion tensor imaging (DTI) metric called structural and functional connectivity index (SFCI) was recently proposed for tracking disease status and progression in multiple sclerosis (MS). The metric combines fcMRI and transverse diffusivity (TD) along different functional pathways involved in principle symptomatic domains of MS. In a longitudinal study of patients with MS receiving the same MS therapy, initial worsening of transcallosal (TC) motor and frontoparietal (FP) cognitive networks, as measured by fcMRI and DTI over the first year was followed by stabilization in the second year of follow-up.

Electrochemical characterization of leached steel-making sludge.

In this work, the electrochemical properties of the leached sludge, magnetite and zinc ferrite were studied. Acetic acid was used as a leaching reagent because, in recent years, there has been a surge of interest in using zinc-containing materials as photocatalysts, with acetic acid finding application in their preparation. Various methodological approaches were used, but the best results were achieved with a combination of 1-3 h leaching in 0.

Extremity compartment syndrome: A review with a focus on non-invasive methods of diagnosis.

The article deals with an overview of acute extremity compartment syndrome with a focus on the option of non-invasive detection of the syndrome. Acute extremity compartment syndrome (ECS) is an urgent complication that occurs most often in fractures or high-energy injuries. There is still no reliable method for detecting ECS.

Identifying barriers for nature-based solutions in flood risk management: An interdisciplinary overview using expert community approach.

The major event that hit Europe in summer 2021 reminds society that floods are recurrent and among the costliest and deadliest natural hazards. The long-term flood risk management (FRM) efforts preferring sole technical measures to prevent and mitigate floods have shown to be not sufficiently effective and sensitive to the environment. Nature-Based Solutions (NBS) mark a recent paradigm shift of FRM towards solutions that use nature-derived features, processes and management options to improve water retention and mitigate floods.

Determinants of Immune Response to Anti-SARS-CoV-2 mRNA Vaccines in Kidney Transplant Recipients: A Prospective Cohort Study.

Background: Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has been recently shown to be impaired in kidney transplant recipients (KTRs), but the underlying factors affecting vaccine effectiveness need to be further elucidated.

Methods: In this prospective cohort study, antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.

Humoral response to SARS-CoV-2 is well preserved and symptom dependent in kidney transplant recipients.

Data on the immune response to SARS-CoV-2 in kidney transplant recipients are scarce. Thus, we conducted a single-center observational study to assess the anti-SARS-CoV-2 IgG seroprevalence in outpatient kidney transplant recipients (KTR; n = 1037) and healthcare workers (HCW; n = 512) during the second wave of the COVID-19 pandemic in fall 2020 and evaluated the clinical variables affecting antibody levels. Antibodies against S1 and S2 subunit of SARS-CoV-2 were evaluated using immunochemiluminescent assay (cut off 9.

Influence of equipment changes on MRI measures of brain atrophy and brain microstructure in a placebo-controlled trial of ibudilast in progressive multiple sclerosis.

Background: Hardware changes can be an unavoidable confound in imaging trials. Understanding the impact of such changes may play an important role in the analysis of imaging data.

Objective: To characterize the effect of equipment changes in a longitudinal, multi-site multiple sclerosis trial.

Neurofilament light chain in a phase 2 clinical trial of ibudilast in progressive multiple sclerosis.

Background: Sensitive and specific biomarkers for use in progressive multiple sclerosis (MS) have not been established. We investigate neurofilament light (NfL) as a treatment response biomarker in progressive MS.

Objective: To evaluate whether ibudilast 100 mg/day alters serum and cerebrospinal fluid (CSF) levels of NfL in progressive MS.

Development and Validation of a Test for Competence in Evidence-Based Medicine.

Background: Medical educators need valid, reliable, and efficient tools to assess evidence-based medicine (EBM) knowledge and skills. Available EBM assessment tools either do not assess skills or are laborious to grade.

Objective: To validate a multiple-choice-based EBM test-the Resident EBM Skills Evaluation Tool (RESET).

Frozen Histories or Narratives of Change? Contextualizing Land-Use Dynamics for Conservation of Historical Rural Landscapes.

Current research has identified extensive changes in land-use structure and land management of Central European rural landscapes due to shifting political and economic trajectories. These changes are exemplified by diverse processes of agricultural intensification, privatization and land fragmentation, land abandonment and overall changes in modes of production. The extensive record of these historically specific processes has posed a fundamental challenge for rural landscape conservation, which is addressed in this paper.

Impact of tissue-based genomic profiling on clinical decision making in the management of patients with metastatic breast cancer at academic centers.

Background: Genomic profiling can identify targetable mutations; however, the impact of tissue-based genomic profiling on clinical decision making for patients with metastatic breast cancer has not been well characterized.

Methods: Patients with stage IV breast cancer who had undergone genomic profiling between 7/2013 and 3/2015 were identified at three academic cancer centers. Genomic analysis was determined to have impacted clinical decision if (A) a patient was enrolled onto a genotype-matched clinical trial or (B) prescribed off-label an FDA-approved therapy targeting an identified mutation.

Retrospective study of the efficacy and safety of neoadjuvant docetaxel, carboplatin, trastuzumab/pertuzumab (TCH-P) in nonmetastatic HER2-positive breast cancer.

Background: Pertuzumab is FDA approved in the preoperative setting in combination with trastuzumab and chemotherapy, in women with nonmetastatic HER2 + breast cancer. The TRYPHAENA trial (n = 77) reported a pathologic complete response rate (pCR), i.e.

Population structure at different minor allele frequency levels.

Inferring population genetic structure from large-scale genotyping of single-nucleotide polymorphisms or variants is an important technique for studying the history and distribution of extant human populations, but it is also a very important tool for adjusting tests of association. However, the structures inferred depend on the minor allele frequency of the variants; this is very important when considering the phenotypic association of rare variants. Using the Genetic Analysis Workshop 18 data set for 142 unrelated individuals, which includes genotypes for many rare variants, we study the following hypothesis: the difference in detected structure is the result of a "scale" effect; that is, rare variants are likely to be shared only locally (smaller scale), while common variants can be spread over longer distances.

Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31.

Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility.

European American stratification in ovarian cancer case control data: the utility of genome-wide data for inferring ancestry.

We investigated the ability of several principal components analysis (PCA)-based strategies to detect and control for population stratification using data from a multi-center study of epithelial ovarian cancer among women of European-American ethnicity. These include a correction based on an ancestry informative markers (AIMs) panel designed to capture European ancestral variation and corrections utilizing un-thinned genome-wide SNP data; case-control samples were drawn from four geographically distinct North-American sites. The AIMs-only and genome-wide first principal components (PC1) both corresponded to the previously described North or Northwest-Southeast axis of European variation.

Development of a panel of genome-wide ancestry informative markers to study admixture throughout the Americas.

Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America.

Rare variant density across the genome and across populations.

Next-generation sequencing allows for a new focus on rare variant density for conducting analyses of association to disease and for narrowing down the genomic regions that show evidence of functionality. In this study we use the 1000 Genomes Project pilot data as distributed by Genetic Analysis Workshop 17 to compare rare variant densities across seven populations. We made the comparisons using regressions of rare variants on total variant counts per gene for each population and Tajima's D values calculated for each gene in each population, using data on 3,205 genes.

Replication of GWAS "Hits" by Race for Breast and Prostate Cancers in European Americans and African Americans.

In this study, we assessed association of genome-wide association studies (GWAS) "hits" by race with adjustment for potential population stratification (PS) in two large, diverse study populations; the Carolina Breast Cancer Study (CBCS; N total = 3693 individuals) and the University of Pennsylvania Study of Clinical Outcomes, Risk, and Ethnicity (SCORE; N total = 1135 individuals). In both study populations, 136 ancestry information markers and GWAS "hits" (CBCS: FGFR2, 8q24; SCORE: JAZF1, MSMB, 8q24) were genotyped. Principal component analysis was used to assess ancestral differences by race.

Analysis of exome sequences with and without incorporating prior biological knowledge.

Next-generation sequencing technology provides new opportunities and challenges in the search for genetic variants that underlie complex traits. It will also presumably uncover many new rare variants, but exactly how these variants should be incorporated into the data analysis remains a question. Several papers in our group from Genetic Analysis Workshop 17 evaluated different methods of rare variant analysis, including single-variant, gene-based, and pathway-based analyses and analyses that incorporated biological information.

Defining genetic determinants of the Metabolic Syndrome in the Framingham Heart Study using association and structural equation modeling methods.

The Metabolic Syndrome (MetSyn), which is a clustering of traits including insulin resistance, obesity, hypertension and dyslipidemia, is estimated to have a substantial genetic component, yet few specific genetic targets have been identified. Factor analysis, a sub-type of structural equation modeling (SEM), has been used to model the complex relationships in MetSyn. Therefore, we aimed to define the genetic determinants of MetSyn in the Framingham Heart Study (Offspring Cohort, Exam 7) using the Affymetrix 50 k Human Gene Panel and three different approaches: 1) an association-based "one-SNP-at-a-time" analysis with MetSyn as a binary trait using the World Health Organization criteria; 2) an association-based "one-SNP-at-a-time" analysis with MetSyn as a continuous trait using second-order factor scores derived from four first-order factors; and, 3) a multivariate SEM analysis with MetSyn as a continuous, second-order factor modeled with multiple putative genes, which were represented by latent constructs defined using multiple SNPs in each gene.