The EXCELC project in Finland : The main descriptive findings from surveys using the Adult Social Care Outcomes Toolkit (ASCOT)

Exploring Comparative Effectiveness and Efficiency in Long-term Care (EXCELC), an international research project, started in 2015 to explore the comparative effectiveness and efficiency of non-institutional long-term care in Austria, England and Finland. The EXCELC project has applied the Adult Social Care Outcomes Toolkit (ASCOT) to measure social care-related quality of life of old service users, their carers and the effectiveness of non-institutional long-term care (www.pssru.ac.uk/ascot/tools). This methodological report describes the process of translating the ASCOT quality of life measures from English into Finnish, the methods of collecting survey data in 12 Finnish regions, and the main descriptive findings from the surveys

So You Discovered a Potential Glycan-Based Biomarker; Now What? We Developed a High-Throughput Method for Quantitative Clinical Glycan Biomarker Validation

Glycomic-based approaches to discover potential biomarkers have shown great promise in their ability to distinguish between healthy and diseased individuals; these methods can identify when aberrant glycosylation is significant, but they cannot practically be adapted into widely implemented diagnostic assays because they are too complex, expensive, and low-throughput. We have developed a new strategy that addresses challenges associated with sample preparation, sample throughput, instrumentation needs, and data analysis to transfer the valuable knowledge provided by protein glycosylation into a clinical environment. Notably, the detection limits of the assay are in the single-digit picomole range. Proof of principle is demonstrated by quantifying the changes in the sialic acid content in fetuin. As the sialic acid content in proteins varies in a number of disease states, this example demonstrates the utility of the method for biomarker analysis. Furthermore, the developed method can be adapted to other biologically important saccharides, affording a broad array of quantitative glycomic analyses that are accessible in a high-throughput, plate-reader format. These studies enable glycomic-based biomarker discovery efforts to transition through the difficult landscape of developing a potential biomarker into a clinical assay

Transposon- and Genome Dynamics in the Fungal Genus Neurospora: Insights from Nearly Gapless Genome Assemblies

A large portion of nuclear DNA is composed of transposable element (TE) sequences, whose transposition is controlled by diverse host defense strategies in order to maintain genomic integrity. One such strategy is the fungal-specific Repeat-Induced Point mutation (RIP) that hyper-mutates repetitive DNA sequences. While RIP is found across Fungi, it has been shown to vary in efficiency. The filamentous ascomycete Neurospora crassa has been a pioneer in the study of RIP, but data on TEs and RIP from other species in the genus is limited. In this study, we investigated 18 nearly gapless genome assemblies of ten Neurospora species, which diverged from a common ancestor about 7 MYA, to determine and compare genome-wide TE distribution and their associated RIP patterns. Four of these assemblies, generated by PacBio technology, represent new genomic datasets. We showed that the TE contents between 8.7-18.9% covary with genome sizes that range between 37.8-43.9 Mb. Degraded copies of Long Terminal Repeat (LTR) retrotransposons were abundant among the identified TEs, and these are distributed across the genome at varying frequencies. In all investigated Neurospora genomes, TE sequences had signs of numerous C-to-T substitutions, suggesting that RIP occurred in all species, and accordingly, RIP signatures correlated with TE-dense regions in all genomes. In conclusion, essentially gapless genome assemblies allowed us to identify TEs in Neurospora genomes, and reveal that TEs contribute to genome size variation in this group. Our study suggests that TEs and RIP are highly correlated in each examined Neurospora species, and hence, the pattern of interaction is conserved over the investigated evolutionary timescale. Finally, with our results, we verify that RIP signatures can be used to facilitate the identification of TE-rich region in the genome. The comprehensive genomic dataset of Neurospora is a rich resource for further in-depth analyses of fungal genomes by the community

The effects of interaction quality on neural synchrony during mother-child problem solving.

Understanding others is fundamental to interpersonal coordination and successful cooperation. One mechanism posited to underlie both effective communication and behavioral coordination is interpersonal neural synchrony. Although presumably foundational for children's social development, research on neural synchrony in naturalistic caregiver-child interactions is lacking. Using dual-functional near-infrared spectroscopy (fNIRS), we examined the effects of interaction quality on neural synchrony during a problem-solving task in 42 dyads of mothers and their preschool children. In a cooperation condition, mothers and children were instructed to solve a tangram puzzle together. In an individual condition, mothers and children performed the same task alone with an opaque screen between them. Wavelet transform coherence (WTC) was used to assess the cross-correlation between the two fNIRS time series. Results revealed increased neural synchrony in bilateral prefrontal cortex and temporo-parietal areas during cooperative as compared to individual problem solving. Higher neural synchrony during cooperation correlated with higher behavioral reciprocity and neural synchrony predicted the dyad's problem-solving success beyond reciprocal behavior between mothers and children. State-like factors, such as maternal stress and child agency during the task, played a bigger role for neural synchronization than trait-like factors, such as child temperament. Our results emphasize neural synchrony as a biomarker for mother-child interaction quality. These findings further highlight the role of state-like factors in interpersonal synchronization processes linked to successful coordination with others and in the long-term might improve the understanding of others

A Case of Novel Coronavirus Disease 19 in a Chronic Hemodialysis Patient Presenting with Gastroenteritis and Developing Severe Pulmonary Disease.

Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease with an alarming case fatality rate up to 5%. The risk factors for severe presentations are concentrated in patients with chronic kidney disease, particularly patients with end-stage renal disease (ESRD) who are dialysis dependent. We report the first US case of a 56-year-old nondiabetic male with ESRD secondary to IgA nephropathy undergoing thrice-weekly maintenance hemodialysis for 3 years, who developed COVID-19 infection. He has hypertension controlled with angiotensin receptor blocker losartan 100 mg/day and coronary artery disease status-post stent placement. During the first 5 days of his febrile disease, he presented to an urgent care, 3 emergency rooms, 1 cardiology clinic, and 2 dialysis centers in California and Utah. During this interval, he reported nausea, vomiting, diarrhea, and low-grade fevers but was not suspected of COVID-19 infection until he developed respiratory symptoms and was admitted to the hospital. Imaging studies upon admission were consistent with bilateral interstitial pneumonia. He was placed in droplet-eye precautions while awaiting COVID-19 test results. Within the first 24 h, he deteriorated quickly and developed acute respiratory distress syndrome (ARDS), requiring intubation and increasing respiratory support. Losartan was withheld due to hypotension and septic shock. COVID-19 was reported positive on hospital day 3. He remained in critical condition being treated with hydroxychloroquine and tocilizumab in addition to the standard medical management for septic shock and ARDS. Our case is unique in its atypical initial presentation and highlights the importance of early testing

Population survival impact of new targeted and immune based therapies for metastatic or unresectable melanoma

Introduction New classes of drugs for metastatic or unresectable melanoma (MM) have shown improved survival in randomized trials (e.g., anti-CTLA-4, anti-PD-1, BRAF/MEK inhibitors). We sought to describe uptake of these new drugs and their impact on population-based survival outcomes of MM. Objectives and Approach We sought to describe uptake of these new drugs and their impact on population-based survival outcomes of MM. This was a retrospective, population-based cohort study of all treated MM in Ontario 2007-2015. Administrative data sources from the Institute for Clinical Evaluative Sciences (ICES) were utilized. Within ICES, cutaneous and non-cutaneous primaries were identified in the Ontario Cancer Registry. Administrative sources from Cancer Care Ontario, Ministry of Health and Long-Term Care, and Canadian Institute for Health Information identified patients treated with palliative systemic therapy, radiotherapy and metastatectomy. Temporal trends in utilization and survival were investigated. Survival by drug class was described. Results We identified 2,793 MM patients. First treatment was systemic therapy (46%), radiotherapy (41%) or metastatectomy (14%). MM patient number increased from 270 in 2007 to 418 in 2015. Systemic treatment rose from 125 MM first treated in 2007 to 343 in 2015. New drug treatments increased from <6% of reported first-line regimens in 2007 to 82\% in 2015. 1-year and 2-year overall survival (OS) was 28% and 15% respectively for all MM in 2007-2009, rising to 46% and 35% for 2014-2015 (logrank p<0.001; adjusted hazard ratio (AHR) 0.56, 95% confidence interval (CI): (0.49,0.63)). Survival gains were largely in the subset treated primarily systemically, where new drugs were increasingly utilized (2-year OS 16% 2007-2009 vs. 44% 2014-2015 logrank p<0.001; AHR 0.46, 95% CI: (0.38,0.56)). Conclusion/Implications Utilization of systemic therapy for MM has increased considerably in routine practice during 2007-2015; at least some of this increase relates to use of novel agents since 2011. In line with randomized trial findings, new drug adoption was associated with substantial increases in population-based MM survival