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We present avidity sequencing, a sequencing chemistry that separately optimizes the processes of stepping along a DNA template and that of identifying each nucleotide within the template. Nucleotide identification uses multivalent nucleotide ligands on dye-labeled cores to form polymerase–polymer–nucleotide complexes bound to clonal copies of DNA targets. These polymer–nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides from micromolar to nanomolar and yield negligible dissociation rates. Avidity sequencing achieves high accuracy, with 96.2% and 85.4% of base calls having an average of one error per 1,000 and 10,000 base pairs, respectively. We show that the average error rate of avidity sequencing remained stable following a long homopolymer.

We present avidity sequencing - a novel sequencing chemistry that separately optimizes the process of stepping along a DNA template and the process of identifying each nucleotide within the template. Nucleotide identification uses multivalent nucleotide ligands on dye-labeled cores to form polymerase-polymer nucleotide complexes bound to clonal copies of DNA targets. These polymer-nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides from micromolar to nanomolar, and yield negligible dissociation rates. We demonstrate the use of avidites as a key component of a sequencing technology that surpasses Q40 accuracy and enables a diversity of applications that include single cell RNA-seq and whole human genome sequencing. We also show the advantages of this technology in sequencing through long homopolymers.

We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining of aggrecan neoepitopes. Cell proliferation was assessed for activated and naïve CD4+ T cells from healthy mice following culture with CM-MSC or co-culture with MSCs. T cell polarization was analysed in CD4+ T cells isolated from spleens and lymph nodes of arthritic mice treated with CM-MSC or MSCs. CM-MSC treatment significantly reduced knee-joint swelling, histopathological signs of AIA, cartilage loss and suppressed TNFα induction. Proliferation of CD4+ cells from spleens of healthy mice was not affected by CM-MSC but reduced when cells were co-cultured with MSCs. In the presence of CM-MSC or MSCs, increases in IL-10 concentration were observed in culture medium. Finally, CD4+ T cells from arthritic mice treated with CM-MSC showed increases in FOXP3 and IL-4 expression and positively affected the Treg:Th17 balance in the tissue. CM-MSC treatment reduces cartilage damage and suppresses immune responses by reducing aggrecan cleavage, enhancing Treg function and adjusting the Treg:Th17 ratio. CM-MSC may provide an effective cell-free therapy for inflammatory arthritis.

Publisher Summary This chapter presents an overview of the managing quality improvement and clinical outcomes in behavioral health settings. The managed health care movement has created a climate of increased competition and accountability for providers of behavioral health services. The managed behavioral health care movement has vastly changed the landscape for service providers and administrators. Quality improvement managers also collect data known as quality indicators and give the organization feedback and descriptive summaries of trends on a regular schedule. According to this chapter, psychologists have unique training to apply toward solving some of the dilemmas faced by behavioral health providers and are best poised to serve as effective guides through this new complex, and sometimes hostile territory. The pressure has caused headaches for mental health administrators but may also bring opportunities for clinical and research-trained psychologists who have a sense of adventure, tolerance for rapidly changing environments, and an interest in seeing their work lead to immediate systems changes. Thus this chapter summarizes that the clinical psychologists in the project play a role in helping other front-line clinicians and staff accept the culture changes that were necessary to implement clinical pathways.

Forty-three studies using independent home observation of conduct-disordered children were analyzed with regard to 17 dimensions: among them journal, year of publication, gender of subjects, sample ages, special sample features, use of control subjects, technology, observational constraints imposed, child and parent behaviors observed, child and parent behavior rates, pre-post changes in child or parent behaviors, experimental and control group differences in child or parent behaviors, and cost analyses. Results revealed a clear increase in the publication of such investigations over the past 11 years and wide disparities in the quality of scientific reporting. Across all investigations, researchers have observed over 170 child and parent behaviors. However, only a few child and parent behavior categories have consistently revealed pre-post changes and/or experimental-control group differences. Sequential event recording was the most frequently used observational technology and, in general, the sophistication of observational methods was considered laudable. Suggestions for future research are offered with specific emphasis upon the development of sensitive, practical alternatives to the highly elaborate, multi-element, complex behavioral coding systems presently employed.