Oracle Based Active Set Algorithm for Scalable Elastic Net Subspace Clustering

State-of-the-art subspace clustering methods are based on expressing each data point as a linear combination of other data points while regularizing the matrix of coefficients with $\ell_1$, $\ell_2$ or nuclear norms. $\ell_1$ regularization is guaranteed to give a subspace-preserving affinity (i.e., there are no connections between points from different subspaces) under broad theoretical conditions, but the clusters may not be connected. $\ell_2$ and nuclear norm regularization often improve connectivity, but give a subspace-preserving affinity only for independent subspaces. Mixed $\ell_1$, $\ell_2$ and nuclear norm regularizations offer a balance between the subspace-preserving and connectedness properties, but this comes at the cost of increased computational complexity. This paper studies the geometry of the elastic net regularizer (a mixture of the $\ell_1$ and $\ell_2$ norms) and uses it to derive a provably correct and scalable active set method for finding the optimal coefficients. Our geometric analysis also provides a theoretical justification and a geometric interpretation for the balance between the connectedness (due to $\ell_2$ regularization) and subspace-preserving (due to $\ell_1$ regularization) properties for elastic net subspace clustering. Our experiments show that the proposed active set method not only achieves state-of-the-art clustering performance, but also efficiently handles large-scale datasets.Comment: 15 pages, 6 figures, accepted to CVPR 2016 for oral presentatio

Technology-enabled Behavioral Health Integration Decreases Emergency Department Utilization

Background: Behavioral health integration allows for patient-centered care, leads to higher levels of provider-patient engagement, and is key to improving patient outcomes. However, behavioral health integration is administratively burdensome and therefore is often not adopted. Technology presents opportunities to increase care team efficiency and improve patient outcomes. The goal of this study was to retrospectively compare clinical outcomes and emergency department utilization in patients using a technology platform compared to patients receiving treatment as usual. Methods: The technology platform, NeuroFlow, was deployed to deliver technology-enabled behavioral health integration in 30 clinics, and 598 electronic health records were analyzed. Results: In the six-month period following technology-enabled behavioral health integration implementation, emergency department utilization decreased by 34% in the treatment group (n=259), while increasing by 58% in the treatment as usual group (n=339). Additionally, statistically significant (p \u3c .01) decreases in PHQ-9 (-17.3%) and GAD-7 (-12.4%) scores were only observed in the treatment group. Conclusion: Findings from this study support use of a technology-enabled behavioral health tool to decrease emergency department use and highlight the importance of measurement-based care. Future research will be key to enhancing behavioral health technology and integration to further improve patient outcomes and reduce emergency department utilization

The heterodimeric structure of heterogeneous nuclear ribonucleoprotein C1/C2 dictates 1,25-dihydroxyvitamin D-directed transcriptional events in osteoblasts

Heterogeneous nuclear ribonucleoprotein (hnRNP) C plays a key role in RNA processing but also exerts a dominant negative effect on responses to 1,25-dihydroxyvitamin D (1,25(OH)(2)D) by functioning as a vitamin D response element-binding protein (VDRE-BP). hnRNPC acts a tetramer of hnRNPC1 (huC1) and hnRNPC2 (huC2), and organization of these subunits is critical to in vivo nucleic acid-binding. Overexpression of either huC1 or huC2 in human osteoblasts is sufficient to confer VDRE-BP suppression of 1,25(OH)(2)D-mediated transcription. However, huC1 or huC2 alone did not suppress 1,25(OH)(2)D-induced transcription in mouse osteoblastic cells. By contrast, overexpression of huC1 and huC2 in combination or transfection with a bone-specific polycistronic vector using a “self-cleaving” 2A peptide to co-express huC1/C2 suppressed 1,25D-mediated induction of osteoblast target gene expression. Structural diversity of hnRNPC between human/NWPs and mouse/rat/rabbit/dog was investigated by analysis of sequence variations within the hnRNP CLZ domain. The predicted loss of distal helical function in hnRNPC from lower species provides an explanation for the altered interaction between huC1/C2 and their mouse counterparts. These data provide new evidence of a role for hnRNPC1/C2 in 1,25(OH)(2)D-driven gene expression, and further suggest that species-specific tetramerization is a crucial determinant of its actions as a regulator of VDR-directed transactivation

Serum and synovial fluid vitamin D metabolites and rheumatoid arthritis

Vitamin D-deficiency has been linked to inflammatory diseases including rheumatoid arthritis (RA). Studies to date have focused on the impact of serum 25-hydroxyvitamin D3 (25(OH)D3), an inactive form of vitamin D, on RA disease activity and progression. However, anti-inflammatory actions of vitamin D are likely to be mediated at sites of RA disease, namely the inflamed joint, and may involve other vitamin D metabolites notably the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). In the current study serum and synovial fluid samples from n = 20 patients with persistent RA and n = 7 patients with reactive arthritis (ReA) were analysed for multiple vitamin D metabolites. Serum data for RA and ReA patients were compared to healthy controls (HC). There was no significant difference between RA or ReA patients relative to HC for 25(OH)D3, 24,25(OH)2D3, 1,25(OH)2D3 or 25(OH)D2. However, 3-epi-25(OH)D3 was significantly lower in RA and ReA patients compared to HC (p < 0.05). All vitamin D metabolites, apart from 25(OH)D2, were lower in SF compared to serum, and SF 1,25(OH)2D3 was unquantifiable in 13/20 RA and 4/7 ReA samples. SF 25(OH)D3, 3-epi-25(OH)D3 and DBP correlated inversely with swollen joint score, and serum 25(OH)D2 and SF DBP correlated directly with C-reactive protein levels. These data indicate that serum 25(OH)D3 provides only limited insight into the role of vitamin D in RA. Alternative serum metabolites such as 3-epi-25(OH)2D3, and SF metabolites, notably lack of SF 1,25(OH)2D3, may be more closely linked to RA disease severity and progress

Associations between total, free and bioavailable 25-hydroxyvitamin D forms with adiponectin and irisin in maternal-neonatal pairs at birth from Greece

Background: Apart from the well-established skeletal effects, vitamin D has been explored as a secretagogue influencing various adipokines, including adiponectin and irisin. Recent evidence suggests that specific forms of 25-Hydroxyvitamin D (25(OHD), such as free and bioavailable 25(OH)D, may provide more accurate measurements of vitamin D status. The relationship between vitamin D status and serum irisin and adiponectin concentrations remains largely unexplored, particularly during pregnancy. Methods: We analyzed data from 67 healthy maternal-neonatal pairs from Northern Greece at birth. Biochemical and hormonal tests were conducted on each maternal-neonatal pair. The vitamin D forms were estimated using validated mathematical models. Subsequently, regression analyses were conducted to determine the association between the vitamin D forms and adipokine levels. Results: Bioavailable maternal 25(OH)D was inversely associated with neonatal irisin concentrations [β=-73.46 (-140.573 to -6.341), p=0.034]. No other associations were observed between maternal vitamin D status and neonatal adipokine concentrations. Conclusion: In conclusion, maternal bioavailable vitamin D concentrations are inversely associated with neonatal serum irisin concentrations, warranting further studies to evaluate the underlying mechanisms for this finding