Care Coordination for Children With Medical Complexity: Whose Care Is It, Anyway?

Children with medical complexity (CMC) have multiple chronic conditions and require an array of medical- and community-based providers. Dedicated care coordination is increasingly seen as key to addressing the fragmented care that CMC often encounter. Often conceptually misunderstood, care coordination is a team-driven activity that organizes and drives service integration. In this article, we examine models of care coordination and clarify related terms such as care integration and case management. The location of care coordination resources for CMC may range from direct practice provision to external organizations such as hospitals and accountable care organizations. We discuss the need for infrastructure building, design and implementation leadership, use of care coordination tools and training modules, and appropriate resource allocation under new payment models

Family-Centered Care: Current Applications and Future Directions in Pediatric Health Care

Family-centered care (FCC) is a partnership approach to health care decision-making between the family and health care provider. FCC is considered the standard of pediatric health care by many clinical practices, hospitals, and health care groups. Despite widespread endorsement, FCC continues to be insufficiently implemented into clinical practice. In this paper we enumerate the core principles of FCC in pediatric health care, describe recent advances applying FCC principles to clinical practice, and propose an agenda for practitioners, hospitals, and health care groups to translate FCC into improved health outcomes, health care delivery, and health care system transformation

Autonomous nuclear waste management

Redundant and non-operational buildings at nuclear sites are decommissioned over a period of time. The process involves demolition of physical infrastructure resulting in large quantities of residual waste material. The resulting waste materials are packed into import containers to be delivered for post-processing, containing either sealed canisters or assortments of miscellaneous objects. At present post-processing does not happen within the United Kingdom. Sellafield Ltd. and National Nuclear Laboratory are developing a process for future operation so that upon an initial inspection, imported waste materials undergo two stages of post-processing before being packed into export containers, namely sort and segregate or sort and disrupt. The post-processing facility will remotely treat and export a wide range of wastes before downstream encapsulation. Certain wastes require additional treatment, such as disruption, before export to ensure suitability for long-term disposal. This article focuses on the design, development, and demonstration of a reconfigurable rational agent-based robotic system that aims to highly automate these processes removing the need for close human supervision. The proposed system is being demonstrated through a downsized, lab-based setup incorporating a small-scale robotic arm, a time-of-flight camera, and high-level rational agent-based decision making and control framework

Integration of heterogeneous expression data sets extends the role of the retinol pathway in diabetes and insulin resistance

Motivation: Type 2 diabetes is a chronic metabolic disease that involves both environmental and genetic factors. To understand the genetics of type 2 diabetes and insulin resistance, the DIabetes Genome Anatomy Project (DGAP) was launched to profile gene expression in a variety of related animal models and human subjects. We asked whether these heterogeneous models can be integrated to provide consistent and robust biological insights into the biology of insulin resistance

Integration of heterogeneous expression data sets extends the role of the retinol pathway in diabetes and insulin resistance

Motivation: Type 2 diabetes is a chronic metabolic disease that involves both environmental and genetic factors. To understand the genetics of type 2 diabetes and insulin resistance, the DIabetes Genome Anatomy Project (DGAP) was launched to profile gene expression in a variety of related animal models and human subjects. We asked whether these heterogeneous models can be integrated to provide consistent and robust biological insights into the biology of insulin resistance

Biological impact of geometric uncertainties: what margin is needed for intra-hepatic tumors?

<p>Abstract</p> <p>Background</p> <p>To evaluate and compare the biological impact on different proposed margin recipes for the same geometric uncertainties for intra-hepatic tumors with different tumor cell types or clinical stages.</p> <p>Method</p> <p>Three different margin recipes based on tumor motion were applied to sixteen IMRT plans with a total of twenty two intra-hepatic tumors. One recipe used the full amplitude of motion measured from patients to generate margins. A second used 70% of the full amplitude of motion, while the third had no margin for motion. The biological effects of geometric uncertainty in these three situations were evaluated with Equivalent Uniform Doses (EUD) for various survival fractions at 2 Gy (SF₂).</p> <p>Results</p> <p>There was no significant difference in the biological impact between the full motion margin and the 70% motion margin. Also, there was no significant difference between different tumor cell types. When the margin for motion was eliminated, the difference of the biological impact was significant among different cell types due to geometric uncertainties. Elimination of the motion margin requires dose escalation to compensate for the biological dose reduction due to the geometric misses during treatment.</p> <p>Conclusions</p> <p>Both patient-based margins of full motion and of 70% motion are sufficient to prevent serious dosimetric error. Clinical implementation of margin reduction should consider the tumor sensitivity to radiation.</p

Cellular Phenotype-Dependent and -Independent Effects of Vitamin C on the Renewal and Gene Expression of Mouse Embryonic Fibroblasts

Vitamin C has been shown to delay the cellular senescence and was considered a candidate for chemoprevention and cancer therapy. To understand the reported contrasting roles of vitamin C: growth-promoting in the primary cells and growth-inhibiting in cancer cells, primary mouse embryonic fibroblasts (MEF) and their isogenic spontaneously immortalized fibroblasts with unlimited cell division potential were used as the model pair. We used microarray gene expression profiling to show that the immortalized MEF possess human cancer gene expression fingerprints including a pattern of up-regulation of inflammatory response-related genes. Using the MEF model, we found that a physiological treatment level of vitamin C (10−5 M), but not other unrelated antioxidants, enhanced cell growth. The growth-promoting effect was associated with a pattern of enhanced expression of cell cycle- and cell division-related genes in both primary and immortalized cells. In the immortalized MEF, physiological treatment levels of vitamin C also enhanced the expression of immortalization-associated genes including a down-regulation of genes in the extracellular matrix functional category. In contrast, confocal immunofluorescence imaging of the primary MEF suggested an increase in collagen IV protein upon vitamin C treatment. Similar to the cancer cells, the growth-inhibitory effect of the redox-active form of vitamin C was preferentially observed in immortalized MEF. All effects of vitamin C required its intracellular presence since the transporter-deficient SVCT2−/− MEF did not respond to vitamin C. SVCT2−/− MEF divided and became immortalized readily indicating little dependence on vitamin C for the cell division. Immortalized SVCT2−/− MEF required higher concentration of vitamin C for the growth inhibition compared to the immortalized wildtype MEF suggesting an intracellular vitamin C toxicity. The relevance of our observation in aging and human cancer prevention was discussed

On Conduction in a Bacterial Sodium Channel

Voltage-gated Na+-channels are transmembrane proteins that are responsible for the fast depolarizing phase of the action potential in nerve and muscular cells. Selective permeability of Na+ over Ca2+ or K+ ions is essential for the biological function of Na+-channels. After the emergence of the first high-resolution structure of a Na+-channel, an anionic coordination site was proposed to confer Na+ selectivity through partial dehydration of Na+ via its direct interaction with conserved glutamate side chains. By combining molecular dynamics simulations and free-energy calculations, a low-energy permeation pathway for Na+ ion translocation through the selectivity filter of the recently determined crystal structure of a prokaryotic sodium channel from Arcobacter butzleri is characterised. The picture that emerges is that of a pore preferentially occupied by two ions, which can switch between different configurations by crossing low free-energy barriers. In contrast to K+-channels, the movements of the ions appear to be weakly coupled in Na+-channels. When the free-energy maps for Na+ and K+ ions are compared, a selective site is characterised in the narrowest region of the filter, where a hydrated Na+ ion, and not a hydrated K+ ion, is energetically stable

Epigenome Microarray Platform for Proteome-Wide Dissection of Chromatin-Signaling Networks

Knowledge of protein domains that function as the biological effectors for diverse post-translational modifications of histones is critical for understanding how nuclear and epigenetic programs are established. Indeed, mutations of chromatin effector domains found within several proteins are associated with multiple human pathologies, including cancer and immunodeficiency syndromes. To date, relatively few effector domains have been identified in comparison to the number of modifications present on histone and non-histone proteins. Here we describe the generation and application of human modified peptide microarrays as a platform for high-throughput discovery of chromatin effectors and for epitope-specificity analysis of antibodies commonly utilized in chromatin research. Screening with a library containing a majority of the Royal Family domains present in the human proteome led to the discovery of TDRD7, JMJ2C, and MPP8 as three new modified histone-binding proteins. Thus, we propose that peptide microarray methodologies are a powerful new tool for elucidating molecular interactions at chromatin