Domain and stripe formation between hexagonal and square ordered fillings of colloidal particles on periodic pinning substrates

Using large scale numerical simulations, we examine the ordering of colloidal particles on square periodic two-dimensional muffin-tin substrates consisting of a flat surface with localized pinning sites. We show that when there are four particles per pinning site, the particles adopt a hexagonal ordering, while for five particles per pinning site, a square ordering appears. For fillings between four and five particles per pinning site, we identify a rich variety of distinct ordering regimes, including disordered grain boundaries, crystalline stripe structures, superlattice orderings, and disordered patchy arrangements. We characterize the different regimes using Voronoi analysis, energy dispersion, and ordering of the domains. We show that many of the boundary formation features we observe occur for a wide range of other fillings. Our results demonstrate that grain boundary tailoring can be achieved with muffin-tin periodic pinning substrates

Brain-responsive neurostimulation for the treatment of adults with epilepsy in tuberous sclerosis complex: A case series

OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic disorder primarily characterized by the development of multisystem benign tumors. Epilepsy is the most common neurologic manifestation, affecting 80%-90% of TSC patients. The diffuse structural brain abnormalities and the multifocal nature of epilepsy in TSC pose diagnostic challenges when evaluating patients for epilepsy surgery. METHODS: We retrospectively reviewed the safety experience and efficacy outcomes of five adult TSC patients who were treated with direct brain-responsive neurostimulation (RNS System, NeuroPace, Inc). RESULTS: The average follow-up duration was 20 months. All five patients were responders (≥50% disabling seizure reduction) at last follow-up. The median reduction in disabling seizures was 58% at 1 year and 88% at last follow-up. Three of the five patients experienced some period of seizure freedom ranging from 3 months to over 1 year. SIGNIFICANCE: In this small case series, we report the first safety experience and efficacy outcomes in patients with TSC-associated drug-resistant focal epilepsy treated with direct brain-responsive neurostimulation

Factors contributing to intervention fidelity in a multi-site chronic disease self-management program

BACKGROUND AND OBJECTIVES: Disease self-management programs have been a popular approach to reducing morbidity and mortality from chronic disease. Replicating an evidence-based disease management program successfully requires practitioners to ensure fidelity to the original program design. METHODS: The Florida Health Literacy Study (FHLS) was conducted to investigate the implementation impact of the Pfizer, Inc. Diabetes Mellitus and Hypertension Disease Self-Management Program based on health literacy principles in 14 community health centers in Florida. The intervention components discussed include health educator recruitment and training, patient recruitment, class sessions, utilization of program materials, translation of program manuals, patient retention and follow-up, and technical assistance. RESULTS: This report describes challenges associated with achieving a balance between adaptation for cultural relevance and fidelity when implementing the health education program across clinic sites. This balance was necessary to achieve effectiveness of the disease self-management program. The FHLS program was implemented with a high degree of fidelity to the original design and used original program materials. Adaptations identified as advantageous to program participation are discussed, such as implementing alternate methods for recruiting patients and developing staff incentives for participation. CONCLUSION: Effective program implementation depends on the talent, skill and willing participation of clinic staff. Program adaptations that conserve staff time and resources and recognize their contribution can increase program effectiveness without jeopardizing its fidelity

Ambulatory function in spinal muscular atrophy: Age-related patterns of progression

Individuals with spinal muscular atrophy (SMA) type 3 are able to walk but they have weakness, gait impairments and fatigue. Our primary study objective was to examine longitudinal changes in the six-minute walk test (6MWT) and to evaluate whether age and SMA type 3 subtype are associated with decline in ambulatory function. Data from three prospective natural history studies were used. Seventy-three participants who performed the 6MWT more than once, at least 6 months apart, were included; follow-up ranged from 0.5–9 years. Only data from patients who completed the 6MWT were included. The mean age of the participants was 13.5 years (range 2.6–49.1), with 52 having disease onset before age 3 years (type 3A). At baseline, type 3A participants walked a shorter distance on average (257.1 m) than type 3B participants (390.2 m) (difference = 133.1 m, 95% confidence interval [CI] 71.8–194.3, p < 0.001). Distance walked was weakly associated with age (r = 0.25, p = 0.04). Linear mixed effects models were used to estimate the mean annual rate of change. The overall mean rate of change was -7.8 m/year (95% CI -13.6 –-2.0, p = 0.009) and this did not differ by subtype (type 3A: -8.5 m/year, type 3B: -6.6 m/year, p = 0.78), but it did differ by age group (< 6: 9.8 m/year; 6–10: -7.9 m/year; 11–19: -20.8 m/year; ≥ 20: -9.7 m/year; p = 0.005). Our results showed an overall decline on the 6MWT over time, but different trajectories were observed depending on age. Young ambulant SMA patients gain function but in adolescence, patients lose function. Future clinical trials in ambulant SMA patients should consider in their design the different trajectories of ambulatory function over time, based on age

Hypergraph models of biological networks to identify genes critical to pathogenic viral response

Background: Representing biological networks as graphs is a powerful approach to reveal underlying patterns, signatures, and critical components from high-throughput biomolecular data. However, graphs do not natively capture the multi-way relationships present among genes and proteins in biological systems. Hypergraphs are generalizations of graphs that naturally model multi-way relationships and have shown promise in modeling systems such as protein complexes and metabolic reactions. In this paper we seek to understand how hypergraphs can more faithfully identify, and potentially predict, important genes based on complex relationships inferred from genomic expression data sets. Results: We compiled a novel data set of transcriptional host response to pathogenic viral infections and formulated relationships between genes as a hypergraph where hyperedges represent significantly perturbed genes, and vertices represent individual biological samples with specific experimental conditions. We find that hypergraph betweenness centrality is a superior method for identification of genes important to viral response when compared with graph centrality. Conclusions: Our results demonstrate the utility of using hypergraphs to represent complex biological systems and highlight central important responses in common to a variety of highly pathogenic viruses

Implementation of a patient-centered remote wound monitoring system for management of diabetic foot ulcers

BackgroundRegular clinical assessment is critical to optimize lower extremity wound healing. However, family and work obligations, socioeconomic, transportation, and time barriers often limit patient follow-up. We assessed the feasibility of a novel, patient-centered, remote wound management system (Healthy.io Minuteful for Wound Digital Management System) for the surveillance of lower extremity wounds.MethodsWe enrolled 25 patients from our outpatient multidisciplinary limb preservation clinic with a diabetic foot ulcer, who had undergone revascularization and podiatric interventions prior to enrollment. Patients and their caregivers were instructed on how to use the digital management system and asked to perform one at-home wound scan per week for a total of 8 weeks using a smartphone application. We collected prospective data on patient engagement, smartphone app useability, and patient satisfaction.ResultsTwenty-five patients (mean age 65.5 ± 13.7 years, 60.0% male, 52.0% Black) were enrolled over 3 months. Mean baseline wound area was 18.0 ± 15.2 cm2, 24.0% of patients were recovering from osteomyelitis, and post-surgical WiFi stage was 1 in 24.0%, 2 in 40.0%, 3 in 28.0%, and 4 in 8.00% of patients. We provided a smartphone to 28.0% of patients who did not have access to one that was compatible with the technology. Wound scans were obtained by patients (40.0%) and caregivers (60.0%). Overall, 179 wound scans were submitted through the app. The mean number of wound scans acquired per patient was 0.72 ± 0.63 per week, for a total mean of 5.80 ± 5.30 scans over the course of 8 weeks. Use of the digital wound management system triggered an early change in wound management for 36.0% of patients. Patient satisfaction was high; 94.0% of patients reported the system was useful.ConclusionThe Healthy.io Minuteful for Wound Digital Management System is a feasible means of remote wound monitoring for use by patients and/or their caregivers

CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis

Background: Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Methods and results: Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0–6 copies per diploid genome (pdg) in Peru, between 0–12 pdg in !Xhosa samples and between 0–10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). Conclusions: The case–control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations