Physiologic Status Monitoring via the Gastrointestinal Tract

Reliable, real-time heart and respiratory rates are key vital signs used in evaluating the physiological status in many clinical and non-clinical settings. Measuring these vital signs generally requires superficial attachment of physically or logistically obtrusive sensors to subjects that may result in skin irritation or adversely influence subject performance. Given the broad acceptance of ingestible electronics, we developed an approach that enables vital sign monitoring internally from the gastrointestinal tract. Here we report initial proof-of-concept large animal (porcine) experiments and a robust processing algorithm that demonstrates the feasibility of this approach. Implementing vital sign monitoring as a stand-alone technology or in conjunction with other ingestible devices has the capacity to significantly aid telemedicine, optimize performance monitoring of athletes, military service members, and first-responders, as well as provide a facile method for rapid clinical evaluation and triage.United States. Dept. of the Air Force (Air Force Contract FA8721-05-C-0002)United States. Dept. of Defense. Assistant Secretary of Defense for Research & EngineeringNational Institutes of Health (U.S.) (Grant EB000244)National Institutes of Health (U.S.) (Grant T32DK7191-38-S1

Modeling Web Services by Iterative Reformulation of Functional and Non-Functional Requirements

Abstract. We propose an approach for incremental modeling of composite Web services. The technique takes into consideration both the functional and nonfunctional requirements of the composition. While the functional requirements are described using symbolic transition systems—transition systems augmented with state variables, function invocations, and guards; non-functional requirements are quantified using thresholds. The approach allows users to specify an abstract and possibly incomplete specification of the desired service (goal) that can be realized by selecting and composing a set of pre-existing services. In the event that such a composition is unrealizable, i.e. the composition is not functionally equivalent to the goal or the non-functional requirements are violated, our system provides the user with the causes for the failure, that can be used to appropriately reformulate the functional and/or non-functional requirements of the goal specification.

An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease

There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. Targeting drugs selectively to the inflamed intestine may improve therapeutic outcomes and minimize systemic toxicity. We report the development of an inflammation-targeting hydrogel (IT-hydrogel) that acts as a drug delivery system to the inflamed colon. Hydrogel microfibers were generated from ascorbyl palmitate, an amphiphile that is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration. IT-hydrogel microfibers loaded with the anti-inflammatory corticosteroid dexamethasone (Dex) were stable, released drug only upon enzymatic digestion, and demonstrated preferential adhesion to inflamed epithelial surfaces in vitro and in two mouse colitis models in vivo. Dex-loaded IT-hydrogel enemas, but not free Dex enemas, administered every other day to mice with colitis resulted in a significant reduction in inflammation and were associated with lower Dex peak serum concentrations and, thus, less systemic drug exposure. Ex vivo analysis of colon tissue samples from patients with ulcerative colitis demonstrated that IT-hydrogel microfibers adhered preferentially to mucosa from inflamed lesions compared with histologically normal sites. The IT-hydrogel drug delivery platform represents a promising approach for targeted enema-based therapies in patients with colonic IBD

Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish

The authors would like to thank the Royal Society of London, the National Eye Research Centre, the Visual Research Trust, Fight for Sight, the W.H. Ross Foundation, the Rosetrees Trust, and the Glasgow Children’s Hospital Charity for supporting this work. This work was also supported by the Deanship of Scientific Research at King Saud University for funding this research (Research Project) grant number ‘RGP – VPP – 219’.Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.Publisher PDFPeer reviewe

Efficient stochastic finite element methods for flow in heterogeneous porous media. Part 2: random lognormal permeability

Efficient and robust iterative methods are developed for solving the linear systems of equations arising from stochastic finite element methods for single phase fluid flow in porous media. Permeability is assumed to vary randomly in space according to some given correlation function. In the companion paper, herein referred to as Part 1, permeability was approximated using a truncated Karhunen‐Loève expansion (KLE). The stochastic variability of permeability is modeled using lognormal random fields and the truncated KLE is projected onto a polynomial chaos basis. This results in a stochastic nonlinear problem since the random fields are represented using polynomial chaos containing terms that are generally nonlinear in the random variables. Symmetric block Gauss‐Seidel used as a preconditioner for CG is shown to be efficient and robust for stochastic finite element method

From START to FINISH : the influence of osmotic stress on the cell cycle

Peer reviewedPublisher PD

Health-related quality of life in patients with primary open-angle glaucoma. An italian multicentre observational study

PurposeAs a progressive condition, glaucoma may impair health-related quality of life (HRQoL), due to vision loss and other factors. This study evaluated HRQoL in a cohort of patients treated for primary open-angle glaucoma (POAG) and assessed its association with clinical features. MethodsThis was an Italian, multicentre, cross-sectional, observational study with the subgroup of newly diagnosed patients with POAG prospectively followed up for one year. Patients with previous or new diagnosis (or strong clinical suspicion) of POAG aged >18years were considered eligible. Information was collected on demographic characteristics, medical history, clinical presentation and POAG treatments. HRQoL was measured using the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and Glaucoma Symptom Scale (GSS). Subscale and total scores were obtained and a Pearson correlation coefficient between instruments' scores calculated. ResultsA total of 3227 patients were enrolled from 2012 to 2013 and 3169 were analysed. Mean age was 66.9years. A total of 93.8% had a previous diagnosis (median duration: 8.0years). Median values for mean deviation and pattern standard deviation were 3.9 and 3.6 dB, respectively. Mean scores on most subscales of the NEI-VFQ-25 exceeded 75.0 and mean GSS subscale scores ranged between 70.8 and 79.7 (with a total mean score of 74.8). HRQoL scores on both scales were significantly inversely associated with POAG severity. ConclusionIn this large sample of Italians treated for POAG, disease severity was limited and HRQoL scores were high. QoL decreased with advancing disease severity. These findings confirm the role of vision loss in impairing QoL in POAG, underlying the importance of timely detection and appropriate treatment

Effectiveness of an executive function training in italian preschool educational services and far transfer effects to pre-academic skills

In this study we examine the effectiveness and far transfer effects of a training that was found to be effective in promoting Executive Function (EF) in a sample of 5-year-old children (Traverso et al., 2015). By contrast with Traverso et al. (2015), the intervention was administered by regular teachers to verify its ecological validity. Far transfer was assessed by evaluating the training effects on pre-academic skills. 126 children attending the last year of Italian preschool educational services took part in the study (mainly 5-year-old children). Pre-and post-test assessments were conducted using a large EF and pre-academic skill task battery. The results indicate that the experimental group outperformed the control group in an interference suppression composite score. Moreover, significant far transfer effects to pre-academic skills in literacy domain were found. In addition, we found that the improvement in the pre academic skills (in both literacy and math domains) was mediated by the improvement in the interference suppression score. The results suggest the possibility that this intervention, which may be easily implemented in the context of educational services, can promote EF during the preschool period before entry to primary school