Ontological support for managing non-functional requirements in pervasive healthcare

We designed and implemented an ontological solution which makes provisions for choosing adequate devices/sensors for remote monitoring of patients who are suffering from post-stroke health complications. We argue that non-functional requirements in pervasive healthcare systems can be elicited and managed through semantics stored in ontological models and reasoning created upon them. Our contribution is twofold: we enrich the elicitation process and specification of non-functional requirements within the requirements engineering discipline and we address the pervasiveness of healthcare software systems through the way of choosing devices embedded in them and users expectations in terms of having access to pervasive services personalized to their needs

Anti-tumor effects of retinoids combined with trastuzumab or tamoxifen in breast cancer cells: induction of apoptosis by retinoid/trastuzumab combinations

INTRODUCTION: HER2 and estrogen receptor (ER) are important in breast cancer and are therapeutic targets of trastuzumab (Herceptin) and tamoxifen, respectively. Retinoids inhibit breast cancer growth, and modulate signaling by HER2 and ER. We hypothesized that treatment with retinoids and simultaneous targeting of HER2 and/or ER may have enhanced anti-tumor effects. METHODS: The effects of retinoids combined with trastuzumab or tamoxifen were examined in two human breast cancer cell lines in culture, BT474 and SKBR3. Assays of proliferation, apoptosis, differentiation, cell cycle distribution, and receptor signaling were performed. RESULTS: In HER2-overexpressing/ER-positive BT474 cells, combining all-trans retinoic acid (atRA) with tamoxifen or trastuzumab synergistically inhibited cell growth, and altered cell differentiation and cell cycle. Only atRA/trastuzumab-containing combinations induced apoptosis. BT474 and HER2-overexpressing/ER-negative SKBR3 cells were treated with a panel of retinoids (atRA, 9-cis-retinoic acid, 13-cis-retinoic acid, or N-(4-hydroxyphenyl) retinamide (fenretinide) (4-HPR)) combined with trastuzumab. In BT474 cells, none of the single agents except 4-HPR induced apoptosis, but again combinations of each retinoid with trastuzumab did induce apoptosis. In contrast, the single retinoid agents did cause apoptosis in SKBR3 cells; this was only modestly enhanced by addition of trastuzumab. The retinoid drug combinations altered signaling by HER2 and ER. Retinoids were inactive in trastuzumab-resistant BT474 cells. CONCLUSIONS: Combining retinoids with trastuzumab maximally inhibits cell growth and induces apoptosis in trastuzumab-sensitive cells. Treatment with such combinations may have benefit for breast cancer patients

Accelerated Pulsed High-Fluence Corneal Cross-Linking for Progressive Keratoconus

PURPOSE: To report on 2-year results of accelerated corneal collagen cross-linking (CXL) in progressive ectasia using the Avedro KXL system. DESIGN: Prospective interventional case series. METHODS: A total of 870 patients (1,192 eyes) attending Moorfields Eye Hospital after CXL were included. All patients undergoing CXL had progressive keratoconus. Corneas with a minimum stromal thickness <375 μm were excluded. Riboflavin 0.1% soak duration was 10 minutes. High-fluence pulsed UVA was delivered at 30 mW/cm2 for 4 minutes, with a 1.5-second on/off cycle (total energy 7.2 J/cm2). Subjective refractive, corneal tomography, and specular microscopy were performed at baseline, 6, 12, and 24 months postoperatively. The primary outcome measure was a change in maximum keratometry (Kmax) at 24 months. RESULTS: Twelve- and 24-month follow-up data were available on 543 and 213 patients, respectively (mean age 25.4 ± 6.6 years). In mild cones (Kmax < 55 diopter [D]), mean keratometry remained unchanged at 24 months. In more advanced disease, we observed modest corneal flattening compared to baseline (Kmax 63.2 ± 6.5 D vs 61.9 ± 8.1 D, P = .02), but no significant changes in central keratometry (K1 or K2). Keratometric stabilization was confirmed in 98.3% of eyes. Mean CDVA, manifest refraction and endothelial cell density did not change. Overall, 2.7% of eyes lost more than 2 lines of CDVA. CONCLUSION: Accelerated pulsed CXL is a safe, effective, and refractively neutral intervention (at 2 years) to halt disease progression in keratoconus

Physicochemical Characteristics of Magnesium Hydroxyapatite (MgHA) Derived via Wet Precipitation Method / C. M. Mardziah ... [et al.]

Hydroxyapatite (HA) has been known for so many decades as an implant material for medical applications due to its chemical composition that is very similar to the inorganic component of human bone. However, synthetic HA possesses relatively low mechanical strength characteristic, making it less suitable to be used in load bearing applications. Thus, the presence of metal ion like magnesium (Mg) is expected to improve the properties of synthetic HA as biomedical devices. The main objective of this research is to develop and characterize the magnesium hydroxyapatite (MgHA) nanopowders derived from the wet precipitation method. The amount of Mg, which acts as a metallic dopant in HA were varied at 0, 5 and 10% and calcined at 700C for imperative comparison. The resultant nanopowders were then characterized using thermogravimetric analysis (TGA), X-ray diffraction (XRD) and field-emission scanning electron microscopy (FESEM) to examine their physicochemical properties. Morphological evaluation by FESEM showed that the particle size of 10% MgHA powders was larger and spherical in shape but still highly agglomerated at calcination temperature of 700C. This result coincides with the data obtained from the XRD analysis, which revealed that the particle size of pure HA, 5 and 10% MgHA after calcination was 87 nm, 98 nm and 116 nm, respectively. These results demonstrate that doping Mg into HA has caused an increase in the particle size, proving that Mg acts as a sintering additive during the calcination process

Exposure to solar ultraviolet radiation establishes a novel immune suppressive lipidome in skin-draining lymph nodes

The ability of ultraviolet radiation to suppress the immune system is thought to be central to both its beneficial (protection from autoimmunity) and detrimental (carcinogenic) effects. Previous work revealed a key role for lipids particularly platelet-activating factor and sphingosine-1-phosphate in mediating UV-induced immune suppression. We therefore hypothesized that there may be other UV-induced lipids that have immune regulatory roles. To assess this, mice were exposed to an immune suppressive dose of solar-simulated UV (8 J/cm2). Lipidomic analysis identified 6 lipids (2 acylcarnitines, 2 neutral lipids, and 2 phospholipids) with significantly increased levels in the skin-draining lymph nodes of UV-irradiated mice. Imaging mass spectrometry of the lipids in combination with imaging mass cytometry identification of lymph node cell subsets indicated a preferential location of UV-induced lipids to T cell areas. In vitro co-culture of skin-draining lymph node lipids with lymphocytes showed that lipids derived from UV-exposed mice have no effect on T cell activation but significantly inhibited T cell proliferation, indicating that the lipids play an immune regulatory role. These studies are important first steps in identifying novel lipids that contribute to UV-mediated immune suppression

Intra-day variability observations of S5 0716+714 over 4.5 years at 4.8 GHz

We aim to search for evidence of annual modulation in the time scales of the BL Lac object S5 0716+714. The intra-day variability (IDV) observations were carried out monthly from 2005 to 2009, with the Urumqi 25m radio telescope at 4.8 GHz. The source has shown prominent IDV as well as long-term flux variations. The IDV time scale does show evidence in favor of an annual modulation, suggesting that the IDV of 0716+714 is dominated by interstellar scintillation. The source underwent a strong outburst phase between mid-2008 and mid-2009; a second intense flare was observed in late 2009, but no correlation between the total flux density and the IDV time scale is found, implying that the flaring state of the source does not have serious implications for the general characteristics of its intra-day variability. However, we find that the inner-jet position angle is changing throughout the years, which could result in an annual modulation noise in the anisotropic ISS model fit. There is also an indication that the lowest IDV amplitudes (rms flux density) correspond to the slowest time scales of IDV, which would be consistent with an ISS origin of the IDV of 0716+714.Comment: 6 pages, 7 figures, accepted for publication in A&A; corrected typos in Table

The Commensal Real-time ASKAP Fast Transients (CRAFT) survey

We are developing a purely commensal survey experiment for fast (<5s) transient radio sources. Short-timescale transients are associated with the most energetic and brightest single events in the Universe. Our objective is to cover the enormous volume of transients parameter space made available by ASKAP, with an unprecedented combination of sensitivity and field of view. Fast timescale transients open new vistas on the physics of high brightness temperature emission, extreme states of matter and the physics of strong gravitational fields. In addition, the detection of extragalactic objects affords us an entirely new and extremely sensitive probe on the huge reservoir of baryons present in the IGM. We outline here our approach to the considerable challenge involved in detecting fast transients, particularly the development of hardware fast enough to dedisperse and search the ASKAP data stream at or near real-time rates. Through CRAFT, ASKAP will provide the testbed of many of the key technologies and survey modes proposed for high time resolution science with the SKA.Comment: accepted for publication in PAS

Nuclear factor κB-inducing kinase activation as a mechanism of pancreatic β cell failure in obesity

The nuclear factor κB (NF-κB) pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic β cell dysfunction in the metabolic syndrome. Whereas canonical NF-κB signaling is well studied, there is little information on the divergent noncanonical NF-κB pathway in the context of pancreatic islet dysfunction. Here, we demonstrate that pharmacological activation of the noncanonical NF-κB-inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo. We identify NIK as a critical negative regulator of β cell function, as pharmacological NIK activation results in impaired glucose-stimulated insulin secretion in mouse and human islets. NIK levels are elevated in pancreatic islets isolated from diet-induced obese (DIO) mice, which exhibit increased processing of noncanonical NF-κB components p100 to p52, and accumulation of RelB. TNF and receptor activator of NF-κB ligand (RANKL), two ligands associated with diabetes, induce NIK in islets. Mice with constitutive β cell-intrinsic NIK activation present impaired insulin secretion with DIO. NIK activation triggers the noncanonical NF-κB transcriptional network to induce genes identified in human type 2 diabetes genome-wide association studies linked to β cell failure. These studies reveal that NIK contributes a central mechanism for β cell failure in diet-induced obesity

Linear ubiquitin chain assembly complex coordinates late thymic T-cell differentiation and regulatory T-cell homeostasis.

The linear ubiquitin chain assembly complex (LUBAC) is essential for innate immunity in mice and humans, yet its role in adaptive immunity is unclear. Here we show that the LUBAC components HOIP, HOIL-1 and SHARPIN have essential roles in late thymocyte differentiation, FOXP3(+) regulatory T (Treg)-cell development and Treg cell homeostasis. LUBAC activity is not required to prevent TNF-induced apoptosis or necroptosis but is necessary for the transcriptional programme of the penultimate stage of thymocyte differentiation. Treg cell-specific ablation of HOIP causes severe Treg cell deficiency and lethal immune pathology, revealing an ongoing requirement of LUBAC activity for Treg cell homeostasis. These data reveal stage-specific requirements for LUBAC in coordinating the signals required for T-cell differentiation