Analysis of Transglutaminase-2 in macrophage function

Programmed cell death, apoptosis, is a highly regulated process that removes damaged or unwanted cells in vivo and has significant immunological implications. Defective clearance of apoptotic cells by macrophages (professional phagocytes) is known to result in chronic inflammatory and autoimmune disease. Transglutaminase-2 (TG2) is a Ca2+-dependent protein crosslinking enzyme known to play an important role in apoptotic cell clearance by macrophages through an ill-defined mechanism. Several studies have implicated TG2 in the apoptosis programme e.g. raised TG2 levels in cells undergoing apoptosis; increased cell death with down-regulation of TG2; up-regulation of TG2 in monocytes upon differentiation into macrophages. Defective clearance of apoptotic cells by TG2 null mice has been described though in this context the role of TG2 is yet to be elucidated. Here we aim to characterise the role of TG2 in macrophage function with a focus on apoptotic cell clearance. THP-1 monocytes were induced to differentiate to macrophage-like cells by three different stimulants and were analysed for the presence of TG2. Macrophage-apoptotic cell interaction studies in the presence and absence of irreversible TG2 inhibitors resulted in significant inhibition of interaction indicating a possible role for TG2 in apoptotic cell clearance. TG2 was expressed at the macrophage cell surface and its association with ß3 integrin expression suggests the possible link between TG2 and ß3 integrins. Our current findings suggest that TG2 had got a crucial but yet to be defined role in apoptotic cell clearance.

Combined quality function deployment and logical framework analysis to improve quality of emergency care in Malta

Purpose – The purpose of this paper is to develop an integrated patient-focused analytical framework to improve quality of care in accident and emergency (A&E) unit of a Maltese hospital. Design/methodology/approach – The study adopts a case study approach. First, a thorough literature review has been undertaken to study the various methods of healthcare quality management. Second, a healthcare quality management framework is developed using combined quality function deployment (QFD) and logical framework approach (LFA). Third, the proposed framework is applied to a Maltese hospital to demonstrate its effectiveness. The proposed framework has six steps, commencing with identifying patients’ requirements and concluding with implementing improvement projects. All the steps have been undertaken with the involvement of the concerned stakeholders in the A&E unit of the hospital. Findings – The major and related problems being faced by the hospital under study were overcrowding at A&E and shortage of beds, respectively. The combined framework ensures better A&E services and patient flow. QFD identifies and analyses the issues and challenges of A&E and LFA helps develop project plans for healthcare quality improvement. The important outcomes of implementing the proposed quality improvement programme are fewer hospital admissions, faster patient flow, expert triage and shorter waiting times at the A&E unit. Increased emergency consultant cover and faster first significant medical encounter were required to start addressing the problems effectively. Overall, the combined QFD and LFA method is effective to address quality of care in A&E unit. Practical/implications – The proposed framework can be easily integrated within any healthcare unit, as well as within entire healthcare systems, due to its flexible and user-friendly approach. It could be part of Six Sigma and other quality initiatives. Originality/value – Although QFD has been extensively deployed in healthcare setup to improve quality of care, very little has been researched on combining QFD and LFA in order to identify issues, prioritise them, derive improvement measures and implement improvement projects. Additionally, there is no research on QFD application in A&E. This paper bridges these gaps. Moreover, very little has been written on the Maltese health care system. Therefore, this study contributes demonstration of quality of emergency care in Malta.

Towards the formation of a sustainable South Florida: An analysis of conflict resolution and consensus building in the South Florida Everglades Ecosystem Restoration Initiative

This dissertation examines the sociological process of conflict resolution and consensus building in South Florida Everglades Ecosystem Restoration through what I define as a Network Management Coordinative Interstitial Group (NetMIG). The process of conflict resolution can be summarized as the participation of interested and affected parties (stakeholders) in a forum of negotiation. I study the case of the Governor's Commission for a Sustainable South Florida (GCSSF) that was established to reduce social conflict. Such conflict originated from environmental disputes about the Everglades and was manifested in the form of gridlock among regulatory (government) agencies, Indian tribes, as well as agricultural, environmental conservationist and urban development interests. The purpose of the participatory forum is to reduce conflicts of interest and to achieve consensus, with the ultimate goal of restoration of the original Everglades ecosystem, while cultivating the economic and cultural bases of the communities in the area. Further, the forum aim to formulate consensus through envisioning a common sustainable community by providing means to achieve a balance between human and natural systems. ^ Data were gathered using participant observation and document analysis techniques to conduct a theoretically based analysis of the role of the Network Management Coordinative Interstitial Group (NetMIG). I use conflict resolution theory, environmental conflict theory, stakeholder analysis, systems theory, differentiation and social change theory, and strategic management and planning theory. ^ The purpose of this study is to substantiate the role of the Governor's Commission for a Sustainable South Florida (GCSSF) as a consortium of organizations in an effort to resolve conflict rather than an ethnographic study of this organization. Environmental restoration of the Everglades is a vehicle for recognizing the significance of a Network Management Coordinative Interstitial Group (NetMIG), namely the Governor's Commission for a Sustainable South Florida (GCSSF), as a structural mechanism for stakeholder participation in the process of social conflict resolution through the creation of new cultural paradigms for a sustainable community. ^

Importance of storm events in controlling ecosystem structure and function in a Florida gulf coast estuary

From 8/95 to 2/01, we investigated the ecological effects of intra- and inter-annual variability in freshwater flow through Taylor Creek in southeastern Everglades National Park. Continuous monitoring and intensive sampling studies overlapped with an array of pulsed weather events that impacted physical, chemical, and biological attributes of this region. We quantified the effects of three events representing a range of characteristics (duration, amount of precipitation, storm intensity, wind direction) on the hydraulic connectivity, nutrient and sediment dynamics, and vegetation structure of the SE Everglades estuarine ecotone. These events included a strong winter storm in November 1996, Tropical Storm Harvey in September 1999, and Hurricane Irene in October 1999. Continuous hydrologic and daily water sample data were used to examine the effects of these events on the physical forcing and quality of water in Taylor Creek. A high resolution, flow-through sampling and mapping approach was used to characterize water quality in the adjacent bay. To understand the effects of these events on vegetation communities, we measured mangrove litter production and estimated seagrass cover in the bay at monthly intervals. We also quantified sediment deposition associated with Hurricane Irene's flood surge along the Buttonwood Ridge. These three events resulted in dramatic changes in surface water movement and chemistry in Taylor Creek and adjacent regions of Florida Bay as well as increased mangrove litterfall and flood surge scouring of seagrass beds. Up to 5 cm of bay-derived mud was deposited along the ridge adjacent to the creek in this single pulsed event. These short-term events can account for a substantial proportion of the annual flux of freshwater and materials between the mangrove zone and Florida Bay. Our findings shed light on the capacity of these storm events, especially when in succession, to have far reaching and long lasting effects on coastal ecosystems such as the estuarine ecotone of the SE Everglades.

Ecosystem Structure and Function Still Altered Two Decades After Short-Term Fertilization of a Seagrass Meadow

An oligotrophic phosphorus (P) limited seagrass ecosystem in Florida Bay was experimentally fertilized in a unique way. Perches were installed to encourage seabirds to roost and deliver an external source of nutrients via defecation. Two treatments were examined: (1) a chronic 23-year fertilization and (2) an earlier 28-month fertilization that was discontinued when the chronic treatment was initiated. Because of the low mobility of P in carbonate sediments, we hypothesized long-term changes to ecosystem structure and function in both treatments. Structural changes in the chronic treatment included a shift in the dominant seagrass species from Thalassia testudinum to Halodule wrightii, large increases in epiphytic biomass and sediment chlorophyll-a, and a decline in species richness. Functional changes included increased benthic metabolism and quantum efficiency. Initial changes in the 28-month fertilization were similar, but after 23 years of nutrient depuration T. testudinum has reestablished itself as the dominant species. However, P remains elevated in the sediment and H. wrightii has maintained a presence. Functionally the discontinued treatment remains altered. Biomass exceeds that in the chronic treatment and indices of productivity, elevated relative to control, are not different from the chronic fertilization. Cessation of nutrient loading has resulted in a superficial return to the pre-disturbance character of the community, but due to the nature of P cycles functional changes persist.

Early growth characteristics and the risk of reduced lung function and asthma : a meta-analysis of 25,000 children

Peer reviewed

Early growth characteristics and the risk of reduced lung function and asthma : a meta-analysis of 25,000 children

Peer reviewed

Scale and ecosystem services: how do observation, management, and analysis shift with scale—lessons from Québec

Ecosystem service assessment and management are shaped by the scale at which they are conducted; however, there has been little systematic investigation of the scales associated with ecosystem service processes, such as production, benefit distribution, and management. We examined how social-ecological spatial scale impacts ecosystem service assessment by comparing how ecosystem service distribution, trade-offs, and bundles shift across spatial scales. We used a case study in Québec, Canada, to analyze the scales of production, consumption, and management of 12 ecosystem services and to analyze how interactions among 7 of these ecosystem services change across 3 scales of observation (1, 9, and 75 km²). We found that ecosystem service patterns and interactions were relatively robust across scales of observation; however, we identified 4 different types of scale mismatches among ecosystem service production, consumption, and management. Based on this analysis, we have proposed 4 aspects of scale that ecosystem service assessments should consider.

Ovarian suppression using luteinizing hormonereleasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: A meta-analysis of randomized studies

Background: The role of temporary ovarian suppression with luteinizing hormone-releasing hormone agonists (LHRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) is still controversial. Our meta-analysis of randomized, controlled trials (RCTs) investigates whether the use of LHRHa during chemotherapy in premenopausal breast cancer patients reduces treatment-related POF rate, increases pregnancy rate, and impacts disease-free survival (DFS). Methods: A literature search using PubMed, Embase, and the Cochrane Library, and the proceedings of major conferences, was conducted up to 30 April 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for POF (i.e. POF by study definition, and POF defined as amenorrhea 1 year after chemotherapy completion) and for patients with pregnancy, as well hazard ratios (HRs) and 95% CI for DFS, were calculated for each trial. Pooled analysis was carried out using the fixed- and random-effects models. Results: A total of 12 RCTs were eligible including 1231 breast cancer patients. The use of LHRHa was associated with a significant reduced risk of POF (OR 0.36, 95% CI 0.23-0.57; P < 0.001), yet with significant heterogeneity (I2 = 47.1%, Pheterogeneity = 0.026). In eight studies reporting amenorrhea rates 1 year after chemotherapy completion, the addition of LHRHa reduced the risk of POF (OR 0.55, 95% CI 0.41-0.73, P < 0.001) without heterogeneity (I2 = 0.0%, Pheterogeneity = 0.936). In five studies reporting pregnancies, more patients treated with LHRHa achieved pregnancy (33 versus 19 women; OR 1.83, 95% CI 1.02-3.28, P = 0.041; I2 = 0.0%, Pheterogeneity = 0.629). In three studies reporting DFS, no difference was observed (HR 1.00, 95% CI 0.49-2.04, P = 0.939; I2 = 68.0%, Pheterogeneity = 0.044). Conclusion: Temporary ovarian suppression with LHRHa in young breast cancer patients is associated with a reduced risk of chemotherapy-induced POF and seems to increase the pregnancy rate, without an apparent negative consequence on prognosis.

2C-Cas9: a versatile tool for clonal analysis of gene function.

CRISPR/Cas9-mediated targeted mutagenesis allows efficient generation of loss-of-function alleles in zebrafish. To date, this technology has been primarily used to generate genetic knockout animals. Nevertheless, the study of the function of certain loci might require tight spatiotemporal control of gene inactivation. Here, we show that tissue-specific gene disruption can be achieved by driving Cas9 expression with the Gal4/UAS system. Furthermore, by combining the Gal4/UAS and Cre/loxP systems, we establish a versatile tool to genetically label mutant cell clones, enabling their phenotypic analysis. Our technique has the potential to be applied to diverse model organisms, enabling tissue-specific loss-of-function and phenotypic characterization of live and fixed tissues.

Climate Change Adaptation Case Study: Benefit-Cost Analysis of Coastal Flooding Hazard Mitigation

The damage Hurricane Sandy caused had far-reaching repercussions up and down the East Coast of the United States. Vast coastal flooding accompanied the storm, inundating homes, businesses, and utility and emergency facilities. Since the storm, projects to mitigate similar future floods have been scrutinized. Such projects not only need to keep out floodwaters but also be designed to withstand the effect that climate change might have on rising sea levels and increased flood risk. In this study, we develop an economic model to assess the costs and benefits of a berm (sea wall) to mitigate the effects of flooding from a large storm. We account for the lifecycle costs of the project, which include those for the upfront construction of the berm, ongoing maintenance, land acquisition, and wetland and recreation zone construction. Benefits of the project include avoided fatalities, avoided residential and commercial damages, avoided utility and municipal damages, recreational and health benefits, avoided debris removal expenses, and avoided loss of function of key transportation and commercial infrastructure located in the area. Our estimate of the beneficial effects of the berm includes ecosystem services from wetlands and health benefits to the surrounding community from a park and nature system constructed along the berm. To account for the effects of climate change and verify that the project will maintain its effectiveness over the long term, we allow the risk of flooding to increase over time. Over our 50-year time horizon, we double the risk of 100- and 500-year flood events to account for the effects of sea level rise on coastal flooding. Based on the economic analysis, the project is highly cost beneficial over its 50-year timeframe. This analysis demonstrates that climate change adaptation investments can be cost beneficial even though they mitigate the impacts of low-probability, high-consequence events.

What Does a Domain Analysis Look Like in Form, Function, and Genre?

This article presents an inventory what theorists describe as the definition of domain analysis. Survey writings on and of domain analyses for their distinct attributes and arguments. Compile these components and attributes, linking them to their function, and from there. Describe a proposed ideal form of domain analysis. Evidence that while the debate about the substance and form of the epistemic and ontological character of domain analysis will continue, some might find it useful to give shape to their ideas using a particular form that follows function. If our purpose is to delineate and communicate what it is that we are analyzing when we engage in domain analysis, then I hope this small contribution can be of use.

Analysis of human posterior EEG alpha frequency as a function of implicit learning of probabilistic lateralized stimuli in a visual detection task

Alpha oscillatory activity has long been associated with perceptual and cognitive processes related to attention control. The aim of this study is to explore the task-dependent role of alpha frequency in a lateralized visuo-spatial detection task. Specifically, the thesis focuses on consolidating the scientific literature's knowledge about the role of alpha frequency in perceptual accuracy, and deepening the understanding of what determines trial-by-trial fluctuations of alpha parameters and how these fluctuations influence overall task performance. The hypotheses, confirmed empirically, were that different implicit strategies are put in place based on the task context, in order to maximize performance with optimal resource distribution (namely alpha frequency, associated positively with performance): “Lateralization” of the attentive resources towards one hemifield should be associated with higher alpha frequency difference between contralateral and ipsilateral hemisphere; “Distribution” of the attentive resources across hemifields should be associated with lower alpha frequency difference between hemispheres; These strategies, used by the participants according to their brain capabilities, have proven themselves adaptive or maladaptive depending on the different tasks to which they have been set: "Distribution" of the attentive resources seemed to be the best strategy when the distribution probability between hemifields was balanced: i.e. the neutral condition task. "Lateralization" of the attentive resources seemed to be more effective when the distribution probability between hemifields was biased towards one hemifield: i.e., the biased condition task.