Dynamics of ecosystem metabolism and flocculent detritus transport in estuarine Taylor River

Estuaries and estuarine wetlands are ecologically and societally important systems, exhibiting high rates of primary production that fuel offshore secondary production. Hydrological processes play a central role in shaping estuarine ecosystem structure and function by controlling nutrient loading and the relative contributions of marine and terrestrial influences on the estuary. The Comprehensive Everglades Restoration Plan includes plans to restore freshwater delivery to Taylor Slough, a shallow drainage basin in the southern Everglades, ultimately resulting in increased freshwater flow to the downstream Taylor River estuary. The existing seasonal and inter-annual variability of water flow and source in Taylor River affords the opportunity to investigate relationships between ecosystem function and hydrologic forcing. Estimates of aquatic ecosystem metabolism, derived from free-water, diel changes in dissolved oxygen, were combined with assessments of wetland flocculent detritus quality and transport within the context of seasonal changes in Everglades hydrology. Variation in ecosystem gross primary production and respiration were linked to seasonal changes in estuarine water quality using multiple autoregression models. Furthermore, Taylor River was observed to be net heterotrophic, indicating that an allochthonous source of carbon maintained ecosystem respiration in excess of autochthonous primary production. Wetland-derived detritus appears to be an important vector of energy and nutrients across the Everglades landscape; and in Taylor River, is seasonally flushed into ponded segments of the river where it is then respired. Lastly, seasonal water delivery appears to govern feedbacks regulating water column phosphorus availability in the Taylor River estuary.

Derivation of base-line geochemistry, petrography, and isotopic data for the host rocks to the Lucky Strike deposit and comparison with data from other alteration zones, Buchans Mining Camp, Newfoundland

The Buchans ore bodies of central Newfoundland represent some of the highest grade VMS deposits ever mined. These Kuroko-type deposits are also known for the well developed and preserved nature of the mechanically transported deposits. The deposits are hosted in Cambro-Ordovician, dominantly calc-alkaline, bimodal volcanic and epiclastic sequences of the Notre Dame Subzone, Newfoundland Appalachians. Stratigraphic relationships in this zone are complicated by extensively developed, brittledominated Silurian thrust faulting. Hydrothermal alteration of host rocks is a common feature of nearly all VMS deposits, and the recognition of these zones has been a key exploration tool. Alteration of host rocks has long been described to be spatially associated with the Buchans ore bodies, most notably with the larger in-situ deposits. This report represents a base-line study in which a complete documentation of the geochemical variance, in terms of both primary (igneous) and alteration effects, is presented from altered volcanic rocks in the vicinity of the Lucky Strike deposit (LSZ), the largest in-situ deposit in the Buchans camp. Packages of altered rocks also occur away from the immediate mining areas and constitute new targets for exploration. These zones, identified mostly by recent and previous drilling, represent untested targets and include the Powerhouse (PHZ), Woodmans Brook (WBZ) and Airport (APZ) alteration zones, as well as the Middle Branch alteration zone (MBZ), which represents a more distal alteration facies related to Buchans ore-formation. Data from each of these zones were compared to those from the LSZ in order to evaluate their relative propectivity. Derived litho geochemical data served two functions: (i) to define primary (igneous) trends and (ii) secondary alteration trends. Primary trends were established using immobile, or conservative, elements (i. e., HFSE, REE, Th, Ti0₂, Al₂0₃, P₂0₅). From these, altered volcanic rocks were interpreted in terms of composition (e.g., basalt - rhyodacite) and magmatic affinity (e.g., calc-alkaline vs. tholeiitic). The information suggests that bimodality is a common feature of all zones, with most rocks plotting as either basalt/andesite or dacite (or rhyodacite); andesitic senso stricto compositions are rare. Magmatic affinities are more varied and complex, but indicate that all units are arc volcanic sequences. Rocks from the LSZ/MBZ represent a transitional to calc-alkalic sequence, however, a slight shift in key geochemical discriminants occurs between the foot-wall to the hanging-wall. Specifically, mafic and felsic lavas of the foot-wall are of transitional (or mildly calc-alkaline) affinity whereas the hanging-wall rocks are relatively more strongly calc-alkaline as indicated by enriched LREE/HREE and higher ZrN, NbN and other ratios in the latter. The geochemical variations also serve as a means to separate the units (at least the felsic rocks) into hanging-wall and foot-wall sequences, therefore providing a valuable exploration tool. Volcanic rocks from the WBZ/PHZ (and probably the APZ) are more typical of tholeiitic to transitional suites, yielding flatter mantlenormalized REE patterns and lower ZrN ratios. Thus, the relationships between the immediate mining area (represented by LSZ/MBZ) and the Buchans East (PHZ/WBZ) and the APZ are uncertain. Host rocks for all zones consist of mafic to felsic volcanic rocks, though the proportion of pyroclastic and epiclastic rocks, is greatest at the LSZ. Phenocryst assemblages and textures are common in all zones, with minor exceptions, and are not useful for discrimination purposes. Felsic rocks from all zones are dominated by sericiteclay+/- silica alteration, whereas mafic rocks are dominated by chlorite- quartz- sericite alteration. Pyrite is ubiquitous in all moderately altered rocks and minor associated base metal sulphides occur locally. The exception is at Lucky Strike, where stockwork quartzveining contains abundant base-metal mineralization and barite. Rocks completely comprised of chlorite (chloritite) also occur in the LSZ foot-wall. In addition, K-feldspar alteration occurs in felsic volcanic rocks at the MBZ associated with Zn-Pb-Ba and, notably, without chlorite. This zone represents a peripheral, but proximal, zone of alteration induced by lower temperature hydrothermal fluids, presumably with little influence from seawater. Alteration geochemistry was interpreted from raw data as well as from mass balanced (recalculated) data derived from immobile element pairs. The data from the LSZ/MBZ indicate a range in the degree of alteration from only minor to severe modification of precursor compositions. Ba tends to show a strong positive correlation with K₂0, although most Ba occurs as barite. With respect to mass changes, Al₂0₃, Ti0₂ and P₂0₅ were shown to be immobile. Nearly all rocks display mass loss of Na₂O, CaO, and Sr reflecting feldspar destruction. These trends are usually mirrored by K₂0-Rb and MgO addition, indicating sericitic and chloritic alteration, respectively. More substantial gains ofK₂0 often occur in rocks with K-feldspar alteration, whereas a few samples also displayed excessive MgO enrichment and represent chloritites. Fe₂0₃ indicates both chlorite and sulphide formation. Si0₂ addition is almost always the case for the altered mafic rocks as silica often infills amygdules and replaces the finer tuffaceous material. The felsic rocks display more variability in Si0₂. Silicic, sericitic and chloritic alteration trends were observed from the other zones, but not K-feldspar, chloritite, or barite. Microprobe analysis of chlorites, sericites and carbonates indicate: (i) sericites from all zones are defined as muscovite and are not phengitic; (ii) at the LSZ, chlorites ranged from Fe-Mg chlorites (pycnochlorite) to Mg-rich chlorite (penninite), with the latter occurring in the stockwork zone and more proximal alteration facies; (iii) chlorites from the WBZ were typical of those from the more distal alteration facies of the LSZ, plotting as ripidolite to pycnochlorite; (iv) conversely, chlorite from the PHZ plot with Mg-Al-rich compositions (chlinochlore to penninite); and (v) carbonate species from each zone are also varied, with calcite occurring in each zone, in addition to dolomite and ankerite in the PHZ and WBZ, respectively. Lead isotope ratios for galena separates from the different various zones, when combined with data from older studies, tend to cluster into four distinctive fields. Overall, the data plot on a broad mixing line and indicate evolution in a relatively low-μ environment. Data from sulphide stringers in altered MBZ rocks, as well as from clastic sulphides (Sandfill prospect), plot in the Buchans ore field, as do the data for galena from altered rocks in the APZ. Samples from the Buchans East area are even more primitive than the Buchans ores, with lead from the PHZ plotting with the Connel Option prospect and data from the WBZ matching that of the Skidder prospect. A sample from a newly discovered debris flow-type sulphide occurrence (Middle Branch East) yields lead isotope ratios that are slightly more radiogenic than Buchans and plot with the Mary March alteration zone. Data within each cluster are interpreted to represent derivation from individual hydrothermal systems in which metals were derived from a common source.

Telmisartan to prevent recurrent stroke and cardiovascular events

Background Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin–angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin–angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. Methods In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes. Results The median interval from stroke to randomization was 15 days. During a mean followup of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P = 0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P = 0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P = 0.10). Conclusions Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.)

Probabilistic methods for seasonal forecasting in a changing climate: Cox-type regression models.

For climate risk management, cumulative distribution functions (CDFs) are an important source of information. They are ideally suited to compare probabilistic forecasts of primary (e.g. rainfall) or secondary data (e.g. crop yields). Summarised as CDFs, such forecasts allow an easy quantitative assessment of possible, alternative actions. Although the degree of uncertainty associated with CDF estimation could influence decisions, such information is rarely provided. Hence, we propose Cox-type regression models (CRMs) as a statistical framework for making inferences on CDFs in climate science. CRMs were designed for modelling probability distributions rather than just mean or median values. This makes the approach appealing for risk assessments where probabilities of extremes are often more informative than central tendency measures. CRMs are semi-parametric approaches originally designed for modelling risks arising from time-to-event data. Here we extend this original concept beyond time-dependent measures to other variables of interest. We also provide tools for estimating CDFs and surrounding uncertainty envelopes from empirical data. These statistical techniques intrinsically account for non-stationarities in time series that might be the result of climate change. This feature makes CRMs attractive candidates to investigate the feasibility of developing rigorous global circulation model (GCM)-CRM interfaces for provision of user-relevant forecasts. To demonstrate the applicability of CRMs, we present two examples for El Ni ? no/Southern Oscillation (ENSO)-based forecasts: the onset date of the wet season (Cairns, Australia) and total wet season rainfall (Quixeramobim, Brazil). This study emphasises the methodological aspects of CRMs rather than discussing merits or limitations of the ENSO-based predictors.

Strategic Optimization Techniques For FRTU Deployment and Chip Physical Design

Combinatorial optimization is a complex engineering subject. Although formulation often depends on the nature of problems that differs from their setup, design, constraints, and implications, establishing a unifying framework is essential. This dissertation investigates the unique features of three important optimization problems that can span from small-scale design automation to large-scale power system planning: (1) Feeder remote terminal unit (FRTU) planning strategy by considering the cybersecurity of secondary distribution network in electrical distribution grid, (2) physical-level synthesis for microfluidic lab-on-a-chip, and (3) discrete gate sizing in very-large-scale integration (VLSI) circuit. First, an optimization technique by cross entropy is proposed to handle FRTU deployment in primary network considering cybersecurity of secondary distribution network. While it is constrained by monetary budget on the number of deployed FRTUs, the proposed algorithm identi?es pivotal locations of a distribution feeder to install the FRTUs in different time horizons. Then, multi-scale optimization techniques are proposed for digital micro?uidic lab-on-a-chip physical level synthesis. The proposed techniques handle the variation-aware lab-on-a-chip placement and routing co-design while satisfying all constraints, and considering contamination and defect. Last, the first fully polynomial time approximation scheme (FPTAS) is proposed for the delay driven discrete gate sizing problem, which explores the theoretical view since the existing works are heuristics with no performance guarantee. The intellectual contribution of the proposed methods establishes a novel paradigm bridging the gaps between professional communities.

New palladium catalysed reactions of bromoporphyrins: synthesis and crystal structures of nickel(II) complexes of primary 5-aminoporphyrin, 5,5’-bis(porphyrinyl) secondary amine, and 5-hydroxyporphyrin

Primary aminoporphyrin, secondary bis(porphyrinyl)amine and hydroxyporphyrin complexes have been isolated and characterised both spectroscopically and crystallographically from the reaction of 5-bromo-10,15,20-triphenylporphyrinato-nickel(II) with hydrazine under palladium catalysis.

Depth of focus and visual acuity with primary and secondary spherical aberration

It is known that the depth of focus (DOF) of the human eye can be affected by the higher order aberrations. We estimated the optimal combinations of primary and secondary Zernike spherical aberration to expand the DOF and evaluated their efficiency in real eyes using an adaptive optics system. The ratio between increased DOF and loss of visual acuity was used as the performance indicator. The results indicate that primary or secondary spherical aberration alone shows similar effectiveness in extending the DOF. However, combinations of primary and secondary spherical aberration with different signs provide better efficiency for expanding the DOF. This finding suggests that the optimal combinations of primary and secondary spherical aberration may be useful in the design of optical presbyopic corrections. © 2011 Elsevier Ltd. All rights reserved.

Crisis communication under transformative change : the emergent context and roles of primary and secondary organisations

In an era of complex challenges that draw sustained media attention and entangle multiple organisational actors, this thesis addresses the gap between current trends in society and business, and existing scholarship in public relations and crisis communication. By responding to calls from crisis communication researchers to develop theory (Coombs, 2006a), to examine the interdependencies of crises (Seeger, Sellnow, & Ulmer, 1998), and to consider variation in crisis response (Seeger, 2002), this thesis contributes to theory development in crisis communication and public relations. Through transformative change, this thesis extends existing scholarship built on a preservation or conservation logic where public relations is used to maintain stability by incrementally responding to changes in an organisation‘s environment (Cutlip, Center, & Broom, 2006; Everett, 2001; Grunig, 2000; Spicer, 1997). Based on the opportunity to contribute to ongoing theoretical development in the literature, the overall research problem guiding this thesis asks: How does transformative change during crisis influence corporate actors’ communication? This thesis adopts punctuated equilibrium theory, which describes change as alternating between long periods of stability and short periods of revolutionary or transformative change (Gersick, 1991; Romanelli & Tushman, 1994; Siggelkow, 2002; Tushman, Newman, & Romanelli, 1986; Tushman & Romanelli, 1985). As a theory for change, punctuated equilibrium provides an opportunity to examine public relations and transformative change, building on scholarship that is based primarily on incremental change. Further, existing scholarship in public relations and crisis communication focuses on the actions of single organisations in situational or short-term crisis events. Punctuated equilibrium theory enables the study of multiple crises and multiple organisational responses during transformative change. In doing so, punctuated equilibrium theory provides a framework to explain both the context for transformative change and actions or strategies enacted by organisations during transformative change (Tushman, Newman, & Romanelli, 1986; Tushman & Romanelli, 1985; Tushman, Virany, & Romanelli, 1986). The connections between context and action inform the research questions that guide this thesis: RQ1: What symbolic and substantive strategies persist and change as crises develop from situational events to transformative and multiple linked events? RQ2: What features of the crisis context influence changes in symbolic and substantive strategies? To shed light on these research questions, the thesis adopts a qualitative approach guided by process theory and methods to explicate the events, sequences and activities that were essential to change (Pettigrew, 1992; Van de Ven, 1992). Specifically, the thesis draws on an alternative template strategy (Langley, 1999) that provides several alternative interpretations of the same events (Allison, 1971; Allison & Zelikow, 1999). Following Allison (1971) and Allison and Zelikow (1999), this thesis uses three alternative templates of crisis or strategic response typologies to construct three narratives using media articles and organisational documents. The narratives are compared to identify and draw out different patterns of crisis communication strategies that operate within different crisis contexts. The thesis is based on the crisis events that affected three organisations within the pharmaceutical industry for four years. The primary organisation is Merck, as its product recall crisis triggered transformative change affecting, in different ways, the secondary organisations of Pfizer and Novartis. Three narratives are presented based on the crisis or strategic response typologies of Coombs (2006b), Allen and Caillouet (1994), and Oliver (1991). The findings of this thesis reveal different stories about crisis communication under transformative change. By zooming in to a micro perspective (Nicolini, 2009) to focus on the crisis communication and actions of a single organisation and zooming out to a macro perspective (Nicolini, 2009) to consider multiple organisations, new insights about crisis communication, change and the relationships among multiple organisations are revealed at context and action levels. At the context level, each subsequent narrative demonstrates greater connections among multiple corporate actors. By zooming out from Coombs‘ (2006b) focus on single organisations to consider Allen and Caillouet‘s (1994) integration of the web of corporate actors, the thesis demonstrates how corporate actors add accountability pressures to the primary organisation. Next, by zooming further out to the macro perspective by considering Oliver‘s (1991) strategic responses to institutional processes, the thesis reveals a greater range of corporate actors that are caught up in the process of transformative change and accounts for their varying levels of agency over their environment. By zooming in to a micro perspective and out to a macro perspective (Nicolini, 2009) across alternative templates, the thesis sheds light on sequences, events, and actions of primary and secondary organisations. Although the primary organisation remains the focus of sustained media attention across the four-year time frame, the secondary organisations, even when one faced a similar starting situation to the primary organisation, were buffered by the process of transformative change. This understanding of crisis contexts in transforming environments builds on existing knowledge in crisis communication. At the action level, the thesis also reveals different interpretations from each alternative template. Coombs‘ (2006b) narrative shows persistence in the primary organisation‘s crisis or strategic responses over the four-year time frame of the thesis. That is, the primary organisation consistently applies a diminish crisis response. At times, the primary organisation drew on denial responses when corporate actors questioned its legitimacy or actions. To close the crisis, the primary organisation uses a rebuild crisis posture (Coombs, 2006). These finding are replicated in Allen and Caillouet‘s (1994) narrative, noting this template‘s limitation to communication messages only. Oliver‘s (1991) narrative is consistent with Coombs‘ (2006b) but also demonstrated a shift from a strategic response that signals conformity to the environment to one that signals more active resistance to the environment over time. Specifically, the primary organisation‘s initial response demonstrates conformity but these same messages were used some three years later to set new expectations in the environment in order to shape criteria and build acceptance for future organisational decisions. In summary, the findings demonstrate the power of crisis or strategic responses when considered over time and in the context of transformative change. The conclusions of this research contribute to scholarship in the public relations and management literatures. Based on the significance of organisational theory, the primary contribution of the theory relates to the role of interorganisational linkages or legitimacy buffers that form during the punctuation of equilibrium. The network of linkages among the corporate actors are significant also to the crisis communication literature as they form part of the process model of crisis communication under punctuated equilibrium. This model extends existing research that focuses on crisis communication of single organisations to consider the emergent context that incorporates secondary organisations as well as the localised contests of legitimacy and buffers from regulatory authorities. The thesis also provides an empirical base for punctuated equilibrium in public relations and crisis communication, extending Murphy‘s (2000) introduction of the theory to the public relations literature. In doing this, punctuated equilibrium theory reinvigorates theoretical development in crisis communication by extending existing scholarship around incrementalist approaches and demonstrating how public relations works in the context of transformative change. Further research in this area could consider using alternative templates to study transformative change caused by a range of crisis types from natural disasters to product tampering, and to add further insight into the dynamics between primary and secondary organisations. This thesis contributes to practice by providing guidelines for crisis response strategy selection and indicators related to the emergent context for crises under transformative change that will help primary and secondary organisations‘ responses to crises.

‘Working with the team’ : an exploratory study of improved type 2 diabetes management in a new model of integrated primary/secondary care

This study aimed to explore how a new model of integrated primary/secondary care for type 2 diabetes management, the Brisbane South Complex Diabetes Service (BSCDS), related to improved diabetes management in a selected group of patients. We used a qualitative research design to obtain detailed accounts from the BSCDS via semi-structured interviews with 10 patients. The interviews were fully transcribed and systematically coded using a form of thematic analysis. Participants’ responses were grouped in relation to: (1) Patient-centred care; (2) Effective multiprofessional teamwork; and (3) Empowering patients. The key features of this integrated primary/secondary care model were accessibility and its delivery within a positive health care environment, clear and supportive interpersonal communication between patients and health care providers, and patients seeing themselves as being part of the team-based care. The BSCDS delivered patient-centred care and achieved patient engagement in ways that may have contributed to improved type 2 diabetes management in these participants.

Factors influencing the impact of primary and secondary prevention strategies for cervical cancer among Queensland women

Since the introduction of the National Human Papillomavirus Vaccine Program (NHPVP) in 2007, few studies have assessed women's knowledge, beliefs and attitudes towards cervical screening and human papillomavirus (HPV) vaccination in Australia. It is imperative to ascertain this, as substantial changes are anticipated to the National Cervical Screening Program (NCSP) through a process called 'the Renewal', to ensure any changes that are introduced will be acceptable and well understood by women. The objectives of this study were to describe Queensland women's current knowledge of cervical cancer/screening and HPV, their beliefs and attitudes towards Pap smears and the HPV vaccine and seek their advice on effective methods for communicating changes to the NCSP in their communities. This research was a descriptive-exploratory study that incorporated a combination of qualitative and quantitative methods within the context of the Health Belief Model (HBM). A computer-assisted telephone interview (CATI) survey of 1002 Queensland women was conducted in Phase 1 of the study. During Phase 2 of the study, 23 focus groups were conducted throughout Queensland to gather in-depth information about women's knowledge, awareness and acceptance about cervical cancer prevention strategies. This study found high levels of awareness of HPV (over 60%) and the HPV vaccine (over 86%) amongst Queensland women. However, it also identified considerable uncertainty amongst participants about perceived susceptibility to cervical cancer, especially, the link between cervical cancer, HPV and sexual activity. Women also had limited understanding of the benefit of the Pap smear as a preventative strategy, with many women thinking the main purpose of the Pap smear was for the early detection of cancer. Despite high awareness of HPV, women participating in this study also had significant knowledge deficits about their susceptibility to HPV and the severity of HPV infection. Queensland women had high levels of awareness of the HPV vaccine, which was most commonly via the media. High acceptance of the HPV vaccine was found amongst participants although awareness of the full benefits of vaccination was not evident with little acknowledgement that the quadrivalent vaccine used in the NHPVP would also prevent genital warts. Extensive barriers to having Pap smears, including physical and psychological discomfort, were identified and the most common barriers to vaccination were concerns about side effects and a lack of information upon which to make a decision about consent. Women described enablers for screening participation, such as reminder systems and practitioner characteristics, and expressed positive views towards self collected testing as an enabler, particularly for women who did not attend screening. As this study was conducted with Queensland women it may therefore not be representative of women from other parts of Australia and as participants were more likely to report they were regular screeners than Queensland women overall, these results may not be representative of women least likely to participate in cervical screening. The use of self-reported cervical screening history may also have led to over-reporting of screening status and previous abnormalities by participants. This study reveals significant gaps in Queensland women's knowledge that require effective communication strategies to address. Recommendations from this study highlight the need for increased community education to raise awareness about primary and secondary cervical cancer prevention strategies, training of cervical screening providers in sensitive examination techniques, a reduction in costs associated with screening, the exploration of alternative service models and communication plans that incorporate methods women trust and recommend for disseminating information about changes to the NCSP. This study is the first large study to explore women's perceptions of the Pap smear and barriers to screening, their knowledge about HPV and their attitudes towards the HPV vaccine in Queensland, since the introduction of the NHPVP. It highlights considerable uncertainty about many aspects of cervical cancer and primary and secondary prevention strategies available in Australia and identified many barriers to cervical screening and concerns about HPV vaccination. These knowledge gaps and barriers need to be taken into account and addressed within the context of anticipated changes to the NCSP to ensure benefits are maximised for women in future primary and secondary cervical cancer prevention strategies in the Australian context.

Transfection of MDA-MB-231 human breast carcinoma cells with bone sialoprotein (BSP) stimulates migration and invasion in vitro and growth of primary and secondary tumors in nude mice

We have investigated the role of bone sialoprotein (BSP), a secreted glycoprotein normally found in bone, in breast cancer progression. To explore functions for BSP in human breast cancer invasion and metastasis, the full-length BSP cDNA was transfected into the MDA-MB-231-BAG human breast cancer cell line under the control of the CMV promoter. Clones expressing BSP and vector control clones were isolated. BSP producing clones showed increased monolayer wound healing, a faster rate of stellate outgrowth in Matrigel and increased rate of invasion into a collagen matrix when compared to control clones. Clones were also examined in models of breast cancer growth and metastasis in vivo. BSP transfected clones showed an increased rate of primary tumor growth following mammary fat pad injection of nude mice. BSP transfected clones and vector control clones metastasized to soft organs and bone at a similar rate after intra-cardiac injection as determined by real-time PCR and X-ray analysis. Although these organs were targets for both BSP transfected and non-transfected cells, the size of the metastatic lesion was shown to be significantly larger for BSP expressing clones. This was determined by real-time PCR analysis for soft organs and by X-ray analysis of bone lesions. For bone this was confirmed by intra-tibial injections of cells in nude mice. We conclude that BSP acts to drive primary and secondary tumor growth of breast cancers in vivo.

Integrated chronic disease management in primary-secondary care : a systematic literature review of the evidence

Introduction: Diabetes has traditionally been managed as a single chronic disease state, but it exists with co-morbidities such as depression and metabolic syndrome. Treatment is multifaceted, requiring both primary and secondary care, however, the delivery of diabetes care is often fragmented. Integrated chronic disease management is a growing model of interest, and is underpinned by the chronic care model (CCM), devised as a guide for primary care management of patients with chronic conditions. The model identifies six key elements for effective care, and has shown promise in improving the management of diabetes. Aim: To find empirical evidence of integrated care interventions targeted at co-morbidities including diabetes, across primary/secondary care. Method: A systematic review of peer reviewed literature from PubMed, CINAHL, Embase, Cochrane Library and Joanna Briggs was performed. Studies were reviewed according to inclusion criteria- studies published in English, between 2004-2014, empirical studies, studies with evidence of primary/secondary implementation, and those dealing with chronic co-morbid disease states. Results: 51 studies met the inclusion criteria. Included studies were mostly from the US (38), with five from Australia, UK (2), Canada (2), Netherlands (1), Norway (1), Ireland (1), and one multi-country study. It was found that all interventions adopted at least one (average 3-4) of the chronic care model, with the majority implementing delivery system redesign activities within the primary care practice/s. We found evidence of interventions which significantly reduced emergency department and hospital admissions, improved processes of care, patient health outcomes such as HbA1c, improved patient satisfaction, and reduced costs. Conclusion/Implications for practice: Diabetes exists as a co-morbid disease, requiring both primary and secondary care. We found that integrated care interventions adopting elements of the chronic care model positively impacted on patient outcomes, service utilisation, as well as costs. This review has highlighted that it may not be necessary to adopt all CCM elements to improve clinical outcomes, patient satisfaction and costs.

Primary and secondary neural networks of auditory prepulse inhibition: a functional magnetic resonance imaging study of sensorimotor gating of the human acoustic startle response

Feedforward inhibition deficits have been consistently demonstrated in a range of neuropsychiatric conditions using prepulse inhibition (PPI) of the acoustic startle eye-blink reflex when assessing sensorimotor gating. While PPI can be recorded in acutely decerebrated rats, behavioural, pharmacological and psychophysiological studies suggest the involvement of a complex neural network extending from brainstem nuclei to higher order cortical areas. The current functional magnetic resonance imaging study investigated the neural network underlying PPI and its association with electromyographically (EMG) recorded PPI of the acoustic startle eye-blink reflex in 16 healthy volunteers. A sparse imaging design was employed to model signal changes in blood oxygenation level-dependent (BOLD) responses to acoustic startle probes that were preceded by a prepulse at 120 ms or 480 ms stimulus onset asynchrony or without prepulse. Sensorimotor gating was EMG confirmed for the 120-ms prepulse condition, while startle responses in the 480-ms prepulse condition did not differ from startle alone. Multiple regression analysis of BOLD contrasts identified activation in pons, thalamus, caudate nuclei, left angular gyrus and bilaterally in anterior cingulate, associated with EMGrecorded sensorimotor gating. Planned contrasts confirmed increased pons activation for startle alone vs 120-ms prepulse condition, while increased anterior superior frontal gyrus activation was confirmed for the reverse contrast. Our findings are consistent with a primary pontine circuitry of sensorimotor gating that interconnects with inferior parietal, superior temporal, frontal and prefrontal cortices via thalamus and striatum. PPI processes in the prefrontal, frontal and superior temporal cortex were functionally distinct from sensorimotor gating.