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Background The vital role of evaluation as integral to program planning and program development is well supported in the literature, yet we find little evidence of this in health promotion practice. Evaluation is often a requirement for organisations supported by public funds, and is duly undertaken, however the quality, comprehensiveness and use of evaluation findings are lacking. Practitioner peer-reviewed publications presenting evaluation work are also limited. There are few published examples where evaluation is conducted as part of a comprehensive program planning process or where evaluation findings are used for program development in order to improve health promotion practice. Discussion For even the smallest of programs, there is a diverse array of evaluation that is possible before, during and after program implementation. Some types of evaluation are less prevalent than others. Data that are easy to collect or that are required for compliance purposes are common. Data related to how and why programs work which could be used to refine and improve programs are less commonly collected. This finding is evident despite numerous resources and frameworks for practitioners on how to conduct effective evaluation and increasing pressure from funders to provide evidence of program effectiveness. We identify several organisational, evaluation capacity and knowledge translation factors which contribute to the limited collection of some types of data. In addition, we offer strategies for improving health promotion program evaluation and we identify collaboration of a range of stakeholders as a critical enabler for improved program evaluation. Summary Evaluation of health promotion programs does occur and resources for how to conduct evaluation are readily available to practitioners. For the purposes of program development, multi-level strategies involving multiple stakeholders are required to address the organisational, capacity and translational factors that affect practitioners’ ability to undertake adequate evaluation.

Almost half of older people receiving community care fall each year and this rate has not improved in the last decade. Falls prevention programs targeted at this group are uncommon, and expensively delivered by university trained allied health professionals. To investigate the feasibility of community care workers delivering a falls prevention exercise program to older clients, at low or medium risk of falling, as part of an existing service provision. Community care workers from 10 community care organizations participated in the training for, and delivery to their clients of, an 8-week evidence-based falls prevention exercise program. Community care workers included assessment staff (responsible for identifying the need for community care services through completing an assessment) and support workers (responsible for providing support in the home). Clients were surveyed anonymously at the completion of the intervention and workers participated in a semi-structured interview. Twenty-five community care workers participated in the study. The falls prevention program was delivered to 29 clients, with an average age of 82.7 (SD: 8.72) years and consisting of 65.5% female. The intervention was delivered safely with no adverse events recorded, and the eligibility and assessment tools were completed by the majority of community care workers (93.1%). Assessment staff found it difficult to find time to deliver the intervention. Support workers were able to complete the intervention within their current service delivery period, with the initial assessment taking a small amount of additional time. Support workers reported enjoying the additional responsibility afforded by delivering the falls prevention program and seeing changes in their clients. The majority of clients (82%) reported enjoying the exercises, with 59% reporting that they felt it made a positive change in their health. Clients completed the exercises on average 4.8 (SD: 2.2) days per week. Community care workers who have completed appropriate training are able to deliver a falls prevention exercise program to their clients as part of their current services. Further research is required to determine whether the program reduces the rate of falls for community care clients and whether integration of a falls prevention program into an existing service is cost-effective.

Purpose – The purpose of this paper is to contribute an Australian perspective to the debate on health system integration by identifying some key Australian challenges to integration, policy responses to enhance integration and potential insights from these for international policy makers, researchers and practitioners. Design/methodology/approach – Drawing on the systems theory concept of entropy, the authors contend that there exist factors that contribute to system fragmentation. Whilst policy responses to these challenges are contextual, there are generalisable features worth exploring internationally. Findings – The authors suggest that recognition of inherent system-based barriers is an important initial stage in moving towards integration. Whilst process and people factors are important contributors to integration, the political will to move in this direction is a necessary dynamic to energise the system through appropriate funding, incentives and governance structures. Originality/value – The paper provides a fresh Australian perspective to the international discourse on barriers and opportunities to enhance health system integration.

Single‐use (SU) technology has become an important part of biotechnology research and commercial biomanufacturing. Sustainability is a long‐term holistic approach that evaluates how biological systems remain diverse and productive over time, and also considers concerns of a more immediate and nonbiological focus. Sustainability emphasizes the ability to use natural resources in a way that indefinitely protects the integrity (and limits the fouling or depletion) of existing biological and other environmental systems. Several initial environmental analyses performed for SU biologics production illustrated the need for rational and comprehensive analysis techniques such as life cycle assessment to understand the total, specific, and \"cradle‐to‐grave\" environmental strain imposed by both durable and SU approaches. “End‐of‐life” considerations are a big part of most discussions about SU and the environment because of the visibility of the pre and post‐process material.

Amorphous semiconductors are important in applications such as solar photovoltaic devices, xerography, and thin film transistors. However, the relationships between the structure and properties of amorphous semiconductors are not well understood. Despite a lack of fundamental understanding, it has been shown that amorphous semiconductor properties can be tailored to a specific application by the addition of alloying elements, or by variation in the production process. Characterizing the structures that lead to these desired properties, and determining the effects of processing chemistry on the resulting materials, will lead to an optimization of amorphous semiconductor technology. The amorphous hydrogenated semiconductors that I have studied include amorphous silicon, silicon carbide, silicon nitride, and amorphous carbon. All of these materials were prepared by plasma enhanced chemical vapor deposition, a commonly used deposition technique in the solid-state materials industry. By using Fourier transform infrared spectroscopy, we were able to obtain qualitative information about chemical bonding environments in newly deposited materials. Information about the electronic structure was provided by optical absorption spectroscopy in the near IR, visible, and ultra-violet regions. The atomic compositions of our materials are known from Rutherford backscattering (for the non-hydrogen elements) and proton nuclear magnetic resonance (for the hydrogen). We used solid-state nuclear magnetic resonance (NMR) to provide quantitative and selective information about local bonding configurations. Carbon NMR studies of amorphous carbon have identified the relative amounts of planar and tetrahedral bonding in this material. Studies of amorphous silicon carbide have revealed that doubly bonded carbons exist in this material, even if the ratio of carbon to silicon is less than one. A variation of the basic experiment showed that these doubly bonded carbons are not bound to hydrogen. The microstructure of fluorinated silicon nitride was inferred from the results of silicon, hydrogen, and fluorine NMR experiments. A relatively new technique, multiple quantum NMR, was used to observe the detailed hydrogen microstructure of amorphous silicon and amorphous silicon carbide. In device quality materials, the dominant hydrogen microstructural unit is a group of five to seven hydrogen atoms, all covalently bonded to silicon or carbon.

In this thesis, we investigate the nonlinear dynamics of three systems effectively defined by contour dynamics. Following an introductory chapter, in chapter 2 we investigate a class of curve dynamics in the plane equivalent to the modified Korteweg-de Vries (mKdV) equation. The mKdV equation is integrable, and we show that some of the the standard results of integrable systems theory have geometric interpretations. Finally, we show the relation between the abstract curve dynamics and vortex patch dynamics. In chapter 3, we investigate a class of curve dynamics in three dimensions, equivalent to the integrable nonlinear Schrodinger (NLS) equation. Again, many of the features of NLS have geometric interpretations. We rederive a known result about the relation between NLS and vortex line dynamics in two different ways. Finally, in chapter 4, we investigate the pattern formation of a reaction-diffusion system defined in two spatial dimensions. The patterns are effectively defined by interfaces, so we develop a contour dynamics to describe the time evolution of the patterns. We show that these patterns are not equivalent to Turing patterns and that wildly branched and complex patterns are possible.

Extracellular ATP is a signal of tissue damage and induces macrophage responses that amplify inflammation and coagulation. Here we demonstrate that ATP signaling through macrophage P2X7 receptors uncouples the thioredoxin (TRX)/TRX reductase (TRXR) system and activates the inflammasome through endosome-generated ROS. TRXR and inflammasome activity promoted filopodia formation, cellular release of reduced TRX, and generation of extracellular thiol pathway-dependent, procoagulant microparticles (MPs). Additionally, inflammasome-induced activation of an intracellular caspase-1/calpain cysteine protease cascade degraded filamin, thereby severing bonds between the cytoskeleton and tissue factor (TF), the cell surface receptor responsible for coagulation activation. This cascade enabled TF trafficking from rafts to filopodia and ultimately onto phosphatidylserine-positive, highly procoagulant MPs. Furthermore, caspase-1 specifically facilitated cell surface actin exposure, which was required for the final release of highly procoagulant MPs from filopodia. Together, the results of this study delineate a thromboinflammatory pathway and suggest that components of this pathway have potential as pharmacological targets to simultaneously attenuate inflammation and innate immune cell-induced thrombosis.

Eftozanermin alfa (eftoza), a second-generation tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL-R) agonist, induces apoptosis in tumor cells by activation of death receptors 4/5. This phase 1 dose-escalation/dose-optimization study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary activity of eftoza in patients with advanced solid tumors. Patients received eftoza 2.5–15 mg/kg intravenously on day 1 or day 1/day 8 every 21 days in the dose-escalation phase, and 1.25–7.5 mg/kg once-weekly (QW) in the dose-optimization phase. Dose-limiting toxicities (DLTs) were evaluated during the first treatment cycle to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Pharmacodynamic effects were evaluated in circulation and tumor tissue. A total of 105 patients were enrolled in the study (dose-escalation cohort, n = 57; dose-optimization cohort, n = 48 patients [n = 24, colorectal cancer (CRC); n = 24, pancreatic cancer (PaCA)]). In the dose-escalation cohort, seven patients experienced DLTs. MTD and RP2D were not determined. Most common treatment-related adverse events were increased alanine aminotransferase and aspartate aminotransferase levels, nausea, and fatigue. The one treatment-related death occurred due to respiratory failure. In the dose-optimization cohort, three patients (CRC, n = 2; PaCA, n = 1) had a partial response. Target engagement with regard to receptor saturation, and downstream apoptotic pathway activation in circulation and tumor were observed. Eftoza had acceptable safety, evidence of pharmacodynamic effects, and preliminary anticancer activity. The 7.5-mg/kg QW regimen was selected for future studies on the basis of safety findings, pharmacodynamic effects, and biomarker modulations. (Trial registration number: NCT03082209 (registered: March 17, 2017)).

In vitro studies indicate that binding of talin to the β3 integrin cytoplasmic domain (tail) results in integrin αIIbβ3 (GPIIb–IIIa) activation. Here we tested the importance of talin binding for integrin activation in vivo and its biological significance by generating mice harboring point mutations in the β3 tail. We introduced a β3(Y747A) substitution that disrupts the binding of talin, filamin, and other cytoplasmic proteins and a β3(L746A) substitution that selectively disrupts interactions only with talin. Platelets from animals homozygous for each mutation showed impaired agonist-induced fibrinogen binding and platelet aggregation, providing proof that inside-out signals that activate αIIbβ3 require binding of talin to the β3 tail. β3(L746A) mice were resistant to both pulmonary thromboembolism and to ferric chloride–induced thrombosis of the carotid artery. Pathological bleeding, measured by the presence of fecal blood and development of anemia, occurred in 53% of β3(Y747A) and virtually all β3-null animals examined. Remarkably, less than 5% of β3(L746A) animals exhibited this form of bleeding. These results establish that αIIbβ3 activation in vivo is dependent on the interaction of talin with the β3 integrin cytoplasmic domain. Furthermore, they suggest that modulation of β3 integrin–talin interactions may provide an attractive target for antithrombotics and result in a reduced risk of pathological bleeding.

This study aimed to explore the effects of a decision support intervention (DSI) and shared decision making (SDM) on knowledge, perceptions about treatment, and treatment choice among men diagnosed with localized low-risk prostate cancer (PCa). At a multidisciplinary clinic visit, 30 consenting men with localized low-risk PCa completed a baseline survey, had a nurse-mediated online DS session to clarify preference for active surveillance (AS) or active treatment (AT), and met with clinicians for SDM. Participants also completed a follow-up survey at 30 days. We assessed change in treatment knowledge, decisional conflict, and perceptions and identified predictors of AS. At follow-up, participants exhibited increased knowledge (p < 0.001), decreased decisional conflict (p < 0.001), and more favorable perceptions of AS (p = 0.001). Furthermore, 25 of the 30 participants (83 %) initiated AS. Increased family and clinician support predicted this choice (p < 0.001). DSI/SDM prepared patients to make an informed decision. Perceived support of the decision facilitated patient choice of AS.