Use and outcomes of targeted therapies in early and metastatic HER2-positive breast cancer in Australia: Protocol detailing observations in a whole of population cohort

Background: The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has changed dramatically with the introduction and widespread use of HER2-targeted therapies. However, there is relatively limited real-world information on patterns of use, effectiveness and safety in whole of population cohorts. The research programme detailed in this protocol will generate evidence on the prescribing patterns, safety monitoring and outcomes of patients with BC treated with HER2- targeted therapies in Australia. Methods/design: Our ongoing research programme will involve a series of retrospective cohort studies that include every patient accessing Commonwealth-funded HER2-targeted therapies for the treatment of early BC and advanced BC in Australia. At the time of writing, our cohorts consist of 11 406 patients with early BC and 5631 with advanced BC who accessed trastuzumab and lapatinib between 2001 and 2014. Pertuzumab and trastuzumab emtansine were publicly funded for metastatic BC in 2015, and future data updates will include patients accessing these medicines. We will use dispensing claims for cancer and other medicines, medical service claims and demographics data for each patient accessing HER2- targeted therapies to undertake this research. Ethics and dissemination: Ethics approval has been granted by the Population Health Service Research Ethics Committee and data access approval has been granted by the Australian Department of Human Services (DHS) External Review Evaluation Committee. Our findings will be reported in peer-reviewed publications, conference presentations and policy forums. By providing detailed information on the use and outcomes associated with HER2-targeted therapies in a national cohort treated in routine clinical care, our research programme will better inform clinicians and patients about the real-world use of these treatments and will assist third-party payers to better understand the use and economic costs of these treatments

Spatial distributions of Southern Ocean mesozooplankton communities have been resilient to long-term surface warming

The biogeographic response of oceanic planktonic communities to climatic change has a large influence on the future stability of marine food webs and the functioning of global biogeochemical cycles. Temperature plays a pivotal role in determining the distribution of these communities and ocean warming has the potential to cause major distributional shifts, particularly in polar regions where the thermal envelope is narrow. We considered the impact of long-term ocean warming on the spatial distribution of Southern Ocean mesozooplankton communities through examining plankton abundance in relation to sea surface temperature between two distinct periods, separated by around 60 years. Analyses considered 16 dominant mesozooplankton taxa (in terms of biomass and abundance) in the southwest Atlantic sector of the Southern Ocean, from net samples and in situ temperature records collected during the Discovery Investigations (1926–1938) and contemporary campaigns (1996–2013). Sea surface temperature was found to have increased significantly by 0.74°C between the two eras. The corresponding sea surface temperature at which community abundance peaked was also significantly higher in contemporary times, by 0.98°C. Spatial projections indicated that the geographical location of community peak abundance had remained the same between the two eras despite the poleward advance of sea surface isotherms. If the community had remained within the same thermal envelope as in the 1920s–1930s, community peak abundance would be 500 km further south in the contemporary era. Studies in the northern hemisphere have found that dominant taxa, such as calanoid copepods, have conserved their thermal niches and tracked surface isotherms polewards. The fact that this has not occurred in the Southern Ocean suggests that other selective pressures, particularly food availability and the properties of underlying water masses, place greater constraints on spatial distributions in this region. It further demonstrates that this community is thermally resilient to present levels of sea surface warming

Temporal changes in abundances of large calanoid copepods in the Scotia Sea: comparing the 1930s with contemporary times

To investigate whether impacts of reported climate change in the Antarctic marine environment have affected mesozooplankton populations, we compared the summertime abundances of four species of large calanoid copepods from samples taken during the Discovery Investigations (1926–1938) and contemporary times (1996–2013). Discovery samples were obtained using an N70V closing net fished vertically through three depth horizons encompassing the top 250 m of the water column, whereas contemporary samples were obtained using a Bongo net fished vertically through 200–0 m. Data from a previous study comparing catch efficiencies of the two nets were used to generate calibration factors which were applied to the N70V abundances. Following further corrections for net depth differences and seasonal biases in sampling frequency, three of the four species, Calanoides acutus, Rhincalanus gigas and Calanus simillimus, were found to be between ~ 20–55% more abundant in contemporary times than they were 70 years ago. Calanus propinquus was marginally more abundant in the Discovery era. These results were robust to sensitivity analyses for the net calibration factor, seasonal bias and net depth corrections. Although near-surface ocean temperatures within the Scotia Sea have increased by up to 1.5 °C during the last 70 years, we conclude that the most likely causes of increased copepod abundances are linked to changes in the food-web. In particular, we discuss the reported decrease in krill abundance in the South Atlantic that has potentially increased the amount of food available to copepods while at the same time decreasing predator pressure

Negative Selection during the Peripheral Immune Response to Antigen

Thymic selection depends on positive and negative selective mechanisms based on the avidity of T cell interaction with antigen–major histocompatibility complex complexes. However, peripheral mechanisms for the recruitment and clonal expansion of the responding T cell repertoire remain obscure. Here we provide evidence for an avidity-based model of peripheral T cell clonal expansion in response to antigenic challenge. We have used the encephalitogenic, H-2 Au-restricted, acetylated NH2-terminal nonameric peptide (Ac1-9) epitope from myelin basic protein as our model antigen. Peptide analogues were generated that varied in antigenic strength (as assessed by in vitro assay) based on differences in their binding affinity for Au. In vivo, these analogues elicited distinct repertoires of T cells that displayed marked differences in antigen sensitivity. Immunization with the weakest (wild-type) antigen expanded the high affinity T cells required to induce encephalomyelitis. In contrast, immunization with strongly antigenic analogues led to the elimination of T cells bearing high affinity T cell receptors by apoptosis, thereby preventing disease development. Moreover, the T cell repertoire was consistently tuned to respond to the immunizing antigen with the same activation threshold. This tuning mechanism provides a peripheral control against the expansion of autoreactive T cells and has implications for immunotherapy and vaccine design

Clinical Educators’ Perceptions of Students Following a Simulation-Based Learning Program

Purpose: Clinical education is a key component of speech-language pathology university curriculum, whereby students have the opportunity to apply theoretical knowledge and practical skills learned in the classroom into a real workplace. However, more recently the availability of high quality, consistent clinical placements and learning experiences across the range of practice areas in the discipline is reducing. Therefore, alternative clinical learning opportunities that enable students to develop skills and competencies are being explored. Recently, replacing clinical time with a simulated learning program has been shown to achieve equivalent levels of clinical competency in speech pathology. However, it is unknown how simulation impacts on student learning in traditional clinical placements. Therefore, this research explored clinical educators’ perceptions of students undertaking clinical placements in their workplace immediately following a five-day simulation-based learning program related to the same area of practice. Method: Thirty-five clinical educators who supervised students in the workplace immediately after they completed the simulation program participated in semi-structured interviews. All interviews were transcribed verbatim and analyzed using qualitative methods described by Graneheim and Lundman (2004). Result: The analysis identified four key themes related to the impact of students in the workplace, simulation priming students for learning, the importance of the transition from simulation-based learning to the workplace, and the role of simulation in clinical education programs. Conclusion: The use of simulation to support student learning and develop clinical skills and competencies in adult speech pathology practice is supported by workplace clinical educators. However, results of this study suggest that the simulation program needs to be embedded within the curriculum and clinical education program to enhance transition between learning experiences and maximize benefits of learning experiences in real workplace contexts

“Same But Different”: The Role and Perceptions of the Simulation Clinical Educator

Simulated learning programs are an important component of allied health education. Although the role of simulation clinical educators has been highlighted as critical for student learning within simulation, their perceptions of their role have not yet been investigated. This study aimed to explore the experiences of simulation clinical educators. Participants were ten simulation clinical educators who had supported speech-language pathology students’ learning during a 5-day simulation program focussed on speech-language pathology practice with adult clients in acute hospital and rehabilitation settings. Educators participated in individual semi-structured interviews exploring their role and their perceptions of the simulation-based learning program. Data were analysed using inductive thematic analysis. Three inter-related themes emerged from participants’ views. The major theme of Unique teaching and learning environment incorporated five subthemes: focus on teaching; safe learning environment; authenticity and engagement; structure and intensity of learning, and; feedback opportunities. Two additional themes were identified: Clinical educator role same but different, and Simulation bridges the gap between theory and practice. This study offers new insights into simulation clinical educators’ perceptions of their role when supporting students within simulation and highlight the importance of harnessing the unique benefits of simulation as a teaching pedagogy to maximize its impacts on student learning and justify its costs

Associations between a Universal Free Breakfast Policy and School Breakfast Program Participation, School Attendance, and Weight Status: A District-Wide Analysis

Breakfast consumption among youth is associated with improved diet quality, weight, cognition, and behavior. However, not all youth in the United States consume breakfast. Participation in the School Breakfast Program (SBP) is also low relative to the lunch program. Universal free breakfast (UFB) policies have been implemented to increase breakfast participation by reducing cost and stigma associated with the SBP. This study examined whether a UFB policy implemented in a school district in the Southeast US was associated with changes in breakfast participation, school attendance, and student weight. A longitudinal study of secondary data was conducted, and a mixed modeling approach was used to assess patterns of change in SBP participation. General linear models were used to assess attendance and student weight change. On average, across schools in the district, there was an increase in breakfast participation of 4.1 percentage points following the implementation of the policy. The change in breakfast participation in schools differed by the percent of students in the school who received school meals for free or at a reduced price, the percent of students of color, and the grade level of the school. Increases in SBP participation were not associated with significant changes in attendance or weight. UFB policies may be effective in increasing participation in the SBP

Shifting perspectives on coastal impacts and adaptation

The Intergovernmental Panel on Climate Change reports reflect evolving attitudes in adapting to sea-level rise by taking a systems approach and recognizing that multiple responses exist to achieve a less hazardous coast.info:eu-repo/semantics/publishedVersio

Management of Fracture Risk in Patients with Chronic Obstructive Pulmonary Disease (COPD): Building a UK Consensus Through Healthcare Professional and Patient Engagement

Introduction: Osteoporosis and bone fractures are common in chronic obstructive pulmonary disease (COPD) and contribute significantly to morbidity and mortality. Current national guidance on COPD management recommends addressing bone health in patients, however, does not detail how. This consensus outlines key elements of a structured approach to managing bone health and fracture risk in patients with COPD.Methods: A systematic approach incorporating multifaceted methodologies included detailed patient and healthcare professional (HCP) surveys followed by a roundtable meeting to reach a consensus on what a pathway would look like.Results: The surveys revealed that fracture risk was not always assessed despite being recognised as an important aspect of COPD management by HCPs. The majority of the patients also stated they would be receptive to discussing treatment options if found to be at risk of osteoporotic fractures. Limited time and resource allocation were identified as barriers to addressing bone health during consultations. The consensus from the roundtable meeting was that a proactive systematic approach to assessing bone health should be adopted. This should involve using fracture risk assessment tools to identify individuals at risk, investigating secondary causes of osteoporosis if a diagnosis is made and reinforcing non-pharmacological and preventative measures such as smoking cessation, keeping active and pharmacological management of osteoporosis and medicines management of corticosteroid use. Practically, prioritising patients with important additional risk factors, such as previous fragility fractures, older age and long-term oral corticosteroid use for an assessment, was felt required.Conclusion: There is a need for integrating fracture risk assessment into the COPD pathway. Developing a systematic and holistic approach to addressing bone health is key to achieving this. In tandem, opportunities to disseminate the information and educational resources are also required