Targeted therapy for breast cancer prevention.

With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer

Positional proteomics reveals differences in N-terminal proteoform stability

To understand the impact of alternative translation initiation on a proteome, we performed a proteome-wide study on protein turnover using positional proteomics and ribosome profiling to distinguish between N-terminal proteoforms of individual genes. By combining pulsed SILAC with N-terminal COFRADIC, we monitored the stability of 1,941 human N-terminal proteoforms, including 147N-terminal proteoform pairs that originate from alternative translation initiation, alternative splicing or incomplete processing of the initiator methionine. N-terminally truncated proteoforms were less abundant than canonical proteoforms and often displayed altered stabilities, likely attributed to individual protein characteristics, including intrinsic disorder, but independent of N-terminal amino acid identity or truncation length. We discovered that the removal of initiator methionine by methionine aminopeptidases reduced the stability of processed proteoforms, while susceptibility for N-terminal acetylation did not seem to influence protein turnover rates. Taken together, our findings reveal differences in protein stability between N-terminal proteoforms and point to a role for alternative translation initiation and co-translational initiator methionine removal, next to alternative splicing, in the overall regulation of proteome homeostasis

Improving the integration of mental health services in primary health care at the macro level

Mental disorders are highly prevalent in Australia. The most frequently diagnosed conditions are anxiety, affective and substance use disorders. Comorbidities are common, both in terms of concurrent mental health conditions and concurrent physical and mental health conditions. Many individuals with lived experience of mental illness also face a range of non-medical issues (e.g. housing, employment and education needs). Typically, individuals requiring mental health care for most moderate/mild cases are supported in primary health care (PHC), though specialist care in secondary and tertiary settings is required for more severe conditions. Given the multifaceted nature of mental health conditions, support for individuals experiencing such diagnoses also needs to be multidisciplinary and collaborative. PHC mental health services encompass a range of services, including counselling, pharmacological treatments, referrals and follow-up care, provided by health professionals in PHC settings (e.g. general practice) to treat or prevent mental health problems

Allied health integration: Collaborative care for arthritis and other musculoskeletal conditions

Musculoskeletal conditions, including rheumatoid arthritis, osteoarthritis and osteoporosis, are prevalent in the Australian population, and they impose a substantial burden on the health care system and the community, reflected by their status as a national health priority area. They are the main cause of impaired physical functioning globally. These conditions have high chronicity rates and often have a long term impact, leading to reduced mobility and dexterity, chronic pain, reduced capacity for employment, and negative impact on family and social life. Much of the care for these conditions is provided in primary health care (PHC) settings

Understanding the policy cycle and knowledge translation for researchers (A researcher’s guide)

This RESEARCH ROUNDup introduces knowledge translation, suggests avenues where research evidence can inform different stages of the policy cycle, and provides some practical tips for researchers

Challenges and solutions for Latin named entity recognition

Although spanning thousands of years and genres as diverse as liturgy, historiography, lyric and other forms of prose and poetry, the body of Latin texts is still relatively sparse compared to English. Data sparsity in Latin presents a number of challenges for traditional Named Entity Recognition techniques. Solving such challenges and enabling reliable Named Entity Recognition in Latin texts can facilitate many down-stream applications, from machine translation to digital historiography, enabling Classicists, historians, and archaeologists for instance, to track the relationships of historical persons, places, and groups on a large scale. This paper presents the first annotated corpus for evaluating Named Entity Recognition in Latin, as well as a fully supervised model that achieves over 90% F-score on a held-out test set, significantly outperforming a competitive baseline. We also present a novel active learning strategy that predicts how many and which sentences need to be annotated for named entities in order to attain a specified degree of accuracy when recognizing named entities automatically in a given text. This maximizes the productivity of annotators while simultaneously controlling quality

The health of 'grey nomads': On the move and under the radar?

'Grey nomads' are common on Australian highways. Anecdotal evidence suggests they impose a significant burden on rural/remote health services, including GPs, pharmacists, and hospitals. There have been calls for better resourcing and provision of services, but little reference to good evidence on which to base this. A literature review revealed that quantitative research is limited and largely confined to the tourism literature. Several good qualitative studies have illuminated the experiences of grey nomads. Although health has not generally been the primary focus, useful information has emerged. Like other older Australians, many grey nomads have chronic diseases and high rates of medication use; however, they seem somewhat healthier than their peers. Many are well prepared for travel, but they nevertheless impose a burden on health services, which is poorly documented. This literature review, the first to integrate the limited evidence for a health audience, provides a good starting-point for future research. There is a need for basic epidemiological research, extending the evidence base about the health of grey nomads, and the use and effectiveness of self-care strategies; health systems research, clarifying the demands made on health services; and investigation of strategies to optimise grey nomad wellbeing and healthcare utilisation

Problem-Based Learning Leadership Development Program in a Multi-National Company

This paper reports on the development and implementation of a team leadership training program in a multi-national company. The European Engineering Company (EEC Group) had grown and expanded into many countries in a relatively short time frame as a result of increased demand for the company\u27s products and services in newly developing countries. The EEC Group and the training program had additional issues of culture and basic institutional knowledge. The paper reports on the program, the conceptual framework of the International Leadership Development Program (ILDP), results, and lessons learned. The authors advocate use of a Problem-based Learning (PBL) methodology to train in a multi-national environment. This approach not only resulted in meeting the program\u27s learning goals, but worked to provide all participants with an overview of company products, services and processes