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File includes drug synergy scores for 4 cell lines screened against CPI-637

File includes drug synergy scores for 6 cell lines screened against JQ1

File includes drug synergy scores for 1 cell line screened against OTX015

File includes AlphaScreening values for activity of the screening library against the BET or p300 bromodomains

File contains information on small molecules included in screening library

Supplemental figures, figure legends, table legends, methods, and references

File contains enrichment scores and p-values for gene sets evaluated using GSEA for RNA sequencing data sets

Cardiac sarcoma is a very rare cause of primary cardiac tumor. We present a case of an undifferentiated, pleomorphic cardiac sarcoma, masquerading as a cardiac myxoma on multimodal imaging evaluation, which was definitively diagnosed on intra-operative histopathologic examination followed by surgical resection. LEARNING OBJECTIVE: Evaluate and diagnose a rare primary cardiac tumor via multimodal imaging and a multidisciplinary approach.

Objectives Pharmacist personality traits may explain the incomplete uptake of extended scope pharmacy practice roles. The objective of this study was to explore the personality traits of Australian pharmacists using the Big Five Inventory (BFI). Methods A cross-sectional survey of Australian pharmacists was undertaken. Pharmacists were asked to complete a short demographic survey and the BFI, a 44-item survey that measures the Big Five personality traits: extraversion, agreeableness, conscientiousness, neuroticism and openness. Each trait can be scored out of a maximum of 5. The BFI and multivariate linear regression were used to assess associations between personality traits and demographic variables. Key findings A total of 122 responses were available for analysis. The majority of study participants were female (79.5%), were aged between 30 and 39 years (32.0%) and worked in hospital pharmacy (46.7%). Pharmacists scored (mean (standard deviation)) 3.4 (0.7) for extraversion, 3.9 (0.5) for agreeableness, 4.2 (0.5) for conscientiousness, 2.5 (0.8) for neuroticism and 3.5 (0.6) for openness. Associations were found between agreeableness and qualifications and location of pharmacy practice, neuroticism and working in a practice location (rural versus metropolitan) and age, and openness and practice location (rural versus metropolitan) and principle role in pharmacy. Conclusions Pharmacists displayed high scores on the traits of extraversion, agreeableness, conscientiousness and openness and scored moderately on the trait of openness. Confirmation with a larger sample size and evaluation in the context of pharmacy practice change may assist in overcoming barriers to change in the pharmacy profession.

Graphical abstract, Highlights • Echocardiography is useful in differentiating intracardiac masses. • Cardiac thrombus may be mistaken for atrial myxomas by echocardiography. • Echocardiographic contrast can aid in the diagnosis of atrial thrombus.

There have long been discussions on the professionality of occupational health and safety (OHS) and concerns about standards of practice, with the recognition of OHS as a profession further inhibited by lack of clarity on role and variations in terminology and principles underpinning practice. In 2013, the International Network of Safety and Health Practitioner Organisations (INSHPO) recognized the need for a global approach to reconceptualise OHS professionals as influential leaders who can work to integrate OHS within business processes. The Occupational Health and Safety Professional Capability Framework: A Global Framework for Practice was subsequently developed by this international body representing OHS professional associations across 10 countries with the outcome endorsed by 53 organisations at a ceremonial signing of the Singapore Accord. This paper reviews the development of the framework and the emergence of two clear roles; the OHS Professional and OHS Practitioner. It explores the process for clarifying the roles and required knowledge and skills together with the challenges experienced along the way. The paper recognises that the framework should not be a static document and so concludes by considering the work still to be done.

Here, we report genome sequences of 10 Bacillus cereus group-infecting bacteriophages. Each virus was isolated from an environmental sample, contained a double-stranded DNA genome, and belonged to the Myoviridae family. Nine phages exhibit a conserved genome structure, and one phage appears novel in genome structure, sequence, and protein content.

Background Consistent classification of consult requests may lead to more efficient and collegial conversations about patient care, which could improve work satisfaction and enhance the learning environment. The authors propose a framework of 7 consultation types (Table 1). We aimed to obtain validity evidence for this rubric to consistently classify consultation requests. Table 1. Framework for classifying consults into 7 types Methods A randomly selected sample of 100 de-identified infectious diseases (ID) consult requests from a single academic center were independently coded as 1 of the 7 consultation types by 3 ID specialists and 3 hospitalists. Perfect concordance (6/6 coders) and partial concordance (4/6 or 5/6 coders) was calculated. Total (3/3 coders) and partial (2/3 coders) concordance based on consult subtypes and provider specialty was also calculated. We compared proportions between groups using a chi square test. Results Perfect concordance was 30%, and partial concordance was 60% (Figure 1). Total concordance among ID specialists was 44% and among hospitalists was 54% (Table 2). In cases without perfect concordance (n=70), ID specialists had 20% total concordance and 70% partial concordance, while hospitalists had 34% total concordance and 59% partial concordance. ID specialists were less likely than hospitalists to have perfect concordance for ideal consults (52% vs 73%, P=0.01). ID specialists and hospitalists were similarly likely to classify a consult as ideal (65% vs 69%, P=0.34), but ID specialists were more likely to classify a consult as S.O.S. (25% vs. 17%, p=0.02), and less likely to classify a consult as confirmatory (3% vs 7%, P=0.02) (Table 3). Figure 1. Concordance overall by consensus consult type among hospitalists and infectious disease specialists Table 2. Concordance by consult type stratified among infectious disease specialists and hospitalists Table 3. Consult type by physician subspecialty, among infectious disease specialists and hospitalists Conclusion ID consults can be classified into a novel rubric of 7 subtypes. Overall, partial or perfect concordance between hospitalists and ID consultants was 90%. ID specialists were more likely to classify consult requests as S.O.S than hospitalists, and hospitalists were more likely to classify consults as confirmatory. Opportunities exist to utilize the rubric to improve provider communication and interprofessional education. Disclosures All Authors: No reported disclosures

Resistance exercise training (RET) is well-known to counteract negative age-related changes in both muscle and tendon tissue. Traditional RET consists of both concentric (CON) and eccentric (ECC) contractions; nevertheless, isolated ECC contractions are metabolically less demanding and, thus, may be more suitable for older populations. However, whether submaximal (60% 1RM) CON or ECC contractions differ in their effectiveness is relatively unknown. Further, whether the time course of muscle and tendon adaptations differs to the above is also unknown. Therefore, this study aimed to establish the time course of muscle and tendon adaptations to submaximal CON and ECC RET. Twenty healthy young (24.5 ± 5.1 years) and 17 older males (68.1 ± 2.4 years) were randomly allocated to either isolated CON or ECC RET which took place 3/week for 8 weeks. Tendon biomechanical properties, muscle architecture and maximal voluntary contraction were assessed every 2 weeks and quadriceps muscle volume every 4 weeks. Positive changes in tendon Young’s modulus were observed after 4 weeks in all groups after which adaptations in young males plateaued but continued to increase in older males, suggesting a dampened rate of adaptation with age. However, both CON and ECC resulted in similar overall changes in tendon Young’s modulus, in all groups. Muscle hypertrophy and strength increases were similar between CON and ECC in all groups. However, pennation angle increases were greater in CON, and fascicle length changes were greater in ECC. Notably, muscle and tendon adaptations appeared to occur in synergy, presumably to maintain the efficacy of the muscle–tendon unit.

Background Leadership skills development is a neglected part of addressing the health workforce crisis facing the world. Models of advanced pharmacy practice include competencies related to leadership and management. Transformational leadership, a contemporary leadership theory, is seen as the most suitable for addressing the challenges facing the modern healthcare system. Aim To map leadership and management competencies of the Australian Advanced Pharmacy Practice Framework 2012 (APPF) against an evidence-based model of transformational leadership. Methods Domains of the APPF were mapped against the dimensions of a transformational leadership model developed in the United Kingdom public service. Results There were broad differences between the APPF and a model of transformational leadership. The APPF focuses heavily on ‘organisational’ skills such as strategic vision and setting direction, while the model of transformational leadership focused on the ‘people skills’ of effective leaders. The APPF mapped primarily to the ‘Leading the Organisation’ dimensions of transformational leadership. Conclusion There are significant differences between the leadership and management competencies of the APPF and the dimensions of transformational leadership. Future work on the competency standards for general and advanced levels of practice should include or refer to an evidence-based model of transformational leadership.

In August 2014, a special issue of Safety Science contested the foundations of safety science as a scientific domain on methodological, theoretical and philosophical grounds. Safety specialists in social, behavioural and organisational sciences discussed what seems to be an identity crisis in occupational safety and social sciences. A tension between scientific and societal relevance of the notion of safety was noted, raising doubts about the scientific validity of safety science (Safety Science, 2014). As three of the founding fathers of the Safety Science Group (SSG) at Delft University of Technology (DUT) in 1978, we were challenged by this debate to reflect on our ambitions and mission that were expressed during the inception of safety science at DUT. In addition to what has already been described by Hale and De Kroes (1997) and Hale (2014), we elaborate also on personal experiences and insights, gained over a period of some 40 years of work. These additional experiences were gained in particular by the first two authors in the transport domain from a technological and engineering design methodological perspective. They provide a more encompassing scope on the development of safety science in general as a scientific activity at DUT. Parallel developments in other domains have been described in other papers (Hale, 1985, 2006, 2014; Hale and de Kroes, 1997). First, we have to correct a long term omission by translating the founding documents for safety science at DUT into English to make them accessible for non-Dutch experts. Second, we highlight the development of three basic notions that were identified in 1978, at the inception of the SSG, as the cornerstones for safety science as a scientific discipline, no matter what domain it is related to: interdisciplinarity, problem-solving orientation and systems approach. We document in this paper their development and use in the transport domain in the DUT as a whole, i.e. more broadly than the SSG. Third, we discuss more in general the observations, particularly of the first two authors on the value and unique role of safety investigation methodology and systems engineering as powerful feedback loops with learning potential and drivers of change through their potential to address safety in complex, dynamic and open transport systems. Fourth, we elaborate on three additional basic notions that are needed as extra building blocks for a paradigm shift in safety thinking, irrespective of disciplines and domains – a full information supply, engineering design methodology and multiple intervention strategies. Finally, we advocate a mutual recognition of the value and validity of scientific paradigms as developed in the various disciplines, that in conjunction constitute safety science as a distinct, multidisciplinary activity in the academic community.

Introducao A minha carreira na ciencia da seguranca deixou-me com duas preocupacoes constantes. A primeira e a reaccao que alguem tem quando ouve que passei toda a minha vida profissional a estudar o risco e a seguranca. Depois de um momento de silencio de espanto e um sorriso nervoso, a reaccao e geralmente : “Es louco, como podes ter passado 40 anos a estudar isso ? E somente uma questao de pessoas estupidas que quebram as regras. Nao e incrivelmente aborrecido ?” Quando avanco e digo que, ...

Aortocoronary graft ruptures are a complication of coronary artery bypass grafting. The majority of graft ruptures are iatrogenic and occur after interventional procedures or surgery, whereas graft ruptures are significantly less common. Our case report highlights a clinical presentation of a late spontaneous saphenous vein graft rupture that developed approximately 16 years after initial bypass surgery and captures some of the ensuing complications. Several different imaging modalities were used to diagnose and characterize the lesion, and it was ultimately treated with percutaneous coronary intervention and minimally invasive surgery.

Medication order accuracy checking is an integral and time-consuming component of the current Australian pharmacist’s role. However, the pharmacy profession internationally has moved towards separating the checking task into two parts: a clinical check performed by the registered pharmacist and a technical accuracy check delegated to an appropriately trained pharmacy technician. This case study demonstrates that in an Australian hospital pharmacy context, appropriately trained pharmacy technicians have the potential to be more proficient and time efficient than pharmacists when undertaking accuracy checking of dispensed medications. What is known about the topic?International data have shown that appropriately trained pharmacy technicians can be more precise than pharmacists when performing accuracy checking. What does this paper add?This paper reports the findings of an Australian case study reallocating the accuracy checking task to trained pharmacy technicians and evaluating the time efficiency data, which has not previously been reported. What are the implications for practitioners?These findings provide support for the potential to safely delegate checking tasks to an appropriately trained accuracy checking pharmacy technician.

This special issue invites to a debate to elaborate on differences and similarities between the perspectives of High Reliability Organisation (HRO) and Resilience Engineering (RE). Such a debate may be conducted along both essentialistic and pragmatic lines, and we suggest that the latter approach is potentially more interesting and fruitful than the first. We use the technique of feeding off controversies and expand on what might at first look merely like a polemic disagreement, a question of wording, namely the definition of safety as a dynamic non-event. This elaboration is used as a projector onto a canvas where a number of distinguishing themes between HRO and RE are outlined more clearly; symmetry, normativity, addressee and origin are keywords that show how HRO and RE are different, and why they cannot simply be combined into one grand theory of everything. Other concrete results from these investigations include a review of applications of HRO and RE in health research, an elaboration of the distinction between Safety I and Safety II, and a nuancing of how we may understand and study successful operations. We suggest a research agenda that combines the scopes and methods of HRO and RE, possibly in combination with other theoretical approaches. We also call for a more lively discussion on central themes of HRO and RE, not for fighting over definitions and proving who is right, but with the aim of producing knowledge that makes a difference regardless of theoretical stance.

This paper presents topic maps of six core safety journals, based on analysis of 13,028 articles published in those journals as downloaded from the Web of Science. Bibliometric mapping methods were used to visualize the map of the topics covered in each journal. Analysis was also made of the changes in topics over time. The results show that safety science research in those journals has grown very rapidly over the last half century, with USA as the most productive in total and also in each year in the period. The topic clusters of these journals reveal the focus of each journal, which may be determined by the dominant methodologies used, the activity whose safety is studied or the object of study (e.g. workplace, safety management, regulation, etc.). The different journals also show regional differences in the papers they attract. The field in total is highly multidisciplinary. The topics of Safety Science have been focused on major hazard, transportation and work safety; Journal of Safety Research divides its attention between work and traffic safety, with a smaller cluster on statistics; Accident Analysis and Prevention is concerned almost exclusively with road safety; Injury Prevention is concerned mainly with injury mechanisms, but includes topics not treated by the other 5 journals, such as violence, suicide and other intentional injury and child safety at school and in the home. Reliability Engineering and System Safety and the Journal of Loss Prevention in the Process Industries focus mainly on major hazard, with the latter most concerned with the technology of failure mechanisms and the former on quantitative risk assessment.

The sound of crashing waves, the roar of fast-moving cars – sound conveys important information about the objects in our surroundings. In this work, we show that ambient sounds can be used as a supervisory signal for learning visual models. To demonstrate this, we train a convolutional neural network to predict a statistical summary of the sound associated with a video frame. We show that, through this process, the network learns a representation that conveys information about objects and scenes. We evaluate this representation on several recognition tasks, finding that its performance is comparable to that of other state-of-the-art unsupervised learning methods. Finally, we show through visualizations that the network learns units that are selective to objects that are often associated with characteristic sounds., National Science Foundation (U.S.) (Grant 1524817), National Science Foundation (U.S.) (Grant 1447476), National Science Foundation (U.S.) (Grant 1212849)

Pharmacist prescribing has been introduced in several countries and is a possible future role for pharmacy in Australia.To assess whether patient satisfaction with the pharmacist as a prescriber, and patient experiences in two settings of collaborative doctor-pharmacist prescribing may be barriers to implementation of pharmacist prescribing.Surveys containing closed questions, and Likert scale responses, were completed in both settings to investigate patient satisfaction after each consultation. A further survey investigating attitudes towards pharmacist prescribing, after multiple consultations, was completed in the sexual health clinic.A surgical pre-admission clinic (PAC) in a tertiary hospital and an outpatient sexual health clinic at a university hospital. Two hundred patients scheduled for elective surgery, and 17 patients diagnosed with HIV infection, respectively, recruited to the pharmacist prescribing arm of two collaborative doctor-pharmacist prescribing studies.Consultation satisfaction response rates in PAC and the sexual health clinic were 182/200 (91%) and 29/34 (85%), respectively. In the sexual health clinic, the attitudes towards pharmacist prescribing survey response rate were 14/17 (82%). Consultation satisfaction was high in both studies, most patients (98% and 97%, respectively) agreed they were satisfied with the consultation. In the sexual health clinic, all patients (14/14) agreed that they trusted the pharmacist's ability to prescribe, care was as good as usual care, and they would recommend seeing a pharmacist prescriber to friends.Most of the patients had a high satisfaction with pharmacist prescriber consultations, and a positive outlook on the collaborative model of care in the sexual health clinic.

There is a strong political consensus in a number of countries that occupational safety and health regulation is stifling industrial innovation and development and is feeding a culture of damaging risk aversion and petty bureaucracy. In a number of countries this has led to proposals to repeal regulations and reduce the regulatory burden. The authors were commissioned to prepare a discussion paper on this issue by the Mercatus Center of George Mason University in Arlington, Virginia, aimed particularly at an American audience. The paper is based on previous work of the first two authors, developing a framework of safety rule management at the workplace level (Hale & Borys 2012a and b). Based on a literature study, this paper analyses the similarities and differences between rules at the workplace level and the development, use and enforcement of regulations at the national level to influence and control organisational behaviour. It traces the forces encouraging the growth of regulatory detail and hence the bureaucratic burden of compliance and the options open to reduce that burden without loosening control so much that the level of safety declines. The analysis uses the hierarchy of rules from goals, through process (risk management) rules to detailed action rules as framework for predicting the level of ownership and responsibility felt by the regulated.

The railway industry is based on European Union figures on being the safest form of transport in terms of passenger deaths per person kilometre or in deaths per person travel hour. The railways are one of the favourite mechanisms chosen by people in the Netherlands wishing to kill themselves and it kills some 30 other transport participants per year at level crossings, as well as a number of trespassers. The interviews were based on this framework and were conducted with a range of informants, who worked for the infrastructure company, a train operating company several track maintenance companies, the traffic control and the regulatory bodies. The interviews therefore gave a broad coverage of many aspects of the safety management system and culture of the organisations concerned, as well as the communication and coordination across the organisational boundaries that make up the decentralised railway system. Resilience is only one strategy for achieving very high levels of safety.

Resilience is essentially linked to a dynamic view of risk control. This chapter looks critically at the ARAMIS risk assessment approach designed for evaluating high-hazard chemical plants, which contains a management audit. The ARAMIS models and the auditing techniques developed have a strong emphasis on functional process analysis. The IRMA audit and its close relation, the ARAMIS risk assessment method, have been developed during studies in which the group in Delft has participated, in collaboration with a number of others. The technical modelling of the plant identifies all critical equipment and accident scenarios for the plant concerned and analyses what barriers the company claims to use to control these scenarios. It is essential that this identification process is exhaustive for all potential accidents with major consequences otherwise crucial scenarios may be missed, which may later turn out to be significant.