The experiences and perceptions of rural and remote nurses who provide care to pregnant women in the absence of midwives.

INTRODUCTION: Maternity unit closures in rural and remote settings of Australia have left a substantial gap in services for pregnant women. In the absence of midwives, and when women are unable to attend a maternity facility, registered nurses (RNs) are required to fill the void. While maternity education can attempt to prepare RNs for such encounters, there is little documented to suggest it meets all their physical and psychological needs. The existing challenges for health professionals, practising a vast generalist scope of practice while living and working in a rural and remote location, have been well researched and documented. How nurses feel about the expectation that they work outside their scope of practice to provide maternity care in a rural and remote setting in Australia has not been asked until now. This study explores the perceptions and experiences of RNs who find themselves in this situation. METHODS: The study utilised a hermeneutic phenomenological methodology to examine the experiences and perceptions of rural and remote nurses providing care for pregnant women. RNs working in rural and remote health facilities that had no maternity services were recruited by a purposive sampling method. Semistructured conversational interviews were recorded and transcribed verbatim. Data analysis was guided by van Manen's analytical approach. RESULTS: Eight nurses participated, and from the data three themes, each with several subthemes, emerged: 'being-in-the-world of the rural and remote nurse' - described how participants viewed rural and remote nursing as an entity with unchangeable aspects that could not be considered in isolation; 'scope of practice - unprepared or underprepared' described how, despite their existing and extensive nursing skills, participants felt ill-equipped theoretically, practically and mentally to care for pregnant women; 'moral distress' - participants expanded their feelings of unpreparedness to include inadequacy, fear, and appropriateness of care delivery. DISCUSSION: The realism of rural and remote nursing practice demonstrates that at some point in their career, rural and remote nurses will care for a labouring and/or pregnant woman at high risk for complications. Participants in this study appeared open and honest in their interviews, displaying pride at their extensive nursing skills and job satisfaction. However, they were unanimous in their discussions of what being a nurse and providing maternity care in a rural and remote setting meant to themselves and to pregnant women. They suggested care was fragmented and inadequate from a workforce that is inadequately prepared and stressed. CONCLUSION: This study has highlighted another concerning aspect of rural and remote midwifery care - the experiences and perceptions of eight nurses delivering care that has previously been overlooked. The united voice of the RNs in this study warrants a platform to speak from and deserves acknowledgement and attention from government and midwifery policy drivers. These nurses, and the women receiving their care, deserve more.

Positive allosteric modulators of the α7 nicotinic acetylcholine receptor: SAR investigation around PNU-120596.

The α7 nicotinic acetylcholine receptor is a calcium permeable, ligand-gated ion channel that modulates synaptic transmission in the hippocampus, thalamus, and cerebral cortex. Previously disclosed work described PNU-120596 that acts as a powerful positive allosteric modulator of the α7 nicotinic acetylcholine receptor. The initial structure-activity relationships around PNU-120596 were gleaned from screening a large thiazole library. Independent systematic examination of the aryl and heteroaryl groups resulted in compounds with enhanced potency and improved physico-chemical properties culminating in the identification of 16 (PHA-758454). In the presence of acetylcholine, 16 enhanced evoked currents in rat hippocampal neurons. In a rat model of impaired sensory gating, treatment with 16 led to a reversal of the gating deficit in a dose-dependent manner. These results demonstrate that aryl heteroaryl ureas, like compound 16, may be useful tools for continued exploration of the unique biology of the α7 nicotinic acetylcholine receptor.

The role and scope of contemporary midwifery practice in Australia: A scoping review of the literature.

PROBLEM: Little is known about the breadth of midwifery scope within Australia, and few midwives work to their full scope of practice. BACKGROUND: Midwives in Australia are educated and professionally accountable to work in partnership with childbearing women and their families, yet they are currently hindered from practicing within their full scope of practice by contextual influences. AIMS: To perform a scoping review of the literature to map out the role and scope of contemporary midwifery practice in Australia To identify any key issues that impact upon working within the full scope of midwifery practice in the Australian context METHODS: A scoping review of the literature guided by the Arksey and O'Malley's five-stage methodological framework, and the 'best fit' framework synthesis using the Nursing and Midwifery Board of Australia's Midwifery Standards for Practice. FINDINGS: Key themes that emerged from the review included Partnership with women; The professional role of the midwife; and Contextual influences upon midwifery practice. DISCUSSION: Tensions were identified between the midwifery scope of practice associated with optimal outcomes for women and babies supported by current evidence and the actual role and scope of most midwives employed in models of care in the current Australian public healthcare system. CONCLUSIONS: There is a mismatch between the operational parameters for midwifery practice in Australia and the evidence-based models of continuity of midwifery carer that are associated with optimal outcomes for childbearing women and babies and the midwives themselves.

Proton pump inhibitor use and the risk of peritoneal dialysis associated peritonitis.

BACKGROUND: The use of proton-pump inhibitors (PPI) has been associated with an increased risk of developing spontaneous bacterial peritonitis in patients with cirrhosis. Whether PPI use confers a similar risk in developing peritonitis in peritoneal dialysis (PD) patients remains unclear. AIM: To assess whether PPI use is associated with an increased risk of PD peritonitis. METHODS: Patients on PD were retrospectively identified. Data such as PPI use during PD, underlying diagnoses, comorbidities, and baseline serum tests were collected. Univariable and multivariable analysis was conducted using logistic regression to assess whether PPI use and other factors were associated with PD peritonitis. RESULTS: Fifty-seven patients were identified with a median (interquartile range (IQR)) age of 65.0 (51.5-74.0) years. The median (IQR) time on PD was 29.0 (17.5-45.0) months. Twenty-eight patients were on a PPI during PD. Fifty-seven percent of the PPI group went on to develop peritonitis, compared with 31% of patients without PPI exposure (odds ratio (OR) = 2.96; 95% confidence interval (CI): 1.00, 8.78; P = 0.050). Months on PD (OR = 1.03; 95% CI: 1.00, 1.06; P = 0.026), serum urea (OR = 0.88; 95% CI: 0.80, 0.97; P = 0.017), congestive cardiac failure (OR = 5.44; 95% CI: 1.29, 23.00; P = 0.021) and renovascular disease (OR = 14.59; 95% CI: 1.68, 126.67; P = 0.015) were identified as possible risk factors for peritonitis on univariable analysis. Following adjustment for covariates, serum urea, but not PPI use, was associated with PD peritonitis (OR = 0.87; 95% CI: 0.78, 0.98; P = 0.020). CONCLUSION: PPI use during PD was not associated with peritonitis. Due to the small number of patients and the limited number of studies investigating the effect of PPI use on PD peritonitis, further research is needed.

Women's experiences of gestational breast cancer and their interactions with the healthcare system: A scoping review.

AIM: To report the evidence of women's experiences following a diagnosis of gestational breast cancer (GBC) and their interactions with the healthcare system. DESIGN: A systematic scoping review. DATA SOURCES: This scoping review systematically searched Medline, CINAHL, Psych INFO, EMBASE and SCOPUS, in addition to six grey literature databases in October 2021. A 2020 PRISMA flow diagram depicting the flow of information. REVIEW METHODS: Guided by six steps in Arksey and OMalley's Framework (2005). One researcher completed the literature review, and four independently screened the titles and abstracts related to the eligibility criteria. RESULTS: Totalling 25 articles, these studies comprise 2 quantitative, 20 qualitative, 1 mixed-method and 2 other documents, a book and debate. Thematic analysis was guided by Braun and Clarke (2006) to identify an overarching theme of adjustment that underpinned women's narratives and was reinforced by four major and several minor themes. The four major themes were: psychological impact, motherhood, treatment and communication. The relationship between the themes contextualizes the enormous complexity concerning women's experiences with GBC. CONCLUSION: Cancer management for GBC is complex and multifaceted. At a time of conflicting emotions for women, Multidisciplinary teams are well placed to provide support, normalize the woman's experience of motherhood, demonstrate an understanding of treatment effects, and communicate in a considerate and empathetic manner with information that is timely and relevant. GBC management involves doctors, nurses, midwives and many other healthcare professionals, which can add to the impost of diagnosis. IMPACT: This scoping review contributes to a better understanding of women's experience of GBC. The results may inform improvements in the support and communication for these women with GBC and their families.

What challenges and enablers elicit job satisfaction in rural and remote nursing in Australia: An Integrative review.

AIM: To explore challenges and stressors experienced by rural and remote area nurses and identify any interventions that aided in decreasing stress and increasing job satisfaction. BACKGROUND: Demand for a generalist nursing workforce in rural and remote locations exposes nurses to the same conditions as people residing there: higher mortality rates and higher incidence of chronic diseases and inadequacies in accessing health services. DESIGN: Christmals and Gross's integrative review framework was used with specified inclusion and exclusion criteria. Four databases were searched with no date limits. Only Australian studies were searched as international scope of practice differences for nurses could have distorted findings. FINDINGS: Eighteen studies identified three broad themes: access to education; isolation (geographical, professional and personal) and recognition of role. DISCUSSION: Interlinked themes showed positives and negatives from differing viewpoints. Ambivalence to education stemmed from inadequate exposure to learning and was linked with geographical isolation. Isolation was found to be less of a challenge to nurses who had an existing emotional connection with the community. CONCLUSION: The themes identified were recurrent and interconnecting. The benefits of working in small rural and remote communities are being used as a driver for recruitment. These benefits include higher wages, providing a sense of belonging and allowing nurses to work to their full scope and develop generalist nursing skills. The geographical isolation generates challenges through inequality in access to education and professional support, working outside their scope of practice, safety and vulnerability that comes with living remotely and adapting to extreme weather conditions. TWEETABLE ABSTRACT: What are the challenges and enablers of rural and remote working and living that influence job satisfaction for rural and remote area nurses in Australia?

Discovery of acyl ureas as highly selective small molecule CSF1R kinase inhibitors.

Based on the structure of an early lead identified in Deciphera's proprietary compound collection of switch control kinase inhibitors and using a combination of medicinal chemistry guided structure activity relationships and structure-based drug design, a novel series of potent acyl urea-based CSF1R inhibitors was identified displaying high selectivity for CSF1R versus the other members of the Type III receptor tyrosine kinase (RTK) family members (KIT, PDGFR-α, PDGFR-ß, and FLT3), VEGFR2 and MET. Based on in vitro biology, in vitro ADME and in vivo PK/PD studies, compound 10 was selected as an advanced lead for Deciphera's CSF1R research program.

Factors related to the accurate application of NHSN surveillance definitions for CAUTI and CLABSI in Texas hospitals: A cross-sectional survey.

Previous studies indicate variability in the accurate application of National Healthcare Safety Network surveillance criteria with limited data on possible contributing factors. In this cross-sectional, convenience sampled web-based survey sent to members of Texas infection prevention and control organizations, training, experience, and time spent on surveillance was collected and assessed including 2 case studies. Our results indicate correct identification of catheter-associated urinary tract infection (CAUTI) and central line-associated bloodstream infection (CLABSI) criteria may be associated with 2019 National Healthcare Safety Network training (CAUTI: aOR = 0.17, 95% CI: 0.04, 0.80; CLABSI: aOR = 0.45, 95% CI: 0.045, 4.56) and increased years of infection prevention experience (CAUTI: aOR = 1.35, 95% CI: 0.42, 4.33; CLABSI: aOR = 1.23, 95% CI: 0.24, 6.38). Routinely performing more hours of surveillance may increase accuracy of CLABSI identification, but not CAUTI.

Nursing informatics in undergraduate nursing education in Australia before COVID-19: A scoping review.

Background: Technology can support transformational outcomes of high quality and evidenced-based care and education. Embedding nursing informatics into the undergraduate nursing curriculum enhances nursing students' digital health literacy, whilst preparing them to use health information systems and technological innovations to support their learning both at university and in the clinical environment. Aim: This scoping review aimed to provide an overview of the published literature on how nursing informatics was embedded and integrated into the undergraduate nursing curriculum in Australia before coronavirus disease (COVID-19). Methodology: A scoping review approach guided this study using the Levac, Colquhoun, and O'Brien framework, and the following databases were searched: CINAHL Plus, EMCARE, MEDLINE Ovid, Scopus, ERIC ProQuest, and Web of Science. A total of 26 articles were included: Five quantitative studies, eight qualitative studies and 13 mixed-methods studies. Findings: Few studies focused on the concept of nursing informatics itself, and only two studies described the process of developing curricula that contain nursing informatics competencies and their implementation: the educational scaffolding and modular development approach and a Community of Inquiry Framework (COI). Most studies centred on nursing informatics tools to facilitate teaching and learning in classrooms and skills laboratories. The reported pedagogical strategies were online learning, blended learning, and technology-enabled simulations. Hindrances to nursing informatics being integrated into undergraduate curricula were disparities of the informatics content, a lack of guidelines and/or frameworks, and poor digital literacy. Conclusion: This study provided a baseline perspective of how nursing informatics was embedded and integrated into nursing education in Australia before COVID-19. Overwhelmingly, the focus of research to date was found to be mainly on the utilisation of technological tools to support learning and teaching.

Reassortant Cache Valley Virus Associated With Acute Febrile, Nonneurologic Illness, Missouri.

An adult male from Missouri sought care for fever, fatigue, and gastrointestinal symptoms. He had leukopenia and thrombocytopenia and was treated for a presumed tickborne illness. His condition deteriorated with respiratory and renal failure, lactic acidosis, and hypotension. Next-generation sequencing and phylogenetic analysis identified a reassortant Cache Valley virus.

In what ways does online teaching create a positive attitude towards research in nursing students studying a first year evidence-based practice undergraduate subject online?

Nursing research teaching is seen as central to nurse education and practice, but the impact of exposure to research teaching on students' attitudes towards research remains unclear. The aims of this study were to explore the attitudes towards research of undergraduate nursing students, before and after exposure to research teaching online. A further aim of this study was to better understand students' attitudes towards research, to inform future teaching strategies. This descriptive quasi-experimental study used pre-semester and post-semester data collected by means of an online questionnaire. The Attitudes Towards Nursing Research Scale measured student attitudes via 18 Likert items that assessed four domains: Research Abilities, Usefulness of Research, Personal Interest in Research and Using Research in Clinical Practice. There were no statistically significant changes in the overall Attitude Towards Research Scale. Individual item analysis did show statistically significant changes in two items: Understanding of research terminology increased (p = 0.001), but Intention to conduct research decreased (p = 0.035). This study generated evidence on attitudes of nursing students toward research before and after their exposure to a research subject. Research teaching online may be insufficient to effect a change in student nurses' attitudes towards research. SUMMARY OF RELEVANCE: Issue: Research is a foundational topic in undergraduate nursing curricula, but students often find the topic to be challenging to learn, while academics find it challenging to engage students in learning about research.What is Already Known: A validated instrument, Attitudes Towards Research, can be used to ascertain if teaching affects attitudes.What this Paper Adds: Overall attitudes of first year, second semester students did not change after experiencing a semester long introductory research subject. However, two item statements did show a statistically significant change, in disparate directions. Understanding of Research Terminology increased, while Intention to Conduct Research decreased.

A cross-sectional study of domestic violence instruction in nursing and midwifery programs: Out of step with community and student expectations.

BACKGROUND: Domestic violence is a global health concern. Nurses and midwives must respond to those who experience domestic violence, although many are not prepared to do this. The World Health Organization recommend that domestic violence content be included in all pre-registration training as a matter of urgency. OBJECTIVES: To examine self-reported undergraduate student perceptions of domestic violence content in their programs of study and student attitudes and beliefs about domestic violence. DESIGN: A cross-sectional research design with online survey was employed from June to October 2017. METHODS: Using convenience sampling, 1076 students were recruited to the study from a total population sample of just over 6000 undergraduate nursing and midwifery students; a response rate of 17.9%. Survey data reported the nature and frequency of teaching and learning along with student attitudes and beliefs about domestic violence. Open ended responses were examined via thematic analysis. SETTINGS: Nine Australian universities offering undergraduate nursing and midwifery degrees. PARTICIPANTS: Undergraduate university nursing and midwifery students. RESULTS: Over half of students surveyed (53.7%, n = 578) reported that domestic violence was not addressed in their program of study. A direct correlation was found between students' perceived preparedness to assess and respond to domestic violence, and the amount of taught content in their program of study. CONCLUSION: This major gap in curricula has significant implications for professional practice preparedness. Further research should focus on examining the reasons why quality domestic violence content is lacking in undergraduate nursing and midwifery programs and how prioritisation of domestic violence content can be improved.

Australian nursing and midwifery student beliefs and attitudes about domestic violence: A multi-site, cross-sectional study.

Nurses and midwives have a professional responsibility to identify and provide effective care to those experiencing domestic violence. Pre-registration preparation may develop this capability. In order to inform curriculum development, this study explored Australian nursing and midwifery students' attitudes and beliefs about domestic violence. Data were collected between June and October 2017. Descriptive statistics were calculated and comparative analysis performed on independent variables. Thematic analysis was performed on open-ended qualitative responses. Participants included 1076 students from nine Australian universities. The majority were enrolled in nursing programs (88.4%), followed by midwifery (8.6%), and combined nursing/midwifery (2.4%) programs. There was no statistically significant difference in scores by year level across all subscales, suggesting there was no developmental change in beliefs and attitudes toward domestic violence over the course of study. Nursing students held views that were more violence-tolerant than midwifery students. Australian and Chinese-born males were more likely to refute that domestic violence is more common against women. Students had a limited understanding of domestic violence suggesting a critical need to address undergraduate nursing and midwifery curricula.

Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants.

Ripretinib (DCC-2618) was designed to inhibit the full spectrum of mutant KIT and PDGFRA kinases found in cancers and myeloproliferative neoplasms, particularly in gastrointestinal stromal tumors (GISTs), in which the heterogeneity of drug-resistant KIT mutations is a major challenge. Ripretinib is a "switch-control" kinase inhibitor that forces the activation loop (or activation "switch") into an inactive conformation. Ripretinib inhibits all tested KIT and PDGFRA mutants, and notably is a type II kinase inhibitor demonstrated to broadly inhibit activation loop mutations in KIT and PDGFRA, previously thought only achievable with type I inhibitors. Ripretinib shows efficacy in preclinical cancer models, and preliminary clinical data provide proof-of-concept that ripretinib inhibits a wide range of KIT mutants in patients with drug-resistant GISTs.

Andreev reflection spectroscopy in transition metal oxides.

Here we review the literature concerning measurement of the Andreev reflection between a superconductor (S) and ferromagnet (F), with particular attention to the case where the ferromagnet is a transition metal oxide. We discuss the practicality of utilization of the current models for determination of the transport current spin polarization and examine the evidence for Andreev bound states.This article is part of the theme issue 'Andreev bound states'.

Australian nursing students' knowledge and attitudes towards pressure injury prevention: A cross-sectional study.

AIM: The aim of this study was to assess student nurses' knowledge of and attitudes towards pressure injury prevention evidence-based guidelines. BACKGROUND: Pressure injuries are a substantial problem in many healthcare settings causing major harm to patients, and generating major economic costs for health service providers. Nurses have a crucial role in the prevention of pressure injuries across all health care settings. DESIGN: A multi-centered, cross-sectional study was conducted using a paper-based questionnaire with undergraduate nursing students enrolled in seven universities with campuses across five Australian states (Queensland, New South Wales, Western Australia, Victoria and Tasmania). METHODS: Data were collected from nursing students using two validated instruments (Pressure Ulcer Knowledge Assessment Instrument and Attitude Toward Pressure Ulcer Prevention Instrument), to measure students' pressure injury prevention knowledge and attitudes. RESULTS: Students reported relatively low pressure injury prevention knowledge scores (51%), and high attitude scores (78%). Critical issues in this study were nursing students' lack of knowledge about preventative strategies to reduce the amount and duration of pressure/shear, and lower confidence in their capability to prevent pressure injury. Level of education and exposure to working in a greater number of different clinical units were significantly related to pressure injury prevention knowledge and attitude scores. CONCLUSION: The study findings highlight the need to implement a comprehensive approach to increasing Australian nursing students' pressure injury prevention and management knowledge, as well as ensuring that these students have adequate experiences in clinical units, with a high focus on pressure injury prevention to raise their personal capability.

Retaining early career registered nurses: a case study.

BACKGROUND: A core objective of the Australian health system is to provide high quality, safe health care that meets the needs of all Australians. To achieve this, an adequate and effective workforce must support the delivery of care. With rapidly changing health care systems and consumer demographics, demand for care is increasing and retention of sufficient numbers of skilled staff is now a critical priority to meet current and future health care demands. Nurses are the largest cohort of professionals within the health workforce. Reducing the rates at which nurses leave the profession and supporting nurses to practice in their profession longer will have beneficial implications for the sustainability of a nursing workforce and, ultimately, to patient outcomes. The aim of the study was to describe and explain early career registered nurses' (ECRNs) experiences and support requirements during the first five years of practice for the purposes of identifying strategies that would support greater retention of ECRNs. METHODS: A single case study design focused on early career registered nurses (ECRNs) working in a hospital and health service in northern Australia. The research team adopted Djukic et al's definition of ECRNs as "RNs who have practiced for less than 5 years". Data was collected via three individual interviews and two focus groups. Thirty-five ECRNs participated in the study. RESULTS: Qualitative analysis of data generated during interviews and focus groups, identified the key themes of receiving career advice and choice or no choice. Analysis of study data in the context of the broader literature resulted in the researchers identifying six areas of focus for ECRN retention: 1) well-planned, supported and structured transition periods; 2) consideration of rotation through different areas with a six month minimum for skills development; 3) empowering decision making; 4) placement opportunities and choice in decisions of where to work; 5) career advice and support that considers ECRNs' personalities and skills; and 6) encouragement to reflect on career choices. CONCLUSIONS: Reducing turnover and improving retention relies on understanding the factors that influence nurses' decisions to leave or remain within an organisation and the profession. Ensuring nurses in the current workforce remain engaged and productive, rather than leave the profession, is reliant on addressing factors that cause attrition and implementing strategies that strengthen retention rates and workforce sustainability.

Using a community of inquiry framework to teach a nursing and midwifery research subject: An evaluative study.

BACKGROUND: Postgraduate nursing students' negative perceptions about a core research subject at an Australian university led to a revision and restructure of the subject using a Communities of Inquiry framework. Negative views are often expressed by nursing and midwifery students about the research process. The success of evidence-based practice is dependent on changing these views. A Community of Inquiry is an online teaching, learning, thinking, and sharing space created through the combination of three domains-teacher presence (related largely to pedagogy), social presence, and cognitive presence (critical thinking). OBJECTIVES: Evaluate student satisfaction with a postgraduate core nursing and midwifery subject in research design, theory, and methodology, which was delivered using a Communities of Inquiry framework. SETTING, PARTICIPANTS, AND METHODS: This evaluative study incorporated a validated Communities of Inquiry survey (n=29) and interviews (n=10) and was conducted at an Australian university. Study participants were a convenience sample drawn from 56 postgraduate students enrolled in a core research subject. Survey data were analysed descriptively and interviews were coded thematically. RESULTS: Five main themes were identified: subject design and delivery; cultivating community through social interaction; application-knowledge, practice, research; student recommendations; and technology and technicalities. Student satisfaction was generally high, particularly in the areas of cognitive presence (critical thinking) and teacher presence (largely pedagogy related). Students' views about the creation of a "social presence" were varied but overall, the framework was effective in stimulating both inquiry and a sense of community. CONCLUSIONS: The process of research is, in itself, the creation of a "community of inquiry." This framework showed strong potential for use in the teaching of nurse research subjects; satisfaction was high as students reported learning, not simply the theory and the methods of research, but also how to engage in "doing" research by forging professional and intellectual communities.

Miscarriage in Australia: The geographical inequity of healthcare services.

Complications in early pregnancy can lead to pregnancy loss (miscarriage) and ultimately the presentation of a woman to their local emergency department (ED). Miscarriage is a common occurrence, with one in six pregnancies resulting in pregnancy loss.(1) Unfortunately medical and nursing care does not change the likelihood of a threatened miscarriage progressing to pregnancy loss; this is a highly emotional and stressful time for the woman and her family. Research has shown that women have often felt dissatisfied with the care provided in the emergency department and have reported lower levels of satisfaction (Geller et al., 2010(2), Indig et al., 2011(3)). This paper explores the challenges in the provision of emergency department healthcare for women presenting to metropolitan EDs and compares these to those faced by women who present to non-metropolitan EDs with early pregnancy complications.

Altiratinib Inhibits Tumor Growth, Invasion, Angiogenesis, and Microenvironment-Mediated Drug Resistance via Balanced Inhibition of MET, TIE2, and VEGFR2.

Altiratinib (DCC-2701) was designed based on the rationale of engineering a single therapeutic agent able to address multiple hallmarks of cancer (1). Specifically, altiratinib inhibits not only mechanisms of tumor initiation and progression, but also drug resistance mechanisms in the tumor and microenvironment through balanced inhibition of MET, TIE2 (TEK), and VEGFR2 (KDR) kinases. This profile was achieved by optimizing binding into the switch control pocket of all three kinases, inducing type II inactive conformations. Altiratinib durably inhibits MET, both wild-type and mutated forms, in vitro and in vivo. Through its balanced inhibitory potency versus MET, TIE2, and VEGFR2, altiratinib provides an agent that inhibits three major evasive (re)vascularization and resistance pathways (HGF, ANG, and VEGF) and blocks tumor invasion and metastasis. Altiratinib exhibits properties amenable to oral administration and exhibits substantial blood-brain barrier penetration, an attribute of significance for eventual treatment of brain cancers and brain metastases.