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Discovered in 1822, the haloform reaction is one of the oldest synthetic organic reactions. The haloform reaction enables the synthesis of carboxylic acids, esters or amides from methyl ketones. The reaction proceeds via exhaustive α‐halogenation and then substitution by a nucleophile to liberate a haloform. The methyl group therefore behaves as a masked leaving group. The reaction methodology has undergone several important developments in the last 200 years, transitioning from a diagnostic test of methyl ketones to a synthetically useful tool for accessing complex esters and amides. The success of the general approach has been exhibited through the use of the reaction in the synthesis of many different complex molecules in fields ranging from natural product synthesis, pharmaceuticals, agrochemicals, fragrants and flavourings. The reaction has not been extensively reviewed since 1934. Therefore, herein we provide details of the history and mechanism of the haloform reaction, as well as an overview of the developments in the methodology and a survey of examples, particularly in natural product synthesis, in which the haloform reaction has been used. [ABSTRACT FROM AUTHOR]

Electrosynthetic reactions are performed in either custom‐made reactors that are developed and machined in‐house or commercially available systems that offer good reproducibility but come at a high cost. To bridge this divide between customizability and reproducibility, we have developed the Open‐ESyn, which is a suite of 3D‐printed components compatible with the popular ElectraSyn. This collection of parts increases the electrosynthesis that can be performed with the ElectraSyn, expanding, for example, the scale, temperature and the type of electrodes that can be used. The standardized reactor environment can be inexpensively recreated, thereby maintaining the reproducibility of the ElectraSyn ecosystem. [ABSTRACT FROM AUTHOR]

The haloform reaction from methyl ketones to carboxylic acids is one of the oldest known synthetic organic reactions, which has been used in myriad applications over the decades. The corresponding reaction to produce esters is, however, less developed, as the reaction is generally limited to simple, primary alcohols that are used in solvent‐level quantities, thereby restricting the complexity of esters that can be directly formed. Herein, we detail the development of a general ester‐forming haloform coupling reaction using one equivalent of alcohol. Mechanistic and kinetic modelling studies demonstrated that the key intermediates are formed under equilibrium, which facilitated the development of conditions that are amenable to secondary alcohols. [ABSTRACT FROM AUTHOR]

The haloform reaction from methyl ketones to carboxylic acids is one of the oldest known synthetic organic reactions, which has been used in myriad applications over the decades. The corresponding reaction to produce esters is, however, less developed, as the reaction is generally limited to simple, primary alcohols that are used in solvent‐level quantities, thereby restricting the complexity of esters that can be directly formed. Herein, we detail the development of a general ester‐forming haloform coupling reaction using one equivalent of alcohol. Mechanistic and kinetic modelling studies demonstrated that the key intermediates are formed under equilibrium, which facilitated the development of conditions that are amenable to secondary alcohols. [ABSTRACT FROM AUTHOR]

The aim of this project was to better understand nurse navigators work with children and families who are living with severe autism spectrum disorder to achieve improved health and wellbeing outcomes. Nurse navigators were introduced into the public health sector in Queensland in 2016, with 400 navigators currently working across 16 health services in diverse geographic and demographic settings. Narrative inquiry was used to explore one nurse navigator's journey working with children and families living with severe Autism. The challenges of rigid health systems to adapt to the requirements of children with special needs, particularly in relation to care in the emergency department and where interventional procedures are necessary were apparent. Nurse navigators can effectively co-ordinate the care of an extremely vulnerable patient cohort and provide essential advocacy in a health system that is rigid and lacking the flexibility to deal with individual needs. [ABSTRACT FROM AUTHOR]

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Electrochemical fluorination reactions of organic compounds frequently employ hydrogen fluoride reagents that are corrosive. The corrosive nature of these reagents necessitates either the construction or purchase of cells that are stable to hydrogen fluoride, which require high‐cost materials, machining time and expertise. Herein, we offer an alternative solution using 3D printing, which is an inexpensive and rapid manufacturing technique. We have designed, printed and shared four different cell types in polypropylene and tested them in an electrochemical alkene difluorination reaction in the presence of triethylamine ⋅ 3HF and pyridinium poly ⋅ (HF). [ABSTRACT FROM AUTHOR]

Aim: To understand the impact and causes of 'Failure to Attend' (FTA) labelling, of patients with chronic conditions. Background: Nurse navigators are registered nurses employed by public hospitals in Queensland, Australia, to coordinate the care of patients with multiple chronic conditions, who frequently miss hospital appointments. The role of the nurse navigator is to improve care management of these patients. Evidence for this is measured through improvement in patient self-management of their conditions, a reduction in preventable hospital admissions and compliance with attendance at outpatient clinics. Failure to attend (FTA) is one measure of hospital utilisation, identifying outpatient appointments that are cancelled or not attended. Method: The cohort for this study was patients with multiple chronic conditions, and nurse navigators coordinating their care. Data describing the concept of FTA were thematically analysed twelve months into this three year evaluation. Results: Although the patient is blamed for failing to attend appointments, the reasons appear to be a mixture of systems error/miscommunication between the patient and the health services or social reasons impacting on patient's capacity to attend. Themes emerging from the data were: access barriers; failure to recognise personal stigma of FTA; and bridging the gap. Conclusion: The nurse navigators demonstrate their pivotal role in engaging with outpatient services to reduce FTAs whilst helping patients to become confident in dealing with multiple appointments. There are many reasons why a patient is unable to attend a scheduled appointment. The phrase 'Failure to Attend' has distinctly negative connotations and can lead to a sense of blame and shame for those with complex chronic needs. We propose the use of the neutral phrase "appointment did not proceed" to replace FTA. Implications for Nursing management: This article advocates for further consideration of collaborative models that engage the patient in their care journey and for consideration of the language used within the outpatient acute hospital setting, proposing the term 'appointment did not proceed.' [ABSTRACT FROM AUTHOR]

The choice of electrode material is critical for achieving optimal yields and selectivity in synthetic organic electrochemistry. The material imparts significant influence on the kinetics and thermodynamics of electron transfer, and frequently defines the success or failure of a transformation. Electrode processes are complex and so the choice of a material is often empirical and the underlying mechanisms and rationale for success are unknown. In this review, we aim to highlight recent instances of electrode choice where rationale is offered, which should aid future reaction development. [ABSTRACT FROM AUTHOR]

The choice of electrode material is critical for achieving optimal yields and selectivity in synthetic organic electrochemistry. The material imparts significant influence on the kinetics and thermodynamics of electron transfer, and frequently defines the success or failure of a transformation. Electrode processes are complex and so the choice of a material is often empirical and the underlying mechanisms and rationale for success are unknown. In this review, we aim to highlight recent instances of electrode choice where rationale is offered, which should aid future reaction development. [ABSTRACT FROM AUTHOR]

Introduction: The management of patients who need chronic and complex care is a focus of attention internationally, brought about by an increase in chronic conditions, requiring significantly more care over longer periods of time. The increase in chronic conditions has placed pressure on health services, financially and physically, bringing about changes in the way care is delivered, with hospital avoidance and home-based care encouraged. In this environment, nurses play an important role in co-ordinating care across services. This review formed one part of a funded project that explored the nurse navigator role within a proposed 24-hour telephone-call service in one regional area that has a diverse population in terms of cultural identity and geographical location in relation to service access. Aim: The review reports on the extant literature on the nurse's role in the provision of afterhours telephone services for patients with chronic and complex conditions. The specific aim was to explore the effectiveness of services for patients in geographically isolated locations. Methods: The methodological approach to the review followed the Preferred Reporting System for Meta-Analyses (PRISMA) guidelines. A thematic analysis was used to identify themes with chronic care models underpinning analysis. Results: Three themes were identified; nurse-led decision making; consumer profile; and program outcomes. Each theme was divided into two sub-themes. The two sub-themes for decision making were: the experience of the staff who provided the service and the tool or protocol used. The two sub-themes for consumers profile were; the geographic/demographic identity of the consumers, and consumer satisfaction. The final theme of outcomes describes how the effectiveness of the service is measured, broken into two sub-themes: the economic/workforce outcomes and the consumer outcomes. Discussion: The provision of an after-hours telephone service, in whatever model used should align with a Chronic Care Model. In this way, after-hours telephone services provided by experienced nurses, supported by ongoing professional development and relevant protocols, form part of the ongoing improvement for chronic and complex care management as a health priority. [ABSTRACT FROM AUTHOR]

Background: Patients with complex chronic conditions experience fragmentation of care, unnecessary hospitalization and reduced quality of life, with an increased incidence of poor health outcomes. Aim(s): The aim of this paper was to explore how nurse navigators manage client care. This was achieved through an examination of narratives provided by the nurse navigator that evaluated their scope of practice. Method(s): All nurse navigators employed by Queensland Health were invited to participate in a study evaluating the effectiveness of the service. Eighty‐four self‐reported vignettes were thematically analysed to understand the work from the nurses' perspectives. Results: Two themes emerged from the vignettes. Theme 1, the layers of complexity, is comprised of three sub‐themes: the complex patient, the complex system and patient outcomes. Theme 2, professional attributes, has two sub‐themes: person‐centred care and clinical excellence. Conclusion: Navigators innovatively integrate services and address the fragmented nature of the health system. They apply expert clinical and social skills, through consistent and robust communication, to meet the needs of those with multiple chronic conditions. Implications for nursing management: Results provide insight into the new role, illuminating the work they achieve, despite system complexities. [ABSTRACT FROM AUTHOR]

Mid-life hypertension and cerebrovascular dysfunction are associated with increased risk of later life dementia, including Alzheimer's disease (AD). The classical renin–angiotensin system (cRAS), a physiological regulator of blood pressure, functions independently within the brain and is overactive in AD. cRAS-targeting anti-hypertensive drugs are associated with reduced incidence of AD, delayed onset of cognitive decline, and reduced levels of Aβ and tau in both animal models and human pathological studies. cRAS activity is moderated by a downstream regulatory RAS pathway (rRAS), which is underactive in AD and is strongly associated with pathological hallmarks in human AD, and cognitive decline in animal models of CNS disease. We now show that enhancement of brain ACE2 activity, a major effector of rRAS, by intraperitoneal administration of diminazene aceturate (DIZE), an established activator of ACE2, lowered hippocampal Aβ and restored cognition in mid-aged (13–14-month-old) symptomatic Tg2576 mice. We confirmed that the protective effects of DIZE were directly mediated through ACE2 and were associated with reduced hippocampal soluble Aβ42 and IL1-β levels. DIZE restored hippocampal MasR levels in conjunction with increased NMDA NR2B and downstream ERK signalling expression in hippocampal synaptosomes from Tg2576 mice. Chronic (10 weeks) administration of DIZE to pre-symptomatic 9–10-month-old Tg2576 mice, and acute (10 days) treatment in cognitively impaired 12–13-month-old mice, prevented the development of cognitive impairment. Together these data demonstrate that ACE2 enhancement protects against and reverses amyloid-related hippocampal pathology and cognitive impairment in a preclinical model of AD. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the paper is to explore how the national, state and organisational health policies in Australia support the implementation of person-centred care in managing chronic care conditions.Design/methodology/approach: A qualitative content analysis was performed regarding the national, state and organisational Queensland Health policies using Elo and Kyngas' (2008) framework.Findings: Although the person-centred care as an approach is well articulated in health policies, there is still no definitive measure or approach to embedding it into operational services. Complex funding structures and competing priorities of the governments and the health organisations carry the risk that person-centred care as an approach gets lost in translation. Three themes emerged: the patient versus the government; health care delivery versus the political agenda; and health care organisational processes versus the patient.Research Limitations/implications: Given that person-centred care is the recommended approach for responding to chronic health conditions, further empirical research is required to evaluate how programs designed to deliver person-centred care achieve that objective in practice.Practical Implications: This research highlights the complex environment in which the person-centred approach is implemented. Short-term programmes created specifically to focus on person-centred care require the right organisational infrastructure, support and direction. This review demonstrates the need for alignment of policies related to chronic disease management at the broader organisational level.Originality/value: Given the introduction of the nurse navigator program to take up a person-centred care approach, the review of the recent policies was undertaken to understand how they support this initiative. [ABSTRACT FROM AUTHOR]

Background: Hospitals and other health care providers frequently experience difficulties contacting patients and their carers who live remotely from the town where the health service is located. In 2016 Nurse Navigator positions were introduced into the health services by Queensland Health, to support and navigate the care of people with chronic and complex conditions. One hospital in Far North Queensland initiated an additional free telephone service to provide another means of communication for patients and carers with the NNs and for off-campus health professionals to obtain details about a patient utilising the service. Calls made between 7am and 10pm, seven days per week are answered by a nurse navigator. Aim: To report utilisation of the service by navigated clients and remotely located clinicians compared to use of navigators' individual work numbers and direct health service numbers. We report the reason for calls to the free number and examine features of these calls. Methods: Statistical analysis examined the call reason, duration of calls, setting from where calls originated and stream of calls. Interactions between the reasons for calls and the features of calls, such as contact method, were examined. Results: The major reason for calls was clinical issues and the source of calls was primarily patients and carers. Clinical calls were longer in duration. Shorter calls were mainly non-clinical, made by a health professional. Setting for calls was not related to the reason. The most frequent number used was the individual mobile number of the NN, followed by the hospital landline. Although the free number was utilised by patients and carers, it was not the preferred option. Conclusion: As patients and carers preferred to access their NN directly than via the 1800 number, further research should explore options best suited to this group of patients outside normal business hours. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively investigate tumor responses of lung SBRT patients for different prescriptions. To analyze the relation between optimal biologically equivalent dose (BED) and tumor responses. Methods and Materials: Tumor responses after lung SBRT were compared by examining 48 treatments used four prescriptions. This study used simplified tumor response criteria: (a) Complete Response (CR) — post max SUV (SUVpost) after SBRT in the treated tumor region was almost the same as the SUVs in the surrounding regions; (b) Partial Response (PR) — SUVpost was smaller than previous max SUV (SUVpre), but was greater than the SUVs in the surrounding regions; (c) No Response (NR) — SUVpost was the same as or greater than SUVpre. Some SUVpost reported as mild or favorable responses were classified as CR/PR. BED calculated using α/β of 10 Gy were analyzed with assessments of tumor responses for SBRT prescriptions. Results: For the prescriptions (9 Gy × 5, 10 Gy × 5, 11 Gy × 5, and 12 Gy × 4) historically recommended by RTOG, we observed that higher BED10 and lower tumor volume would achieve a higher complete response rate. The highest complete response rate was observed for smallest tumor volume (PTVave = 6.8 cc) with higher BED10 (105.6) of 12 Gy × 4 prescription. For 11 Gy × 5 prescription, the BED10 (115.5) was the highest, but its complete response rate (58%) was lower than 79% of 12 Gy × 4 prescription. We observed the PTVave of 11 Gy × 5 prescription was more than double of the PTVave of 12 Gy × 4 prescription. For the same lung SBRT prescription (BED10 > 100) earlier staging tumor had more favorable local control. Conclusion: We demonstrated post max SUV read from PET/CT could efficiently and accurately assess tumor response after lung SBRT. Although SBRT with prescriptions resulting in a BED10 > 100 experienced favorable tumor responses for early staging cancer, escalation of BED10 to higher levels would be beneficial for lung cancer patients with later staging and larger volume tumors. [ABSTRACT FROM AUTHOR]

The field of predictive toxicology requires the development of open, public, computable, standardized toxicology vocabularies and ontologies to support the applications required by in silico, in vitro, and in vivo toxicology methods and related analysis and reporting activities. In this article we review ontology developments based on a set of perspectives showing how ontologies are being used in predictive toxicology initiatives and applications. Perspectives on resources and initiatives reviewed include OpenTox, eTOX, Pistoia Alliance, ToxWiz, Virtual Liver, EU-ADR, BEL, ToxML, and Bioclipse. We also review existing ontology developments in neighboring fields that can contribute to establishing an ontological framework for predictive toxicology. A significant set of resources is already available to provide a foundation for an ontological framework for 21st century mechanistic-based toxicology research. Ontologies such as ToxWiz provide a basis for application to toxicology investigations, whereas other ontologies under development in the biological, chemical, and biomedical communities could be incorporated in an extended future framework. OpenTox has provided a semantic web framework for the implementation of such ontologies into software applications and linked data resources. Bioclipse developers have shown the benefit of interoperability obtained through ontology by being able to link their workbench application with remote OpenTox web services. Although these developments are promising, an increased international coordination of efforts is greatly needed to develop a more unified, standardized, and open toxicology ontology framework. [ABSTRACT FROM AUTHOR]

Foreign substances can have a dramatic and unpredictable adverse effect on human health. In the development of new therapeutic agents, it is essential that the potential adverse effects of all candidates be identified as early as possible. The field of predictive toxicology strives to profile the potential for adverse effects of novel chemical substances before they occur, both with traditional in vivo experimental approaches and increasingly through the development of in vitro and computational methods which can supplement and reduce the need for animal testing. To be maximally effective, the field needs access to the largest possible knowledge base of previous toxicology findings, and such results need to be made available in such a fashion so as to be interoperable, comparable, and compatible with standard toolkits. This necessitates the development of open, public, computable, and standardized toxicology vocabularies and ontologies so as to support the applications required by in silico, in vitro, and in vivo toxicology methods and related analysis and reporting activities. Such ontology development will support data management, model building, integrated analysis, validation and reporting, including regulatory reporting and alternative testing submission requirements as required by guidelines such as the REACH legislation, leading to new scientific advances in a mechanistically-based predictive toxicology. Numerous existing ontology and standards initiatives can contribute to the creation of a toxicology ontology supporting the needs of predictive toxicology and risk assessment. Additionally, new ontologies are needed to satisfy practical use cases and scenarios where gaps currently exist. Developing and integrating these resources will require a well-coordinated and sustained effort across numerous stakeholders engaged in a public-private partnership. In this communication, we set out a roadmap for the development of an integrated toxicology ontology, harnessing existing resources where applicable. We describe the stakeholders' requirements analysis from the academic and industry perspectives, timelines, and expected benefits of this initiative, with a view to engagement with the wider community. [ABSTRACT FROM AUTHOR]

There is a widespread awareness that the wealth of preclinical toxicity data that the pharmaceutical industry has generated in recent decades is not exploited as efficiently as it could be. Enhanced data availability for compound comparison ("read-across"), or for data mining to build predictive tools, should lead to a more efficient drug development process and contribute to the reduction of animal use (3Rs principle). In order to achieve these goals, a consortium approach, grouping numbers of relevant partners, is required. The eTOX ("electronic toxicity") consortium represents such a project and is a public-private partnership within the framework of the European Innovative Medicines Initiative (IMI). The project aims at the development of in silico prediction systems for organ and in vivo toxicity. The backbone of the project will be a database consisting of preclinical toxicity data for drug compounds or candidates extracted from previously unpublished, legacy reports from thirteen European and European operation-based pharmaceutical companies. The database will be enhanced by incorporation of publically available, high quality toxicology data. Seven academic institutes and five small-to-medium size enterprises (SMEs) contribute with their expertise in data gathering, database curation, data mining, chemoinformatics and predictive systems development. The outcome of the project will be a predictive system contributing to early potential hazard identification and risk assessment during the drug development process. The concept and strategy of the eTOX project is described here, together with current achievements and future deliverables. [ABSTRACT FROM AUTHOR]

Examines the pharmaceutical innovation and research and development (R&D) investments in Great Britain. Increase in R&D expenditure; Rate of introduction of novel medicines and their sales; Decline in the average effective patent life of new products.

Unfortunately, the acknowledgement section was not included in the original publication. [ABSTRACT FROM AUTHOR]