Copper-Mediated Dehydrogenative C(sp3)-H Borylation of Alkanes.

Borylations of inert carbon-hydrogen bonds are highly useful for transforming feedstock chemicals into versatile organoboron reagents. Catalysis of these reactions has historically relied on precious-metal complexes, which promote dehydrogenative borylations with diboron reagents under oxidant-free conditions. Recently, photoinduced radical-mediated borylations involving hydrogen atom transfer pathways have emerged as attractive alternatives because they provide complimentary regioselectivities and proceed under metal-free conditions. However, these net oxidative processes require stoichiometric oxidants and therefore cannot compete with the high atom economy of their precious-metal-catalyzed counterparts. Herein, we report that CuCl2 catalyzes radical-mediated, dehydrogenative C(sp3)-H borylations of alkanes with bis(catecholato)diboron under oxidant-free conditions. This is a result of an unexpected dual role of the copper catalyst, which promotes oxidation of the diboron reagent to generate an electrophilic bis-boryloxide that acts as an effective borylating agent in subsequent redox-neutral photocatalytic C-H borylations.

De Novo Synthesis of Dihydrobenzofurans and Indolines and Its Application to a Modular, Asymmetric Synthesis of Beraprost.

Dihydrobenzofurans and indolines are important constituents of pharmaceuticals. Herein, we describe a novel strategy for their construction in which the aromatic ring is created de novo through an inverse-electron demand Diels-Alder reaction and cheletropic extrusion sequence of a 2-halothiophene-1,1-dioxide with an enol ether/enamide, followed by aromatization. Unusually, the aromatization process proved to be highly challenging, but it was discovered that treatment of the halocyclohexadienes with a base effected an α-elimination-aromatization reaction. Mechanistic investigation of this step using deuterium-labeling studies indicated the intermediacy of a carbene which undergoes a 1,2-hydrogen shift and subsequent aromatization. The methodology was applied to a modular and stereoselective total synthesis of the antiplatelet drug beraprost in only 8 steps from a key enal-lactone. This lactone provided the core of beraprost to which both its sidechains could be appended through a 1,4-conjugate addition process (lower ω-sidechain), followed by de novo construction of beraprost's dihydrobenzofuran (upper α-sidechain) using our newly developed methodology. Additionally, we have demonstrated the breadth of our newly established protocol in the synthesis of functionalized indolines, which occurred with high levels of regiocontrol. According to density-functional theory (DFT) calculations, the high selectivity originates from attractive London dispersion interactions in the TS of the Diels-Alder reaction.

Selective hydroboration of electron-rich isocyanates by an NHC-copper(I) alkoxide.

The (IPr)CuOtBu catalysed reduction of 11 aryl and alkyl isocyanates with pinacolborane gave only the boraformamides, pinBN(R)C(O)H, in most cases. Overreduction, which hampers almost all isocyanate hydroborations, was restricted to electron poor aryl isocyanates (4-NC-C6H4NCO, 4-F3C-C6H4NCO, 3-O2N-C6H4NCO). Computational analysis showed stability of [(IPr)CuH]2, which was proposed to be the catalyst resting state, drives selectivity, suggesting an approach to prevent overreduction in future work. In the case of iPrNCO, formation of this species renders overreduction kinetically inaccessible. For 4-NC-C6H4NCO, however, the barrier height for the first step of over-reduction is much lower, even relative to [(IPr)CuH]2, resulting in unselective reduction.

C-H Insertion in Dirhodium Tetracarboxylate-Catalyzed Reactions despite Dynamical Tendencies toward Fragmentation: Implications for Reaction Efficiency and Catalyst Design.

Rh-catalyzed C-H insertion reactions to form ß-lactones suffer from post-transition state bifurcations, with the same transition states leading to ketones and ketenes via fragmentation in addition to ß-lactones. In such a circumstance, traditional transition state theory cannot predict product selectivity, so we employed ab initio molecular dynamics simulations to do so and provide a framework for rationalizing the origins of said selectivity. Weak interactions between the catalyst and substrate were studied using energy decomposition and noncovalent interaction analyses, which unmasked an important role of the 2-bromophenyl substituent that has been used in multiple ß-lactone-forming C-H insertion reactions. Small and large catalysts were shown to behave differently, with the latter providing a means of overcoming dynamically preferred fragmentation by lowering the barrier for the recombination of the product fragments in the grip of the large catalyst active site cavity.

Effective Characteristics of Iranian Nursing Students in Their Relationship with Clinical Nurses.

Introduction: The purpose of this study was to explore the characteristics of undergraduate nursing students, which may determine the nature of their relationship with clinical nurses. Relationships between nursing students and clinical nurses are critical to maximize student learning outcomes and produce skilled graduates for the future health workforce. Methods: This qualitative content analysis study was conducted from January to August 2016. Twenty nine semi-structured in-depth interviews were conducted with 20 undergraduate nursing students in Tabriz nursing and midwifery faculty. Interviews were recorded and transcribed verbatim (in Persian), and analyzed using conventional content analysis to identify themes. Results: Four key themes emerged: educational factors (cognitive knowledge and practical skills, and learning motivation); communication skills; perceived support (perceived support from nurses and educators); and psychological state (fear of the relationship and self-confidence). Self-confidence is an emphasized concept in nursing students' willingness and ability to relate with clinical nurses. Conclusion: The results of the study showed that educational, communicative and psychological factors are important determinants of student communication with nurses. However, self-confidence is the most important factor in establishing such relationship. Self-confidence could be further assessed to identify nursing students who need greater support or would benefit from greater educational interventions to achieve relational skills.

Ex Vivo Analysis of Tryptophan Metabolism Using 19F NMR.

Tryptophan, an essential amino acid, is metabolized into a variety of small molecules capable of impacting human physiology, and aberrant tryptophan metabolism has been linked to a number of diseases. There are three principal routes by which tryptophan is degraded, and thus methods for measuring metabolic flux through these pathways can be used to understand the factors that perturb tryptophan metabolism and potentially to measure disease biomarkers. Here, we describe a method utilizing 6-fluorotryptophan as a probe for detecting tryptophan metabolites in ex vivo tissue samples via 19F nuclear magnetic resonance. As a proof of concept, we demonstrate that 6-fluorotryptophan can be used to measure changes in tryptophan metabolism resulting from antibiotic-induced changes in gut microbiota composition. Taken together, we describe a general strategy for monitoring amino acid metabolism using 19F nuclear magnetic resonance that is operationally simple and does not require chromatographic separation of metabolites.

Treating infants with neonatal abstinence syndrome: an examination of three protocols.

OBJECTIVE: Describe the characteristics of infants with NAS and determine if treatment outcomes varied between three protocols. STUDY DESIGN: Based on medical record data, infant treatment for NAS-related withdrawal reflected one of three protocols: (1) No rescue dose (n = 836, 52.7%): Prescriber ordered initiation and escalation doses and determined when infants were eligible for weaning, (2) Rescue dose (n = 233, 14.7%): No rescue dose with the addition of a prescriber-ordered rescue dose, (3) Rescue dose by order set (n = 516, 32.6%): Rescue dose with addition of nurse-assisted order of morphine during escalation. RESULTS: The no rescue dose group had longer length of stay, days to wean, and inpatient days, and greater initial morphine dose than the two rescue dose groups (p < 0.001). Treatment outcomes between the two rescue dose protocols did not differ. CONCLUSIONS: The benefits related to rescue dosing further inform the development of a standardized NAS treatment protocol.

The Development of an International Oncofertility Competency Framework: A Model to Increase Oncofertility Implementation.

BACKGROUND: Despite international evidence about fertility preservation (FP), several barriers still prevent the implementation of equitable FP practice. Currently, oncofertility competencies do not exist. The aim of this study was to develop an oncofertility competency framework that defines the key components of oncofertility care, develops a model for prioritizing service development, and defines the roles that health care professionals (HCPs) play. MATERIALS AND METHOD: A quantitative modified Delphi methodology was used to conduct two rounds of an electronic survey, querying and synthesizing opinions about statements regarding oncofertility care with HCPs and patient and family advocacy groups (PFAs) from 16 countries (12 high and 4 middle income). Statements included the roles of HCPs and priorities for service development care across ten domains (communication, oncofertility decision aids, age-appropriate care, referral pathways, documentation, oncofertility training, reproductive survivorship care and fertility-related psychosocial support, supportive care, and ethical frameworks) that represent 33 different elements of care. RESULTS: The first questionnaire was completed by 457 participants (332 HCPs and 125 PFAs). One hundred and thirty-eight participants completed the second questionnaire (122 HCPs and 16 PFAs). Consensus was agreed on 108 oncofertility competencies and the roles HCPs should play in oncofertility care. A three-tier service development model is proposed, with gradual implementation of different components of care. A total of 92.8% of the 108 agreed competencies also had agreement between high and middle income participants. CONCLUSION: FP guidelines establish best practice but do not consider the skills and requirements to implement these guidelines. The competency framework gives HCPs and services a structure for the training of HCPs and implementation of care, as well as defining a model for prioritizing oncofertility service development. IMPLICATIONS FOR PRACTICE: Despite international evidence about fertility preservation (FP), several barriers still prevent the implementation of equitable FP practice. The competency framework gives 108 competencies that will allow health care professionals (HCPs) and services a structure for the development of oncofertility care, as well as define the role HCPs play to provide care and support. The framework also proposes a three-tier oncofertility service development model which prioritizes the development of components of oncofertility care into essential, enhanced, and expert services, giving clear recommendations for service development. The competency framework will enhance the implementation of FP guidelines, improving the equitable access to medical and psychological oncofertility care.

Formal [4 + 2] Cycloadditions of Anhydrides and α,ß-Unsaturated N-Tosyl Ketimines.

A method for the diastereoselective synthesis of highly substituted ß-enamino ketones from anhydrides and ketone-derived imines is reported. Cyclic, enolizable anhydrides undergo a base-promoted conjugate addition reaction with α,ß-unsaturated N-tosyl ketimines, followed by an intramolecular acylation to give formal [4 + 2] cycloaddition products. The carboxylic acid-containing products are formed with modest selectivity for the cis-diastereomer and can be fully epimerized to the trans-diastereomer upon esterification.

Primary care experience of older Australians with chronic illness.

This large (>1000) cross-sectional study investigates patient-reported primary care experiences of older people with chronic illness. Previous research has found that approximately half of patients with chronic illness receive optimal chronic illness care and outcomes in Australian general practice. A survey was administered via a double opt-in panel method to people aged ≥55 years who have one or more self-reported major chronic diseases (diabetes and/or chronic heart, kidney, lung, mental health and/or musculoskeletal conditions). Health professionals were found to be important to the majority of Australians surveyed. Well-known chronic illness support resources such as care plans and recalls/reminders were reported to be wanting by up to 50 per cent of respondents. Across all chronic illness groups, <42 per cent of respondents reported the provision of information on community resources and 25 per cent reported not having a sound understanding about their medications. Regular local surveys for older people with chronic illness would allow a timely understanding of primary care experiences, needs and preferences of this group, to support quality improvement and drive enhanced patient outcomes.

How can we improve oncofertility care for patients? A systematic scoping review of current international practice and models of care.

BACKGROUND: Fertility preservation (FP) is an important quality of life issue for cancer survivors of reproductive age. Despite the existence of broad international guidelines, the delivery of oncofertility care, particularly amongst paediatric, adolescent and young adult patients, remains a challenge for healthcare professionals (HCPs). The quality of oncofertility care is variable and the uptake and utilization of FP remains low. Available guidelines fall short in providing adequate detail on how oncofertility models of care (MOC) allow for the real-world application of guidelines by HCPs. OBJECTIVE AND RATIONALE: The aim of this study was to systematically review the literature on the components of oncofertility care as defined by patient and clinician representatives, and identify the barriers, facilitators and challenges, so as to improve the implementation of oncofertility services. SEARCH METHODS: A systematic scoping review was conducted on oncofertility MOC literature published in English between 2007 and 2016, relating to 10 domains of care identified through consumer research: communication, oncofertility decision aids, age-appropriate care, referral pathways, documentation, training, supportive care during treatment, reproductive care after cancer treatment, psychosocial support and ethical practice of oncofertility care. A wide range of electronic databases (CINAHL, Embase, PsycINFO, PubMed, AEIPT, Education Research Complete, ProQuest and VOCED) were searched in order to synthesize the evidence around delivery of oncofertility care. Related citations and reference lists were searched. The review was undertaken following registration (International prospective register of systematic reviews (PROSPERO) registration number CRD42017055837) and guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). OUTCOMES: A total of 846 potentially relevant studies were identified after the removal of duplicates. All titles and abstracts were screened by a single reviewer and the final 147 papers were screened by two reviewers. Ten papers on established MOC were identified amongst the included papers. Data were extracted from each paper and quality scores were then summarized in the oncofertility MOC summary matrix. The results identified a number of themes for improving MOC in each domain, which included: the importance of patients receiving communication that is of a higher quality and in different formats on their fertility risk and FP options; improving provision of oncofertility care in a timely manner; improving access to age-appropriate care; defining the role and scope of practice of all HCPs; and improving communication between different HCPs. Different forms of decision aids were found useful for assisting patients to understand FP options and weigh up choices. WIDER IMPLICATIONS: This analysis identifies core components for delivery of oncofertility MOC. The provision of oncofertility services requires planning to ensure services have safe and reliable referral pathways and that they are age-appropriate and include medical and psychological oncofertility care into the survivorship period. In order for this to happen, collaboration needs to occur between clinicians, allied HCPs and executives within paediatric and adult hospitals, as well as fertility clinics across both public and private services. Training of both cancer and non-cancer HCPs is needed to improve the knowledge of HCPs, the quality of care provided and the confidence of HCPs with these consultations.

Chronic disease management support in Australian workplaces-low base, rising need.

ISSUE ADDRESSED: This study investigates the current nature, levels and perceived need for workplace support among mature age Australian workers with chronic illness. METHODS: A cross-sectional population survey was conducted via a double opt-in panel sample of Australian workers aged 45 years and older with one or more of six major chronic diseases (diabetes and/or chronic heart, kidney, lung, mental health and/or musculoskeletal conditions). RESULTS: Three hundred and fourteen respondents reported being in the workforce and having at least one of the chronic conditions under investigation, of which almost one third reported having more than one of the conditions. The findings reveal a number of considerable gaps in Australian workplace support for employees 45 years and older with chronic illness, including workplace flexibility, supportive policies and co-worker support. CONCLUSIONS: This research adds to a scarce existing literature base on workplace support for workers with chronic illness in Australia. Future research is needed to identify opportunities for effective public policy and implementation of workplace interventions to better support this cohort. SO WHAT?: If timely progress is not made in this area, the projected increase in the aged population and scheduled public policy changes impacting retirement age will multiply potential adverse effects on the health of employees with chronic illness and Australia's labour market productivity.

The Patient's Voice: Australian Health Care Quality and Safety Regulation from the Perspective of the Public.

The quality and safety of health care is a topic of permanent debate in the field of health services policy and regulation. Often absent from this debate, however, are the views and values of the public. These are excluded by a dominant narrative of health care regulation which understands the regulation of quality and safety in health care as principally a technical and instrumental undertaking. This approach constrains the application of law and legal regulation, devaluing their normative and expressive function in this field. In-part as a form of corrective, we offer an analysis based on recent survey data, of the attitudes and perceptions held by the Australian public towards stakeholder responsibility for, and the regulation of, health care quality and safety.

Prediction of 19F NMR Chemical Shifts for Fluorinated Aromatic Compounds.

Scaling factors are reported for use in predicting 19F NMR chemical shifts for fluorinated (hetero)aromatic compounds with relatively low levels of theory. Our recommended scaling factors were developed using a curated data set of 52 compounds, with 100 individual 19F shifts spanning a range of 153 ppm. With a maximum deviation of 6.5 ppm between experimental and computed shifts, or 4% of the range tested, these scaling factors allow for the assignment of chemical shifts to specific fluorines in multifluorinated aromatics. The utility of this approach is highlighted by several structural reassignments.

Home care in Australia: an integrative review.

The home care sector comprises one of Australia's fastest growing workforces, yet few papers capture the overall landscape of Australian home care. This integrative review investigates home care with the aim of better understanding care recipients and their needs, funding, and regulation; care worker skills, tasks, demographics, employment conditions, and training needs. Over 2,700 pieces of literature were analyzed to inform this review. Results suggest sector fragmentation and a home care workforce who, although well-placed to improve outcomes for care recipients, are in need of better training and employment support. Suggestions for future research regarding Australian home care include studies that combine both aged and disability aspects of care, more research around care recipients, priority needs and strategies for addressing them, and how best to prepare home care workers for their roles.

Application of Computational Chemical Shift Prediction Techniques to the Cereoanhydride Structure Problem-Carboxylate Complications.

Despite the vast array of techniques available to modern-day chemists, structural misassignments still occur. These misassignments are often only realized upon attempted synthesis, when the spectra of synthesized products do not match previously reported spectra. This was the case with marine natural product cereoanhydride. The originally proposed 7-membered ring anhydride (1) was shown to be incorrect, although a likely precursor to the correct structure (2) in both its laboratory synthesis and biosynthesis. Herein, in addition to showing how NMR computations could have been used to arrive at the correct structure, we show that the conversion of 1 to 2 is indeed energetically viable, and we highlight complications in predicting NMR chemical shifts for molecules with acidic protons.

Right care, right place, right time: improving the timeliness of health care in New South Wales through a public-private hospital partnership.

Objective The overall aim of the study was to investigate and assess the feasibility of improving the timeliness of public hospital care through a New South Wales (NSW)-wide public-private hospital partnership. Methods The study reviewed the academic and professional grey literature, and undertook exploratory analyses of secondary data acquired from two national health data repositories informing in-patient access and utilisation across NSW public and private hospitals. Results In 2014-15, the NSW public hospital system was unable to deliver care within the medically recommended time frame for over 27400 people who were awaiting elective surgery. Available information indicates that the annual commissioning of 15% of public in-patient rehabilitation bed days to the private hospital system would potentially free up enough capacity in the NSW public hospital system to enable elective surgery for all public patients within recommended time frames. Conclusions The findings of the study justify a strategic whole-of-health system approach to reducing public patient wait times in NSW and highlight the need for research efforts aimed at securing a better understanding of available hospital capacity across the public and private hospital systems, and identifying and testing workable models that improve the timeliness of public hospital care. What is known about the topic? There are very few studies available to inform public-private hospital service partnerships and the opportunities available to improve timely health care access through such partnerships. What does this paper add? This paper has the potential to open and prompt timely discussion and debate, and generate further fundamental investigation, on public-private hospital service partnerships in Australia where opportunity is available to address elective surgery wait times in a reliable and effective manner. What are the implications for practitioners? The NSW Ministry of Health and its Local Health Districts have the potential to realise a key objective, namely to deliver the 'right care, in the right place, at the right time', through the core value of collaboration, using available infrastructure.