A simulated 'can't intubate, can't oxygenate' manikin crossover study investigating a modified front-of-neck access airway device.

A 'can't intubate, can't oxygenate' (CICO) situation is an uncommon and time-critical emergency. Many institutions have adopted a 'scalpel-bougie-endotracheal tube (ETT)' technique based on evidence produced by the 4th National Audit Project of the Royal College of Anaesthetists and 2015 Difficult Airway Society guidelines. We made a modification to the traditional 'scalpel-bougie-ETT' technique, using a shortened bougie and replacing the ETT with a cuffed Melker airway in a preassembled device (called 'Secure Airway for Front-of-neck Emergencies' (SAFE airway device)), which we felt might reduce cognitive load on a single operator in an emergency CICO situation.

Erlotinib or Gefitinib for Treating Advanced Epidermal Growth Factor Receptor Mutation-Positive Lung Cancer in Aotearoa New Zealand: Protocol for a National Whole-of-Patient-Population Retrospective Cohort Study and Results of a Validation Substudy.

Background: Starting in 2010, the epidermal growth factor receptor (EGFR) kinase inhibitors erlotinib and gefitinib were introduced into routine use in Aotearoa New Zealand (NZ) for treating advanced lung cancer, but their impact in this setting is unknown.

Objective: The study described in this protocol aims to understand the effectiveness and safety of these new personalized lung cancer treatments and the contributions made by concomitant medicines and other factors to adverse outcomes in the general NZ patient population. A substudy aimed to validate national electronic health databases as the data source and the methods for determining patient eligibility and identifying outcomes and variables.

Cyclic Ion Mobility for Hydrogen/Deuterium Exchange-Mass Spectrometry Applications.

Hydrogen/deuterium exchange-mass spectrometry (HDX-MS) has emerged as a powerful tool to probe protein dynamics. As a bottom-up technique, HDX-MS provides information at peptide-level resolution, allowing structural localization of dynamic changes. Consequently, the HDX-MS data quality is largely determined by the number of peptides that are identified and monitored after deuteration.

Structural Premise of Selective Deubiquitinase USP30 Inhibition by Small-Molecule Benzosulfonamides.

Dampening functional levels of the mitochondrial deubiquitylating enzyme Ubiquitin-specific protease 30 (USP30) has been suggested as an effective therapeutic strategy against neurodegenerative disorders such as Parkinson's Disease. USP30 inhibition may counteract the deleterious effects of impaired turnover of damaged mitochondria, which is inherent to both familial and sporadic forms of the disease. Small-molecule inhibitors targeting USP30 are currently in development, but little is known about their precise nature of binding to the protein.

Chromatographic Phospholipid Trapping for Automated H/D Exchange Mass Spectrometry of Membrane Protein-Lipid Assemblies.

Lipid interactions modulate the function, folding, structure, and organization of membrane proteins. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) has emerged as a useful tool to understand the structural dynamics of these proteins within lipid environments. Lipids, however, have proven problematic for HDX-MS analysis of membrane-embedded proteins due to their presence of impairing proteolytic digestion, causing liquid chromatography column fouling, ion suppression, and/or mass spectral overlap.

Ligand binding and conformational dynamics of the nicotinamide nucleotide transhydrogenase revealed by hydrogen/deuterium exchange mass spectrometry.

Nicotinamide nucleotide transhydrogenases are integral membrane proteins that utilizes the proton motive force to reduce NADP to NADPH while converting NADH to NAD. Atomic structures of various transhydrogenases in different ligand-bound states have become available, and it is clear that the molecular mechanism involves major conformational changes. Here we utilized hydrogen/deuterium exchange mass spectrometry (HDX-MS) to map ligand binding sites and analyzed the structural dynamics of transhydrogenase.

Testing a Model of Resilience in Family Members of Relatives with Traumatic Brain Injury vs Spinal Cord Injury: Multigroup Analysis.

Objective: To test a model comprising explanatory (neurologic impairment, coping, personality) and mediating (resilience, self-efficacy, hope, social support) variables on psychological adjustment and burden among family caregivers of individuals with traumatic brain injury (TBI) vs spinal cord injury (SCI).

Design: Structural equation modeling with multigroup analysis.

Setting: Six rehabilitation centers across New South Wales and Queensland, Australia.

Validation of ion mobility spectrometry - mass spectrometry as a screening tool to identify type II kinase inhibitors of FGFR1 kinase.

Rationale: The protein kinase FGFR1 regulates cellular processes in human development. As over-activity of FGFR1 is implicated with cancer, effective inhibitors are in demand. Type I inhibitors, which bind to the active form of FGFR1, are less effective than type II inhibitors, which bind to the inactive form.

A prospective audit on the use of prophylactic antiemetics and rates of CINV in patients receiving carboplatin AUC≥4 or combination anthracycline-cyclophosphamide.

Background: Chemotherapy-induced nausea and vomiting (CINV) are two of the most frequently experienced and distressing side effects of cancer treatment. Recent updates by ESMO/MASCC and ASCO on guidelines for prevention of CINV have recommended the addition of a neurokinin-1 receptor antagonist to antiemetic regimens for patients receiving carboplatin-based chemotherapy area under the curve (AUC) ≥4 mg/mL per minute, and an addition of olanzapine for those receiving combination anthracycline/cyclophosphamide chemotherapy.

Aims: To assess current use of prophylactic antiemetics and rates of CINV in patients under the care of MidCentral Regional Cancer Treatment Service (MRCTS) receiving carboplatin AUC≥4 or combination anthracycline/cyclophosphamide.

Spirituality and resilience among family caregivers of survivors of stroke: A scoping review.

Background: Stroke is the leading cause of disability in Australia and the third-leading cause of disability worldwide and a significant burden on caregivers.

Objective: To map the extent, range and nature of the literature investigating spirituality and resilience among family caregivers of survivors of stroke.

Method: A scoping review.

Do spirituality, resilience and hope mediate outcomes among family caregivers after traumatic brain injury or spinal cord injury? A structural equation modelling approach.

Background: A deficits approach to understanding psychological adjustment in family caregivers of individuals with a neurological disability is extensive, but further research in the field of positive psychology (spirituality, resilience, hope) may provide a potential avenue for broadening knowledge of the family caregiver experience after traumatic brain injury (TBI) or spinal cord injury (SCI).

Objective: To test a proposed model of spirituality among family caregivers of individuals with TBI or SCI, using structural equation modelling (SEM).

Methods: A cross-sectional design was employed to survey ninety-nine family participants (TBI = 76, SCI = 23) from six rehabilitation units from NSW and Queensland.

Investigating strategies to improve clinical trial opportunities for patients with cancer in New Zealand-INSIGHT.

Aims: Fewer than 5% of adult cancer patients participate in clinical trials, with multiple patient, clinician and institutional barriers identified. This study aimed to explore patient factors that impact access to cancer trials in New Zealand.

Methods: A questionnaire that included demographics and factors that might impact trial participation was circulated via nine district health boards (DHBs) and four cancer foundations to patients with a cancer diagnosis.

A predictive model of resilience among family caregivers supporting relatives with traumatic brain injury (TBI): A structural equation modelling approach.

Constructs from positive psychology were employed to create an explicit model of caregiver resilience. Predictive and mediating relationships among resilience and related variables (personality, coping, self-efficacy, hope, social support) were then tested for their association with burden and psychological adjustment among family members caring for relatives with severe TBI. Family participants ( = 131) from six rehabilitation units from New South Wales and Queensland completed assessments which elicited explanatory (Eysenck Personality Questionnaire, Ways of Coping Questionnaire), mediating (Connor-Davidson Resilience Scale, General Self-Efficacy Scale, Herth Hope Scale, Medical Outcome Study Social Support Survey), and caregiver outcome (Caregiver Burden Scale, Mental Health sub-Scale-SF36, General Health Questionnaire, and Positive and Negative Affect Scale) variables.

A study of whether individual and dyadic relations between spirituality and resilience contribute to psychological adjustment among individuals with spinal cord injuries and their family members.

Objective: To test a model of spiritual well-being and resilience among individuals with spinal cord injuries and their family members.

Design: Prospective cross-sectional observational data were analyzed by structural equation modelling.

Setting: Inpatient and community services at one rehabilitation hospital.

Neoadjuvant chemotherapy in non-metastatic breast cancer: a study on practice trends in a regional cancer treatment service.

Background: Neoadjuvant chemotherapy (NACT) is increasingly used for managing locally advanced and high risk non-metastatic breast cancer.

Aims: To describe trends in NACT use, assess compliance to best practice recommendations and determine treatment response rates in a regional cancer treatment service.

Methods: In this retrospective cross- sectional study, electronic records of patients who underwent NACT in centres covered by the MidCentral Regional Cancer Treatment Service in 2013 and 2017 were reviewed.

Direct evidence for conformational dynamics in major histocompatibility complex class I molecules.

Major histocompatibility complex class I molecules (MHC I) help protect jawed vertebrates by binding and presenting immunogenic peptides to cytotoxic T lymphocytes. Peptides are selected from a large diversity present in the endoplasmic reticulum. However, only a limited number of peptides complement the polymorphic MHC specificity determining pockets in a way that leads to high-affinity peptide binding and efficient antigen presentation.

Enhanced Detection of Low-Abundance Host Cell Protein Impurities in High-Purity Monoclonal Antibodies Down to 1 ppm Using Ion Mobility Mass Spectrometry Coupled with Multidimensional Liquid Chromatography.

The enormous dynamic range of proteinaceous species present in protein biotherapeutics poses a significant challenge for current mass spectrometry (MS)-based methods to detect low-abundance HCP impurities. Previously, an HCP assay based on two-dimensional chromatographic separation (high pH/low pH) coupled to high-resolution quadrupole time-of-flight (QTOF) mass spectrometry and developed in the author's laboratory has been shown to achieve a detection limit of about 50 ppm (parts per milion) for the identification and quantification of HCPs present in monoclonal antibodies following Protein A purification.1 To improve the HCP detection limit we have explored the utility of several new analytical techniques for HCP analysis and thereby developed an improved liquid chromatography-mass spectrometry (LC-MS) methodology for enhanced detection of HCPs.

Chapter 7 the relationship between coping and psychological adjustment in family caregivers of individuals with traumatic brain injury: a systematic review.

A systematic review was conducted to evaluate the association between coping (as measured by the Ways of Coping Questionnaire [WOCQ]) and psychological adjustment in caregivers of individuals with traumatic brain injury (TBI). A search conducted using the CINAHL, Medline, and PsycINFO databases yielded 201 citations between 1974 and 2014. A total of seven articles met the inclusion criteria; namely, the respondents who completed the WOCQ were family caregivers of individuals with TBI (including 66-item, 42-item, or 21-item versions).

Small molecule binding sites on the Ras:SOS complex can be exploited for inhibition of Ras activation.

Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP.

Pooling serum to identify cohorts of nonmilking cattle likely to be infected with Bovine viral diarrhea virus by testing for specific antibodies.

Testing for specific antibodies against Bovine viral diarrhea virus (BVDV) in pooled serum may present an opportunity to decrease the cost of screening for herds of high seroprevalence and increased likelihood of active infection. Experimental serum pools (n = 280) were created by combining equal aliquots of serum from between 5 and 25 individuals. A further 188 serum pools were generated from field serum samples.

The impact of neurobehavioral impairment on family functioning and the psychological well-being of male versus female caregivers of relatives with severe traumatic brain injury: multigroup analysis.

Objective: To examine the differential effect of neurobehavioral impairments (cognitive, behavioral, and social) on family functioning, family roles, and psychological distress in male versus female caregivers of relatives with severe traumatic brain injury (TBI).

Design: Structural equation modeling with multigroup analysis conducted in a cross-sectional sample to test an established theoretical model.

Participants: An aggregated sample of 122 caregivers (46 male, 76 female) of people with severe TBI.

Sero-prevalence of Neospora caninum and Besnoitia besnoiti in South Australian beef and dairy cattle.

A serological survey for Neospora caninum and Besnoitia besnoiti was carried out in beef and dairy cattle in South Australia. Serum samples of dairy cattle (n=133) from 9 properties and tank milk samples from a further 122 dairy herds were tested. An additional 810 sera from beef cattle from 51 properties were also tested.

Nurse Executives' Perceptions of the Executive Training for Research Application (EXTRA) Program.

Background: To improve the overall quality and effectiveness of the Canadian health care system through better decisions supported by research-based evidence (RBE), the Canadian Health Services Research Foundation (CHSRF) and partners have created the Executive Training for Research Application (EXTRA) program.

Objectives: To evaluate how nurse executive fellows perceive changes in their levels of knowledge of RBE and in their level of use of RBE following participation in the EXTRA program.

Methods: Nurse executives in the first four cohorts of the program (2004-2007) completed a survey during their 2-year fellowship period.

The relevance of personal characteristics in health care rationing: what the Australian public thinks and why.

This article examines the preferences of the general public in Australia regarding health care resource allocation. While previous studies have revealed that the public is willing to give priority to particular groups of patients based on their personal characteristics, the present article goes beyond previous efforts in attempting to explain these results. In the present study, there was strong support among respondents for giving “equal priority” to people regardless of their personal characteristics.