Multiple observers ranked set samples for shrinkage estimators.

Ranked set sampling (RSS) is used as a powerful data collection technique for situations where measuring the study variable requires a costly and/or tedious process while the sampling units can be ranked easily (e.g. osteoporosis research).

Impact of digital health on the quadruple aims of healthcare: A correlational and longitudinal study (Digimat Study).

Background: Digital healthcare aims to deliver on the quadruple aim: enhance patient experiences, improve population health, reduce costs and improve provider experiences. Despite large investments, it is unclear how advancing digital health enables these healthcare aims.

Objective: Our objectives were to: 1) measure the correlation between digital capability and health system outcomes mapped to the quadruple aim, and 2) measure the longitudinal impact of electronic medical record implementations upon health system outcomes.

Knockout or inhibition of USP30 protects dopaminergic neurons in a Parkinson's disease mouse model.

Mutations in SNCA, the gene encoding α-synuclein (αSyn), cause familial Parkinson's disease (PD) and aberrant αSyn is a key pathological hallmark of idiopathic PD. This α-synucleinopathy leads to mitochondrial dysfunction, which may drive dopaminergic neurodegeneration. PARKIN and PINK1, mutated in autosomal recessive PD, regulate the preferential autophagic clearance of dysfunctional mitochondria ("mitophagy") by inducing ubiquitylation of mitochondrial proteins, a process counteracted by deubiquitylation via USP30.

A Cancer Care Ontario Consensus-Based Organizational Guideline for the Planning and Delivery of Spine Stereotactic Body Radiation Therapy Treatment in Ontario.

The proposed recommendations are primarily based on the consensus opinion and in-field experience of the Ontario Health/Cancer Care Ontario stereotactic body radiation therapy (SBRT) for Spine Metastasis Guideline Development Group and published literature when available. Primary consideration was given to the perceived benefits for patients and the small likelihood of harm arising from recommendation implementation. Apart from the magnetic resonance imaging (MRI) follow-up strategy, all evidence was considered indirect and was provided by the working group in conjunction with their collective expertise in the field of SBRT.

Perceived Impact of Digital Health Maturity on Patient Experience, Population Health, Health Care Costs, and Provider Experience: Mixed Methods Case Study.

Background: Health care organizations understand the importance of new technology implementations; however, the best strategy for implementing successful digital transformations is often unclear. Digital health maturity assessments allow providers to understand the progress made toward technology-enhanced health service delivery. Existing models have been criticized for their lack of depth and breadth because of their technology focus and neglect of meaningful outcomes.

Comparison of first-pass intubation success rates between two different videolaryngoscopes in an Australian prehospital and retrieval medicine service.

Objective: To determine the effectiveness of the GlideScope Go videolaryngoscope (VL) in tracheal intubation in an Australian physician-staffed critical care prehospital and retrieval medicine service.

Methods: Our service has used VLs for several years, including the McGrath Mac, and from February 2019 the GlideScope Go. Clinicians may alternatively use direct laryngoscopy with a Macintosh laryngoscope.

Evaluating Digital Health Capability at Scale Using the Digital Health Indicator.

Background: Health service providers must understand their digital health capability if they are to drive digital transformation in a strategic and informed manner. Little is known about the assessment and benchmarking of digital maturity or capability at scale across an entire jurisdiction. The public health care system across the state of Queensland, Australia has an ambitious 10-year digital transformation strategy.

The Impact of a Cyberattack at a Radiation Oncology Department: Immediate Response and Future Preparedness.

Cyberattacks are increasing year after year and many organizations, including hospitals, are becoming targets. Radiation oncology is especially vulnerable because of the reliance on computer and network capabilities to transfer relevant patient information for safe and effective patient treatment. In early 2019, our institution was hit by a ransomware attack that brought down our oncology information system (OIS).

Apolipoprotein E Genotype Moderation of the Association Between Physical Activity and Brain Health. A Systematic Review and Meta-Analysis.

Introduction: Possession of one or two e4 alleles of the apolipoprotein E () gene is associated with cognitive decline and dementia risk. Some evidence suggests that physical activity may benefit carriers of the e4 allele differently.

Method: We conducted a systematic review and meta-analysis of studies which assessed differences in the association between physical activity and: lipid profile, Alzheimer's disease pathology, brain structure and brain function in healthy adults.

GSK137, a potent small-molecule BCL6 inhibitor with in vivo activity, suppresses antibody responses in mice.

B-cell lymphoma 6 (BCL6) is a zinc finger transcriptional repressor possessing a BTB-POZ (BR-C, ttk, and bab for BTB; pox virus and zinc finger for POZ) domain, which is required for homodimerization and association with corepressors. BCL6 has multiple roles in normal immunity, autoimmunity, and some types of lymphoma. Mice bearing disrupted BCL6 loci demonstrate suppressed high-affinity antibody responses to T-dependent antigens.

The development of highly potent and selective small molecule correctors of Z α-antitrypsin misfolding.

α1-antitrypsin deficiency is characterised by the misfolding and intracellular polymerisation of mutant α1-antitrypsin protein within the endoplasmic reticulum (ER) of hepatocytes. Small molecules that bind and stabilise Z α-antitrypsin were identified via a DNA-encoded library screen. A subsequent structure based optimisation led to a series of highly potent, selective and cellular active α1-antitrypsin correctors.

The Operation of Canada's Only Virtually Operated Radiation Oncology Service During the COVID-19 Pandemic.

Purpose: Our institution operates a remote radiation oncology service in Northern Ontario, Canada. Since the start of the coronavirus disease 2019 pandemic, this center has operated without radiation oncologists on site owing to safety precautions, and this study seeks to understand the effect of this shift.

Methods And Materials: Departmental level data reports were used to investigate differences in metrics between April to May of 2019 and April to May 2020.

A Potent and Selective Kallikrein-5 Inhibitor Delivers High Pharmacological Activity in Skin from Patients with Netherton Syndrome.

Regulation of proteolytic activity in the skin plays a pivotal role in epidermal homeostasis. This is best exemplified in Netherton syndrome, a severe genetic skin condition caused by loss-of-function mutations in the gene serine protease inhibitor Kazal-type 5 encoding lympho-epithelial Kazal-type-related inhibitor, a serine protease inhibitor that regulates kallikrein (KLK)-related peptidase 5, 7, and 14 activities. KLK5 plays a central role in stratum corneum shedding and inflammatory cell signaling, activates KLK7 and KLK14, and is therefore an optimal therapeutic target.

Development of a small molecule that corrects misfolding and increases secretion of Z α -antitrypsin.

Severe α -antitrypsin deficiency results from the Z allele (Glu342Lys) that causes the accumulation of homopolymers of mutant α -antitrypsin within the endoplasmic reticulum of hepatocytes in association with liver disease. We have used a DNA-encoded chemical library to undertake a high-throughput screen to identify small molecules that bind to, and stabilise Z α -antitrypsin. The lead compound blocks Z α -antitrypsin polymerisation in vitro, reduces intracellular polymerisation and increases the secretion of Z α -antitrypsin threefold in an iPSC model of disease.

Responding to the COVID-19 pandemic: The experiences of South Australia's Rescue, Retrieval and Aviation Services.

COVID-19 poses significant challenges to pre-hospital and retrieval medicine (PHRM) clinicians - and many are unique to this area of clinical practice. We share the experiences of the South Australian Ambulance Service (SAAS) MedSTAR Emergency Medical Retrieval Service in preparing for the COVID-19 pandemic in the pre-hospital and retrieval setting - including the role of a multidisciplinary leadership team; challenges and potential approaches to screening for COVID-19; personal protective equipment for pre-hospital and aeromedical taskings; issues arising with interstate retrievals; and the role of telehealth. Although novel solutions allowed SAAS MedSTAR to continue to deliver high-quality care, considering the resource implications involved in undertaking the transfer of patients with COVID-19, it is clear that significant community disease transmission threatens to overwhelm any PHRM service.

The molecular species responsible for α -antitrypsin deficiency are suppressed by a small molecule chaperone.

The formation of ordered Z (Glu342Lys) α -antitrypsin polymers in hepatocytes is central to liver disease in α -antitrypsin deficiency. In vitro experiments have identified an intermediate conformational state (M*) that precedes polymer formation, but this has yet to be identified in vivo. Moreover, the mechanism of polymer formation and their fate in cells have been incompletely characterised.

Decision support tool and suggestions for the development of guidelines for the helicopter transport of patients with COVID-19.

The novel coronavirus SARS-CoV2 emerged in December 2019 and is now pandemic. Initial analysis suggests that 5% of infected patients will require critical care, and that respiratory failure requiring intubation is associated with high mortality.Sick patients are geographically dispersed: most patients will remain in situ until they are in need of critical care.

Design and development of a series of borocycles as selective, covalent kallikrein 5 inhibitors.

The connection between Netherton syndrome and overactivation of epidermal/dermal proteases, particularly Kallikrein 5 (KLK5) has been well established and it is expected that a KLK5 inhibitor would improve the dermal barrier and also reduce the pain and itch that afflict Netherton syndrome patients. One of the challenges of covalent protease inhibitors has been achieving selectivity over closely related targets. In this paper we describe the use of structural insight to design and develop a selective and highly potent reversibly covalent KLK5 inhibitor from an initial weakly binding fragment.

Predictors of Prehospital On-Scene Time in an Australian Emergency Retrieval Service.

Introduction: Prehospital physicians balance the need to stabilize patients prior to transport, minimizing the delay to transport patients to the appropriate level of care. Literature has focused on which interventions should be performed in the prehospital environment, with airway management, specifically prehospital intubation (PHI), being a commonly discussed topic. However, few studies have sought additional factors which influence scene time or quantify the impact of mission characteristics or therapeutic interventions on scene time.

Evaluation of a crystallographic surrogate for kallikrein 5 in the discovery of novel inhibitors for Netherton syndrome.

The inhibition of kallikrein 5 (KLK5) has been identified as a potential strategy for treatment of the genetic skin disorder Netherton syndrome, in which loss-of-function mutations in the SPINK5 gene lead to down-regulation of the endogenous inhibitor LEKTI-1 and profound skin-barrier defects with severe allergic manifestations. To aid in the development of a medicine for this target, an X-ray crystallographic system was developed to facilitate fragment-guided chemistry and knowledge-based drug-discovery approaches. Here, the development of a surrogate crystallographic system in place of KLK5, which proved to be challenging to crystallize, is described.

Evaluation of a targeted, theory-informed implementation intervention designed to increase uptake of emergency management recommendations regarding adult patients with mild traumatic brain injury: results of the NET cluster randomised trial.

Background: Evidence-based guidelines for management of mild traumatic brain injury (mTBI) in the emergency department (ED) are now widely available; however, clinical practice remains inconsistent with these guidelines. A targeted, theory-informed implementation intervention (Neurotrauma Evidence Translation (NET) intervention) was designed to increase the uptake of three clinical practice recommendations regarding the management of patients who present to Australian EDs with mild head injuries. The intervention involved local stakeholder meetings, identification and training of nursing and medical local opinion leaders, train-the-trainer workshops and standardised education materials and interactive workshops delivered by the opinion leaders to others within their EDs during a 3 month period.