Challenges and consensus: A survey of the management of neonatal hypoglycaemia within the Pacific Islands.

Aim: To describe the management of neonatal hypoglycaemia within Pacific Island countries and territories by surveying practising clinicians.

Methods: Survey questions were adapted from a similar survey conducted across Australian and New Zealand neonatal nurseries. An anonymous, electronic survey link and QR code were disseminated to clinicians via our partner organisations, Facebook and direct email.

From Hinengaro to Hineora: Tracing the origins of Intergenerational Trauma to attain Intergenerational Healing.

In Aotearoa New Zealand, colonisation continues to impact Indigenous Māori lived realities. However, Māori have been steadily progressing towards reclamation of all that was suppressed during colonisation, including tūpuna (ancestor) understandings of trauma and healing, of which wairua (referring to spirit) is at the centre. My research aimed to understand the role of wairua in the intergenerational transmission of trauma and healing through exploring my own lived experiences of trauma and healing.

Impact of and research priorities in early onset epilepsy: An investigation of parental concerns.

[Background and aim] Early onset epilepsy is a neurological condition with significant developmental consequences, and presents affected children and families with challenges which pervade many aspects of family life. Whilst the concerns of parents and the impact on quality of life is well documented in qualitative research, little emphasis has been placed on the context of 'early onset', and the implications of these concerns for research priority setting. We aimed to explore parental perspectives regarding concerns and the impact of early onset epilepsy on the child and family, and to identify priorities for future paediatric epilepsy research.

Reversal of High Fat Diet-Induced Obesity, Systemic Inflammation, and Astrogliosis by the NLRP3 Inflammasome Inhibitors NT-0249 and NT-0796.

Systemic and cerebral inflammatory responses are implicated in the pathogenesis of obesity and associated metabolic impairment. While the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome has been linked to obesity-associated inflammation, whether it contributes to the development or maintenance of obesity is unknown. We provide support for a direct role of saturated fatty acids, such as palmitic acid, as NLRP3 activating stimuli in obese states.

Classification of EMG signals with CNN features and voting ensemble classifier.

Electromyography (EMG) signals are primarily used to control prosthetic hands. Classifying hand gestures efficiently with EMG signals presents numerous challenges. In addition to overcoming these challenges, a successful combination of feature extraction and classification approaches will improve classification accuracy.

Multi-scale EMG classification with spatial-temporal attention for prosthetic hands.

A classification framework for hand gestures using Electromyography (EMG) signals in prosthetic hands is presented. Leveraging the multi-scale characteristics and temporal nature of EMG signals, a Convolutional Neural Network (CNN) is used to extract multi-scale features and classify them with spatial-temporal attention. A multi-scale coarse-grained layer introduced into the input of one-dimensional CNN (1D-CNN) facilitates multi-scale feature extraction.

Early development and epilepsy in tuberous sclerosis complex: A prospective longitudinal study.

Aim: To characterize early changes in developmental ability, language, and adaptive behaviour in infants diagnosed with tuberous sclerosis complex (TSC), and determine whether clinical features of epilepsy influence this pathway.

Method: Prospective, longitudinal data were collected within the Early Development in Tuberous Sclerosis (EDiTS) Study to track development of infants with TSC (n = 32) and typically developing infants (n = 33) between 3 and 24 months of age. Questionnaire and observational measures were used at up to seven timepoints to assess infants' adaptive behaviour, developmental ability, language, and epilepsy.

Near-Death Experiences and Sleep Disturbance: An Exploratory Study Using Wrist Actigraphy.

Near-death experiences (NDEs) are nonordinary states of consciousness typically occurring on the brink of death. Sleep changes after NDEs have been described, including shorter sleep duration, longer sleep latency, and more sleep disturbances; however, objective verification is lacking. In this exploratory research, 57 participants took part in a 14-day actigraphy study and were assigned to three groups: those who have had an NDE ( n = 26); those who experienced a near-death event but without NDE ( n = 12); and those who had never come close to death ( n = 19).

Altruism or self-interest in tomorrow's veterinarians? A metric conjoint experiment and cluster analysis.

Introduction: Altruism is considered a trait of veterinary and other health professionals, but the level of altruism in the veterinary profession is unknown. We designed a metric conjoint experiment to reveal other-orientation (an individual's caring concern for the wellbeing of others) and self-interest. We draw on the 'Theory of Other-Orientation', which states that individuals' decision-making heuristics can be impacted by their other-orientation independent of their self-interest.

Business Intentions of Australian Veterinary Students-My Business or Yours? A Cluster Analysis.

Little is known about veterinary entrepreneurial predisposition. Yet entrepreneurship and intrapreneurship (entrepreneurial behaviour of employees) foster business innovation and growth and support wealth creation and employment in both privately and corporately owned businesses which deliver contemporary veterinary services. We used responses from 515 final-year students in Australian entrepreneurship, nursing, and veterinary programs to capture entrepreneurial intention (EI), outcome expectations (OE-sb), entrepreneurial self-efficacy (ESE), and corporate/large organisation work intentions (CWIs).

What keeps an island community COVID-19 free in a global pandemic?

The COVID pandemic has offered opportunities for islands and other relatively isolated communities to establish pandemic-protection boundaries. A July 2020 survey of Waiheke Island residents sought views on how the island had remained COVID-19 free, despite proximity to a city of 1.6 million (Auckland, NZ).

Care of Pregnant Women With a History of Bariatric Surgery.

In recent years, the incidence of bariatric surgery has increased among women of reproductive age. Health care providers should be knowledgeable about the impact bariatric surgery has on women and developing fetuses to effectively provide care from preconception through postpartum. Although pregnancy in women with normal weight or with excess weight after bariatric surgery has better outcomes when compared to pregnancy complicated by obesity, it is associated with complications such as nutritional deficiencies, low birth weight, and fetal growth restriction.

Optimization of an Imidazo[1,2-]pyridine Series to Afford Highly Selective Type I1/2 Dual Mer/Axl Kinase Inhibitors with Efficacy.

Inhibition of Mer and Axl kinases has been implicated as a potential way to improve the efficacy of current immuno-oncology therapeutics by restoring the innate immune response in the tumor microenvironment. Highly selective dual Mer/Axl kinase inhibitors are required to validate this hypothesis. Starting from hits from a DNA-encoded library screen, we optimized an imidazo[1,2-]pyridine series using structure-based compound design to improve potency and reduce lipophilicity, resulting in a highly selective probe compound .

AZD0364 Is a Potent and Selective ERK1/2 Inhibitor That Enhances Antitumor Activity in -Mutant Tumor Models when Combined with the MEK Inhibitor, Selumetinib.

The RAS-regulated RAF-MEK1/2-ERK1/2 (RAS/MAPK) signaling pathway is a major driver in oncogenesis and is frequently dysregulated in human cancers, primarily by mutations in or genes. The clinical benefit of inhibitors of this pathway as single agents has only been realized in -mutant melanoma, with limited effect of single-agent pathway inhibitors in -mutant tumors. Combined inhibition of multiple nodes within this pathway, such as MEK1/2 and ERK1/2, may be necessary to effectively suppress pathway signaling in -mutant tumors and achieve meaningful clinical benefit.

Quality of English inpatient mental health services for people with anxiety or depressive disorders: Findings and recommendations from the core audit of the National Clinical Audit of Anxiety and Depression.

Background: Clinical audit is a sustained cyclical quality improvement process seeking to improve patient care and outcomes by evaluating services against explicit standards and implementing necessary changes. National audits aim to improve population-level clinical care by identifying unwarranted variations and making recommendations for clinicians, managers and service commissioners. The National Clinical Audit of Anxiety and Depression aimed to improve clinical care for people admitted to English hospitals for treatment of anxiety and depression, to provide comparative data on quality of care, and to support local quality improvement initiatives by identifying and sharing examples of best practice.

Variation in clinical care associated with weekend admission and discharge in psychiatric in-patient units: retrospective case-note review.

Background: Questions have been raised regarding differences in the standards of care that patients receive when they are admitted to or discharged from in-patient units at weekends.

Aims: To compare the quality of care received by patients with anxiety and depressive disorders who were admitted to or discharged from psychiatric hospital at weekends with those admitted or discharged during the 'working week'.

Method: Retrospective case-note review of 3795 admissions to in-patient psychiatric wards in England.

One medical school's experience of sustaining general practice teaching in the time of COVID-19.

Challenges have been encountered in maintaining the Western Sydney University general practice program but effective strategies have been adopted to manage the impact of COVID-19.

Discovery of a Potent and Selective Oral Inhibitor of ERK1/2 (AZD0364) That Is Efficacious in Both Monotherapy and Combination Therapy in Models of Nonsmall Cell Lung Cancer (NSCLC).

The RAS/MAPK pathway is a major driver of oncogenesis and is dysregulated in approximately 30% of human cancers, primarily by mutations in the BRAF or RAS genes. The extracellular-signal-regulated kinases (ERK1 and ERK2) serve as central nodes within this pathway. The feasibility of targeting the RAS/MAPK pathway has been demonstrated by the clinical responses observed through the use of BRAF and MEK inhibitors in BRAF V600E/K metastatic melanoma; however, resistance frequently develops.

Discovery of a Series of 5-Azaquinazolines as Orally Efficacious IRAK4 Inhibitors Targeting MyD88 Mutant Diffuse Large B Cell Lymphoma.

In this article, we report the discovery of a series of 5-azaquinazolines as selective IRAK4 inhibitors. From modestly potent quinazoline , we introduced a 5-aza substitution to mask the 4-NH hydrogen bond donor (HBD). This allowed us to substitute the core with a 2-aminopyrazole, which showed large gains in cellular potency despite the additional formal HBD.

A commentary on land, health, and Indigenous knowledge(s).

This commentary explores the relationships between land, knowledge, and health for Indigenous peoples. Indigenous knowledge is fundamentally relational, linked to the land, language and the intergenerational transmission of songs, ceremonies, protocols, and ways of life. Colonialism violently disrupted relational ways, criminalizing cultural practices, restricting freedom of movement, forcing relocation, removing children from families, dismantling relational worldviews, and marginalizing Indigenous lives.

Optimization of permeability in a series of pyrrolotriazine inhibitors of IRAK4.

We have developed a series of orally efficacious IRAK4 inhibitors, based on a scaffold hopping strategy and using rational structure based design. Efforts to tackle low permeability and high efflux in our previously reported pyrrolopyrimidine series (Scott et al., 2017) led to the identification of pyrrolotriazines which contained one less formal hydrogen bond donor and were intrinsically more lipophilic.

Discovery and Optimization of Pyrrolopyrimidine Inhibitors of Interleukin-1 Receptor Associated Kinase 4 (IRAK4) for the Treatment of Mutant MYD88 Diffuse Large B-Cell Lymphoma.

Herein we report the optimization of a series of pyrrolopyrimidine inhibitors of interleukin-1 receptor associated kinase 4 (IRAK4) using X-ray crystal structures and structure based design to identify and optimize our scaffold. Compound 28 demonstrated a favorable physicochemical and kinase selectivity profile and was identified as a promising in vivo tool with which to explore the role of IRAK4 inhibition in the treatment of mutant MYD88 diffuse large B-cell lymphoma (DLBCL). Compound 28 was shown to be capable of demonstrating inhibition of NF-κB activation and growth of the ABC subtype of DLBCL cell lines in vitro at high concentrations but showed greater effects in combination with a BTK inhibitor at lower concentrations.

Glimpses into the transition world: New graduate nurses' written reflections.

Background: This study was born out of our reflections as educators responsible for helping new graduate nurses transition into their first year of professional practice through a formal education programme. Finding ourselves wondering about many of the questions the students raised with us, we set about looking more closely at what could be gleaned from the students' experience, captured in their written work over the course of a year.

Objectives: To identify the challenges and learning experiences revealed in reflective assignments written by new graduate nurses undertaking a postgraduate course as part of their transition to registered nurse practice.