Evaluation of the Prescribing Skills Assessment implementation, performance and medical student experience in Australia and New Zealand.

Aims: The UK Prescribing Safety Assessment was modified for use in Australia and New Zealand (ANZ) as the Prescribing Skills Assessment (PSA). We investigated the implementation, student performance and acceptability of the ANZ PSA for final-year medical students.

Methods: This study used a mixed-method approach involving student data (n = 6440) for 2017-2019 (PSA overall score and 8 domain subscores).

Time to embrace sepsis pathways and antibiotic prescribing decision support in the emergency department: Observations from a retrospective single site clinical audit.

Objective: To compare clinician documentation of sepsis for infective presentations in the ED against a formal sepsis pathway in the ED and to assess appropriateness of the initial parenteral antibiotic prescription for adult patients in ED.

Methods: A retrospective, clinical audit of adult patients who received at least one parenteral antibiotic in ED over a 10-week period in 2018. Documented initial clinical impression was compared with an approved sepsis pathway.

Neural Mechanisms of Human Decision-Making.

We present a theory and neural network model of the neural mechanisms underlying human decision-making. We propose a detailed model of the interaction between brain regions, under a proposer-predictor-actor-critic​ ​framework. This theory is based on detailed animal data and theories of action-selection.

A systems-neuroscience model of phasic dopamine.

We describe a neurobiologically informed computational model of phasic dopamine signaling to account for a wide range of findings, including many considered inconsistent with the simple reward prediction error (RPE) formalism. The central feature of this PVLV framework is a distinction between a primary value (PV) system for anticipating primary rewards (Unconditioned Stimuli [USs]), and a learned value (LV) system for learning about stimuli associated with such rewards (CSs). The LV system represents the amygdala, which drives phasic bursting in midbrain dopamine areas, while the PV system represents the ventral striatum, which drives shunting inhibition of dopamine for expected USs (via direct inhibitory projections) and phasic pausing for expected USs (via the lateral habenula).

How Sequential Interactive Processing Within Frontostriatal Loops Supports a Continuum of Habitual to Controlled Processing.

We address the distinction between habitual/automatic vs. goal-directed/controlled behavior, from the perspective of a computational model of the frontostriatal loops. The model exhibits a continuum of behavior between these poles, as a function of the interactive dynamics among different functionally-specialized brain areas, operating iteratively over multiple sequential steps, and having multiple nested loops of similar decision making circuits.

Use of waxy maize heat modified starch in the treatment of children between 2 and 5 years with glycogen storage disease type I: A retrospective study.

Background: Glycogen storage disease type I (GSDI) is caused by deficiency of the enzyme glucose-6-phosphatase or glucose-6-phosphate transporter. Mainstay of treatment is provision of uncooked cornstarch (and/or continuous nocturnal pump feed (CNPF) to maintain normoglycemia). Waxy maize heat modified starch (WMHMS) is another treatment option to maintain normoglycemia overnight.

Computational models of motivated frontal function.

Computational models of frontal function have made important contributions to understanding how the frontal lobes support a wide range of important functions, in their interactions with other brain areas including, critically, the basal ganglia (BG). We focus here on the specific case of how different frontal areas support goal-directed, motivated decision-making, by representing three essential types of information: possible plans of action (in more dorsal and lateral frontal areas), affectively significant outcomes of those action plans (in ventral, medial frontal areas including the orbital frontal cortex), and the overall utility of a given plan compared to other possible courses of action (in anterior cingulate cortex). Computational models of goal-directed action selection at multiple different levels of analysis provide insight into the nature of learning and processing in these areas and the relative contributions of the frontal cortex versus the BG.

The NSIGHT1-randomized controlled trial: rapid whole-genome sequencing for accelerated etiologic diagnosis in critically ill infants.

Genetic disorders are a leading cause of morbidity and mortality in infants in neonatal and pediatric intensive care units (NICU/PICU). While genomic sequencing is useful for genetic disease diagnosis, results are usually reported too late to guide inpatient management. We performed an investigator-initiated, partially blinded, pragmatic, randomized, controlled trial to test the hypothesis that rapid whole-genome sequencing (rWGS) increased the proportion of NICU/PICU infants receiving a genetic diagnosis within 28 days.

Erratum: Constellation: a tool for rapid, automated phenotype assignment of a highly polymorphic pharmacogene, , from whole-genome sequences.

[This corrects the article DOI: 10.1038/npjgenmed.2015.

A Prospective Case Study of the Safety and Efficacy of Lysine-Restricted Diet and Arginine Supplementation Therapy in a Patient With Pyridoxine-Dependent Epilepsy Caused by Mutations in ALDH7A1.

Background: Pyridoxine-dependent epilepsy (PDE) is caused by mutations in ALDH7A1 (PDE-ALDH7A1), which encodes α-aminoadipic semialdehyde dehydrogenase in the lysine catabolic pathway, resulting in accumulation of α-aminoadipic-acid-semialdehyde.

Patient Description And Results: We present a three-year treatment outcome of a child with PDE-ALDH7A1 on pyridoxine (started at age three weeks of age), lysine-restricted diet (started at age seven months), and arginine supplementation therapy (started at age 26 months). He had a markedly elevated urinary α-aminoadipic-acid-semialdehyde (39.

Cerebral Oximetry Monitoring to Maintain Normal Cerebral Oxygen Saturation during High-risk Cardiac Surgery: A Randomized Controlled Feasibility Trial.

Background: Cerebral oxygen desaturation during cardiac surgery has been associated with adverse perioperative outcomes. Before a large multicenter randomized controlled trial (RCT) on the impact of preventing desaturations on perioperative outcomes, the authors undertook a randomized prospective, parallel-arm, multicenter feasibility RCT to determine whether an intervention algorithm could prevent desaturations.

Methods: Eight Canadian sites randomized 201 patients between April 2012 and October 2013.

Constellation: a tool for rapid, automated phenotype assignment of a highly polymorphic pharmacogene, , from whole-genome sequences.

An important component of precision medicine-the use of whole-genome sequencing (WGS) to guide lifelong healthcare-is electronic decision support to inform drug choice and dosing. To achieve this, automated identification of genetic variation in genes involved in drug absorption, distribution, metabolism, excretion and response (ADMER) is required. is a major enzyme for drug bioactivation and elimination.

A 26-hour system of highly sensitive whole genome sequencing for emergency management of genetic diseases.

While the cost of whole genome sequencing (WGS) is approaching the realm of routine medical tests, it remains too tardy to help guide the management of many acute medical conditions. Rapid WGS is imperative in light of growing evidence of its utility in acute care, such as in diagnosis of genetic diseases in very ill infants, and genotype-guided choice of chemotherapy at cancer relapse. In such situations, delayed, empiric, or phenotype-based clinical decisions may meet with substantial morbidity or mortality.

Whole-genome sequencing for identification of Mendelian disorders in critically ill infants: a retrospective analysis of diagnostic and clinical findings.

Background: Genetic disorders and congenital anomalies are the leading causes of infant mortality. Diagnosis of most genetic diseases in neonatal and paediatric intensive care units (NICU and PICU) is not sufficiently timely to guide acute clinical management. We used rapid whole-genome sequencing (STATseq) in a level 4 NICU and PICU to assess the rate and types of molecular diagnoses, and the prevalence, types, and effect of diagnoses that are likely to change medical management in critically ill infants.

Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders.

Neurodevelopmental disorders (NDDs) affect more than 3% of children and are attributable to single-gene mutations at more than 1000 loci. Traditional methods yield molecular diagnoses in less than one-half of children with NDD. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) can enable diagnosis of NDD, but their clinical and cost-effectiveness are unknown.

A neural network model of individual differences in task switching abilities.

We use a biologically grounded neural network model to investigate the brain mechanisms underlying individual differences specific to the selection and instantiation of representations that exert cognitive control in task switching. Existing computational models of task switching do not focus on individual differences and so cannot explain why task switching abilities are separable from other executive function (EF) abilities (such as response inhibition). We explore hypotheses regarding neural mechanisms underlying the "Shifting-Specific" and "Common EF" components of EF proposed in the Unity/Diversity model (Miyake & Friedman, 2012) and similar components in related theoretical frameworks.

Strategic cognitive sequencing: a computational cognitive neuroscience approach.

We address strategic cognitive sequencing, the "outer loop" of human cognition: how the brain decides what cognitive process to apply at a given moment to solve complex, multistep cognitive tasks. We argue that this topic has been neglected relative to its importance for systematic reasons but that recent work on how individual brain systems accomplish their computations has set the stage for productively addressing how brain regions coordinate over time to accomplish our most impressive thinking. We present four preliminary neural network models.

Recurrent Processing during Object Recognition.

How does the brain learn to recognize objects visually, and perform this difficult feat robustly in the face of many sources of ambiguity and variability? We present a computational model based on the biology of the relevant visual pathways that learns to reliably recognize 100 different object categories in the face of naturally occurring variability in location, rotation, size, and lighting. The model exhibits robustness to highly ambiguous, partially occluded inputs. Both the unified, biologically plausible learning mechanism and the robustness to occlusion derive from the role that recurrent connectivity and recurrent processing mechanisms play in the model.

Assembling old tricks for new tasks: a neural model of instructional learning and control.

We can learn from the wisdom of others to maximize success. However, it is unclear how humans take advice to flexibly adapt behavior. On the basis of data from neuroanatomy, neurophysiology, and neuroimaging, a biologically plausible model is developed to illustrate the neural mechanisms of learning from instructions.

The Role of Competitive Inhibition and Top-Down Feedback in Binding during Object Recognition.

How does the brain bind together visual features that are processed concurrently by different neurons into a unified percept suitable for processes such as object recognition? Here, we describe how simple, commonly accepted principles of neural processing can interact over time to solve the brain's binding problem. We focus on mechanisms of neural inhibition and top-down feedback. Specifically, we describe how inhibition creates competition among neural populations that code different features, effectively suppressing irrelevant information, and thus minimizing illusory conjunctions.

A unified framework for inhibitory control.

Inhibiting unwanted thoughts, actions and emotions figures centrally in daily life, and the prefrontal cortex (PFC) is widely viewed as a source of this inhibitory control. We argue that the function of the PFC is best understood in terms of representing and actively maintaining abstract information, such as goals, which produces two types of inhibitory effects on other brain regions. Inhibition of some subcortical regions takes a directed global form, with prefrontal regions providing contextual information relevant to when to inhibit all processing in a region.

From an executive network to executive control: a computational model of the n-back task.

A paradigmatic test of executive control, the n-back task, is known to recruit a widely distributed parietal, frontal, and striatal "executive network," and is thought to require an equally wide array of executive functions. The mapping of functions onto substrates in such a complex task presents a significant challenge to any theoretical framework for executive control. To address this challenge, we developed a biologically constrained model of the n-back task that emergently develops the ability to appropriately gate, bind, and maintain information in working memory in the course of learning to perform the task.

Computational models of cognitive control.

Cognitive control refers to the ability to perform task-relevant processing in the face of other distractions or other forms of interference, in the absence of strong environmental support. It depends on the integrity of the prefrontal cortex and associated biological structures (e.g.