Background: Intravenous immunoglobulin (IVIG) may benefit many inflammatory central nervous system (CNS) disorders based on multiple immunomodulatory effects. IVIg is being used in inflammatory CNS conditions however robust evidence and guidelines are lacking in many disorders. Over the last 5 years, the percentage of IVIg used for CNS indications within neurology almost doubled in British Columbia (BC), Canada. Clear local guidelines may guide rational use. Methods: Consensus guidelines for IVIG use for CNS indications were developed by a panel of subspecialty neurologists and the Provincial Blood Coordinating Office, informed by focused literature review. Guidelines were structured similarly to existing BC peripheral nervous system guidelines and Australian Consensus Guidelines. Utilization and efficacy will be monitored provincewide on an ongoing basis. Results: Categories of conditions for Conditionally Approved (N=11) and Exceptional Circumstance Use (N=5) were created based on level of evidence for efficacy. Dosing and monitoring recommendations were made and outcomes measures defined. Rationale for Not Indicated conditions (N=2) was included. Guidelines were distributed to BC neurologists for feedback. This system will be re-evaluated after 1 year. Conclusions: IVIG use in CNS inflammatory conditions has an emerging role. Guidelines for use and monitoring of outcomes will help improve resource utilization and provide further evidence regarding effectiveness.

Eating disorders have the highest mortality rate of any psychiatric condition. Since the COVID-19 pandemic, the number of patients who have required medical stabilisation on paediatric wards has increased significantly. Likewise, the number of patients who have required medical stabilisation against their will as a lifesaving intervention has increased. This paper highlights a fictional case study aiming to explore the legal, ethical and practical considerations a trainee should be aware of. By the end of this article, readers will be more aware of this complex issue and how it might be managed, as well as the impact it can have on the patient, their family and ward staff.

Background: Intravenous immunoglobulin (IVIG) may benefit many inflammatory central nervous system (CNS) disorders based on multiple immunomodulatory effects. IVIG is being used in inflammatory CNS conditions however robust evidence and guidelines are lacking in many disorders. Over the last 5 years, the percentage of IVIG used for CNS indications within neurology almost doubled in British Columbia (BC), Canada. Clear local guidelines may guide rational use. Methods: Consensus guidelines for IVIG use for CNS indications were developed by a panel of subspecialty neurologists and the Provincial Blood Coordinating Office, informed by focused literature review. Guidelines were structured similarly to existing BC peripheral nervous system guidelines and Australian Consensus Guidelines. Utilization and efficacy will be monitored provincewide on an ongoing basis. Results: Categories of conditions for Possible Indication (N=11) and Exceptional Circumstance Use (N=4) were created based on level of evidence for efficacy. Dosing and monitoring recommendations were made and outcomes measures defined. Rationale for Not Indicated conditions (N=3) was included. Guidelines will be distributed to BC neurologists for feedback and re-evaluated after 1 year. Conclusions: IVIG use in CNS inflammatory conditions has an emerging role. Guidelines for use and monitoring of outcomes will help improve resource utilization and provide further evidence regarding effectiveness.

In this paper, we describe the system design and capabilities of the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope at the conclusion of its construction project and commencement of science operations. ASKAP is one of the first radio telescopes to deploy phased array feed (PAF) technology on a large scale, giving it an instantaneous field of view that covers $31\,\textrm{deg}^{2}$ at $800\,\textrm{MHz}$. As a two-dimensional array of 36$\times$12 m antennas, with baselines ranging from 22 m to 6 km, ASKAP also has excellent snapshot imaging capability and 10 arcsec resolution. This, combined with 288 MHz of instantaneous bandwidth and a unique third axis of rotation on each antenna, gives ASKAP the capability to create high dynamic range images of large sky areas very quickly. It is an excellent telescope for surveys between 700 and $1800\,\textrm{MHz}$ and is expected to facilitate great advances in our understanding of galaxy formation, cosmology, and radio transients while opening new parameter space for discovery of the unknown.

Performance-based managed entry agreements (PB-MEAs) might allow patient access to new medicines, but practical hurdles make competent authorities for pricing and reimbursement (CAPR) reluctant to implement PB-MEAs. We explored if the feasibility of PB-MEAs might improve by better aligning regulatory postauthorization requirements with the data generation of PB-MEAs and by active collaboration and data sharing. Reviewers from seven CAPRs provided structured assessments of the information available at the European Medicines Agency (EMA) Web site on regulatory postauthorization requirements for fifteen recently authorized products. The reviewers judged to what extent regulatory postauthorization studies could help implement PB-MEAs by addressing uncertainty gaps. Study domains assessed were: patient population, intervention, comparators, outcomes, time horizon, anticipated data quality, and anticipated robustness of analysis. Reviewers shared general comments about PB-MEAs for each product and on cooperation with other CAPRs. Reviewers rated regulatory postauthorization requirements at least partly helpful for most products and across domains except the comparator domain. One quarter of responses indicated that public information provided by the EMA was insufficient to support the implementation of PB-MEAs. Few PB-MEAs were in place for these products, but the potential for implementation of PB-MEAs or collaboration across CAPRs was seen as more favorable. Responses helped delineate a set of conditions where PB-MEAs may help reduce uncertainty. In conclusion, PB-MEAs are not a preferred option for CAPRs, but we identified conditions where PB-MEAs might be worth considering. The complexities of implementing PB-MEAs remain a hurdle, but collaboration across silos and more transparency on postauthorization studies could help overcome some barriers.

There is a growing body of evidence highlighting the presence of a single general dimension of psychopathology that can account for multiple associations across mental and substance use disorders. However, relatively little evidence has emerged regarding the validity of this model with respect to a range of factors that have been previously implicated across multiple disorders. The current study utilized a cross-sectional population survey of adolescents (n = 2,003) to examine the extent to which broad psychopathology factors account for specific associations between psychopathology and key validators: poor sleep, self-harm, suicidality, risky sexual behavior, and low self-esteem. Confirmatory factor models, latent class models, and factor mixture models were estimated to identify the best structure of psychopathology. Structural equation models were then estimated to examine the broad and specific associations between each psychopathology indicator and the validators. A confirmatory factor model with three lower-order factors, representing internalizing, externalizing, and psychotic-like experiences, and a single higher-order factor evidenced the best fit. The associations between manifest indicators of psychopathology and validators were largely nonspecific. However, significant and large direct effects were found between several pairwise associations. These findings have implications for the identification of potential targets for intervention and/or tailoring of prevention programs.

Nerve transfer surgery for patients with nerve and spinal cord injuries can result in dramatic functional improvements. As a result, interdisciplinary complex nerve injury programs (CNIPs) have been established in many Canadian centers, providing electrodiagnostic and surgical consultations in a single encounter. We sought to determine which allied health care services are included in Canadian CNIPs, at the 3rd Annual Canadian Peripheral Nerve Symposium. Twenty CNIPs responded to a brief survey and reported access as follows: occupational therapy = 60%, physiotherapy = 40%, social work = 20%, and mental health = 10%. Access to allied health services is variable in CNIPs across Canada, possibly resulting in heterogeneity in patient care.

We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from $z = 0.35$ to 3; and a deep, high-redshift HI IM survey over 100 deg2 from $z = 3$ to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to $z \sim 3$ with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to $z = 6$ . These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.

In this paper, we revisit our previous work in which we derive an effective macroscale description suitable to describe the growth of biological tissue within a porous tissue-engineering scaffold. The underlying tissue dynamics is described as a multiphase mixture, thereby naturally accommodating features such as interstitial growth and active cell motion. Via a linearization of the underlying multiphase model (whose nonlinearity poses a significant challenge for such analyses), we obtain, by means of multiple-scale homogenization, a simplified macroscale model that nevertheless retains explicit dependence on both the microscale scaffold structure and the tissue dynamics, via so-called unit-cell problems that provide permeability tensors to parameterize the macroscale description. In our previous work, the cell problems retain macroscale dependence, posing significant challenges for computational implementation of the eventual macroscopic model; here, we obtain a decoupled system whereby the quasi-steady cell problems may be solved separately from the macroscale description. Moreover, we indicate how the formulation is influenced by a set of alternative microscale boundary conditions.

Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.