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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.
This book stems from what might seem like a simple question: What sort of LGBTQ+ books for young readers are being written around the world? To develop this initial query further, we wondered how different languages and different cultures approach LGBTQ+ topics, especially in works for children and young adults. We had seen little written about this in English, which is not a surprise given how myopic English-speaking cultures tend to be about literature from other countries (Post suggests that the number of translations to English is holding steady at 2 to 4 per cent (2019, n.p.)), and we felt it was time to rectify this gap in knowledge and to bring a comparative approach to a growing field of study, namely LGBTQ+ children's literature.
As the academic study of children's literature has developed over the past few decades (see, among many other examples, work such as Coats 2017; Hunt 1994, 2005; Lerer 2008; Lurie 1990; Maybin and Watson 2009; Nikolajeva 1996; Nikolajeva and Scott 2006; Nodelman and Reimer 2002; Reynolds 2005, 2007, 2011; Reynolds and Tucker 1998; Rose 1993; and Townsend 1990), more attention has been paid to topics such as the depiction of gender identity and sexuality (for example, Abate and Kidd 2011; Bruhm and Hurley 2004; Cart and Jenkins 2006; Epstein 2013; Flanagan 2008; Gillis and Simpson 2015; James 2009; Jenkins and Cart 2018; and Naidoo 2012). Furthermore, there has been an increased focus on diversity and multicultural literature more generally (Gopalakrishnan 2011; Nel 2017; O’Sullivan 2005; Ramdarshan Bold 2019; Sands-O’Connor 2017); the translation of children's books (Epstein 2012; Lathey 2006, 2010; Oittinen 2000); the roles of authors, illustrators, publishers, editors, translators, librarians, teachers and others in the production and usage of books for children (which is touched on in many of the works already cited here); and the interaction of words and images (Hamer et al. 2017; Kummerling-Meibauer 2018; Nodelman 1988), among many other issues relevant to the discussions in this book.
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.
Suicide plans and attempts rarely occur without prior suicidal ideation but are hard to predict. Early intervention efforts need to focus on subgroups of the population who are more likely to transition from ideation to suicidal plans and attempts. The current study utilised data from a large nationally representative sample to investigate the time taken to transition and the demographic and mental health correlates of transitioning to suicidal plans and attempts among those with suicidal ideation.
Methods
Data were from 1237 Australians aged 16–85 years who reported suicidal thoughts at some point in their life. Discrete time survival analysis was used to retrospectively examine the time in years and correlates of transitioning from suicidal ideation to suicide plans and suicide attempt.
Results
The majority of those who transitioned to suicide plans or attempts typically did so within 2 years of first experiencing suicidal ideation. Several factors were independently associated with increased speed to transition, including alcohol use disorder, drug use disorder, major depressive episode, obsessive compulsive disorder, sexual minority status, and non-urban location. Older age, being male, older age of first ideation and greater family support were associated with a slower transition.
Conclusion
The current study suggests that pre-existing mental or substance use disorders, particularly drug use disorder, as well as sexual minority status, sex and greater family support play an important role in the transition from suicidal ideation to plans or attempts. These results highlight the potential importance of suicide prevention programs that aim to improve social connectedness.
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.
Neuropsychological assessment via videoconference could assist in bridging service access gaps due to geographical, mobility, or infection control barriers. We aimed to compare performances on neuropsychological measures across in-person and videoconference-based administrations in community-based survivors of stroke.
Method:
Participants were recruited through a stroke-specific database and community advertising. Stroke survivors were eligible if they had no upcoming neuropsychological assessment, concurrent neurological and/or major psychiatric diagnoses, and/or sensory, motor, or language impairment that would preclude standardised assessment. Thirteen neuropsychological measures were administered in-person and via videoconference in a randomised crossover design (2-week interval). Videoconference calls were established between two laptop computers, facilitated by Zoom. Repeated-measures t tests, intraclass correlation coefficients (ICCs), and Bland–Altman plots were used to compare performance across conditions.
Results:
Forty-eight participants (26 men; Mage = 64.6, SD = 10.1; Mtime since stroke = 5.2 years, SD = 4.0) completed both sessions on average 15.8 (SD = 9.7) days apart. For most measures, the participants did not perform systematically better in a particular condition, indicating agreement between administration methods. However, on the Hopkins Verbal Learning Test – Revised, participants performed poorer in the videoconference condition (Total Recall Mdifference = −2.11). ICC estimates ranged from .40 to .96 across measures.
Conclusions:
This study provides preliminary evidence that in-person and videoconference assessment result in comparable scores for most neuropsychological tests evaluated in mildly impaired community-based survivors of stroke. This preliminary evidence supports teleneuropsychological assessment to address service gaps in stroke rehabilitation; however, further research is needed in more diverse stroke samples.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
Methods:
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
Results:
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Conclusion:
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
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.
The authors offer their appreciation of the astute commentaries by Scott and Pilkonis and Niedtfeld, Paret, and Schmahl regarding their chapter on borderline personality disorder. Scott and Pilkonis address some very important big picture themes regarding the conceptualization, etiology, and treatment of BPD, and Niedtfeld et al. more specifically comment on innovative research highlighting the interplay of neuroscience and psychotherapy. In this rejoinder, the authors comment on these and other issues and suggest that a developmental psychopathology framework for theory and research has promise for illuminating the nature and etiology of BPD and highlighting important directions for prevention and treatment.
Characterized by a combination of interpersonal, emotional, behavioral, and cognitive instability, borderline personality disorder (BPD) is a serious and often misunderstood condition. The prevalence of BPD is approximately 1.4 to 6%, with substantially higher estimates among psychiatric outpatients and inpatients. Beyond the personal costs of BPD in terms of suffering, BPD is strongly associated with functional impairment and high societal costs for mental healthcare. Clinical descriptions of BPD first appeared before the mid-twentieth century and have evolved to the present conceptualization of an overarching BPD construct represented by the key domains of emotion dysregulation, impulsivity, and interpersonal disturbance. BPD has a varying course, with many individuals achieving remission or recovery, but emotional and interpersonal vulnerabilities and functional impairments often persist for many years, even after structured treatment. The success of treatment for BPD over the past few decades, however, has countered common clinical lore that BPD patients are recalcitrant. Further, novel developments in research on the putative core vulnerabilities underlying BPD, as well as evidence that these vulnerabilities can be addressed in treatment, illuminate important future directions and hope for patients and loved ones affected by this disorder.
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.
LEARNING OBJECTIVES
This presentation will enable the learner to:
1. Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis
2. Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management
The rocky shores of New Zealand (NZ) and Australia provide many interesting comparisons in their intertidal species and structuring processes. Both countries are in the biogeographic realm of temperate Australasia and share many common species and closely related taxa. Here we review similarities and contrasts in communities and structuring processes, especially involving grazing invertebrates and macroalgae. We consider the similarity of the structure of intertidal shores of NZ and south-eastern Australia, a suite of important trophic interactions within and between regions, the utility of local-scale experiments in understanding large-scale processes and how we might better plan for and manage our coasts. The major comparisons are between warm-temperate areas of northern NZ and New South Wales, and the cooler areas of southern NZ and south-eastern Australia. In the quest for ‘ecosystem’-level understanding, which perforce involves large-scale events, there is an increasing tendency to minimise or ignore the hard-won insights gained from well-structured experiments across multiple sites. Because all large-scale effects must be manifested at local sites, it is incumbent on us to determine what scales up or down, and the caveats that make comparisons across biogeographic regions challenging. Here, we discuss these issues using austral shores as models.