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Is China's rise a threat to international order? Fractured China shows that it depends on what one means by 'China', for China is not the monolithic, unitary actor that many assume. Forty years of state transformation – the fragmentation, decentralisation and internationalisation of party-state apparatuses – have profoundly changed how its foreign policy is made and implemented. Today, Chinese behaviour abroad is often not the product of a coherent grand strategy, but results from a sometimes-chaotic struggle for power and resources among contending politico-business interests, within a surprisingly permissive Chinese-style regulatory state. Presenting a path-breaking new analytical framework, Fractured China transforms the central debate in International Relations and provides new tools for scholars and policymakers seeking to understand and respond to twenty-first century rising powers. Drawing on extensive fieldwork in China and Southeast Asia, it includes three major case studies – the South China Sea, non-traditional security cooperation, and development financing–to demonstrate the framework's explanatory power.
Psychiatric intensive care units (or PICU’s) emerged to manage high acuity patients outside the justice system. Studies have sought to better understand characteristics of those admitted to forensic or civilian PICU’s. Few, in contrast, have explored the frequency and contributors to readmission. The following study was conducted on Apsley unit, a Forensic PICU based in Melbourne, Australia, and seeks to understand the differences which would allow early identification of patients likely to require readmission and the provision of targeted interventions.
Examine rates of and contributors to forensic PICU readmission over a 6-month period.
A retrospective audit was conducted to collect clinical, problem behaviour (and strategies to manage), forensic history and demographic information for consecutively admitted patients to an 8-bed forensic PICU between March-September 2019.
Data analysis is ongoing. Interim analysis found that 96 patients were admitted during the 6-month study period: 74 (77.1%) had a single admission; 22 (22.9%) required readmission. Almost all were admitted from prison (96.9%), most had a psychosis diagnosis (80.2%) and substance abuse history (96.9%), and many had a personality disorder (24.0%) and history of adolescent antisocial behaviour (46.5%). Patients requiring readmission were significantly more likely to have been previously under compulsory mental health treatment (95.5% vs 75.3%, p=.039) and have a Positive Behaviour Support Plan developed during admission (85.7% vs 54.8%, p=.010).
Interim analysis highlighted the multicomplexity for forensic PICU patients alongside the occurrence of problem behaviour during admission and history of compulsory treatment as indicators of increased risk for re-admission.
Testosterone (T) and cortisol (C) are the end products of neuroendocrine axes that interact with the process of shaping brain structure and function. Relative levels of T:C (TC ratio) may alter prefrontal–amygdala functional connectivity in adulthood. What remains unclear is whether TC-related effects are rooted to childhood and adolescence. We used a healthy cohort of 4–22-year-olds to test for associations between TC ratios, brain structure (amygdala volume, cortical thickness (CTh), and their coordinated growth), as well as cognitive and behavioral development. We found greater TC ratios to be associated with the growth of specific brain structures: 1) parietal CTh; 2) covariance of the amygdala with CTh in visual and somatosensory areas. These brain parameters were in turn associated with lower verbal/executive function and higher spatial working memory. In sum, individual TC profiles may confer a particular brain phenotype and set of cognitive strengths and vulnerabilities, prior to adulthood.
Testosterone (T) and cortisol (C) are steroid hormones that have been argued to play opposing roles in shaping physical and behavioral development in humans. While there is evidence linking T and C to different memory processes during adulthood, it remains unclear how the relative levels of T and C (TC ratio) may influence brain and behavioral development, whether they are influenced by sex of the child, and whether or not they occur as a result of stable changes in brain structure (organizational changes), as opposed to transient changes in brain function (activational changes). As such, we tested for associations among TC ratio, cortico-hippocampal structure, and standardized tests of executive, verbal, and visuo-spatial function in a longitudinal sample of typically developing 4–22-year-old children and adolescents. We found greater TC ratios to be associated with greater coordinated growth (i.e. covariance) between the hippocampus and cortical thickness in several areas primarily devoted to visual function. In addition, there was an age-related association between TC ratio and parieto-hippocampal covariance, as well as a sex-specific association between TC ratio and prefrontal-hippocampal covariance. Differences in brain structure related to TC ratio were in turn associated with lower verbal/executive function, as well as greater attention in tests of visuo-spatial abilities. These results support the notion that TC ratio may shift the balance between top-down (cortex to hippocampus) and bottom-up (hippocampus to cortex) processes, impairing more complex, cortical-based tasks and optimizing visuospatial tasks relying primarily on the hippocampus.
Subglacial hydrological systems require innovative technological solutions to access and observe. Wireless sensor platforms can be used to collect and return data, but their performance in deep and fast-moving ice requires quantification. We report experimental results from Cryoegg: a spherical probe that can be deployed into a borehole or moulin and transit through the subglacial hydrological system. The probe measures temperature, pressure and electrical conductivity in situ and returns all data wirelessly via a radio link. We demonstrate Cryoegg's utility in studying englacial channels and moulins, including in situ salt dilution gauging. Cryoegg uses VHF radio to transmit data to a surface receiving array. We demonstrate transmission through up to 1.3 km of cold ice – a significant improvement on the previous design. The wireless transmission uses Wireless M-Bus on 169 MHz; we present a simple radio link budget model for its performance in cold ice and experimentally confirm its validity. Cryoegg has also been tested successfully in temperate ice. The battery capacity should allow measurements to be made every 2 h for more than a year. Future iterations of the radio system will enable Cryoegg to transmit data through up to 2.5 km of ice.
Social anxiety disorder (SAD) is a prevalent chronic condition with a large demand for treatment. This community outpatient study examined the effectiveness of a group intervention version of the established one-to-one cognitive therapy derived from the Clark and Wells model for SAD. Questionnaires were completed pre-treatment and post-treatment for SAD symptoms (Social Phobia Scale, Social Interaction Anxiety Scale), depressive symptoms (BDI-II), self-focused attention, safety behaviours (Social Phobia Weekly Summary Scale and Subtle Avoidance Frequency Examination), and impaired functioning (Work and Social Adjustment Scale). From an initial sample of 159 participants, 101 completed at least seven of the nine weekly group sessions (Mage = 34.1 years, SDage = 10.8 years, 53% female). Significant improvements were demonstrated on all measures. Large effect sizes were found for social anxiety symptoms and safety behaviour use. Self-focused attention, depressive symptoms, and impaired functioning had moderate effect sizes. Effect sizes for anxiety (d = 1.00 and 1.32) and mood measures (d = 0.71) were as high, or in some cases, higher than previous group treatment studies. Results suggest group cognitive therapy for SAD based on the Clark and Wells model is effective in a clinical setting for individuals with moderate/severe and treatment-resistant social anxiety.
Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.
To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.
We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.
Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015–0.017), with carriers being 7.5–7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.
This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.
Social and economic changes associated with new roads can bring about rapid nutritional transitions. To study this process, we: (1) describe trends in adult overweight and obesity (OW/OB) among rural Afro-Ecuadorians over time and across a gradient of community remoteness from the nearest commercial centre; (2) examine the relationship between male and female adult OW/OB and factors associated with market integration such as changing livelihoods and (3) examine the co-occurrence of adult OW/OB and under-five stunting and anaemia.
Adult anthropometry was collected through serial case–control studies repeated over a decade across twenty-eight communities. At the same time, anthropometry and Hb were measured for all children under 5 years of age in every community.
Northern coastal Ecuador.
Adults (n 1665) and children under 5 years of age (n 2618).
From 2003 and 2013, OW/OB increased from 25·1 % to 44·8 % among men and 59·9 % to 70·2 % among women. The inverse relationship between remoteness and OW/OB in men was attenuated when adjusting for urban employment, suggesting that livelihoods mediated the remoteness–OW/OB relationship. No such relationship was observed among women. Communities with a higher prevalence of male OW/OB also had a greater prevalence of stunting, but not anaemia, in children under 5 years of age.
The association between male OW/OB and child stunting at the community level, but not the household level, suggests that changing food environments, rather than household- or individual-level factors, drove these trends. A closer examination of changing socio-economic structures and food environments in communities undergoing rapid development could help mitigate future public health burdens.
This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
Background: Stollery Children’s Hospital (SCH) is a tertiary-care pediatric hospital with a complex infrastructure: 3 NICUs located at 3 different hospitals, and all of the pediatric inpatient beds, PICU, PCICU, and a medical-surgical NICU at the main SCH site shared buildings with an academic adult hospital. We describe a collaborative process used to develop standardized SCH Infection Prevention and Control (IPC) recommendations. Methods: The SCH IPC formed a working group with Patient and Family-Centered Care (PFCC) and family representatives in 2014 to enhance the engagement of families in regards to IPC issues and initiatives. The working group identified inconsistent messages provided to families when a child was admitted as a patient requiring additional precautions (PRAP). The working group then developed a framework of key questions to be answered for family care providers of PRAP. The working group held several consultative meetings with frontline staff followed by a review of published guidelines and consultations with other pediatric hospitals about contentious issues. A consensus meeting with all key stakeholders was held to finalize IPC recommendations. Results: The key contentious issues included (1) whether personal protective equipment is required for family care providers who stay overnight with PRAP and (2) whether family care providers of PRAP are allowed to access nutrition centers on clinical units and family lounges in PCICU–PICU–NICU that were stocked with free hot meals for the families. No directly applicable recommendation was available IPC guidelines on these issues. Discussions of these topics were directed by PFCC at family councils of various clinical programs with efforts to seek opinions from more family representatives. Expert opinions and current practice were also obtained from Canadian hospitals through emails and from US hospitals through SHEA Open Forum by ICP. A final consensus meeting revisiting all available information was held, and a new Stollery IPC guideline was created with families as partners sharing the IPC vision of minimizing transmission risk at SCH. Conclusions: A consultative engagement and consensus process was successful in the development of IPC recommendations for family care providers for PRAP for implementation at a tertiary-care pediatric hospital with a complex infrastructure. The next step is to develop family-friendly educational and resource materials with clear and concise messages.
The COVID-19 pandemic has had a major impact on clinical practice. Safe standards of practice are essential to protect health care workers while still allowing them to provide good care. The Canadian Society of Clinical Neurophysiologists, the Canadian Association of Electroneurophysiology Technologists, the Association of Electromyography Technologists of Canada, the Board of Registration of Electromyography Technologists of Canada, and the Canadian Board of Registration of Electroencephalograph Technologists have combined to review current published literature about safe practices for neurophysiology laboratories. Herein, we present the results of our review and provide our expert opinion regarding the safe practice of neurophysiology during the COVID-19 pandemic in Canada.
Case-Finding for Complex Chronic Conditions in Seniors 75+ (C5-75) is a systematic approach to identify frailty using gait speed and hand-grip strength and to screen for co-morbid conditions. We identified the C5-75 features offering the highest yield for identifying frailty and to streamline the screening program. Analyses included 1,948 C5-75 assessments completed from 2013 to 2018. Age 85 or older, less than regular physical activity, and more than two falls in the previous six months had the strongest associations with frailty. Exempting patients under 85 who reported regular physical activity and less than two falls excluded 39.1 per cent of the cohort while maintaining a sensitivity of 95.2 per cent and a negative predictive value of 99.4 per cent for frailty. These findings provide insight into optimizing screening for frailty, making it more feasible to implement and to identify co-existing conditions that may contribute to or be affected by frailty.
While extensive modelling - both physical and virtual - is imperative to develop right-first-time products, the parallel use of virtual and physical models gives rise to two interrelated issues: the lack of revision control for physical prototypes; and the need for designers to manually inspect, measure, and interpret modifications to either virtual or physical models, for subsequent update of the other. The Digital Twin paradigm addresses similar problems later in the product life-cycle, and while these digital twins, or the “twinning” process, have shown significant value, there is little work to date on their implementation in the earlier design stages. With large prospective benefits in increased product understanding, performance, and reduced design cycle time and cost, this paper explores the concept of using the Digital Twin in early design, including an introduction to digital twinning, examination of opportunities for and challenges of their implementation, a presentation of the structure of Early Stage Twins, and evaluation via two implementation cases.
Medicines regulation has become increasingly adaptive to support earlier patient access but the immature clinical data is often challenging for health technology assessment decision-makers due to high levels of uncertainty on long term risks and benefits. Scottish Medicines Consortium (SMC) is therefore exploring new, more adaptive approaches to help manage this challenge.
SMC consulted with key stakeholders including clinicians, the pharmaceutical industry and patient groups on a number of options that would allow the committee to make an interim decision that would be revisited based on later evidence. The ability to collect robust patient level data given data capabilities in National Health Service Scotland (NHSScotland) was an important consideration.
To ensure that additional evidence would be available to inform a re-assessment, the new approach applies to medicines with a Conditional Marketing Authorisation (MA) from the European Medicines Agency (EMA). This obligates the company to provide specified clinical data to the regulator within a pre-set timeframe. For these medicines, the SMC decision-making committee can accept or not recommend the medicine as at present but can also accept the medicine on an interim basis, if the regulator's mandated Specific Obligations are likely to address the uncertainties in the clinical evidence. When the regulator converts the MA from conditional to standard, the company is required to make a further SMC submission to allow a reassessment and a final decision. The company can also provide additional supplementary post-licensing patient level evidence at reassessment.
This new decision option allows SMC to test an approach to managing uncertainty targeted at a small number of promising new medicines where there is unmet patient need, with the reassurance that a final decision will be supported by additional clinical data.
Medicines for very rare conditions present challenges for healthcare globally due to uncertain evidence and often extremely high costs. In 2014, SMC introduced an ultra-orphan framework placing less emphasis on the cost per quality adjusted life year (QALY). Despite this, many medicines continued to be not recommended. A new pathway aimed at improved patient access based on further evidence collection is now being implemented.
The development of the new pathway has involved collaboration with key stakeholders including patient groups, the pharmaceutical industry, and clinicians. Medicines that meet a new definition (based on four criteria including the prevalence of the condition treated) will be appraised by the SMC committee and a data collection plan will then be agreed with the pharmaceutical company.
From April 2019, medicines validated as ultra-orphans will initially be appraised using the broader decision-making framework and the SMC committee will outline key uncertainties in the clinical effectiveness. The medicine will then be available for a period of at least three years while further data are gathered, potentially comprising ongoing clinical trials, registry data, and patient reported outcome measures. SMC will then re-assess the clinical and economic evidence to inform a final decision on routine use of the medicine in NHS Scotland.
The new pathway for ultra-orphan medicines will allow further evidence on their longer-term clinical benefits to be collected before a final decision on routine use. This approach reflects the current direction of travel in medicines regulation, by making medicines that address an unmet need available to patients at an earlier stage of development.
Although relapse in psychosis is common, a small proportion of patients will not relapse in the long term. We examined the proportion and predictors of patients who never relapsed in the 10 years following complete resolution of positive symptoms from their first psychotic episode.
Patients who previously enrolled in a 12-month randomized controlled trial on medication discontinuation and relapse following first-episode psychosis (FEP) were followed up after 10 years. Relapse of positive symptoms was operationalized as a change from a Clinical Global Impression scale positive score of <3 for at least 3 consecutive months to a score of ⩾3 (mild or more severe). Baseline predictors included basic demographics, premorbid functioning, symptoms, functioning, and neurocognitive functioning.
Out of 178 first-episode patients, 37 (21%) never relapsed during the 10-year period. Univariate predictors (p ⩽ 0.1) of patients who never relapsed included a duration of untreated psychosis (DUP) ⩽30 days, diagnosed with non-schizophrenia spectrum disorders, having less severe negative symptoms, and performing better in logical memory immediate recall and verbal fluency tests. A multivariate logistic regression analysis further suggested that the absence of any relapsing episodes was significantly related to better short-term verbal memory, shorter DUP, and non-schizophrenia spectrum disorders.
Treatment delay and neurocognitive function are potentially modifiable predictors of good long-term prognosis in FEP. These predictors are informative as they can be incorporated into an optimum risk prediction model in the future, which would help with clinical decision making regarding maintenance treatment in FEP.
Brain tumor behavior is driven by aberrations in the genome and epigenome. Many of these changes, such as IDH mutations in diffuse low-grade glioma (DLGG), are common amongst the same class of tumour and can be incorporated into the diagnostic criteria. However, any given tumor may have other, less common genomic aberrations that are essential for its biological behavior and may inform on underlying aberrant cellular pathways, and potential therapeutic agents. Precision oncology is a genomics-based approach which profiles these alterations to better manage cancer patients and has established itself within the practice of oncology and is slowly making its way into neuro-oncology. The BC Cancer’s Personalized OncoGenomics (POG) program has profiled 16 adult tumours originating from the central nervous system using whole genome and transcriptome analysis (WGTA), for the first time, within a meaningful clinical timeframe/setting. As expected, primary genomic drivers were consistent with their respective diagnoses, though secondary drivers were found to be unique to each tumour. Although these analyses did not result in altered clinical management for these patients, primarily due to availability of drug or clinical trials, they highlight the heterogeneity of secondary drivers in cancers and provide clinicians with meaningful biological information. Lastly, the data generated by POG has highlighted the frequency and complexity of novel driver fusions which are predicted to behave similarly to canonical driver events in their respective tumours. The information available to clinicians through POG has provided paramount knowledge into the biology of each unique tumour.