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International investment law and arbitration is a rapidly evolving field, and can be difficult for students to acquire a firm understanding of, given the considerable number of published awards and legal writings. The first edition of this text, cited by courts in Singapore and Colombia, overcame this challenge by interweaving extracts from these arbitral decisions, treaties and scholarly works with concise, up-to-date and reliable commentary. Now fully updated and with a new chapter on arbitrators, the second edition retains this practical structure along with the carefully curated end-of-chapter questions and readings. The authors consider the new chapter an essential revision to the text, and a discussion which is indispensable to understanding the present calls for reform of investment arbitration. The coverage of the book has also been expanded, with the inclusion of over sixty new awards and judicial decisions, comprising both recent and well-established jurisprudence. This textbook will appeal to graduates studying international investment law and international arbitration, as well as being of interest to practitioners in this area.
Biological materials represent a major source of inspiration to engineer protein-based polymers that can replicate the properties of living systems. Combined with our ability to control the molecular structure of proteins at the single amino acid level, this results in a vast array of attractive possibilities for materials science, an interest that is undeniably related to simplified procedures in gene synthesis, cloning, and biotechnological production. In parallel, it has been increasingly appreciated that living organisms exploit liquid–liquid phase separation (LLPS) to fabricate extracellular structures. In this article, we discuss the central role of protein LLPS in the fabrication of selected biological structures, including biological adhesives and hard biomolecular composites, and how physicochemical lessons from these systems are being replicated in synthetic analogs. Recent translational applications of protein LLPS are highlighted, notably aqueous-resistant adhesives, stimuli-responsive therapeutics carriers, and matrix materials for green structural composites.
A progressive decrement in muscle mass and muscle function, sarcopoenia, accompanies ageing. The loss of skeletal muscle mass and function is the main feature of sarcopoenia. Preventing the loss of muscle mass is relevant since sarcopoenia can have a significant impact on mobility and the quality of life of older people. Dietary protein and physical activity have an essential role in slowing muscle mass loss and helping to maintain muscle function. However, the current recommendations for daily protein ingestion for older persons appear to be too low and are in need of adjustment. In this review, we discuss the skeletal muscle response to protein ingestion, and review the data examining current dietary protein recommendations in the older subjects. Furthermore, we review the concept of protein quality and the important role that nutrient-dense protein (NDP) sources play in meeting overall nutrient requirements and improving dietary quality. Overall, the current evidence endorses an increase in the daily ingestion of protein with emphasis on the ingestion of NDP choices by older adults.
The coronavirus disease 2019 (COVID-19) pandemic has led to significant strain on front-line healthcare workers.
In this multicentre study, we compared the psychological outcomes during the COVID-19 pandemic in various countries in the Asia-Pacific region and identified factors associated with adverse psychological outcomes.
From 29 April to 4 June 2020, the study recruited healthcare workers from major healthcare institutions in five countries in the Asia-Pacific region. A self-administrated survey that collected information on prior medical conditions, presence of symptoms, and scores on the Depression Anxiety Stress Scales and the Impact of Events Scale-Revised were used. The prevalence of depression, anxiety, stress and post-traumatic stress disorder (PTSD) relating to COVID-19 was compared, and multivariable logistic regression identified independent factors associated with adverse psychological outcomes within each country.
A total of 1146 participants from India, Indonesia, Singapore, Malaysia and Vietnam were studied. Despite having the lowest volume of cases, Vietnam displayed the highest prevalence of PTSD. In contrast, Singapore reported the highest case volume, but had a lower prevalence of depression and anxiety. In the multivariable analysis, we found that non-medically trained personnel, the presence of physical symptoms and presence of prior medical conditions were independent predictors across the participating countries.
This study highlights that the varied prevalence of psychological adversity among healthcare workers is independent of the burden of COVID-19 cases within each country. Early psychological interventions may be beneficial for the vulnerable groups of healthcare workers with presence of physical symptoms, prior medical conditions and those who are not medically trained.
This work investigated the photophysical pathways for light absorption, charge generation, and charge separation in donor–acceptor nanoparticle blends of poly(3-hexylthiophene) and indene-C60-bisadduct. Optical modeling combined with steady-state and time-resolved optoelectronic characterization revealed that the nanoparticle blends experience a photocurrent limited to 60% of a bulk solution mixture. This discrepancy resulted from imperfect free charge generation inside the nanoparticles. High-resolution transmission electron microscopy and chemically resolved X-ray mapping showed that enhanced miscibility of materials did improve the donor–acceptor blending at the center of the nanoparticles; however, a residual shell of almost pure donor still restricted energy generation from these nanoparticles.
We have previously shown that higher intake of cruciferous vegetables is inversely associated with carotid artery intima-media thickness. To further test the hypothesis that an increased consumption of cruciferous vegetables is associated with reduced indicators of structural vascular disease in other areas of the vascular tree, we aimed to investigate the cross-sectional association between cruciferous vegetable intake and extensive calcification in the abdominal aorta. Dietary intake was assessed, using a FFQ, in 684 older women from the Calcium Intake Fracture Outcome Study. Cruciferous vegetables included cabbage, Brussels sprouts, cauliflower and broccoli. Abdominal aortic calcification (AAC) was scored using the Kauppila AAC24 scale on dual-energy X-ray absorptiometry lateral spine images and was categorised as ‘not extensive’ (0–5) or ‘extensive’ (≥6). Mean age was 74·9 (sd 2·6) years, median cruciferous vegetable intake was 28·2 (interquartile range 15·0–44·7) g/d and 128/684 (18·7 %) women had extensive AAC scores. Those with higher intakes of cruciferous vegetables (>44·6 g/d) were associated with a 46 % lower odds of having extensive AAC in comparison with those with lower intakes (<15·0 g/d) after adjustment for lifestyle, dietary and CVD risk factors (ORQ4 v. Q1 0·54, 95 % CI 0·30, 0·97, P = 0·036). Total vegetable intake and each of the other vegetable types were not related to extensive AAC (P > 0·05 for all). This study strengthens the hypothesis that higher intake of cruciferous vegetables may protect against vascular calcification.
Catatonia is a psychomotor dysregulation syndrome of diverse aetiology, increasingly recognised as a prominent feature of N-methyl-d-aspartate receptor antibody encephalitis (NMDARE) in adults. No study to date has systematically assessed the prevalence and symptomatology of catatonia in children with NMDARE. We analysed 57 paediatric patients with NMDARE from the literature using the Bush-Francis Catatonia Rating Scale. Catatonia was common (occurring in 86% of patients), manifesting as complex clusters of positive and negative features within individual patients. It was both underrecognised and undertreated. Immunotherapy was the only effective intervention, highlighting the importance of prompt recognition and treatment of the underlying cause of catatonia.
Anthrax is a potential biological weapon and can be used in an air-borne or mail attack, such as in the attack in the United States in 2001. Planning for such an event requires the best available science. Since large-scale experiments are not feasible, mathematical modelling is a crucial tool to inform planning. The aim of this study is to systematically review and evaluate the approaches to mathematical modelling of inhalational anthrax attack to support public health decision making and response.
A systematic review of inhalational anthrax attack models was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The models were reviewed based on a set of defined criteria, including the inclusion of atmospheric dispersion component and capacity for real-time decision support.
Of 13 mathematical modelling studies of human inhalational anthrax attacks, there were six studies that took atmospheric dispersion of anthrax spores into account. Further, only two modelling studies had potential utility for real-time decision support, and only one model was validated using real data.
The limited modelling studies available use widely varying methods, assumptions, and data. Estimation of attack size using different models may be quite different, and is likely to be under-estimated by models which do not consider weather conditions. Validation with available data is crucial and may improve models. Further, there is a need for both complex models that can provide accurate atmospheric dispersion modelling, as well as for simpler modelling tools that provide real-time decision support for epidemic response.
Mania induced by initiation of antidepressants is well documented, as is a withdrawal syndrome following sudden discontinuation of antidepressants. Mania occurring after withdrawal of antidepressants, however, has only been reported infrequently.
We describe antidepressant-discontinuation mania in two older patients initially diagnosed with unipolar depression.
Case 1: Madam P is a 66-year-old Chinese housewife diagnosed with major depressive disorder (MDD) in 2012. She was started on Escitalopram 10mg nocte but discontinued it within 3 weeks without any adverse effects. Escitalopram was re-started in December 2013 when she became depressed again, but she stopped taking it again after three months. Two weeks later, she presented in a manic state. Her mood stabilized with Risperidone 1mg nocte.
Case 2: Mr W is a 76-year-old Chinese retiree diagnosed with MDD in 2009. He was stable on Venlafaxine 75mg nocte and Fluvoxamine 150mg nocte until November 2013, when he requested to stop Venlafaxine. It was tapered off over one month, leaving him on Fluvoxamine alone. Three weeks after stopping Venlafaxine completely, he was admitted for mania with psychotic features. He was stabilized on Sodium Valproate 1000mg nocte and Olanzapine 10mg nocte.
Most antidepressant classes, including SSRIs, TCAs and SNRIs, have been reported to cause antidepressant-withdrawal mania, but this is the first report of Escitalopram being implicated. It is unclear whether antidepressant-withdrawal mania indicates a latent bipolar disorder, with attendant implications on treatment. Cholinergic overdrive is postulated to be the underlying mechanism but more research is needed to understand this rare phenomena.
Understanding the effects of crop management practices on weed survival and seed production is imperative in improving long-term weed management strategies, especially for herbicide-resistant weed populations. Kochia [Bassia scoparia (L.) A.J. Scott] is an economically important weed in western North American cropping systems for many reasons, including prolific seed production and evolved resistance to numerous herbicide sites of action. Field studies were conducted in 2014 in a total of four field sites in Wyoming, Montana, and Nebraska to quantify the impact of different crop canopies and herbicide applications on B. scoparia density and seed production. Crops used in this study were spring wheat (Triticum aestivum L.), dry bean (Phaseolus vulgaris L.), sugar beet (Beta vulgaris L.), and corn (Zea mays L.). Herbicide treatments included either acetolactate synthase (ALS) inhibitors effective on non-resistant B. scoparia or a non–ALS inhibiting herbicide effective for both ALS-resistant and ALS-susceptible B. scoparia. Bassia scoparia density midseason was affected more by herbicide choice than by crop canopy, whereas B. scoparia seed production per plant was affected more by crop canopy compared with herbicide treatment. Our results suggest that crop canopy and herbicide treatments were both influential on B. scoparia seed production per unit area, which is likely a key indicator of long-term management success for this annual weed species. The lowest germinable seed production per unit area was observed in spring wheat treated with non–ALS inhibiting herbicides, and the greatest germinable seed production was observed in sugar beet treated with ALS-inhibiting herbicides. The combined effects of crop canopy and herbicide treatment can minimize B. scoparia establishment and seed production.
The objective of this family-based whole exome sequencing (WES) is to examine genetic variants of autism spectrum disorder (ASD) in Korean population.
The probands with ASD and their biological parents were recruited in this study. We ascertained diagnosis based on DSM-5™ criteria, using Autism Diagnostic Observation Schedule and Autism Diagnostic Interview–Revised. We selected probands with typical phenotypes of ASD both in social interaction/communication and repetitive behaviour/limited interest domains, with intellectual disability (IQ < 70), for attaining homogeneity of the phenotypes. First, we performed WES minimum 50× for 13 probands and high-coverage pooled sequencing for their parents. We performed additional WES for 38 trio families, at least 100× depth. De novo mutations were confirmed by Sanger sequencing. All the sequence reads were mapped onto the human reference genome (hg19 without Y chromosome). Bioinformatics analyses were performed by BWA-MEM, Picard, GATK, and snpEff for variant annotation. We selected de novo mutation candidates from probands, which are neither detected in two pooled samples nor both parents.
Fifty-one subjects with ASD (5 females, 40∼175 months, mean IQ 42) and their families were included in this study. We discovered 109 de novo variants from 46 families. Twenty-nine variants are expected to be amino acid changing, potentially causing deleterious effects. We assume CELSR3, MYH1, ATXN1, IDUA, NFKB1, and C4A/C4B may have adverse effect on central nerve system.
We observed novel de novo variants which are assumed to contribute to development of ASD with typical phenotypes and low intelligence in WES study.
Disclosure of interest
This work has been supported by Healthcare Technology R&D project (No: A120029) by Ministry of Health and Welfare, Republic of Korea.
Recent studies have indicated a lack of ENT training at the undergraduate and post-graduate levels. This study aimed to review the impact of recent educational innovations in improving ENT training for medical students and junior doctors in the UK.
Three independent investigators conducted a literature search of published articles on ENT education. Included studies were analysed using qualitative synthesis methods.
An initial search yielded 2008 articles; 44 underwent full-text evaluation and 5 were included for final analysis. Most included studies demonstrated benefits for students when compared to existing teaching standards in terms of objective assessment (knowledge and skills gained) or subjective assessment (confidence and preference) following implemented educational innovations.
This study identified educational innovations developed in the past 15 years to enhance the teaching of core ENT competencies. More research is needed to establish their impact on the state of ENT medical education in the UK.
To analyse the results of treatment for nasolabial cysts according to whether an intraoral sublabial or endoscopic transnasal approach was used, and to determine the recent surgical trend in our hospital.
Twenty-four patients with a histopathologically and radiologically confirmed nasolabial cyst between January 2010 and December 2017 were enrolled in this study.
Nasolabial cysts were predominant in females (91.7 per cent) and on the left side (54.2 per cent). Treatment involved an intraoral sublabial approach in 12 cases (48.0 per cent) and a transnasal endoscopic approach in 13 cases (52.0 per cent). In 13 cases (52.0 per cent) surgery was performed under local anaesthesia, while in 12 cases (48.0 per cent) it was conducted under general anaesthesia. The most common post-operative complications were numbness of the upper lip or teeth (n = 9, 36.0 per cent). Only one patient (4.0 per cent), who underwent a transnasal endoscopic approach, experienced a reoccurrence.
Surgical resection through an intraoral sublabial or transnasal endoscopic approach is the best treatment for a nasolabial cyst, showing very good results and a low recurrence rate. The recent surgical trend in our hospital is to treat nasolabial cysts using a transnasal endoscopic approach under local anaesthesia.
Epidemiological studies indicate that individuals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a diverse range of population-based surveys.
The WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women.
Each prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4; range 5.2–110.8, interquartile range = 6.0–19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1–2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs.
Survey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.
Insurance industry practitioners have deep knowledge of their industry, but there is a lack of a simple-to-understand, practical blueprint on applying distributed ledger technology solutions, including blockchain. This paper provides a practical guide for actuaries, risk professionals, insurance companies and their Boards on blockchain, including an education piece to provide an understanding of the technology. Examples of real-world applications and use cases in insurance are provided to illustrate the capability of the technology. The current risks and challenges in adopting the technology are also considered. Finally, a checklist of issues to consider in adopting a blockchain solution for insurance business problems is provided.
To identify and synthesise the literature on the cost of mental disorders.
Systematic literature searches were conducted in the databases PubMed, EMBASE, Web of Science, EconLit, NHS York Database and PsychInfo using key terms for cost and mental disorders. Searches were restricted to January 1980–May 2019. The inclusion criteria were: (1) cost-of-illness studies or cost-analyses; (2) diagnosis of at least one mental disorder; (3) study population based on the general population; (4) outcome in monetary units. The systematic review was preregistered on PROSPERO (ID: CRD42019127783).
In total, 13 579 potential titles and abstracts were screened and 439 full-text articles were evaluated by two independent reviewers. Of these, 112 articles were included from the systematic searches and 31 additional articles from snowball searching, resulting in 143 included articles. Data were available from 48 countries and categorised according to nine mental disorder groups. The quality of the studies varied widely and there was a lack of studies from low- and middle-income countries and for certain types of mental disorders (e.g. intellectual disabilities and eating disorders). Our study showed that certain groups of mental disorders are more costly than others and that these rankings are relatively stable between countries. An interactive data visualisation site can be found here: https://nbepi.com/econ.
This is the first study to provide a comprehensive overview of the cost of mental disorders worldwide.
The suspended provisions of Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTTP will not substantially affect the Trans-Pacific Partnership (TPP) Chapter 17 on State-owned enterprises (SOEs). As a consequence, the original TPP scheme remains an important treaty model and poses complex questions notwithstanding a growing literature. This article discusses TPP but unlike current writings which focus on comparative treaty methods of SOE regulation, we focus on how TPP/CPTPP will actually operate, paying attention to how its framers have defined an SOE not least in how they have viewed complex crossholdings, excluded non-profits, and preserved a role for State monopolies. Our answers differ from some of the existing literature – particularly on complex cross-holdings. We also provide detailed illustrations of how TPP's non-discrimination, commercial basis, and non-commercial assistance rules might work and comment on the chances of a rule cascade triggered by TPP, particularly in the current state of heightened Sino-American rivalry and allegations of State control in China's economy.
The association between methicillin-resistant Staphylococcus aureus (MRSA) colonisation and/or infection with increased morbidity and mortality among hospital patients has long been recognised. We sought to build on previous studies to identify modifiable risk factors associated with the acquisition of MRSA colonisation and infection by conducting a retrospective cohort study on patients admitted through the Emergency Department of an acute tertiary-care general hospital in Singapore which implemented universal on-admission MRSA screening. Patients were assigned to the acquisition or non-acquisition group depending on whether they acquired MRSA during their admission. We used logistic regression models with a patient being in the acquisition group as the binary outcome to identify factors associated with MRSA acquisition. A total of 1302 acquisition and 37 949 non-acquisition group patients were analysed. Fifteen variables were included in the multivariate model. A dose–response relationship between length of stay and odds of MRSA acquisition was observed, with a length of stay 3 weeks or more (Adj OR 11.78–57.36, all P < 0.001) being the single biggest predictor of MRSA acquisition. Other variables significantly associated with MRSA acquisition were: male gender, age 65 or greater, previous MRSA colonisation or infection, exposure to certain antibiotics and surgery, and history of diabetes.