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Services preferential trade agreements (PTAs) have grown rapidly since the turn of the millennium, going from exception to common occurrence. In recent years, they have increasingly linked a number of larger economies. The chapter reviews the main innovations brought by PTAs in the global governance of services trade, and highlights some limits. The contribution of services PTAs is analysed along three key angles, against the background of the multilateral trading system: 1) market access commitments; 2) rulemaking; and 3) architecture and liberalisation modalities. While WTO+ market access commitments have been an important feature of services PTAs early on, progress on rulemaking has been modest. In terms of architecture, services PTAs have produced major advances in relation to liberalisation modalities, with negative-list agreements outnumbering the General Agreement on Trade in Services (GATS)-type positive-list agreements. Recently, agreements between larger economies have been associated with several architectural innovations, moving away from the simple choice between the traditional positive and negative listing models. Overall, this has resulted in the extension of some of the key features of the negative-list approach to new countries and served to further emphasise, sometimes through innovative solutions, the importance of transparency of market access conditions across sectors and modes.
To examine patterns of cognitive function among a clinical sample of patients seeking treatment for Post-Acute Sequelae of COVID-19 (PASC).
Participants and Methods:
One hundred nineteen patients each completed a baseline neuropsychological evaluation, including clinical diagnostic interview, cognitive assessments, and a comprehensive battery of self-report questionnaires. Patients had a mean age of 50 years (range:18 to 74, SD=10.1) and a mean of 15.5 years (SD=2.54) of formal education. Patients were primarily female (74%) and of White/Caucasian race (75%). Hierarchical agglomerative clustering was used to partition the data into groups based on cognitive performance. Euclidean distance was used as the similarity measure for the continuous variables and within-cluster variance was minimized using Ward’s method. The optimal number of clusters was determined empirically by fitting models with 1 to 15 clusters, with the best number of clusters selected using the silhouette index. All analyses were conducted using the NbClust package, an R package for determining the relevant number of clusters in a data set.
Results:
Clustering yielded two distinct clusters of cognitive performance. Group 1 (n=57) performed worse than Group 2 (n=62) on most cognitive variables (including a brief cognitive screener and tests of attention/working memory, executive function, processing speed, learning and delayed recall). Of note, there were no significant differences between groups on an infection severity scale, hospitalizations/ICU admissions, initial or current COVID-19 symptoms, or prior comorbidities. Groups did not differ in age or gender, but Group 1 had a lower education level than Group 2 (M=14.7, SD=2.45 vs. M=16.2, SD=2.42; p=.001). Group 1 also had significantly more minorities than Group 2 (40% vs. 8%; p<.001). No other demographic differences (income, living arrangement, or marital status) were observed. In comparison to Group 2 patients, Group 1 patients self-reported significantly higher levels of anxiety and depression and functional impairment (Functional Activities Questionnaire: M=11.3, SD=8.33 vs. M=7.65, SD=7.97), perceived stress (Perceived Stress Scale: M=24.7, SD=7.90 vs. M=20.3, SD=7.89), insomnia (Insomnia Severity Index: M=16.0, SD=6.50 vs. M=13.1, SD=6.76), and subjective cognitive functioning (Cognitive Failures Questionnaire: M=58.8, SD=16.9 vs. M=50.3, SD=18.6; p’s<.05).
Conclusions:
Findings indicate two predominant subtypes of patients seeking treatment for PASC, with one group presenting as more cognitively impaired and reporting greater levels of anxiety, depression, insomnia, perceived stress, functional limitations, and subjective cognitive impairment. Future directions include follow-up assessments with these patients to determine cognitive trajectories over time and tailoring treatment adjuncts to address mood symptoms, insomnia, functional ability, and lifestyle variables. Understanding mechanisms of differences in cognitive and affective symptoms is needed in future work. Limitations to the study were that patients were referred for evaluation based on the complaint of “brain fog” and the sample was a homogenous, highly educated, younger group of individuals who experienced generally mild COVID-19 course.
Non-motor symptoms, such as mild cognitive impairment and dementia, are an overwhelming cause of disability in Parkinson’s disease (PD). While subthalamic nucleus deep brain stimulation (STN DBS) is safe and effective for motor symptoms, declines in verbal fluency after bilateral DBS surgery have been widely replicated. However, little is known about cognitive outcomes following unilateral surgeries.
Participants and Methods:
We enrolled 31 PD patients who underwent unilateral STN-DBS in a randomized, cross-over, double-blind study (SUNDIAL Trial). Targets were chosen based on treatment of the most symptomatic side (n = 17 left hemisphere and 14 right hemisphere). All participants completed a neuropsychological battery (FAS/CFL, AVLT, DKEFS Color-Word Test) at baseline, then 2, 4, and 6 months post-surgery. Outcomes include raw scores for verbal fluency, immediate and delayed recall, and DKEFS Color-Word Inhibition trial (Trial 3) completion time. At 2, 4, and 6 months, the neurostimulation type (directional versus ring mode) was randomized for each participant. We compared baseline scores for all cognitive outcome measures using Welch’s two-sample t-tests and used linear mixed effects models to examine longitudinal effects of hemisphere and stimulation on cognition. This test battery was converted to a teleneuropsychology administration because of COVID-19 mid-study, and this was included as a covariate in all statistical models, along with years of education, baseline cognitive scores, and levodopa equivalent medication dose at each time point.
Results:
At baseline, patients who underwent left hemisphere implants scored lower on verbal fluency than right implants (t(20.66) = -2.49, p = 0.02). There were not significant differences between hemispheres in immediate recall (p = 0.57), delayed recall (p = 0.22), or response inhibition (p = 0.51). Post-operatively, left STN DBS patients experienced significant declines in verbal fluency over the study period (p = 0.02), while patients with right-sided stimulation demonstrated improvements (p < .001). There was no main effect of stimulation parameters (directional versus ring) on verbal fluency, memory, or inhibition, but there was a three-way interaction between time, stimulation parameters, and hemisphere on inhibition, such that left STN DBS patients receiving ring stimulation completed the inhibition trial faster (p = 0.035). After surgery, right STN DBS patients displayed faster inhibition times than patients with left implants (p = 0.015).
Conclusions:
Declines in verbal fluency after bilateral stimulation are the most commonly reported cognitive sequalae of DBS for movement disorders. Here we found group level declines in verbal fluency after unilateral left STN implants, but not right STN DBS up to 6 months after surgery. Patients with right hemisphere implants displayed improvements in verbal fluency. Compared to bilateral DBS, unilateral DBS surgery, particularly in the right hemisphere, is likely a modifiable risk factor for verbal fluency declines in patients with Parkinson’s disease.
Depression and anxiety are the leading contributors to the global burden of disease among young people, accounting for over a third (34.8%) of years lived with disability. Yet there is limited evidence for interventions that prevent adolescent depression and anxiety in low- and middle-income countries (LMICs), where 90% of adolescents live. This article introduces the ‘Improving Adolescent mentaL health by reducing the Impact of poVErty (ALIVE)’ study, its conceptual framework, objectives, methods and expected outcomes. The aim of the ALIVE study is to develop and pilot-test an intervention that combines poverty reduction with strengthening self-regulation to prevent depression and anxiety among adolescents living in urban poverty in Colombia, Nepal and South Africa.
Methods
This aim will be achieved by addressing four objectives: (1) develop a conceptual framework that identifies the causal mechanisms linking poverty, self-regulation and depression and anxiety; (2) develop a multi-component selective prevention intervention targeting self-regulation and poverty among adolescents at high risk of developing depression or anxiety; (3) adapt and validate instruments to measure incidence of depression and anxiety, mediators and implementation parameters of the prevention intervention; and (4) undertake a four-arm pilot cluster randomised controlled trial to assess the feasibility, acceptability and cost of the selective prevention intervention in the three study sites.
Results
The contributions of this study include the active engagement and participation of adolescents in the research process; a focus on the causal mechanisms of the intervention; building an evidence base for prevention interventions in LMICs; and the use of an interdisciplinary approach.
Conclusions
By developing and evaluating an intervention that addresses multidimensional poverty and self-regulation, ALIVE can make contributions to evidence on the integration of mental health into broader development policy and practice.
We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems.
Technical summary
The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference.
Social media summary
We highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts.
To study the respiratory patterns and the hemodynamic variations related to postural changes in inpatients with coronavirus disease (COVID-19).
Methods:
This report is a prospective study in a cohort of inpatients admitted with COVID-19. We recruited 10 patients admitted to the hospital with moderate or severe COVID-19 who showed improvement in oxygen saturation with prone positioning. We performed cardiorespiratory polygraphy and hemodynamic evaluations by thoracic electrical bioimpedance.
Results:
We observed a median minimum oxygen saturation of 85.00% (IQR: 7.00) in the supine position versus 91.00% (IQR: 8.00) (P = 0.173) in the prone position. The airflow restriction in the supine position was 2.70% (IQR: 6.55) versus 1.55% (IQR: 2.80) (P = 0.383) in the prone position. A total of 36.4% of patients were classified as having a normo-hemodynamic state in the supine position, whereas 54.5% were classified in this group in the prone position (P = 0.668). A decrease in vascular resistance was observed in the prone position (18.2% of vasoconstriction) compared to the supine position (36.4% of vasoconstriction) (P = 0.871).
Conclusion:
This brief report describes the effects of prone positioning on respiratory and hemodynamic variables in 10 patients with moderate or severe COVID-19.
The 260 m thick Andoni Formation, deposited by an ancestor to the Cubango/Okavango River, forms the symmetrical, ultra-low gradient (~ 0.017°) Cubango Megafan, 350 km long and 300 km wide. As part of the thick, Cenozoic ‘Kalahari succession’ of northern Namibia, the formation consists of fine-grained, unsorted, silt- to clay-rich sands; fine-grained, well-sorted and unconsolidated aquifer sands; and minor aquitard clays. Avulsive deposition under seasonal, semi-arid conditions in a grassland savanna environment was highly intermittent. Periodic flood events were separated by long intervals of non-deposition. Extensive post-depositional bioturbation and pedogenesis of each layer to depths of > 1 m took place during subaerial exposure, destroying bedding and sediment sorting. Bioturbation consists of meniscate backfilled burrows likely produced by beetle larvae, soil bug nymphs, and other invertebrates in the A, B, and C horizons. As climate became drier, these features were overprinted by pedogenic calcrete and phreatic carbonate nodules. Unsorted clay- and silt-rich sands suggest weak depositional currents, but aquifer sands point to wetter conditions with greater runoff. The pedogenic calcretes are indicative of limited annual rainfall (< 550 mm) and extremely stable land surfaces upon which no new sediment was deposited for centuries or even millennia.
We summarize what we assess as the past year's most important findings within climate change research: limits to adaptation, vulnerability hotspots, new threats coming from the climate–health nexus, climate (im)mobility and security, sustainable practices for land use and finance, losses and damages, inclusive societal climate decisions and ways to overcome structural barriers to accelerate mitigation and limit global warming to below 2°C.
Technical summary
We synthesize 10 topics within climate research where there have been significant advances or emerging scientific consensus since January 2021. The selection of these insights was based on input from an international open call with broad disciplinary scope. Findings concern: (1) new aspects of soft and hard limits to adaptation; (2) the emergence of regional vulnerability hotspots from climate impacts and human vulnerability; (3) new threats on the climate–health horizon – some involving plants and animals; (4) climate (im)mobility and the need for anticipatory action; (5) security and climate; (6) sustainable land management as a prerequisite to land-based solutions; (7) sustainable finance practices in the private sector and the need for political guidance; (8) the urgent planetary imperative for addressing losses and damages; (9) inclusive societal choices for climate-resilient development and (10) how to overcome barriers to accelerate mitigation and limit global warming to below 2°C.
Social media summary
Science has evidence on barriers to mitigation and how to overcome them to avoid limits to adaptation across multiple fields.
This chapter looks at the ways new digital trends and technologies have stimulated the information component of services trade and consequently enhanced trade in goods and services that embody knowledge. It illustrates the role that ICTs have taken on as conduits for digital and digitally-enabled trade and describes recent digital developments such as cloud services, large scale data analytics, Internet of things, artificial intelligence, robotics, and three-dimensional printing. It presents the relevant trade data and then covers, in broad strokes, the landscape of policy challenges that governments confront as they seek to adapt, and examples of ways trade negotiators have begun to shape new legal frameworks. The rise of such technologies and corresponding growth in services that trade internationally by means of the global movements of information has led policymakers to believe a new or enhanced legal regime could be needed. Not always well understood, digital trends can lead to exaggerated fears and cataclysmic predictions. Over-reaction to these transformations can hold the risk of disproportionate policy responses, which may harm not only trade, but also the sharing of knowledge across borders. One significant challenge, the article nevertheless raises, is that international trade rules are founded on the premise that national governments can implement them at or within their borders. Yet, many of the policy and legal responses that arise from an unanticipated shift in services trade from commercial presence to cross-border supply, have a variety of interjurisdictional consequences. Therefore, whatever trade rules may be employed, existing or new, the article concludes that enhanced efforts at collaboration among governments will be needed to complement and coordinate national initiatives.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) refractory to conventional therapy can lead to marked disability and represents a therapeutic challenge.
Objective:
To report five cases of treatment-refractory disabling CIDP treated with autologous hematopoietic stem cell transplantation (AHSCT).
Methods:
This was a retrospective cohort study from a tertiary care referral center for both neuromuscular disease and AHSCT. Patients with CIDP treated with AHSCT between 2008 and 2020 were included. All patients had major persistent and disabling neuropathic deficits despite combinations of intensive immunosuppressive therapy. The primary outcome measures were: Medical Research Council sum score, Overall Neuropathy Limitations Scale and requirement for ongoing CIDP immunotherapy after transplantation. We also analyzed safety outcomes by documenting all severe AHSCT-related complications.
Results:
Five patients with refractory CIDP underwent AHSCT. Three were classified as manifesting a typical syndrome, two were classified as the multifocal Lewis Sumner variant. The mean age at time of CIDP diagnosis was 33.4 years (range 24–46 years), with a median delay of 46 months (range 21–135 months) between diagnosis and AHSCT. The median follow-up period was 41 months. All five patients were able to wean off CIDP-related immunotherapy. Marked improvements in Medical Research Council scale and overall Neuropathy Limitations Scale were noted in 4/5 patients. One patient with longstanding neurogenic atrophy showed no improvement in disability scales. There were no treatment-related deaths or critical illnesses.
Conclusions:
AHSCT can achieve marked sustained clinical improvement of refractory CIDP and may allow for weaning off long-term complex immunotherapies.
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.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
Methods
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
Conclusions
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Objective: This study aimed to systematically review the effects of currently prescribed antiparkinson medication on cognition in patients with mild-to-moderate Parkinson’s disease (PD) who were either cognitively intact or mildly impaired. Methods: English- and French-language studies published between 1969 and 2017 were accessed via MedLine, PsychNET, EMBASE and EBSCO databases. Methodological quality (MQ) was evaluated with the quality assessment instrument of the Cochrane Collaboration Depression, Anxiety and Neurosis Review (scores from 0% to 44% indicate very low quality; scores from 45% to 64% indicate low quality; scores from 65% to 84% indicate medium quality; and scores from 85% to 100% indicate high quality). Hedges’ g and Student’s t-test were performed on all cognitive outcome measures reported. Results: In total, 14 studies assessed the cognitive effects of levodopa (L-D), pramipexole (PRX), selegiline (SEL) and rasagiline (RAS) in mild-to-moderate non-demented PD patients. The MQ was overall low, with an average score of 49.1%. Results for L-D showed deleterious effects on a test of cognitive inhibition, as well as benefits on tests of attention/processing speed/working memory, executive functions and episodic memory. Pramipexole was associated with a worsening of episodic memory and impulse control. Results on SEL indicated a deterioration of global cognition over time and of concept formation. Rasagiline had some benefits on working memory and verbal fluency. Conclusion: Antiparkinson medications can have deleterious (L-D; PRX; SEL) and beneficial (L-D; RAS) effects on cognition. However, randomized double-blind placebo-controlled trials with larger sample sizes are required to better elucidate this issue.
We present predictions for the spatial distribution of 21 cm brightness temperature fluctuations from high-dynamic-range simulations for AGN-dominated reionization histories that have been tested against available Lyα and CMB data. We model AGN by extrapolating the observed Mbh–σ relation to high redshifts and assign them ionizing emissivities consistent with recent UV luminosity function measurements. AGN-dominated reionization histories increase the variance of the 21 cm emission by a factor of up to ten compared to similar reionization histories dominated by faint galaxies, to values close to 100 mK2 at scales accessible to experiments (k ≲ 1 cMpc−1h). This is lower than the sensitivity reached by ongoing experiments by only a factor of about two or less. AGN dominated reionization should be easily detectable by LOFAR (and later HERA and SKA1) at their design sensitivity.
Austral summer sea-ice processes were investigated in January 1999 during a cruise of the R.V. Nathaniel B. Palmer in the central and eastern Ross Sea, Antarctica. The crystal texture, 18O/16O ratios, density and salinity of ice cores and of ice blocks ‘perched’ on slush at the ice surface were studied. The perched ice blocks had a distinctive polygonal granular (PG) crystal texture and very negative isotope signature that were also characteristic of layers at the top of first-year floes and of layers ‘buried’ below the surface in multi-year floes. The PG ice is superimposed ice that results from melting in the snow cover and refreezing at the slush surface and directly on top of ice floes. If PG ice is buried after the ice surface floods and the resultant slush freezes, then snow ice forms above the PG ice. The contribution of superimposed ice to floe surface mass balance and some implications with respect to weather and climate are discussed.