98 research outputs found
Ethnicity and the Writing of Medieval Scottish history
Historians have long tended to define medieval Scottish society in terms of interactions between ethnic groups. This approach was developed over the course of the long nineteenth century, a formative period for the study of medieval Scotland. At that time, many scholars based their analysis upon scientific principles, long since debunked, which held that medieval 'peoples' could only be understood in terms of 'full ethnic packages'. This approach was combined with a positivist historical narrative that defined Germanic Anglo-Saxons and Normans as the harbingers of advances of Civilisation. While the prejudices of that era have largely faded away, the modern discipline still relies all too often on a dualistic ethnic framework. This is particularly evident in a structure of periodisation that draws a clear line between the 'Celtic' eleventh century and the 'Norman' twelfth. Furthermore, dualistic oppositions based on ethnicity continue, particularly in discussions of the law, kingship, lordship and religion
In search of the authentic nation: landscape and national identity in Canada and Switzerland
While the study of nationalism and national identity has flourished in the last decade, little attention has been devoted to the conditions under which natural environments acquire significance in definitions of nationhood. This article examines the identity-forming role of landscape depictions in two polyethnic nation-states: Canada and Switzerland. Two types of geographical national identity are identified. The first ā what we call the ānationalisation of natureāā portrays zarticular landscapes as expressions of national authenticity. The second pattern ā what we refer to as the ānaturalisation of the nationāā rests upon a notion of geographical determinism that depicts specific landscapes as forces capable of determining national identity. The authors offer two reasons why the second pattern came to prevail in the cases under consideration: (1) the affinity between wild landscape and the Romantic ideal of pure, rugged nature, and (2) a divergence between the nationalist ideal of ethnic homogeneity and the polyethnic composition of the two societies under consideration
Defining Research to Improve Health Systems
Robert Terry and colleagues present working definitions of operational research, implementation research, and health systems research within the context of research to strengthen health systems
Clinical Utility of Random AntiāTumor Necrosis Factor DrugāLevel Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis
Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.Ā Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.Ā Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibodyāpositive patients received lower median dosages of methotrexate compared with antidrug antibodyānegative patients (15 mg/week versus 20 mg/week; Pā=ā0.01) and had a longer disease duration (14.0 versus 7.7 years; Pā=ā0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], Pā=ā0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ā„30 kg/m2 and poor adherence were associated with lower drug levels.Ā Conclusion: Pharmacologic testing in antiātumor necrosis factorātreated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months
Air exposure of coral is a significant source of dimethylsulfide (DMS) to the atmosphere
Corals are prolific producers of dimethylsulfoniopropionate (DMSP). High atmospheric concentrations of the DMSP breakdown product dimethylsulfide (DMS) have been linked to coral reefs during low tides. DMS is a potentially key sulfur source to the tropical atmosphere, but DMS emission from corals during tidal exposure is not well quantified. Here we show that gas phase DMS concentrations (DMSgas) increased by an order of magnitude when three Indo-Pacific corals were exposed to air in laboratory experiments. Upon re-submersion, an additional rapid rise in DMSgas was observed, reflecting increased production by the coral and/or dissolution of DMS-rich mucus formed by the coral during air exposure. Depletion in DMS following re-submersion was likely due to biologically-driven conversion of DMS to dimethylsulfoxide (DMSO). Fast Repetition Rate fluorometry showed downregulated photosynthesis during air exposure but rapid recovery upon re-submersion, suggesting that DMS enhances coral tolerance to oxidative stress during a process that can induce photoinhibition. We estimate that DMS emission from exposed coral reefs may be comparable in magnitude to emissions from other marine DMS hotspots. Coral DMS emission likely comprises a regular and significant source of sulfur to the tropical marine atmosphere, which is currently unrecognised in global DMS emission estimates and Earth System Models
Global, regional, and national burden of other musculoskeletal disorders, 1990ā2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021
Background
Musculoskeletal disorders include more than 150 different conditions affecting joints, muscles, bones, ligaments, tendons, and the spine. To capture all health loss from death and disability due to musculoskeletal disorders, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) includes a residual musculoskeletal category for conditions other than osteoarthritis, rheumatoid arthritis, gout, low back pain, and neck pain. This category is called other musculoskeletal disorders and includes, for example, systemic lupus erythematosus and spondylopathies. We provide updated estimates of the prevalence, mortality, and disability attributable to other musculoskeletal disorders and forecasted prevalence to 2050.
Methods
Prevalence of other musculoskeletal disorders was estimated in 204 countries and territories from 1990 to 2020 using data from 68 sources across 23 countries from which subtraction of cases of rheumatoid arthritis, osteoarthritis, low back pain, neck pain, and gout from the total number of cases of musculoskeletal disorders was possible. Data were analysed with Bayesian meta-regression models to estimate prevalence by year, age, sex, and location. Years lived with disability (YLDs) were estimated from prevalence and disability weights. Mortality attributed to other musculoskeletal disorders was estimated using vital registration data. Prevalence was forecast to 2050 by regressing prevalence estimates from 1990 to 2020 with Socio-demographic Index as a predictor, then multiplying by population forecasts.
Findings
Globally, 494 million (95% uncertainty interval 431ā564) people had other musculoskeletal disorders in 2020, an increase of 123Ā·4% (116Ā·9ā129Ā·3) in total cases from 221 million (192ā253) in 1990. Cases of other musculoskeletal disorders are projected to increase by 115% (107ā124) from 2020 to 2050, to an estimated 1060 million (95% UI 964ā1170) prevalent cases in 2050; most regions were projected to have at least a 50% increase in cases between 2020 and 2050. The global age-standardised prevalence of other musculoskeletal disorders was 47Ā·4% (44Ā·9ā49Ā·4) higher in females than in males and increased with age to a peak at 65ā69 years in male and female sexes. In 2020, other musculoskeletal disorders was the sixth ranked cause of YLDs globally (42Ā·7 million [29Ā·4ā60Ā·0]) and was associated with 83ā100 deaths (73ā600ā91ā600).
Interpretation
Other musculoskeletal disorders were responsible for a large number of global YLDs in 2020. Until individual conditions and risk factors are more explicitly quantified, policy responses to this burden remain a challenge. Temporal trends and geographical differences in estimates of non-fatal disease burden should not be overinterpreted as they are based on sparse, low-quality data.publishedVersio
Global, regional, and national burden of rheumatoid arthritis, 1990ā2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021
Background
Rheumatoid arthritis is a chronic autoimmune inflammatory disease associated with disability and premature death. Up-to-date estimates of the burden of rheumatoid arthritis are required for health-care planning, resource allocation, and prevention. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, we provide updated estimates of the prevalence of rheumatoid arthritis and its associated deaths and disability-adjusted life-years (DALYs) by age, sex, year, and location, with forecasted prevalence to 2050.
Methods
Rheumatoid arthritis prevalence was estimated in 204 countries and territories from 1990 to 2020 using Bayesian meta-regression models and data from population-based studies and medical claims data (98 prevalence and 25 incidence studies). Mortality was estimated from vital registration data with the Cause of Death Ensemble model (CODEm). Years of life lost (YLL) were calculated with use of standard GBD lifetables, and years lived with disability (YLDs) were estimated from prevalence, a meta-analysed distribution of rheumatoid arthritis severity, and disability weights. DALYs were calculated by summing YLLs and YLDs. Smoking was the only risk factor analysed. Rheumatoid arthritis prevalence was forecast to 2050 by logistic regression with Socio-Demographic Index as a predictor, then multiplying by projected population estimates.
Findings
In 2020, an estimated 17Ā·6 million (95% uncertainty interval 15Ā·8ā20Ā·3) people had rheumatoid arthritis worldwide. The age-standardised global prevalence rate was 208Ā·8 cases (186Ā·8ā241Ā·1) per 100ā000 population, representing a 14Ā·1% (12Ā·7ā15Ā·4) increase since 1990. Prevalence was higher in females (age-standardised female-to-male prevalence ratio 2Ā·45 [2Ā·40ā2Ā·47]). The age-standardised death rate was 0Ā·47 (0Ā·41ā0Ā·54) per 100ā000 population (38ā300 global deaths [33ā500ā44ā000]), a 23Ā·8% (17Ā·5ā29Ā·3) decrease from 1990 to 2020. The 2020 DALY count was 3ā060ā000 (2ā320ā000ā3ā860ā000), with an age-standardised DALY rate of 36Ā·4 (27Ā·6ā45Ā·9) per 100ā000 population. YLDs accounted for 76Ā·4% (68Ā·3ā81Ā·0) of DALYs. Smoking risk attribution for rheumatoid arthritis DALYs was 7Ā·1% (3Ā·6ā10Ā·3). We forecast that 31Ā·7 million (25Ā·8ā39Ā·0) individuals will be living with rheumatoid arthritis worldwide by 2050.
Interpretation
Rheumatoid arthritis mortality has decreased globally over the past three decades. Global age-standardised prevalence rate and YLDs have increased over the same period, and the number of cases is projected to continue to increase to the year 2050. Improved access to early diagnosis and treatment of rheumatoid arthritis globally is required to reduce the future burden of the disease.publishedVersio
Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans
Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have
fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in
25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16
regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of
correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP,
while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in
Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium
(LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region.
Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant
enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the
refined data for existing association signals, we estimate that these loci now explain ā¼38.9% of the familial relative risk of PrCa,
an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of
PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent
signals within the same regio
Transcriptomic analysis supports similar functional roles for the two thymuses of the tammar wallaby
Background: The thymus plays a critical role in the development and maturation of T-cells. Humans have a single thoracic thymus and presence of a second thymus is considered an anomaly. However, many vertebrates have multiple thymuses. The tammar wallaby has two thymuses: a thoracic thymus (typically found in all mammals) and a dominant cervical thymus. Researchers have known about the presence of the two wallaby thymuses since the 1800s, but no genome-wide research has been carried out into possible functional differences between the two thymic tissues. Here, we used pyrosequencing to compare the transcriptomes of a cervical and thoracic thymus from a single 178 day old tammar wallaby.Results: We show that both the tammar thoracic and the cervical thymuses displayed gene expression profiles consistent with roles in T-cell development. Both thymuses expressed genes that mediate distinct phases of T-cells differentiation, including the initial commitment of blood stem cells to the T-lineage, the generation of T-cell receptor diversity and development of thymic epithelial cells. Crucial immune genes, such as chemokines were also present. Comparable patterns of expression of non-coding RNAs were seen. 67 genes differentially expressed between the two thymuses were detected, and the possible significance of these results are discussed.Conclusion: This is the first study comparing the transcriptomes of two thymuses from a single individual. Our finding supports that both thymuses are functionally equivalent and drive T-cell development. These results are an important first step in the understanding of the genetic processes that govern marsupial immunity, and also allow us to begin to trace the evolution of the mammalian immune system
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