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Incidence and Viral Etiology of Acute Respiratory Infections and Pneumonia among Children Under Two Years: A Birth Cohort Study in Dhaka, Bangladesh
Get PDFGlobally, acute respiratory infections (ARI), including pneumonia, remain the leading infectious causes of morbidity and mortality among children under-two years of age. We conducted this longitudinal birth cohort study in a low-income urban community in Dhaka, Bangladesh, to estimate the incidence of ARI and pneumonia and assess their viral etiology. From May 2015 to March 2016, 447 children were enrolled and followed till 2022. In this analysis, we included data from the first two years of children's lives, which contributed to a total observation of 778 child-years. Nasopharyngeal wash samples were collected during symptomatic episodes, which were tested using rRT-PCR for rhinovirus (RV), respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza virus, human parainfluenza virus (HPIV), and adenovirus. We calculated incidence rates using Poisson-based methods with 95% confidence intervals (CI) and stratified age-specific rates into three groups: 0 to <6 months, 6 to <12 months, and 12 to 24 months. A total of 2,335 ARIs and 314 pneumonia episodes were documented. At least one respiratory virus was detected in 71% of ARI and 75% of pneumonia episodes. RV was the most frequently detected virus (54% in ARI, 40% in pneumonia), followed by RSV, HPIV, and influenza. The incidence of viral ARI was 212/100 child-years (95% CI: 202-223), and that of viral pneumonia was 30/100 child-years (95% CI: 27-35). The observed incidence of viral ARI and pneumonia during early childhood underscores the need for targeted interventions. Future research should examine environmental and socioeconomic influences, assess preventive strategies, and improve early detection and treatment
Contextualising the contrafacta of trouvere song
Get PDFScholarship on medieval contrafacture has long been engaged in the Kontrafakturjagd, the hunt for songs whose textual and structural similarities suggest they might also share melodies. By making melodies freely exchangeable, this practice has tended to treat the music of medieval song as if it were an empty vessel, overlooking the ways in which contrafacta might construct musical meaning to serve various political, devotional, or aesthetic ends. Rather than making a case for contrafacture among songs whose shared melodies are questionable, this dissertation provides a context rich perspective on certain groups of 'close contrafacta'—songs whose status as contrafacta is already known and supported by strong musical, textual, and contextual evidence. In five case studies, all of which take at least one song from the trouvère repertory, and which represent the most common contrafact genres—political serventois, Marian song, and crusade song—I consider the ways in which their melodies could signify. More specifically, I examine the interrelated layers of the melody's performed sound structures, its cuing of previous texts on the listener, and its integration of old and new contexts. The case studies reveal a culture that cared about melodic association and used it in sophisticated ways. In the first two chapters, which address political contrafacture, the music's textual associations form a background against which the contrafact text reacts ironically, while its melodic origins evoke precise geopolitical loyalties or antagonisms. The third and fourth chapters on Marian song, conversely, point toward efforts to intensify and develop a song's meaning through contrafacture, while the fifth chapter's contrafact text cites its own affective reason for melodic re-use. In all case studies, not only does the music cue text and context synoptically; its performed structures also intensify and subvert textual meanings, showing how music can enrich literary interpretations of medieval song
Majesty and music in royal worship: the English Chapel Royal, 1558–1625
Get PDFThis article revises interpretations of the post-Reformation English Chapel Royal as a place for the performance of ‘conservative’ or ‘traditional’ forms of the Book of Common Prayer and establishes its importance as a space for negotiating Protestant royal worship. By detailed analysis of the sound and appearance of royal chapels under Elizabeth and James, the Chapel Royal is emphasised not for its anticipation of a Laudian ascendancy, but its sensitivity to the ceremonial boundaries of the reformed Church of England, and ability to negotiate a form of Protestant majesty in royal worship
Strong hydrogen trapping by tangled dislocations in cold-drawn pearlitic steels
No full textThe presence of diffusible hydrogen atoms can lead to hydrogen embrittlement in steels, compromising their structural integrity. A potential solution is incorporating strong hydrogen traps into the microstructures to immobilize hydrogen solute atoms and prevent their diffusion towards stress-prone areas where embrittlement is most likely to occur. However, creating materials with effective hydrogen traps usually involves adding expensive alloying elements, which increase the production costs, hindering the adoption of this strategy in the steel industry. Here we show that cold drawing of pearlitic steel rods introduces a high density of dislocations that accumulate and tangle at cementite-ferrite interfaces; this strengthens the steel and make it less susceptible to embrittlement. We use atom probe tomography to confirm that these tangled dislocations firmly trap hydrogen in a steel that displays low embrittlement susceptibility. Our findings suggest a pathway for producing metallic materials that have an excellent combination of high strength and hydrogen embrittlement resistance, underscoring the potential of using structural defects as cost-effective hydrogen traps
Global, regional, and national prevalence of child and adolescent overweight and obesity, 1990-2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021
No full textBackgroundDespite the well documented consequences of obesity during childhood and adolescence and future risks of excess body mass on non-communicable diseases in adulthood, coordinated global action on excess body mass in early life is still insufficient. Inconsistent measurement and reporting are a barrier to specific targets, resource allocation, and interventions. In this Article we report current estimates of overweight and obesity across childhood and adolescence, progress over time, and forecasts to inform specific actions.MethodsUsing established methodology from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021, we modelled overweight and obesity across childhood and adolescence from 1990 to 2021, and then forecasted to 2050. Primary data for our models included 1321 unique measured and self-reported anthropometric data sources from 180 countries and territories from survey microdata, reports, and published literature. These data were used to estimate age-standardised global, regional, and national overweight prevalence and obesity prevalence (separately) for children and young adolescents (aged 5-14 years, typically in school and cared for by child health services) and older adolescents (aged 15-24 years, increasingly out of school and cared for by adult services) by sex for 204 countries and territories from 1990 to 2021. Prevalence estimates from 1990 to 2021 were generated using spatiotemporal Gaussian process regression models, which leveraged temporal and spatial correlation in epidemiological trends to ensure comparability of results across time and geography. Prevalence forecasts from 2022 to 2050 were generated using a generalised ensemble modelling approach assuming continuation of current trends. For every age-sex-location population across time (1990-2050), we estimated obesity (vs overweight) predominance using the log ratio of obesity percentage to overweight percentage.FindingsBetween 1990 and 2021, the combined prevalence of overweight and obesity in children and adolescents doubled, and that of obesity alone tripled. By 2021, 93·1 million (95% uncertainty interval 89·6-96·6) individuals aged 5-14 years and 80·6 million (78·2-83·3) aged 15-24 years had obesity. At the super-region level in 2021, the prevalence of overweight and of obesity was highest in north Africa and the Middle East (eg, United Arab Emirates and Kuwait), and the greatest increase from 1990 to 2021 was seen in southeast Asia, east Asia, and Oceania (eg, Taiwan [province of China], Maldives, and China). By 2021, for females in both age groups, many countries in Australasia (eg, Australia) and in high-income North America (eg, Canada) had already transitioned to obesity predominance, as had males and females in a number of countries in north Africa and the Middle East (eg, United Arab Emirates and Qatar) and Oceania (eg, Cook Islands and American Samoa). From 2022 to 2050, global increases in overweight (not obesity) prevalence are forecasted to stabilise, yet the increase in the absolute proportion of the global population with obesity is forecasted to be greater than between 1990 and 2021, with substantial increases forecast between 2022 and 2030, which continue between 2031 and 2050. By 2050, super-region obesity prevalence is forecasted to remain highest in north Africa and the Middle East (eg, United Arab Emirates and Kuwait), and forecasted increases in obesity are still expected to be largest across southeast Asia, east Asia, and Oceania (eg, Timor-Leste and North Korea), but also in south Asia (eg, Nepal and Bangladesh). Compared with those aged 15-24 years, in most super-regions (except Latin America and the Caribbean and the high-income super-region) a greater proportion of those aged 5-14 years are forecasted to have obesity than overweight by 2050. Globally, 15·6% (12·7-17·2) of those aged 5-14 years are forecasted to have obesity by 2050 (186 million [141-221]), compared with 14·2% (11·4-15·7) of those aged 15-24 years (175 million [136-203]). We forecasted that by 2050, there will be more young males (aged 5-14 years) living with obesity (16·5% [13·3-18·3]) than overweight (12·9% [12·2-13·6]); while for females (aged 5-24 years) and older males (aged 15-24 years), overweight will remain more prevalent than obesity. At a regional level, the following populations are forecast to have transitioned to obesity (vs overweight) predominance before 2041-50: children and adolescents (males and females aged 5-24 years) in north Africa and the Middle East and Tropical Latin America; males aged 5-14 years in east Asia, central and southern sub-Saharan Africa, and central Latin America; females aged 5-14 years in Australasia; females aged 15-24 years in Australasia, high-income North America, and southern sub-Saharan Africa; and males aged 15-24 years in high-income North America.InterpretationBoth overweight and obesity increased substantially in every world region between 1990 and 2021, suggesting that current approaches to curbing increases in overweight and obesity have failed a generation of children and adolescents. Beyond 2021, overweight during childhood and adolescence is forecast to stabilise due to further increases in the population who have obesity. Increases in obesity are expected to continue for all populations in all world regions. Because substantial change is forecasted to occur between 2022 and 2030, immediate actions are needed to address this public health crisis.FundingBill & Melinda Gates Foundation and Australian National Health and Medical Research Council
UBA6 specificity for ubiquitin E2 conjugating enzymes reveals a priority mechanism of BIRC6
No full textIn mammals, ubiquitylation is orchestrated by the canonical ubiquitin-activating E1 enzyme UBA1 and the orthogonal E1 UBA6. Growing evidence underscores the essentiality of both E1s, which differentiate between 29 active ubiquitin-conjugating enzymes (E2s). The mechanisms governing this distinction have remained unclear. Here we establish a framework for ubiquitin E1–E2 specificity. Focusing on UBA6-controlled ubiquitylation cascades, we reveal that BIRC6, a UBA6-exclusive E2, gains priority over all other UBA6-competent E2s, underpinning the functional importance of defined UBA6–BIRC6 ubiquitylation events in regulating cell death, embryogenesis and autophagy. By capturing BIRC6 receiving ubiquitin from UBA6 in different states, we observe BIRC6 engaging with the UBA6 ubiquitin fold domain, driving an exceptionally high-affinity interaction that is modulated by the UBA6 Cys-Cap loop. Using this interaction as a template, we demonstrate how to confer activity between E2s and their noncognate E1, providing a tool to delineate E1–E2-dependent pathways. Lastly, we explain how BIRC6 priority does not lead to inhibition of UBA6, through a bespoke thioester switch mechanism that disengages BIRC6 upon receiving ubiquitin. Our findings propose a concept of hierarchy of E2 activity with cognate E1s, which may explain how ubiquitin E1s can each function with over a dozen E2s and orchestrate E2-specific cellular functions
miR-107 represses DMPK and is sequestered by CUG repeats triggering the MSI2/miR-7 pathogenesis axis in myotonic dystrophy
No full textMyotonic dystrophy type 1 (DM1) is a multisystem genetic disorder characterized by muscle disease, including muscle atrophy partially originating from excessive autophagy. We have previously demonstrated that excessive Musashi-2 (MSI2) repressed the biogenesis of miR-7, which derepressed autophagy, ultimately contributing to muscle atrophy, but the root cause of MSI2 dysregulation is unknown. Herein, we investigate the intricate role of miR-107 in DM1 pathogenesis, focusing on its involvement in the MSI2>miR-7>autophagy axis as this microRNA (miRNA) directly regulates MSI2. We found that in DM1, miR-107 function is impaired because expanded CUG repeats sequester it, causing an increase in the expression of its targets, including MSI2. Through different experimental approaches, including luciferase reporter assays, differential scanning fluorimetry, and electrophoretic mobility shift assay (EMSA), we confirm that miR-107 directly binds to CUG repeats in mutant DMPK transcripts. DMPK posttranscriptional regulation by miR-107 was also demonstrated. Modulation of miR-107 in a DM1 cell model context significantly affects its downstream targets, MSI2 and miR-7, thus decreasing excessive autophagic markers and restoring pathological phenotypes such as ribonuclear foci and impaired fusion capacity. These findings underscore the critical role of miR-107 in regulating the MSI2>miR-7>autophagy axis and support this miRNA as a promising therapeutic target for correcting muscle dysfunction in DM1
On ‘necrolocutors’ in political ecology: A response from Yaoundé
No full textI consider Gibson's notion of the ‘necrolocutor’: a racialised, gendered subject mediating institutional engagements with power, knowledge, and death, who reveals and embodies the neoliberal academy's reliance on co-opted ‘local’ voices for legitimacy. I argue that these extractive dynamics of research collaboration echo historical colonial, corporate, and militarised formations, wherein participation functioned as consent, and the ‘native informant’ was instrumentalised to validate imperial narratives. Extending these critiques, my commentary examines the economic and epistemic inequalities shaping global knowledge production, highlighting ‘racialised localwashing’, the ongoing commodification of intellectual labour, and the rejections of superficial inclusivity in favour of reciprocal, anti-imperial scholarship. I draw from Marxist and decolonial insights that acknowledge the im/possibilities and transformative potentials of academic collaborations in necropolitical environments
Impact of tunnel alignment on local seismic lining actions
No full textThe seismic performance of long, embedded tunnels can be significantly influenced by spatial variation in ground motion, particularly when the tunnel length approaches the wavelength of seismic waves. This study presents an integrated two-stage modelling approach to evaluate the effect of global (alignment-scale) effects on the local (lining-scale) seismic response of the 27 km circular large hadron collider (LHC) tunnel at CERN. A beam on non-linear Winkler foundation (BNWF) model is first used to simulate the effects of asynchronous wave passage and alignment curvature under three-dimensional (3D) seismic scenarios. The results reveal that asynchronous excitation induces wave-like differential displacements and non-planar forces, particularly intensified at tunnel–cavern interfaces due to stiffness contrasts. These global actions are then applied as dynamic boundary conditions in high-fidelity 3D non-linear finite-element analyses (FEA) of a critical tunnel section. The 3D FEA captures detailed local responses within the reinforced concrete lining, revealing that conventional two-dimensional plane-strain models underestimate hoop forces and overlook alignment-induced amplifications of seismic actions. The results demonstrate the necessity of accounting for alignment effects in seismic tunnel design and demonstrate the effectiveness of the proposed BNWF–FEA hybrid methodology
Āryadeva’s treatise on the division of parts
No full textThe short Indian work translated and annotated here is traditionally attributed to Āryadeva. Composed in verse and accompanied by a prose commentary, the Treatise on the Division of Parts provides a very concise discussion of several ideas central to the Madhyamaka school of Mahāyāna Buddhism