Summary Background Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the ...efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis. Methods In this randomised, double-blind trial, undertaken in 80 sites in 16 countries, 481 patients presenting with a clinically isolated syndrome with unifocal manifestation, and two or more T2-weighted brain lesions measuring 6 mm or more, were randomly assigned to receive either subcutaneous glatiramer acetate 20 mg per day (n=243) or placebo (n=238) for up to 36 months, unless they converted to clinically definite multiple sclerosis. The randomisation scheme used SAS-based blocks stratified by centre, and patients and all personnel were masked to treatment assignment. The primary endpoint was time to clinically definite multiple sclerosis, based on a second clinical attack. Analysis was by intention to treat. A preplanned interim analysis was done for data accumulated from 81% of the 3-year study exposure. This study was registered with ClinicalTrials.gov , number NCT00666224. Findings All randomly assigned participants were analysed for the primary outcome. Glatiramer acetate reduced the risk of developing clinically definite multiple sclerosis by 45% compared with placebo (hazard ratio 0·55, 95% CI 0·40–0·77; p=0·0005). The time for 25% of patients to convert to clinically definite disease was prolonged by 115%, from 336 days for placebo to 722 days for glatiramer acetate. The most common adverse events in the glatiramer acetate group were injection-site reactions (135 56% glatiramer acetate vs 56 24% placebo) and immediate post-injection reactions (47 19% vs 12 5%). Interpretation Early treatment with glatiramer acetate is efficacious in delaying conversion to clinically definite multiple sclerosis in patients presenting with clinically isolated syndrome and brain lesions detected by MRI. Funding Teva Pharmaceutical Industries, Israel.
Here we demonstrate how the Fermi surface topology and quantum many-body interactions can be manipulated via epitaxial strain in the spin-triplet superconductor Sr_{2}RuO_{4} and its isoelectronic ...counterpart Ba_{2}RuO_{4} using oxide molecular beam epitaxy, in situ angle-resolved photoemission spectroscopy, and transport measurements. Near the topological transition of the γ Fermi surface sheet, we observe clear signatures of critical fluctuations, while the quasiparticle mass enhancement is found to increase rapidly and monotonically with increasing Ru-O bond distance. Our work demonstrates the possibilities for using epitaxial strain as a disorder-free means of manipulating emergent properties, many-body interactions, and potentially the superconductivity in correlated materials.
Background
The coronavirus disease 2019 (COVID-19) pandemic is having a profound impact on the health and development of children worldwide. There is limited evidence on the impact of COVID-19 and ...its related school closures and disease-containment measures on the psychosocial wellbeing of children; little research has been done on the characteristics of vulnerable groups and factors that promote resilience.
Methods
We conducted a large-scale cross-sectional population study of Hong Kong families with children aged 2–12 years. Parents completed an online survey on family demographics, child psychosocial wellbeing, functioning and lifestyle habits, parent–child interactions, and parental stress during school closures due to COVID-19. We used simple and multiple linear regression analyses to explore factors associated with child psychosocial problems and parental stress during the pandemic.
Results
The study included 29,202 individual families; of which 12,163 had children aged 2–5 years and 17,029 had children aged 6–12 years. The risk of child psychosocial problems was higher in children with special educational needs, and/or acute or chronic disease, mothers with mental illness, single-parent families, and low-income families. Delayed bedtime and/or inadequate sleep or exercise duration, extended use of electronic devices were associated with significantly higher parental stress and more psychosocial problems among pre-schoolers.
Conclusions
This study identifies vulnerable groups of children and highlights the importance of strengthening family coherence, adequate sleep and exercise, and responsible use of electronic devices in promoting psychosocial wellbeing during the COVID-19 pandemic.
Africa, the ancestral home of all modern humans, is the most informative continent for understanding the human genome and its contribution to complex disease. To better understand the genetics of ...schizophrenia, we studied the illness in the Xhosa population of South Africa, recruiting 909 cases and 917 age-, gender-, and residence-matched controls. Individuals with schizophrenia were significantly more likely than controls to harbor private, severely damaging mutations in genes that are critical to synaptic function, including neural circuitry mediated by the neurotransmitters glutamine, γ-aminobutyric acid, and dopamine. Schizophrenia is genetically highly heterogeneous, involving severe ultrarare mutations in genes that are critical to synaptic plasticity. The depth of genetic variation in Africa revealed this relationship with a moderate sample size and informed our understanding of the genetics of schizophrenia worldwide.
Several transition-metal dichalcogenides exhibit a striking crossover from indirect to direct band gap semiconductors as they are thinned down to a single monolayer. Here, we demonstrate how an ...electronic structure characteristic of the isolated monolayer can be created at the surface of a bulk MoS2 crystal. This is achieved by intercalating potassium in the interlayer van der Waals gap, expanding its size while simultaneously doping electrons into the conduction band. Our angle-resolved photoemission measurements reveal resulting electron pockets centered at the K̅ and K′ points of the Brillouin zone, providing the first momentum-resolved measurements of how the conduction band dispersions evolve to yield an approximately direct band gap of ∼1.8 eV in quasi-freestanding monolayer MoS2. As well as validating previous theoretical proposals, this establishes a novel methodology for manipulating electronic structure in transition-metal dichalcogenides, opening a new route for the generation of large-area quasi-freestanding monolayers for future fundamental study and use in practical applications.
Proposes the analysis of bioavailable radiogenic isotopes of strontium as markers to trace the provenance of locally produced animals and plants being transported across Aotearoa NZ as a biosecurity ...measure to protect against pest threats, both by certifying the origin of the products while also helping to determine if new pest detections were of locally breeding populations or not, or to raise awareness of imported illegal agricultural products. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Groundwater quality is a concern in alluvial aquifers underlying agricultural areas worldwide. Nitrate from land applied fertilizers or from animal waste can leach to groundwater and contaminate ...drinking water resources. The San Joaquin Valley, California, is an example of an agricultural landscape with a large diversity of field, vegetable, tree, nut, and citrus crops, but also confined animal feeding operations (CAFOs, here mostly dairies) that generate, store, and land apply large amounts of liquid manure. As in other such regions around the world, the rural population in the San Joaquin Valley relies almost exclusively on shallow domestic wells (≤150m deep), of which many have been affected by nitrate. Variability in crops, soil type, and depth to groundwater contribute to large variability in nitrate occurrence across the underlying aquifer system. The role of these factors in controlling groundwater nitrate contamination levels is examined. Two hundred domestic wells were sampled in two sub-regions of the San Joaquin Valley, Stanislaus and Merced (Stan/Mer) and Tulare and Kings (Tul/Kings) Counties. Forty six percent of well water samples in Tul/Kings and 42% of well water samples in Stan/Mer exceeded the MCL for nitrate (10mg/L NO3-N). For statistical analysis of nitrate contamination, 78 crop and landuse types were considered by grouping them into ten categories (CAFO, citrus, deciduous fruits and nuts, field crops, forage, native, pasture, truck crops, urban, and vineyards). Vadose zone thickness, soil type, well construction information, well proximity to dairies, and dominant landuse near the well were considered. In the Stan/Mer area, elevated nitrate levels in domestic wells most strongly correlate with the combination of very shallow (≤21m) water table and the presence of either CAFO derived animal waste applications or deciduous fruit and nut crops (synthetic fertilizer applications). In Tulare County, statistical data indicate that elevated nitrate levels in domestic well water are most strongly associated with citrus orchards when located in areas with a very shallow (≤21m) water table. Kings County had relatively few nitrate MCL exceedances in domestic wells, probably due to the deeper water table in Kings County.
•200 wells were sampled for nitrate across a large basin with intensive agriculture.•44% of samples did not meet the USEPA drinking water standard for nitrate.•Landuse, soil, water level depth, and well specs were considered as factors.•Tree-fruit and nuts, citrus, dairies/forage, and urban show most elevated nitrate.•Depth to groundwater and well depth critically control nitrate in well water.
Based on our previous work on the clinical activity of cetuximab in recurrent nasopharyngeal carcinoma (NPC), we evaluated the feasibility of adding cetuximab to concurrent cisplatin and ...intensity-modulated radiotherapy (IMRT) in locoregionally advanced NPC.
Patients with American Joint Committee on Cancer stage III–IVB NPC were given an initial dose of cetuximab (400 mg/m2) 7–10 days before receiving concurrent IMRT, weekly cisplatin (30 mg/m2/week) and cetuximab (250 mg/m2/week).
Thirty patients (median age of 45 years) with stage III (67%), IVA (30%) and IVB (3%) nonkeratinizing NPC were enrolled. Grade 3–4 oropharyngeal mucositis occurred in 26 (87%) patients and 10 (33%) patients required short-term nasogastric feeding. Grade 3 radiotherapy-related dermatitis occurred in six patients (20%) and three patients (10%) had grade 3 cetuximab-related acneiform rash. These grade 3–4 skin and mucosal toxic effects were manageable and reversible. At a median follow-up of 31.8 months 95% confidence interval (CI) 26.2–32.1 months, the 2-year progression-free survival was 86.5% (95% CI 74.3% to 98.8%).
Concurrent administration of cetuximab, weekly cisplatin and IMRT is a feasible strategy against locoregionally advanced NPC. Preliminary survival data compare favorably with historic data and further follow-up is warranted.
Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation and establishing laterality. Cilia motility defects cause primary ciliary dyskinesia (PCD, MIM244400), a ...disorder affecting 1:15,000-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive ciliary bending. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD-linked loci. Here we show that the zebrafish cilia paralysis mutant schmalhans (smh(tn222)) encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a-regulated gene product. Screening 146 unrelated PCD families identified individuals in six families with reduced outer dynein arms who carried mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103/Pr46b functions as a tightly bound, axoneme-associated protein. These results identify Ccdc103 as a dynein arm attachment factor that causes primary ciliary dyskinesia when mutated.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To prospectively determine the diagnostic accuracy of diffusion-weighted magnetic resonance (MR) imaging for discrimination of malignant neck nodes due to lymphoma, squamous cell carcinoma (SCC), and ...undifferentiated nasopharyngeal carcinoma (NPC), with histologic findings and imaging criteria as reference standards.
Ethics committee approval and informed consent were obtained. Patients with malignant lymphadenopathy underwent 1.5-T diffusion-weighted MR imaging. A region of interest was drawn around the malignant node on apparent diffusion coefficient (ADC) maps; ADC values were compared (Kruskal-Wallis test). Receiver operating characteristic analysis was employed to investigate whether ADC values could aid in discrimination among malignancies.
Forty-three patients (34 men, nine women; mean age, 54 years) with 43 nodes underwent imaging. Mean ADC values for lymphoma (n = 8), NPC (n = 17), and SCC (n = 18) were (0.664 +/- 0.071 standard deviation) x 10(-3) mm(2)/sec, (0.802 +/- 0.128) x 10(-3) mm(2)/sec, and (1.057 +/- 0.169) x 10(-3) mm(2)/sec, respectively, with significant differences between SCC and lymphoma or NPC (P < .001) and between NPC and lymphoma (P = .04). To optimize sensitivity and specificity with equal weighting, ADC threshold values for distinguishing between SCC and NPC, between SCC and lymphoma, and between NPC and lymphoma were 0.894 x 10(-3) mm(2)/sec, 0.824 x 10(-3) mm(2)/sec, and 0.694 x 10(-3) mm(2)/sec, respectively. To produce a 100% specificity while sensitivity is maximized, the following ADC threshold values were obtained for prediction of differentiation between malignancies: (a) SCC versus lymphoma, greater than 0.824 x 10(-3) mm(2)/sec (sensitivity, 94%), and lymphoma versus SCC, less than 0.767 x 10(-3) mm(2)/sec (sensitivity 88%); (b) NPC versus SCC, less than 0.764 x 10(-3) mm(2)/sec (sensitivity, 47%), and SCC versus NPC, greater than 1.093 x 10(-3) mm(2)/sec (sensitivity, 39%); (c) NPC versus lymphoma, greater than 0.788 x 10(-3) mm(2)/sec (sensitivity, 53%), and lymphoma versus NPC, no suitable threshold value.
Diffusion-weighted MR imaging shows significant differences among malignant nodes of SCC, lymphoma, and NPC. ADC threshold values can help distinguish SCC from lymphoma.
http://radiology.rsnajnls.org/cgi/content/full/2451061804/DC1.
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