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Background: Anti-CD20 monoclonal antibodies are highly effective for RMS treatment. Ocrelizumab (OCR) is standard, while Rituximab (RTX) is an alternative. The impact of anti-CD20 therapies on immune markers remains understudied, though deficiencies are frequently observed and have been associated with increased risk of infection. Our objective is to characterize and compare lymphocyte, neutrophil, and immunoglobulin levels in OCR- versus RTX-treated persons with RMS. Methods: This retrospective chart review included RMS patients on OCR or RTX (2017–2023). Pre- and post-treatment levels of lymphocytes, neutrophils, and immunoglobulins (IgG, IgA, IgM) were analyzed. Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models were used for survival analysis. Results: 350 patients (OCR=175, RTX=175) were included. The mean treatment length was 60.9 (SD 19.1) months for OCR and 42.7 (SD 19.5) months for RTX. RTX was associated with a significantly shorter time to IgM deficiency (29.6 vs. 40.0 months, p=0.02). Cox analysis confirmed RTX increased IgM deficiency risk (HR=1.54, 95% CI: 1.06-2.23, p=0.02). No differences were seen for lymphocytes, neutrophils, IgG, or IgA. Conclusions: RTX was associated with a shorter time to and increased risk of IgM hypogammaglobulinemia compared to OCR, highlighting the importance of long-term monitoring. Further research is needed to guide treatment decisions.
The Australian SKA Pathfinder (ASKAP) offers powerful new capabilities for studying the polarised and magnetised Universe at radio wavelengths. In this paper, we introduce the Polarisation Sky Survey of the Universe’s Magnetism (POSSUM), a groundbreaking survey with three primary objectives: (1) to create a comprehensive Faraday rotation measure (RM) grid of up to one million compact extragalactic sources across the southern $\sim50$% of the sky (20,630 deg$^2$); (2) to map the intrinsic polarisation and RM properties of a wide range of discrete extragalactic and Galactic objects over the same area; and (3) to contribute interferometric data with excellent surface brightness sensitivity, which can be combined with single-dish data to study the diffuse Galactic interstellar medium. Observations for the full POSSUM survey commenced in May 2023 and are expected to conclude by mid-2028. POSSUM will achieve an RM grid density of around 30–50 RMs per square degree with a median measurement uncertainty of $\sim$1 rad m$^{-2}$. The survey operates primarily over a frequency range of 800–1088 MHz, with an angular resolution of 20” and a typical RMS sensitivity in Stokes Q or U of 18 $\mu$Jy beam$^{-1}$. Additionally, the survey will be supplemented by similar observations covering 1296–1440 MHz over 38% of the sky. POSSUM will enable the discovery and detailed investigation of magnetised phenomena in a wide range of cosmic environments, including the intergalactic medium and cosmic web, galaxy clusters and groups, active galactic nuclei and radio galaxies, the Magellanic System and other nearby galaxies, galaxy halos and the circumgalactic medium, and the magnetic structure of the Milky Way across a very wide range of scales, as well as the interplay between these components. This paper reviews the current science case developed by the POSSUM Collaboration and provides an overview of POSSUM’s observations, data processing, outputs, and its complementarity with other radio and multi-wavelength surveys, including future work with the SKA.
Shortly after construction of a subdivision in the southwest Denver metropolitan area in 1986, a portion of the subdivision built directly on steeply-dipping strata of the Pierre Shale began experiencing damaging differential movements, causing house foundations to fail and pavements to warp and crack. This formation is a Late Cretaceous marine clay-shale composed predominantly of fluvial mixed-layer illite/smectite and quartz. During deposition of the shale, periodic and explosive volcanism generated thin beds of bentonite, consisting initially of volcanic ash and subsequently altered to nearly pure smectite. Some of these bentonite beds were exposed in a trench adjacent to the subdivision and perpendicular to the strike of the steeply-dipping strata. The thickest bentonite beds correlated well with linear heave features that these beds parallel the bedrock strike throughout the subdivision were mapped via severely deformed pavements. Mineralogical data show the bentonite bed that correlates with the worst damage within the subdivision consists of about 62% smectite by weight with mixed-layer illite/smectite expandability of 92%. By comparison, a sample of the typical silty claystone, which is fluvial mixed-layer illite/smectite mixed with detrital quartz from the adjacent strata, had about 23% smectite by weight with 70% to 90% illite/smectite expandability. Geotechnical tests for swell potential show that samples of 2 bentonite beds swelled 39% to 43% compared to 2% to 8% for samples of the typical silty claystone. It is proposed that differential swell resulting from stratigraphically-controlled differences in clay mineralogy and grain-size is the primary factor controlling extreme damage for this geologic setting.
We use patent citation data to map the flows of technical knowledge, and in particular to test three hypotheses. First, that the net flow of technical knowledge tends to be from more developed to less developed countries. Second, that the trajectory of climate change-mitigation knowledge flow increased (especially from developed to developing countries) after the 1997 Kyoto Protocol and the 2015 Paris Agreement on climate change. Third, that the trajectory of pharmaceutical knowledge flow increased after the conclusion of the TRIPS Agreement. We find that massive amounts of technical information are exchanged, among countries around the world, in sometimes surprising patterns. Developed country patents supply a disproportionate amount of patent citations compared to patents from developing countries, and the importance of technical knowledge thereby transferred is disproportionately high. However, we observe some evidence that this imbalance in knowledge flow may be beginning to reverse itself, as developing country patents have become increasingly cited by those in developed countries, and the importance of developing world patents has grown. We did not discern evidence that the Kyoto Protocol has spurred knowledge flow in climate-mitigation technology, but found some preliminary evidence consistent with an effect by the Paris Agreement. We did find evidence consistent with the possibility that the TRIPS Agreement may have spurred pharmaceutical (and more general) knowledge flow.
There are many categories of information that defy easy systematic computational analysis. Patents are not one of them. Ever since the earliest litterae patentes were granted by host countries to foreigners willing to share their knowledge with their hosts, the monopoly rights granted by governments have been meticulously documented. The richness of data detailing both the monopoly right to exclude – granted to a patent’s owner – and the patent document’s informational disclosure of how to make and use a claimed invention – intended to enrich the metaphorical storehouse of knowledge – has accumulated at an accelerating pace since the days of the first letters patent. So rapidly has the information embodied in patents grown that analytical techniques for sorting and computationally evaluating that information have always lagged far behind the deluge of accumulating data. In lieu of precise algorithmic methods for understanding the contents of patents, a specialized guild of patent attorneys has evolved to sell their largely subjective interpretations of what patents disclose, cover, and are worth. Since patent attorneys must pass a challenging patent bar exam, in addition to a state bar exam, their numbers are controlled, allowing their fees to be high. However, recent years have seen the inexorable rise of more objective, falsifiable, mathematical, and computational methods for analyzing patents. Progress in patent analytics has accelerated rapidly in recent years, democratizing, elucidating, and making more rigorous the interpretation of patent data.
Maternal systemic inflammation during pregnancy may restrict embryo−fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal−newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53–0.76) and 0.40 (0.33–0.50) g/l, and 0.56 (0.25–1.54) and 1.07 (0.43–2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10−6), and 0.45 (P = 3.1 × 10−5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10−7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein.
Fast ice flow is associated with the deformation of subglacial sediment. Seismic shear velocities, Vs, increase with the rigidity of material and hence can be used to distinguish soft sediment from hard bedrock substrates. Depth profiles of Vs can be obtained from inversions of Rayleigh wave dispersion curves, from passive or active-sources, but these can be highly ambiguous and lack depth sensitivity. Our novel Bayesian transdimensional algorithm, MuLTI, circumvents these issues by adding independent depth constraints to the inversion, also allowing comprehensive uncertainty analysis. We apply MuLTI to the inversion of a Rayleigh wave dataset, acquired using active-source (Multichannel Analysis of Surface Waves) techniques, to characterise sediment distribution beneath the frontal margin of Midtdalsbreen, an outlet of Norway's Hardangerjøkulen ice cap. Ice thickness (0–20 m) is constrained using co-located GPR data. Outputs from MuLTI suggest that partly-frozen sediment (Vs 500–1000 m s−1), overlying bedrock (Vs 2000–2500 m s−1), is present in patches with a thickness of ~4 m, although this approaches the resolvable limit of our Rayleigh wave frequencies (14–100 Hz). Uncertainties immediately beneath the glacier bed are <280 m s−1, implying that MuLTI cannot only distinguish bedrock and sediment substrates but does so with an accuracy sufficient for resolving variations in sediment properties.
This study investigated the effect of water restriction on wool and blood cortisol concentrations and water consumption patterns in heat-stressed sheep. Nine Corriedale female sheep (average BW=43±6.5 kg) were individually fed diets based on maintenance requirement in metabolic crates. They were assigned to three treatments according to a Latin square design (3×3) for three periods with a 21-day duration for each period (nine sheep per treatment). Treatments included free access to water (FAW), 2 h water restriction (2hWR) and 3 h water restriction (3hWR) after feeding. Average temperature–humidity index in the experimental room was 27.9 throughout the experiment that defines heat stress conditions. Wool samples were taken at the end of each period on day 21. No differences were found in cortisol concentration in each fragment (dried, washed and residual extract) of wool (P<0.05). Total wool cortisol concentration was higher in the 3hWR group than the other treatments (P<0.05). Blood cortisol was not different among the treatments (P>0.05) and resulted in higher variable data compared with wool cortisol. Blood neutrophils and neutrophil/lymphocyte ratio suppressed in FAW and 3hWR groups compared with the 2hWR group (P<0.05). The duration of water consumption recorded after feeding in the 3hWR group was higher than in the 2hWR group when recorded in the afternoon (P<0.01). Water consumption rate was higher in the 3hWR group than in the 2hWR group (P<0.01). However, total water consumed was lower in the 3hWR group compared with other treatments (P>0.05). It can be concluded that wool cortisol provides more precise and accurate data than blood cortisol during heat stress conditions. Water restriction for 3 h after feeding can act as a stressor and is critical for sheep during heat stress as the consumption of water decreases with restriction.
The results reported in this paper are part of a study of the biology and control of black flies in the forests of Eastern Canada conducted on the north shore of the St. Lawrence River, near Baie Comeau, Quebec, during 1954, 1955, and 1956. Reference to this study is made in a review by Peterson and Wolfe (1958). The identification and biology of the black flies of this region has been reported on by Wolfe and Peterson (1959) who also describe the topography of the region. The important feature of this rugged area is an abundance of fast-flowing streams which provide highly suitable environments for the development of black-fly populations.
Data from black fly traps in Deep River over the past 5 years indicate that larvicides applied to breeding sites in streams surrounding the town have substantially reduced the numbers of this pest. Very high numbers occurred in 1972, the result of invasion associated with high westerly and northerly winds at a critical period of time or with heavy protective snow cover during the preceding winter. The lowest population levels occurred in 1975, when treatment included a stream near the town which had not been treated previously. The results indicate that with proper stream management it is possible to substantially reduce the nuisance value of black flies in a small northern town.
Investigations of the March Gravels of Northam Pit, Eye, Cambridgeshire, have provided previously undescribed molluscan, ostracod and foraminiferal faunas together with pollen spectra, which enable a detailed palaeoenvironmental synthesis to be developed. The sediments were laid down in brackish-water conditions and a temperate environment, during a Late Pleistocene temperate stage.
A new allele of microphthalmia (mi) in the mouse was discovered among the progeny of a male that had been treated with the potent mutagen ethylnitrosourea. Homozygotes have white coats, mildly defective bone resorption and small eyes (about 60% of the normal size) with very little pigmentation. The iris and retina are abnormal, there is no vitreous body and iris pigmentation is restricted to a rim around the pupil. No haematopoietic defect was detected. Genetic studies showed that the mutation is linked to lurcher (Lc) on chromosome 6 and crosses with Miwh/ + and mi/ + mice indicate that the mutation is allelic with these two alleles of the microphthalmia (mi) locus. We designate the new allele microphthalmia-defective iris (midi). Some midi/+ heterozygotes (including the original mutant animal showed a bright ‘red-reflex’ when light was shone directly into the eye and this may have been caused by reduced choroidal pigmentation. Otherwise midi/ + mice appeared normal. The midi/mi compound heterozygotes had white coats, small eyes, and small teeth; bone resorption was more severely defective than in midi/mi homozygotes. The osteopetrosis was corrected by treatment of midi/mi mice with parental mi/ + bone marrow which suggests that the defect is intrinsic to midi/mi marrow cells. The coats of midi/Miwh compound heterozygotes were white; the irises were more symmetrical and iris pigmentation was less severely reduced than in midi/midi homozygotes but pupil dilation appeared to be restricted. Partial complementation occurred in the midi/Miwh compound heterozygotes with respect to eye size, which was usually near normal.
A total of 701 comets received names between July 2005 and June 2008. Comets observed only from the SOHO and STEREO missions, as well as further comets recognized from the long-defunct SOLWIND satellite, accounted for 520 of these names.