To evaluate 5-year outcomes after lower limb realignment and test the hypothesis that surgery-induced changes in selected biomechanical risk factors for medial knee osteoarthritis (OA) are associated ...with clinically important improvements.
We prospectively evaluated patient-reported outcomes, full-limb standing radiographs and gait biomechanics before, 6 months (surgery-induced change) and 5 years after medial opening wedge high tibial osteotomy (HTO) in 170 patients (46.4 ± 8.9 years, 135 males) with knee OA and varus alignment. Logistic regression tested the associations of 6-month changes in mechanical axis angle and knee adduction moment with achieving an increase of ≥10 points in the Knee injury and Osteoarthritis Outcome Score (KOOS)4 at 5 years, with and without adjusting for covariates. Gait data were also compared to existing data from healthy controls.
Mean 5-year changes (95% confidence interval (CI)) were: KOOS4: +14.2 (10.8, 17.6); mechanical axis angle: +8.21° (7.58, 8.83); knee adduction moment: −1.49 %BW*Ht (−1.35, −1.63). The postoperative knee adduction moments were typically lower than values for healthy controls. When divided into quartiles, although all strata improved significantly, patients with reductions in knee adduction moment of 1.14–1.74 %BW*Ht (neither largest nor smallest changes) had highest 5-year KOOS4 scores. The 6-month change in knee adduction moment (odds ratios (OR) = 0.38; 95% CI: 0.22, 0.67), preoperative KOOS4 (OR = 0.96; 95% CI: 0.94, 0.99) and preoperative medial tibiofemoral narrowing grade (OR = 0.62; 95% CI: 0.37, 1.00) were negatively associated with having a 5-year clinically important improvement (C-statistic = 0.70).
Substantial improvements in biomechanical risk factors and patient-reported outcomes are observed 5 years after medial opening wedge HTO. The surgery-induced change in load distribution during walking is significantly associated with long-term clinically important improvement.
We report results of a search for oscillations involving a light sterile neutrino over distances of 1.04 and 735 km in a ν_{μ}-dominated beam with a peak energy of 3 GeV. The data, from an exposure ...of 10.56×10^{20} protons on target, are analyzed using a phenomenological model with one sterile neutrino. We constrain the mixing parameters θ_{24} and Δm_{41}^{2} and set limits on parameters of the four-dimensional Pontecorvo-Maki-Nakagawa-Sakata matrix, |U_{μ4}|^{2} and |U_{τ4}|^{2}, under the assumption that mixing between ν_{e} and ν_{s} is negligible (|U_{e4}|^{2}=0). No evidence for ν_{μ}→ν_{s} transitions is found and we set a world-leading limit on θ_{24} for values of Δm_{41}^{2}≲1 eV^{2}.
We modelled the utility of applying a personalised screening approach for colorectal cancer (CRC) when compared with standard age-based screening. In this personalised screening approach, eligibility ...is determined by absolute risk which is calculated from age and polygenic risk score (PRS), where the PRS is relative risk attributable to common genetic variation. In contrast, eligibility in age-based screening is determined only by age.
We calculated absolute risks of CRC from UK population age structure, incidence and mortality rate data, and a PRS distribution which we derived for the 37 known CRC susceptibility variants. We compared the number of CRC cases potentially detectable by personalised and age-based screening. Using Genome-Wide Complex Trait Analysis to calculate the heritability attributable to common variation, we repeated the analysis assuming all common CRC risk variants were known.
Based on the known CRC variants, individuals with a PRS in the top 1% have a 2.9-fold increased CRC risk over the population median. Compared with age-based screening (aged 60: 10-year absolute risk 1.96% in men, 1.19% in women, as per the UK NHS National Bowel Screening Programme), personalised screening of individuals aged 55–69 at the same risk would lead to 16% fewer men and 17% fewer women being eligible for screening with 10% and 8%, respectively, fewer screen-detected cases. If all susceptibility variants were known, individuals with a PRS in the top 1% would have an estimated 7.7-fold increased risk. Personalised screening would then result in 26% fewer men and women being eligible for screening with 7% and 5% fewer screen-detected cases.
Personalised screening using PRS has the potential to optimise population screening for CRC and to define those likely to maximally benefit from chemoprevention. There are however significant technical and operational details to be addressed before any such programme is introduced.
Anticipating and managing the impacts of sea‐level rise for nations astride active tectonic margins requires understanding of rates of sea surface elevation change in relation to coastal land ...elevation. Vertical land motion (VLM) can either exacerbate or reduce sea‐level changes with impacts varying significantly along a coastline. Determining rate, pattern, and variability of VLM near coasts leads to a direct improvement of location‐specific relative sea level (RSL) estimates for coastal hazard risk assessment. Here, we utilize vertical velocity field from interferometric synthetic aperture radar (InSAR) data, calibrated with campaign and continuous Global Navigation Satellite System data, to determine the VLM for the entire coastline of New Zealand. Guided by available knowledge of the seismic cycle, the VLM data infer secular, interseismic rates of land surface deformation. Using the Framework for Assessing Changes to Sea‐level (FACTS), we build probabilistic RSL projections using the same emissions scenarios employed in IPCC Assessment Report 6 and local VLM data at 8,179 sites, thereby enhancing spatial coverage that was previously limited to four tide gauges. We present ensembles of probability distributions of RSL for each scenario to 2150, and for low confidence sea‐level processes to 2300. Where land subsidence is occurring at rates >2 mm/y VLM makes a significant contribution to RSL projections for all scenarios out to 2150. Our approach can be applied to similar locations across the world and has significant implications for adaptation planning, as timing of threshold exceedance for coastal inundation can be brought forward (or delayed) by decades.
Plain Language Summary
This study outlines an approach for deriving probabilistic projections of relative sea‐level change that account for changes in land surface elevation continuously along a coastline. Previous sea‐level projections that included vertical land movements (VLMs) were restricted to tide gauge locations. To provide spatial‐resolution required by practitioners for effective adaptation planning, we have combined elevations measured using satellite radar data with measurements from land‐based Global Navigation Satellite System (GNSS) receivers to build a continuous VLM database showing land uplift and subsidence (sinking) for the entire coastline of New Zealand. We integrate these data into probabilistic sea‐level projection methodology used in Intergovernmental Panel on Climate Change (IPCC) Assessment Report 6 (AR6) for the range of future climate scenarios. Our approach could be applied to any region of the world where the coastline is affected by VLM due to secular tectonic deformation. Downward land movement >2 mm/y makes a significant contribution in sea‐level projections for all climate scenarios out to the end of this century. This means that adaptation planning decision thresholds, such as those linked to the impacts of coastal flooding and inundation, may be brought forward by decades.
Key Points
Anticipating impacts of sea‐level rise for active tectonic margins requires location‐specific knowledge of vertical land movement (VLM)
VLM from geodetic measurements integrated with IPCC AR6 projections to provide probabilistic RSL estimates for dynamic coastlines
Downward VLM > 2 mm/y makes a significant contribution to RSL projections bringing forward adaptation decision thresholds by decades
We report the results of a search for muon-neutrino disappearance by the Main Injector Neutrino Oscillation Search. The experiment uses two detectors separated by 734 km to observe a beam of ...neutrinos created by the Neutrinos at the Main Injector facility at Fermi National Accelerator Laboratory. The data were collected in the first 282 days of beam operations and correspond to an exposure of 1.27e20 protons on target. Based on measurements in the Near Detector, in the absence of neutrino oscillations we expected 336 +/- 14 muon-neutrino charged-current interactions at the Far Detector but observed 215. This deficit of events corresponds to a significance of 5.2 standard deviations. The deficit is energy dependent and is consistent with two-flavor neutrino oscillations according to delta m-squared = 2.74e-3 +0.44/-0.26e-3 eV^2 and sin^2(2 theta) > 0.87 at 68% confidence level.
2D covalent organic frameworks (2D COFs) are a unique materials platform that combines covalent connectivity, structural regularity, and molecularly precise porosity. However, 2D COFs typically form ...insoluble aggregates, thus limiting their processing via additive manufacturing techniques. In this work, colloidal suspensions of boronate‐ester‐linked 2D COFs are used as a spray‐coating ink to produce large‐area 2D COF thin films. This method is synthetically general, with five different 2D COFs prepared as colloidal inks and subsequently spray‐coated onto a diverse range of substrates. Moreover, this approach enables the deposition of multiple 2D COF materials simultaneously, which is not possible by polymerizing COFs on substrates directly. When combined with stencil masks, spray‐coated 2D COFs are rapidly deposited as thin films larger than 200 cm2 with line resolutions below 50 µm. To demonstrate that this deposition scheme preserves the desirable attributes of 2D COFs, spray‐coated 2D COF thin films are incorporated as the active material in acoustic sensors. These 2D‐COF‐based sensors have a 10 ppb limit‐of‐quantification for trimethylamine, which places them among the most sensitive sensors for meat and seafood spoilage. Overall, this work establishes a scalable additive manufacturing technique that enables the integration of 2D COFs into thin‐film device architectures.
High‐resolution, large‐scale fabrication of 2D covalent organic framework (COF) thin films is achieved by spray‐coating colloidal inks of these materials. Using this additive manufacturing approach, 2D COF thin films are integrated into acoustic sensing platforms. These sensors achieve superlative detection of volatile amines including a limit‐of‐quantification of 10 ppb for trimethylamine, which is a target analyte for the detection of food spoilage.
A fundamental goal of the Earth Science community is to understand how perturbations on Earth's surface are preserved in the stratigraphic record. Recent Source to Sink (S2S) studies of the Waipaoa ...Sedimentary System (WSS), New Zealand, are synthesized herein to provide a holistic perspective of the processes that generate, transport and preserve sedimentary strata and organic carbon on the Waipaoa margin in the late Quaternary. Rapid uplift associated with subduction processes and weak sedimentary units have conspired to generate rapid rates of incision and erosion in the Waipaoa catchment since the Last Glacial Maximum (LGM). We show that although much of the sediment exported offshore during this time interval originated from valley excavation, a substantial portion emanated from hillslopes, mostly through deep-seated landslide and earthflow processes that were vigorous during periods of rapid fluvial incision just prior to the Pleistocene–Holocene transition. Lacustrine sediments deposited in naturally-dammed 7-ky-old Lake Tutira provide a record of Holocene environmental controls on upper catchment sedimentation in the WSS, with 1400 storms identified. Storm frequency is modulated by the waxing and waning of atmospheric teleconnections between the tropics and Antarctica. Furthermore, clear long-term changes in sediment yield are evident from the Lake Tutira record following human settlement as conversion to pasture is accompanied by a 3-fold increase in the long-term lake sediment accumulation rate.
Whereas there is ample evidence that Waipaoa River flood deposits are routinely deposited offshore in the sheltered confines of Poverty Bay, over the longer term, waves and currents subsequently resuspend and transport these deposits both landward (sandy fraction) and seaward (finer fraction). Thus, the timing of sediment supply to areas of net sediment accumulation is more often driven by wave events that are not associated with river flooding. Therefore, we conclude that asynchronicity of river-sediment delivery and of wave resuspension in most instances precludes the direct preservation of flood events in the stratigraphic record of the Waipaoa Shelf. Over the longer term, the sediment package preserved on the shelf and slope since the LGM can be explained in large measure by sequence-stratigraphic models forced by varying sea level and ongoing tectonic deformation of the margin. As sea level rose, sediment supply to the slope was reduced by about a factor of 5 due to shelf trapping. Despite this reduction, turbidites are found at similar frequency throughout the LGM–Present, as the dominant trigger appears to be subduction earthquakes, with large ones having a return interval of about 200±100years. Sediment-budget exercises that consider both modern (river discharge versus centennial accumulation rates) and post-LGM (terrestrial production versus offshore isopachs) mass balances indicate that about half of the total sediment production from the Waipaoa escapes the study area. Moreover, a coupled sediment transport-hydrodynamic model and observations of textural trends on the shelf indicate that a large fraction of the sediment is carried outside the study area along the shelf to the northeast by the river plume or by combined current/wave activity. Therefore, we conclude that the WSS is an open system with sediment escape from the present day through the LGM.
The organic matter associated with sediment as it moves from upland source to marine sink is a product of particle history, and provides a record of materials that have cycled over timescales of days to millions of years. The ubiquity of fossil Organic Carbon (OC) in both the terrestrial and marine realms of the Waipaoa attests both to the chronic nature of its source, crumbling mudstones further destabilized by land use, and its biogeochemical recalcitrance. Modern OC persists by virtue of its continual production along the S2S transit, and is buried and preserved within the adjacent marine depocenters. The Waipaoa contrasts with dispersal systems on wide, energetic shelves (e.g., the Amazon and Fly Rivers) where sediment is extensively refluxed in oxygenated overlying water resulting in the biogeochemical incineration of particulate OC. The Waipaoa, like other small mountainous rivers on active margins, exhibits a high riverine OC preservation efficiency (>50%) in its marine depocenters because of the relatively rapid, event-driven accumulation of sediment.
Purpose: To evaluate short-term outcomes of combined ab intemo canaloplasty and trabeculotomy in pseudophakic eyes with openangle glaucoma. Patients and Methods: Series included all pseudophakic eyes ...with open-angle glaucoma treated with up to 360degrees ab interno canaloplasty and up to 360degrees ab interno trabeculotomy using a purpose-engineered device (OMNI, Sight Sciences Inc). Data collected prior to surgery and out to 6-months postoperative. Surgical success defined as a 20% reduction in intraocular pressure (IOP) without increase in glaucoma medication, or discontinuation of at least one glaucoma medication without increase in IOP. Other primary endpoints included mean IOP and number of glaucoma medications. Results: The study included 67 eyes of 52 patients with a mean age of 76.5 + or - 8.9 years. Preoperative mean IOP was 22.1 + or - 8.0 mmHg on 2.3 + or - 1.4 glaucoma medications. Pressure lowering effects were sustained out to 6 months postoperative with a mean IOP of 15.2 + or - 4.9 mmHg (p < 0.001) and mean medication reduction of 0.7 + or - 1.4 (p < 0.001). Surgical success rate was 69.8% (30 eyes) and correlated with preoperative IOP. Two patients required a secondary surgical intervention. Conclusion: Combined ab interno canaloplasty and trabeculotomy as a standalone procedure is an effective means of reducing IOP and medication burden in pseudophakic eyes with open-angle glaucoma. Keywords: glaucoma, pseudophakia, MIGS, Schlemm canal
Chromosomal instability in cancer consists of dynamic changes to the number and structure of chromosomes
. The resulting diversity in somatic copy number alterations (SCNAs) may provide the variation ...necessary for tumour evolution
. Here we use multi-sample phasing and SCNA analysis of 1,421 samples from 394 tumours across 22 tumour types to show that continuous chromosomal instability results in pervasive SCNA heterogeneity. Parallel evolutionary events, which cause disruption in the same genes (such as BCL9, MCL1, ARNT (also known as HIF1B), TERT and MYC) within separate subclones, were present in 37% of tumours. Most recurrent losses probably occurred before whole-genome doubling, that was found as a clonal event in 49% of tumours. However, loss of heterozygosity at the human leukocyte antigen (HLA) locus and loss of chromosome 8p to a single haploid copy recurred at substantial subclonal frequencies, even in tumours with whole-genome doubling, indicating ongoing karyotype remodelling. Focal amplifications that affected chromosomes 1q21 (which encompasses BCL9, MCL1 and ARNT), 5p15.33 (TERT), 11q13.3 (CCND1), 19q12 (CCNE1) and 8q24.1 (MYC) were frequently subclonal yet appeared to be clonal within single samples. Analysis of an independent series of 1,024 metastatic samples revealed that 13 focal SCNAs were enriched in metastatic samples, including gains in chromosome 8q24.1 (encompassing MYC) in clear cell renal cell carcinoma and chromosome 11q13.3 (encompassing CCND1) in HER2
breast cancer. Chromosomal instability may enable the continuous selection of SCNAs, which are established as ordered events that often occur in parallel, throughout tumour evolution.
The NuMI neutrino beam Adamson, P.; Andrews, R.; Augustine, D. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
01/2016, Letnik:
806
Journal Article
Recenzirano
Odprti dostop
This paper describes the hardware and operations of the Neutrinos at the Main Injector (NuMI) beam at Fermilab. It elaborates on the design considerations for the beam as a whole and for individual ...elements. The most important design details of individual components are described. Beam monitoring systems and procedures, including the tuning and alignment of the beam and NuMI long-term performance, are also discussed.
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