The historical surface temperature data set HadCRUT provides a record of surface temperature trends and variability since 1850. A new version of this data set, HadCRUT3, has been produced, benefiting ...from recent improvements to the sea surface temperature data set which forms its marine component, and from improvements to the station records which provide the land data. A comprehensive set of uncertainty estimates has been derived to accompany the data: Estimates of measurement and sampling error, temperature bias effects, and the effect of limited observational coverage on large‐scale averages have all been made. Since the mid twentieth century the uncertainties in global and hemispheric mean temperatures are small, and the temperature increase greatly exceeds its uncertainty. In earlier periods the uncertainties are larger, but the temperature increase over the twentieth century is still significantly larger than its uncertainty.
Radiotherapy is still a treatment of choice for many malignancies, often in combination with other strategies. However, its efficacy is limited by the dose that can be safely administered without ...eliciting serious side-effects, as well as the fact that recurrence is common, particularly in large tumours. Combining radiotherapy with drugs that could sensitise cells to radiation and/or reduce the factors that promote the recovery of the surviving cancer cells is a promising approach. Ionising radiation has been shown to induce senescence and the accumulation of senescent cells creates a microenvironment that facilitates neoplastic growth. This provides a rationale to test the addition of anti-senescent drugs, some of which are already available in the clinic, to radiotherapy protocols. Here, we discuss the relevance of radiotherapy-induced senescent cell accumulation and the potential interventions to minimise its negative effects.
Longitudinal data analysis can improve our understanding of the influences on health trajectories across the life-course. There are a variety of statistical models which can be used, and their ...fitting and interpretation can be complex, particularly where there is a nonlinear trajectory. Our aim was to provide an accessible guide along with applied examples to using four sophisticated modelling procedures for describing nonlinear growth trajectories.
This expository paper provides an illustrative guide to summarising nonlinear growth trajectories for repeatedly measured continuous outcomes using (i) linear spline and (ii) natural cubic spline linear mixed-effects (LME) models, (iii) Super Imposition by Translation and Rotation (SITAR) nonlinear mixed effects models, and (iv) latent trajectory models. The underlying model for each approach, their similarities and differences, and their advantages and disadvantages are described. Their application and correct interpretation of their results is illustrated by analysing repeated bone mass measures to characterise bone growth patterns and their sex differences in three cohort studies from the UK, USA, and Canada comprising 8500 individuals and 37,000 measurements from ages 5-40 years. Recommendations for choosing a modelling approach are provided along with a discussion and signposting on further modelling extensions for analysing trajectory exposures and outcomes, and multiple cohorts.
Linear and natural cubic spline LME models and SITAR provided similar summary of the mean bone growth trajectory and growth velocity, and the sex differences in growth patterns. Growth velocity (in grams/year) peaked during adolescence, and peaked earlier in females than males e.g., mean age at peak bone mineral content accrual from multicohort SITAR models was 12.2 years in females and 13.9 years in males. Latent trajectory models (with trajectory shapes estimated using a natural cubic spline) identified up to four subgroups of individuals with distinct trajectories throughout adolescence.
LME models with linear and natural cubic splines, SITAR, and latent trajectory models are useful for describing nonlinear growth trajectories, and these methods can be adapted for other complex traits. Choice of method depends on the research aims, complexity of the trajectory, and available data. Scripts and synthetic datasets are provided for readers to replicate trajectory modelling and visualisation using the R statistical computing software.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Multiple myeloma is a plasma cell disorder that is characterised by clonal proliferation of malignant plasma cells in the bone marrow, monoclonal paraprotein in the blood or urine and associated ...organ dysfunction. It accounts for approximately 1% of cancers and 13% of haematological cancers. Myeloma arises from an asymptomatic proliferation of monoclonal plasma cells termed monoclonal gammopathy of undetermined significance (MGUS).
MicroRNA expression profiling of serum samples was performed on three patient groups as well as normal controls. Validation of the nine microRNAs detected as promising biomarkers was carried out using TaqMan quantitative reverse transcription PCR. MicroRNA levels in serum were normalised using standard curves to determine the numbers of microRNAs per μl of serum.
Three serum microRNAs, miR-720, miR-1308 and miR-1246, were found to have potential as diagnostic biomarkers in myeloma. Use of miR-720 and miR-1308 together provides a powerful diagnostic tool for distinguishing normal healthy controls, as well as patients with unrelated illnesses, from pre-cancerous myeloma and myeloma patients. In addition, the combination of miR-1246 and miR-1308 can distinguish MGUS from myeloma patients.
We have developed a biomarker signature using microRNAs extracted from serum, which has potential as a diagnostic and prognostic tool for multiple myeloma.
Protein misfolding underlies the pathology of a large number of human disorders, many of which are age-related. An exception to this is preeclampsia, a leading cause of pregnancy-associated morbidity ...and mortality in which misfolded proteins accumulate in body fluids and the placenta. We demonstrate that pregnancy zone protein (PZP), which is dramatically elevated in maternal plasma during pregnancy, efficiently inhibits in vitro the aggregation of misfolded proteins, including the amyloid beta peptide (Aβ) that is implicated in preeclampsia as well as with Alzheimer’s disease. The mechanism by which this inhibition occurs involves the formation of stable complexes between PZP and monomeric Aβ or small soluble Aβ oligomers formed early in the aggregation pathway. The chaperone activity of PZP is more efficient than that of the closely related protein alpha-2-macroglobulin (α₂M), although the chaperone activity of α₂M is enhanced by inducing its dissociation into PZP-like dimers. By immunohistochemistry analysis, PZP is found primarily in extravillous trophoblasts in the placenta. In severe preeclampsia, PZP-positive extravillous trophoblasts are adjacent to extracellular plaques containing Aβ, but PZP is not abundant within extracellular plaques. Our data support the conclusion that the up-regulation of PZP during pregnancy represents a major maternal adaptation that helps to maintain extracellular proteostasis during gestation in humans. We propose that overwhelming or disrupting the chaperone function of PZP could underlie the accumulation of misfolded proteins in vivo. Attempts to characterize extracellular proteostasis in pregnancy will potentially have broad-reaching significance for understanding disease-related protein misfolding.
Revision knee arthroplasty presents a number of challenges, not least of which is obtaining solid primary fixation of implants into host bone. Three anatomical zones exist within both femur and tibia ...which can be used to support revision implants. These consist of the joint surface or epiphysis, the metaphysis and the diaphysis. The methods by which fixation in each zone can be obtained are discussed. The authors suggest that solid fixation should be obtained in at least two of the three zones and emphasise the importance of pre-operative planning and implant selection.
We present J′ and K′ imaging linear polarimetric adaptive optics observations of NGC 1068 using MMT-Pol on the 6.5-m MMT. These observations allow us to study the torus from a magnetohydrodynamical ...(MHD) framework. In a 0.5 arcsec (30 pc) aperture at K′, we find that polarization arising from the passage of radiation from the inner edge of the torus through magnetically aligned dust grains in the clumps is the dominant polarization mechanism, with an intrinsic polarization of 7.0 ± 2.2 per cent. This result yields a torus magnetic field strength in the range of 4–82 mG through paramagnetic alignment, and 139
$^{+11}_{-20}$
mG through the Chandrasekhar–Fermi method. The measured position angle (P.A.) of polarization at K′ is found to be similar to the P.A. of the obscuring dusty component at few parsec scales using infrared interferometric techniques. We show that the constant component of the magnetic field is responsible for the alignment of the dust grains, and aligned with the torus axis on to the plane of the sky. Adopting this magnetic field configuration and the physical conditions of the clumps in the MHD outflow wind model, we estimate a mass outflow rate ≤0.17 M⊙ yr−1 at 0.4 pc from the central engine for those clumps showing near-infrared dichroism. The models used were able to create the torus in a time-scale of ≥105 yr with a rotational velocity of ≤1228 km s−1 at 0.4 pc. We conclude that the evolution, morphology and kinematics of the torus in NGC 1068 can be explained within a MHD framework.
Approximately 1700 Pg of soil carbon (C) are stored in the northern circumpolar permafrost zone, more than twice as much C than in the atmosphere. The overall amount, rate, and form of C released to ...the atmosphere in a warmer world will influence the strength of the permafrost C feedback to climate change. We used a survey to quantify variability in the perception of the vulnerability of permafrost C to climate change. Experts were asked to provide quantitative estimates of permafrost change in response to four scenarios of warming. For the highest warming scenario (RCP 8.5), experts hypothesized that C release from permafrost zone soils could be 19–45 Pg C by 2040, 162–288 Pg C by 2100, and 381–616 Pg C by 2300 in CO
2
equivalent using 100-year CH
4
global warming potential (GWP). These values become 50 % larger using 20-year CH
4
GWP, with a third to a half of expected climate forcing coming from CH
4
even though CH
4
was only 2.3 % of the expected C release. Experts projected that two-thirds of this release could be avoided under the lowest warming scenario (RCP 2.6). These results highlight the potential risk from permafrost thaw and serve to frame a hypothesis about the magnitude of this feedback to climate change. However, the level of emissions proposed here are unlikely to overshadow the impact of fossil fuel burning, which will continue to be the main source of C emissions and climate forcing.
The aim of this consensus was to develop a definition of post-operative fibrosis of the knee.
An international panel of experts took part in a formal consensus process composed of a discussion phase ...and three Delphi rounds.
Post-operative fibrosis of the knee was defined as a limited range of movement (ROM) in flexion and/or extension, that is not attributable to an osseous or prosthetic block to movement from malaligned, malpositioned or incorrectly sized components, metal hardware, ligament reconstruction, infection (septic arthritis), pain, chronic regional pain syndrome (CRPS) or other specific causes, but due to soft-tissue fibrosis that was not present pre-operatively. Limitation of movement was graded as mild, moderate or severe according to the range of flexion (90° to 100°, 70° to 89°, < 70°) or extension deficit (5° to 10°, 11° to 20°, > 20°). Recommended investigations to support the diagnosis and a strategy for its management were also agreed.
The development of standardised, accepted criteria for the diagnosis, classification and grading of the severity of post-operative fibrosis of the knee will facilitate the identification of patients for inclusion in clinical trials, the development of clinical guidelines, and eventually help to inform the management of this difficult condition. Cite this article: Bone Joint J 2016;98-B:1479-88.
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