Twenty five year follow-up for breast cancer incidence and mortality of the Canadian national breast screening study: randomised screening trial

Annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available. Abstract Objective: To compare breast cancer incidence and mortality up to 25 years in women aged 40-59 who did or did not undergo mammography screening. Design: Follow-up of randomised screening trial by centre coordinators, the study’s central office, and linkage to cancer registries and vital statistics databases. Setting: 15 screening centres in six Canadian provinces,1980-85 (Nova Scotia, Quebec, Ontario, Manitoba, Alberta, and British Columbia). Participants: 89 835 women, aged 40-59, randomly assigned to mammography (five annual mammography screens) or control (no mammography). Interventions: Women aged 40-49 in the mammography arm and all women aged 50-59 in both arms received annual physical breast examinations. Women aged 40-49 in the control arm received a single examination followed by usual care in the community. Main outcome measure: Deaths from breast cancer. Results: During the five year screening period, 666 invasive breast cancers were diagnosed in the mammography arm (n=44 925 participants) and 524 in the controls (n=44 910), and of these, 180 women in the mammography arm and 171 women in the control arm died of breast cancer during the 25 year follow-up period. The overall hazard ratio for death from breast cancer diagnosed during the screening period associated with mammography was 1.05 (95% confidence interval 0.85 to 1.30). The findings for women aged 40-49 and 50-59 were almost identical. During the entire study period, 3250 women in the mammography arm and 3133 in the control arm had a diagnosis of breast cancer, and 500 and 505, respectively, died of breast cancer. Thus the cumulative mortality from breast cancer was similar between women in the mammography arm and in the control arm (hazard ratio 0.99, 95% confidence interval 0.88 to 1.12). After 15 years of follow-up a residual excess of 106 cancers was observed in the mammography arm, attributable to over-diagnosis. Conclusion: Annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available. Overall, 22% (106/484) of screen detected invasive breast cancers were over-diagnosed, representing one over-diagnosed breast cancer for every 424 women who received mammography screening in the trial

Meningococcal disease in children in Merseyside, England:a 31 year descriptive study

Meningococcal disease (MCD) is the leading infectious cause of death in early childhood in the United Kingdom, making it a public health priority. MCD most commonly presents as meningococcal meningitis (MM), septicaemia (MS), or as a combination of the two syndromes (MM/MS). We describe the changing epidemiology and clinical presentation of MCD, and explore associations with socioeconomic status and other risk factors. A hospital-based study of children admitted to a tertiary children's centre, Alder Hey Children's Foundation Trust, with MCD, was undertaken between 1977 to 2007 (n = 1157). Demographics, clinical presentations, microbiological confirmation and measures of deprivation were described. The majority of cases occurred in the 1-4 year age group and there was a dramatic fall in serogroup C cases observed with the introduction of the meningococcal C conjugate (MCC) vaccine. The proportion of MS cases increased over the study period, from 11% in the first quarter to 35% in the final quarter. Presentation with MS (compared to MM) and serogroup C disease (compared to serogroup B) were demonstrated to be independent risk factors for mortality, with odds ratios of 3.5 (95% CI 1.18 to 10.08) and 2.18 (95% CI 1.26 to 3.80) respectively. Cases admitted to Alder Hey were from a relatively more deprived population (mean Townsend score 1.25, 95% CI 1.09 to 1.41) than the Merseyside reference population. Our findings represent one of the largest single-centre studies of MCD. The presentation of MS is confirmed to be a risk factor of mortality from MCD. Our study supports the association between social deprivation and MCD

Identification of sequence changes in myosin II that adjust muscle contraction velocity.

The speed of muscle contraction is related to body size; muscles in larger species contract at slower rates. Since contraction speed is a property of the myosin isoform expressed in a muscle, we investigated how sequence changes in a range of muscle myosin II isoforms enable this slower rate of muscle contraction. We considered 798 sequences from 13 mammalian myosin II isoforms to identify any adaptation to increasing body mass. We identified a correlation between body mass and sequence divergence for the motor domain of the 4 major adult myosin II isoforms (β/Type I, IIa, IIb, and IIx), suggesting that these isoforms have adapted to increasing body mass. In contrast, the non-muscle and developmental isoforms show no correlation of sequence divergence with body mass. Analysis of the motor domain sequence of β-myosin (predominant myosin in Type I/slow and cardiac muscle) from 67 mammals from 2 distinct clades identifies 16 sites, out of 800, associated with body mass (padj 0.05). Both clades change the same small set of amino acids, in the same order from small to large mammals, suggesting a limited number of ways in which contraction velocity can be successfully manipulated. To test this relationship, the 9 sites that differ between human and rat were mutated in the human β-myosin to match the rat sequence. Biochemical analysis revealed that the rat-human β-myosin chimera functioned like the native rat myosin with a 2-fold increase in both motility and in the rate of ADP release from the actin-myosin crossbridge (the step that limits contraction velocity). Thus, these sequence changes indicate adaptation of β-myosin as species mass increased to enable a reduced contraction velocity and heart rate

Impact of Naja nigricollis Venom on the Production of Methaemoglobin

Snakebite envenomation is an affliction currently estimated to be killing upwards of 100,000 people annually. Snakebite is associated with a diverse pathophysiology due to the magnitude of variation in venom composition that is observed worldwide. The haemolytic (i.e., lysis of red blood cells) actions of snake venoms are well documented, although the direct impact of venoms on haemoglobin is not fully understood. Here we report on the varied ability of a multitude of snake venoms to oxidise haemoglobin into methaemoglobin. Moreover, our results demonstrate that the venom of an elapid, the black necked spitting cobra, Naja nigricollis, oxidises oxyhaemoglobin (Fe2+) into methaemoglobin (Fe3+) in a time- and concentration-dependent manner that is unparalleled within the 47 viper and elapid venoms evaluated. The treatment of venom with a reducing agent, dithiothreitol (DTT) is observed to potentiate this effect at higher concentrations, and the use of denatured venom demonstrates that this effect is dependent upon the heat-sensitive proteinaceous elements of the venom. Together, our results suggest that Naja nigricollis venom appears to promote methaemoglobin production to a degree that is rare within the Elapidae family, and this activity appears to be independent of proteolytic activities of venom components on haemoglobin

Equatorial winds on Saturn and the stratospheric oscillation

The zonal jets on the giant planets have been thought to be stable in time. A decline in the velocity of Saturn’s equatorial jet has been identified, on the basis of a comparison of cloud-tracking data across two decades, but the differences in cloud speeds have since been suggested to stem from changes in cloud altitude in combination with vertical wind shear, rather than from temporal changes in wind strength at a given height. Here, we combine observations of cloud tracks and of atmospheric temperatures taken by two instruments on the Cassini spacecraft to reveal a significant temporal variation in the strength of the high-altitude equatorial jet on Saturn. Specifically, we find that wind speeds at atmospheric pressure levels of 60 mbar, corresponding to Saturn’s tropopause, increased by about 20 m s^(−1) between 2004 and 2008, whereas the wind speed has been essentially constant over time in the southern equatorial troposphere. The observations further reveal that the equatorial jet intensified by about 60 m s^(−1) between 2005 and 2008 in the stratosphere, that is, at pressure levels of 1–5 mbar. Because the wind acceleration is weaker near the tropopause than higher up, in the stratosphere, we conclude that the semi-annual equatorial oscillation of Saturn’s middle atmosphere is also damped as it propagates downwards

Strong Temporal Variation Over One Saturnian Year: From Voyager to Cassini

Here we report the combined spacecraft observations of Saturn acquired over one Saturnian year (~29.5 Earth years), from the Voyager encounters (1980–81) to the new Cassini reconnaissance (2009–10). The combined observations reveal a strong temporal increase of tropic temperature (~10 Kelvins) around the tropopause of Saturn (i.e., 50 mbar), which is stronger than the seasonal variability (~a few Kelvins). We also provide the first estimate of the zonal winds at 750 mbar, which is close to the zonal winds at 2000 mbar. The quasi-consistency of zonal winds between these two levels provides observational support to a numerical suggestion inferring that the zonal winds at pressures greater than 500 mbar do not vary significantly with depth. Furthermore, the temporal variation of zonal winds decreases its magnitude with depth, implying that the relatively deep zonal winds are stable with time

Saturn's emitted power

Long-term (2004–2009) on-orbit observations by Cassini Composite Infrared Spectrometer are analyzed to precisely measure Saturn's emitted power and its meridional distribution. Our evaluations suggest that the average global emitted power is 4.952 ± 0.035 W m^(−2) during the period of 2004–2009. The corresponding effective temperature is 96.67 ± 0.17 K. The emitted power is 16.6% higher in the Southern Hemisphere than in the Northern Hemisphere. From 2005 to 2009, the global mean emitted power and effective temperature decreased by ~2% and ~0.5%, respectively. Our study further reveals the interannual variability of emitted power and effective temperature between the epoch of Voyager (~1 Saturn year ago) and the current epoch of Cassini, suggesting changes in the cloud opacity from year to year on Saturn. The seasonal and interannual variability of emitted power implies that the energy balance and internal heat are also varying

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente