Delay in symptomatic presentation leading to advanced stage at diagnosis may contribute to poor cancer survival. To inform public health approaches to promoting early symptomatic presentation, we ...aimed to identify risk factors for delay in presentation across several cancers.
We surveyed 2371 patients with 15 cancers about nature and duration of symptoms using a postal questionnaire. We calculated relative risks for delay in presentation (time from symptom onset to first presentation >3 months) by cancer, symptoms leading to diagnosis and reasons for putting off going to the doctor, controlling for age, sex and deprivation group.
Among 1999 cancer patients reporting symptoms, 21% delayed presentation for >3 months. Delay was associated with greater socioeconomic deprivation but not age or sex. Patients with prostate (44%) and rectal cancer (37%) were most likely to delay and patients with breast cancer least likely to delay (8%). Urinary difficulties, change of bowel habit, systemic symptoms (fatigue, weight loss and loss of appetite) and skin symptoms were all common and associated with delay. Overall, patients with bleeding symptoms were no more likely to delay presentation than patients who did not have bleeding symptoms. However, within the group of patients with bleeding symptoms, there were significant differences in risk of delay by source of bleeding: 35% of patients with rectal bleeding delayed presentation, but only 9% of patients with urinary bleeding. A lump was a common symptom but not associated with delay in presentation. Twenty-eight percent had not recognised their symptoms as serious and this was associated with a doubling in risk of delay. Embarrassment, worry about what the doctor might find, being too busy to go to the doctor and worry about wasting the doctor's time were also strong risk factors for delay, but were much less commonly reported (<6%).
Approaches to promote early presentation should aim to increase awareness of the significance of cancer symptoms and should be designed to work for people of the lowest socioeconomic status. In particular, awareness that rectal bleeding is a possible symptom of cancer should be raised.
Bacteria belonging to the genus
are the first inhabitants of the oral cavity, which can be acquired right after birth and thus play an important role in the assembly of the oral microbiota. In this ...article, we discuss the different oral environments inhabited by streptococci and the species that occupy each niche. Special attention is given to the taxonomy of
, because this genus is now divided into eight distinct groups, and oral species are found in six of them. Oral streptococci produce an arsenal of adhesive molecules that allow them to efficiently colonize different tissues in the mouth. Also, they have a remarkable ability to metabolize carbohydrates via fermentation, thereby generating acids as byproducts. Excessive acidification of the oral environment by aciduric species such as
is directly associated with the development of dental caries. However, less acid-tolerant species such as
and
produce large amounts of alkali, displaying an important role in the acid-base physiology of the oral cavity. Another important characteristic of certain oral streptococci is their ability to generate hydrogen peroxide that can inhibit the growth of
. Thus, oral streptococci can also be beneficial to the host by producing molecules that are inhibitory to pathogenic species. Lastly, commensal and pathogenic streptococci residing in the oral cavity can eventually gain access to the bloodstream and cause systemic infections such as infective endocarditis.
We present the fifth portion of an unbiased survey of the Galactic plane, |b| ≤ 2°, for 6668-MHz methanol masers. This section of the survey completes the Galactic longitude range visible to the ...Parkes radio telescope, incorporating the longitude range 20°–60°. Within this section of the survey we find 265 methanol masers, 64 new to the survey, bringing the total number of methanol masers detected across the full longitude coverage (186°, through 0°, to 60°) to 972 sources.
In order to determine the location of the gamma-ray emission site in blazars, we investigate the time-domain relationship between their radio and gamma-ray emission. Light curves for the brightest ...detected blazars from the first 3 yr of the mission of the Fermi Gamma-ray Space Telescope are cross-correlated with 4 yr of 15 GHz observations from the Owens Valley Radio Observatory 40 m monitoring programme. The large sample and long light-curve duration enable us to carry out a statistically robust analysis of the significance of the cross-correlations, which is investigated using Monte Carlo simulations including the uneven sampling and noise properties of the light curves. Modelling the light curves as red noise processes with power-law power spectral densities, we find that only one of 41 sources with high-quality data in both bands shows correlations with significance larger than 3σ (AO 0235+164), with only two more larger than even 2.25σ (PKS 1502+106 and B2 2308+34). Additionally, we find correlated variability in Mrk 421 when including a strong flare that occurred in 2012 July–September. These results demonstrate very clearly the difficulty of measuring statistically robust multiwavelength correlations and the care needed when comparing light curves even when many years of data are used. This should be a caution. In all four sources, the radio variations lag the gamma-ray variations, suggesting that the gamma-ray emission originates upstream of the radio emission. Continuous simultaneous monitoring over a longer time period is required to obtain high significance levels in cross-correlations between gamma-ray and radio variability in most blazars.
ABSTRACT We present 1625 new 15 GHz (2 cm) VLBA images of 295 jets associated with active galactic nuclei (AGNs) from the MOJAVE and 2 cm VLBA surveys, spanning observations between 1994 August 31 ...and 2013 August 20. For 274 AGNs with at least 5 VLBA epochs, we have analyzed the kinematics of 961 individual bright features in their parsec-scale jets. A total of 122 of these jets have not been previously analyzed by the MOJAVE program. In the case of 451 jet features that had at least 10 epochs, we also examined their kinematics for possible accelerations. At least half of the well-sampled features have non-radial and/or accelerating trajectories, indicating that non-ballistic motion is common in AGN jets. Since it is impossible to extrapolate any accelerations that occurred before our monitoring period, we could only determine reliable ejection dates for of those features that had significant proper motions. The distribution of maximum apparent jet speeds in all 295 AGNs measured by our program to date is peaked below , with very few jets with apparent speeds above . The fastest speed in our survey is , measured in the jet of the quasar PKS 0805−07, and is indicative of a maximum jet Lorentz factor of ∼50 in the parent population. An envelope in the maximum jet speed versus redshift distribution of our sample provides additional evidence of this upper limit to the speeds of radio-emitting regions in parsec-scale AGN jets. The Fermi-LAT-detected gamma-ray AGNs in our sample have, on average, higher jet speeds than non-LAT-detected AGNs, indicating a strong correlation between parsec-scale jet speed and the gamma-ray Doppler boosting factor. We have identified 11 moderate-redshift ( ) AGNs with fast apparent speeds ( ) that are strong candidates for future TeV gamma-ray detection. Of the five gamma-ray loud narrow-lined Seyfert I AGNs in our sample, three show highly superluminal jet motions, while the others have sub-luminal speeds. This indicates that some narrow-lined Seyfert I AGNs possess powerful jets with Lorentz factors in excess of 10, and viewing angles less than , consistent with those of typical BL Lac objects and flat-spectrum radio quasars.
Fermi has provided the largest sample of gamma -ray-selected blazars to date. In this work we use a complete sample of flat spectrum radio quasars (FSRQs) detected during the first year of operation ...to determine the luminosity function (LF) and its evolution with cosmic time. The number density of FSRQs grows dramatically up to redshift ~0.5-2.0 and declines thereafter. The redshift of the peak in the density is luminosity dependent, with more luminous sources peaking at earlier times; thus the LF of gamma -ray FSRQs follows a luminosity-dependent density evolution similar to that of radio-quiet active galactic nuclei. Also, using data from the Swift Burst Alert Telescope we derive the average spectral energy distribution (SED) of FSRQs in the 10 keV-300 GeV band and show that there is no correlation between the luminosity at the peak of the gamma -ray emission component and its peak frequency. Using this luminosity-independent SED with the derived LF allows us to predict that the contribution of FSRQs to the Fermi isotropic gamma -ray background is 9.3 super(+1.6) sub(-1.0)% (+ or -3% systematic uncertainty) in the 0.1-100 GeV band. Finally we determine the LF of unbeamed FSRQs, finding that FSRQs have an average Lorentz factor of gamma = 11.7 super(+3.3) sub(-2.2), that most are seen within 5degrees of the jet axis, and that they represent only ~0.1 % of the parent population.
We describe the parsec-scale kinematics of 200 active galactic nucleus (AGN) jets based on 15 GHz Very Long Baseline Array (VLBA) data obtained between 1994 August 31 and 2011 May 1. We present new ...VLBA 15 GHz images of these and 59 additional AGNs from the MOJAVE and 2 cm Survey programs. Nearly all of the 60 most heavily observed jets show significant changes in their innermost position angle over a 12-16 yr interval, ranging from 10degrees to 150degrees on the sky, corresponding to intrinsic variations of ~0degrees.5 to ~2degrees. We have derived vector proper motions for 887 moving features in 200 jets having at least five VLBA epochs. For 557 well-sampled features, there are sufficient data to additionally study possible accelerations. We find that the moving features are generally non-ballistic, with 70% of the well-sampled features showing either significant accelerations or non-radial motions.
Asians are predisposed to a lean heart failure (HF) phenotype. Data on the 'obesity paradox', reported in Western populations, are scarce in Asia and have only utilised the traditional classification ...of body mass index (BMI). We aimed to investigate the association between obesity (defined by BMI and abdominal measures) and HF outcomes in Asia.
Utilising the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry (11 Asian regions including Taiwan, Hong Kong, China, India, Malaysia, Thailand, Singapore, Indonesia, Philippines, Japan, and Korea; 46 centres with enrolment between 1 October 2012 and 6 October 2016), we prospectively examined 5,964 patients with symptomatic HF (mean age 61.3 ± 13.3 years, 26% women, mean BMI 25.3 ± 5.3 kg/m2, 16% with HF with preserved ejection fraction HFpEF; ejection fraction ≥ 50%), among whom 2,051 also had waist-to-height ratio (WHtR) measurements (mean age 60.8 ± 12.9 years, 24% women, mean BMI 25.0 ± 5.2 kg/m2, 7% HFpEF). Patients were categorised by BMI quartiles or WHtR quartiles or 4 combined groups of BMI (low, <24.5 kg/m2 lean, or high, ≥24.5 kg/m2 obese) and WHtR (low, <0.55 thin, or high, ≥0.55 fat). Cox proportional hazards models were used to examine a 1-year composite outcome (HF hospitalisation or mortality). Across BMI quartiles, higher BMI was associated with lower risk of the composite outcome (ptrend < 0.001). Contrastingly, higher WHtR was associated with higher risk of the composite outcome. Individuals in the lean-fat group, with low BMI and high WHtR (13.9%), were more likely to be women (35.4%) and to be from low-income countries (47.7%) (predominantly in South/Southeast Asia), and had higher prevalence of diabetes (46%), worse quality of life scores (63.3 ± 24.2), and a higher rate of the composite outcome (51/232; 22%), compared to the other groups (p < 0.05 for all). Following multivariable adjustment, the lean-fat group had higher adjusted risk of the composite outcome (hazard ratio 1.93, 95% CI 1.17-3.18, p = 0.01), compared to the obese-thin group, with high BMI and low WHtR. Results were consistent across both HF subtypes (HFpEF and HF with reduced ejection fraction HFrEF; pinteraction = 0.355). Selection bias and residual confounding are potential limitations of such multinational observational registries.
In this cohort of Asian patients with HF, the 'obesity paradox' is observed only when defined using BMI, with WHtR showing the opposite association with the composite outcome. Lean-fat patients, with high WHtR and low BMI, have the worst outcomes. A direct correlation between high WHtR and the composite outcome is apparent in both HFpEF and HFrEF.
Asian Sudden Cardiac Death in HF (ASIAN-HF) Registry ClinicalTrials.gov Identifier: NCT01633398.
Natriuretic peptide-guided (NP-guided) treatment of heart failure has been tested against standard clinically guided care in multiple studies, but findings have been limited by study size. We sought ...to perform an individual patient data meta-analysis to evaluate the effect of NP-guided treatment of heart failure on all-cause mortality.
Eligible randomized clinical trials were identified from searches of Medline and EMBASE databases and the Cochrane Clinical Trials Register. The primary pre-specified outcome, all-cause mortality was tested using a Cox proportional hazards regression model that included study of origin, age (<75 or ≥75 years), and left ventricular ejection fraction (LVEF, ≤45 or >45%) as covariates. Secondary endpoints included heart failure or cardiovascular hospitalization. Of 11 eligible studies, 9 provided individual patient data and 2 aggregate data. For the primary endpoint individual data from 2000 patients were included, 994 randomized to clinically guided care and 1006 to NP-guided care. All-cause mortality was significantly reduced by NP-guided treatment hazard ratio = 0.62 (0.45-0.86); P = 0.004 with no heterogeneity between studies or interaction with LVEF. The survival benefit from NP-guided therapy was seen in younger (<75 years) patients 0.62 (0.45-0.85); P = 0.004 but not older (≥75 years) patients 0.98 (0.75-1.27); P = 0.96. Hospitalization due to heart failure 0.80 (0.67-0.94); P = 0.009 or cardiovascular disease 0.82 (0.67-0.99); P = 0.048 was significantly lower in NP-guided patients with no heterogeneity between studies and no interaction with age or LVEF.
Natriuretic peptide-guided treatment of heart failure reduces all-cause mortality in patients aged <75 years and overall reduces heart failure and cardiovascular hospitalization.
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