Mammography screening can lead to overdiagnosis-that is, screen-detected breast cancer that would not have caused symptoms or signs in the remaining lifetime. There is no consensus about the ...frequency of breast cancer overdiagnosis.
To estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer.
Bayesian inference of the natural history of breast cancer using individual screening and diagnosis records, allowing for nonprogressive preclinical cancer. Combination of fitted natural history model with life-table data to predict the rate of overdiagnosis among screen-detected cancer under biennial screening.
Breast Cancer Surveillance Consortium (BCSC) facilities.
Women aged 50 to 74 years at first mammography screen between 2000 and 2018.
Screening mammograms and screen-detected or interval breast cancer.
The cohort included 35 986 women, 82 677 mammograms, and 718 breast cancer diagnoses. Among all preclinical cancer cases, 4.5% (95% uncertainty interval UI, 0.1% to 14.8%) were estimated to be nonprogressive. In a program of biennial screening from age 50 to 74 years, 15.4% (UI, 9.4% to 26.5%) of screen-detected cancer cases were estimated to be overdiagnosed, with 6.1% (UI, 0.2% to 20.1%) due to detecting indolent preclinical cancer and 9.3% (UI, 5.5% to 13.5%) due to detecting progressive preclinical cancer in women who would have died of an unrelated cause before clinical diagnosis.
Exclusion of women with first mammography screen outside BCSC.
On the basis of an authoritative U.S. population data set, the analysis projected that among biennially screened women aged 50 to 74 years, about 1 in 7 cases of screen-detected cancer is overdiagnosed. This information clarifies the risk for breast cancer overdiagnosis in contemporary screening practice and should facilitate shared and informed decision making about mammography screening.
National Cancer Institute.
Purpose
We examined whether eccrine sweat glands ion reabsorption rate declined with age in 35 adults aged 50–84 years. Aerobic fitness (VO
2max
) and salivary aldosterone were measured to see if ...they modulated ion reabsorption rates.
Methods
During a passive heating protocol (lower leg 42 °C water submersion) the maximum ion reabsorption rates from the chest, forearm and thigh were measured, alongside other thermophysiological responses. The maximum ion reabsorption rate was defined as the inflection point in the slope of the relation between galvanic skin conductance and sweat rate.
Results
The maximum ion reabsorption rate at the forearm, chest and thigh (0.29 ± 0.16, 0.33 ± 0.15, 0.18 ± 0.16 mg/cm
2
/min, respectively) were weakly correlated with age (
r
≤ − 0.232,
P
≥ 0.05) and salivary aldosterone concentrations (
r
≤ − 0.180,
P
≥ 0.179). A moderate positive correlation was observed between maximum ion reabsorption rate at the thigh and VO
2max
(
r
= 0.384,
P
= 0.015). Salivary aldosterone concentration moderately declined with age (
r
= − 0.342,
P
= 0.021). Whole body sweat rate and pilocarpine-induced sudomotor responses to iontophoresis increased with VO
2max
(
r
≥ 0.323,
P
≤ 0.027) but only moderate (
r
= − 0.326,
P
= 0.032) or no relations (
r
≤ − 0.113,
P
≥ 0.256) were observed with age.
Conclusion
The eccrine sweat glands’ maximum ion reabsorption rate is not affected by age, spanning 50–84 years. Aldosterone concentration in an aged cohort does not appear to modulate the ion reabsorption rate. We provide further support for maintaining cardiorespiratory fitness to attenuate any decline in sudomotor function.
Brain-derived neutrophic factor (BDNF) is a member of the neutrophin family that is known to activate the high-affinity tropomyosin-related receptor kinase B (TrkB). This study aimed to clarify the ...clinical and biological significance of the BDNF/TrkB pathway in gastric cancer.
We analysed BDNF and TrkB expression in gastric cancer samples by real-time reverse transcription PCR and immunohistochemistry. To investigate the biological role of BDNF/TrkB axis, recombinant human BDNF (rhBDNF) and the Trk antagonist K252a were used for in vitro and in vivo analysis.
The BDNF expression at the invasive front of primary tumours was significantly elevated compared with that in the tumour core and adjacent normal mucosa. Increased BDNF expression at the invasive front was significantly correlated with factors reflecting disease progression, and poor prognosis. Increased co-expression of the BDNF/TrkB axis was significantly correlated with poor prognosis. Gastric cancer cells expressed BDNF, and administration of rhBDNF promoted proliferation, migration, invasion, and inhibition of anoikis. These effects were generally inhibited by K252a. In an in vivo assay, BDNF(+)/TrkB(+) gastric cancer cells injected into nude mice established peritoneal dissemination, whereas K252a inhibited tumour growth.
The BDNF/TrkB pathway might be deeply involved in gastric cancer disease progression.
Abstract This report presents the results of the work by a joint task force of the International and European Restless Legs Syndrome Study Groups and World Association of Sleep Medicine that revised ...and updated the current standards for recording and scoring leg movements (LM) in polysomnographic recordings (PSG). First, the background of the decisions made and the explanations of the new rules are reported and then specific standard rules are presented for recording, detecting, scoring and reporting LM activity in PSG. Each standard rule has been classified with a level of evidence. At the end of the paper, Appendix 1 provides algorithms to aid implementation of these new standards in software tools. There are two main changes introduced by these new rules: 1) Candidate LM (CLM), are any monolateral LM 0.5-10 s long or bilateral LM 0.5-15 s long; 2) periodic LM (PLM) are now defined by runs of at least 4 consecutive CLM with an intermovement interval ≥10 and ≤90 s without any CLM preceded by an interval <10 s interrupting the PLM series. There are also new options defining LM associated with respiratory events. The PLM rate may now first be determined for all CLM not excluding any related to respiration (providing a consistent number across studies regardless of the rules used to define association with respiration) and, subsequently, the PLM rate should also be calculated without considering the respiratory related events. Finally, special considerations for pediatric studies are provided. The expert visual scoring of LM has only been altered by the new standards to require accepting all LM >0.5 s regardless of duration, otherwise the technician scores the LM as for the old standards. There is a new criterion for the morphology of LM that applies only to computerized LM detection to better match expert visual detection. Available automatic scoring programs will incorporate all the new rules so that the new standards should reduce technician burden for scoring PLMS.
Presenteeism refers to being present at work but experiencing reduced productivity due to health problems, and has been known to be related to sleep loss. Workers commonly sleep longer on days off ...than on workdays, and presenteeism may be reduced with extended sleep on days off.
This study aimed to determine the association between sleep duration both on workdays and days off and presenteeism.
The participants were 1967 workers who engaged in work for 5 days and rested for 2 days weekly. Sleep duration was classified into less than 6 hours (short; S), 6-8 hours (medium; M), and 9 hours or longer (long; L), for workdays and days off, respectively. Presenteeism was assessed using the World Health Organization Health and Work Performance Questionnaire.
On both workdays and days off, compared to medium sleep duration, short sleep duration was significantly associated with increased odds of presenteeism. The odds of presenteeism were significantly increased for S-S (odds ratio OR 2.17, 95% confidence interval CI1.40-3.37), S-M (OR 1.59, 95% CI 1.14-2.22), S-L (OR 2.71, 95% CI 1.05-7.00), and M-S (OR 6.82, 95% CI 2.71-17.17) combined sleep duration for workdays and days off, respectively, compared to an M-M (reference).
Sleep loss on workdays cannot be compensated for with longer sleep on days off. This study suggests that sufficient sleep duration on both workdays and days off is important for reducing presenteeism.
ABSTRACT The origin of the extragalactic γ-ray background (EGB) has been debated for some time. The EGB comprises the γ-ray emission from resolved and unresolved extragalactic sources, such as ...blazars, star-forming galaxies, and radio galaxies, as well as radiation from truly diffuse processes. This Letter focuses on the blazar source class, the most numerous detected population, and presents an updated luminosity function and spectral energy distribution model consistent with the blazar observations performed by the Fermi-Large Area Telescope (LAT). We show that blazars account for 50 % of the EGB photons (>0.1 GeV), and that Fermi-LAT has already resolved ∼70% of this contribution. Blazars, and in particular hard-spectrum sources such as BL Lacs, are responsible for most of the EGB emission above 100 GeV. We find that the extragalactic background light, which attenuates blazars' high-energy emission, is responsible for the high-energy cutoff observed in the EGB spectrum. Finally, we show that blazars, star-forming galaxies, and radio galaxies can naturally account for the amplitude and spectral shape of the background in the 0.1-820 GeV range, leaving only modest room for other contributions. This allows us to set competitive constraints on the dark matter annihilation cross section.
Arterial spin-labeling MR imaging permits safe, repeated CBF measurement. We investigated the potential and technical factors of arterial spin-labeling imaging in assessing cerebrovascular reactivity ...to acetazolamide.
The regional CBF was measured in 8 healthy volunteers by use of a 3D pseudocontinuous arterial spin-labeling sequence. Arterial spin labeling imaging was performed at rest and every 2 minutes after intravenous acetazolamide injection. To evaluate repeatability, regional CBF measurements were repeated without acetazolamide within an imaging session and on a separate day. Additionally, arterial spin-labeling imaging was performed at rest and after acetazolamide injection with different postlabeling delays, and regional cerebrovascular reactivity was calculated.
The regional CBF started to increase immediately after acetazolamide injection and peaked at approximately 10 minutes, followed by a slow decrease. Favorable intrasession repeatability was demonstrated, especially when scanner tuning was omitted between scans. Rest regional CBF was slightly lower with a postlabeling delay of 2525 ms than with a postlabeling delay of 1525 ms, and the postlabeling delay-dependent difference was more evident for regional CBF after acetazolamide injection and regional cerebrovascular reactivity.
Arterial spin-labeling imaging allows evaluation of the distribution, magnitude, and time course of cerebrovascular response to acetazolamide. The influence of the postlabeling delay on the estimated cerebrovascular reactivity should be noted.
Objectives
To evaluate the efficacy, safety, and tolerability of perampanel, a selective, non‐competitive, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonist, as an ...adjunctive treatment for patients with refractory partial‐onset seizures (POS) from Asia‐Pacific.
Materials & methods
This multicenter, randomized, double‐blind, placebo‐controlled trial (ClinicalTrials.gov identifier: NCT01618695) involved patients aged ≥12 years with refractory POS (receiving 1‐3 antiepileptic drugs). Patients were randomized (1:1:1:1) to receive once‐daily placebo or perampanel 4, 8, or 12 mg over a 6‐week titration and 13‐week maintenance double‐blind period. Enzyme‐inducing antiepileptic drugs were equally stratified between groups. The primary efficacy endpoint was percent change in POS frequency per 28 days (double‐blind phase vs baseline). Other efficacy endpoints included ≥50% responder rate and seizure freedom. Treatment‐emergent adverse events (TEAEs) were also monitored.
Results
Of 710 randomized patients, seizure frequency data were available for 704 patients. Median percent changes in POS frequency per 28 days indicated dose‐proportional reductions in seizure frequency: −10.8% with placebo and −17.3% (P = .2330), −29.0% (P = .0003), and −38.0% (P < .0001) with perampanel 4, 8, and 12 mg, respectively. In total, 108 (15.3%) patients discontinued treatment; 44 (6.2%) due to TEAEs. TEAEs occurring in ≥5% of patients, and reported at least twice as frequently with perampanel vs placebo, included dizziness and irritability.
Conclusions
Adjunctive perampanel (8 and 12 mg/d) significantly improved seizure control in patients with refractory POS. Safety and tolerability were acceptable at daily doses of perampanel 4‐12 mg.
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