Serum Calcium and the Risk of Breast Cancer: Findings from the Swedish AMORIS Study and a Meta-Analysis of Prospective Studies

To investigate the association between serum calcium and risk of breast cancer using a large cohort and a systematic review with meta-analysis. From the Swedish Apolipoprotein Mortality Risk (AMORIS) Study we included 229,674 women who had baseline measurements of serum total calcium and albumin. Multivariable Cox regression was used to assess the association between total and albumin-corrected calcium and breast cancer risk. For the systematic review, an electronic search of MEDLINE and EMBASE databases was performed to identify other prospective cohorts assessing the relationship between serum calcium and breast cancer risk. We pooled the results of our AMORIS cohort with other eligible studies in a meta-analysis using a random effects model. I² test was used to assess heterogeneity. In the AMORIS study, 10,863 women were diagnosed with breast cancer (mean follow-up: 19 years). We found an inverse association between total serum calcium and breast cancer when comparing the fourth quartile to the first quartile (HR: 0.94, 95% CI: 0.88-0.99, p value for trend 0.04) and similar results using albumin-corrected calcium. In the systematic review, we identified another two prospective cohorts evaluating pre-diagnostic serum total calcium and breast cancer. Combining these studies and our findings in AMORIS in a meta-analysis showed a protective effect of serum calcium against breast cancer, with a summary RR of 0.80 (95% CI: 0.66-0.97). No substantial heterogeneity was observed. Our findings in AMORIS and the meta-analysis support an inverse association between serum calcium and breast cancer risk, which warrants mechanistic investigations

Resonant nonlinear magneto-optical effects in atoms

In this article, we review the history, current status, physical mechanisms, experimental methods, and applications of nonlinear magneto-optical effects in atomic vapors. We begin by describing the pioneering work of Macaluso and Corbino over a century ago on linear magneto-optical effects (in which the properties of the medium do not depend on the light power) in the vicinity of atomic resonances, and contrast these effects with various nonlinear magneto-optical phenomena that have been studied both theoretically and experimentally since the late 1960s. In recent years, the field of nonlinear magneto-optics has experienced a revival of interest that has led to a number of developments, including the observation of ultra-narrow (1-Hz) magneto-optical resonances, applications in sensitive magnetometry, nonlinear magneto-optical tomography, and the possibility of a search for parity- and time-reversal-invariance violation in atoms.Comment: 51 pages, 23 figures, to appear in Rev. Mod. Phys. in Oct. 2002, Figure added, typos corrected, text edited for clarit

Spatio‐temporal patterns of tree growth as related to carbon isotope fractionation in European forests under changing climate

Aim To decipher Europe-wide spatiotemporal patterns of forest growth dynamics and their associations with carbon isotope fractionation processes inferred from tree rings as modulated by climate warming. Location Europe and North Africa (30‒70°N, 10°W‒35°E). Time period 1901‒2003. Major taxa studied Temperate and Euro-Siberian trees. Methods We characterize changes in the relationship between tree growth and carbon isotope fractionation over the 20th century using a European network consisting of 20 site chronologies. Using indexed tree-ring widths (TRWi), we assess shifts in the temporal coherence of radial growth across sites (synchrony) for five forest ecosystems (Atlantic, Boreal, cold continental, Mediterranean and temperate). We also examine whether TRWi shows variable coupling with leaf-level gas exchange, inferred from indexed carbon isotope discrimination of tree-ring cellulose (Δ13Ci). Results We find spatial autocorrelation for TRWi and Δ13Ci extending over up to 1,000 km among forest stands. However, growth synchrony is not uniform across Europe, but increases along a latitudinal gradient concurrent with decreasing temperature and evapotranspiration. Latitudinal relationships between TRWi and Δ13Ci (changing from negative to positive southwards) point to drought impairing carbon uptake via stomatal regulation for water saving occurring at forests below 60°N in continental Europe. A rise in forest growth synchrony over the 20th century together with increasingly positive relationships between TRWi and Δ13Ci indicate intensifying drought impacts on tree performance. These effects are noticeable in drought-prone biomes (Mediterranean, temperate and cold continental). Main conclusions At the turn of this century, convergence in growth synchrony across European forest ecosystems is coupled with coordinated warming-induced drought effects on leaf physiology and tree growth spreading northwards. Such a tendency towards exacerbated moisture-sensitive growth and physiology could override positive effects of enhanced leaf intercellular CO2 concentrations, possibly resulting in Europe-wide declines of forest carbon gain in the coming decades

Does the age of fine root carbon indicate the age of fine roots in boreal forests?

To test the reliability of the radiocarbon method for determining root age, we analyzed fine roots (originating from the years 1985 to 1993) from ingrowth cores with known maximum root age (1 to 6 years old). For this purpose, three Scots pine (Pinus sylvestris L.) stands were selected from boreal forests in Finland. We analyzed root 14C age by the radiocarbon method and compared it with the above-mentioned known maximum fine root age. In general, ages determined by the two methods (root 14C age and ingrowth core root maximum age) were in agreement with each other for roots of small diameter (<0.5mm). By contrast, in most of the samples of fine roots of larger diameter (1.5-2mm), the 14C age of root samples of 1987-89 exceeded the ingrowth core root maximum age by 1-10 years. This shows that these roots had received a large amount of older stored carbon from unknown sources in addition to atmospheric CO2 directly from photosynthesis. We conclude that the 14C signature of fine roots, especially those of larger diameter, may not always be indicative of root age, and that further studies are needed concerning the extent of possible root uptake of older carbon and its residence time in roots. Keywords: fine root age, Pinus sylvestris, radiocarbon, root carbon, ingrowth cores, tree ringPeer reviewe

Cumulative Prognostic Score Predicting Mortality in Patients Older Than 80 Years Admitted to the ICU.

OBJECTIVES: To develop a scoring system model that predicts mortality within 30 days of admission of patients older than 80 years admitted to intensive care units (ICUs). DESIGN: Prospective cohort study. SETTING: A total of 306 ICUs from 24 European countries. PARTICIPANTS: Older adults admitted to European ICUs (N = 3730; median age = 84 years [interquartile range = 81-87 y]; 51.8% male). MEASUREMENTS: Overall, 24 variables available during ICU admission were included as potential predictive variables. Multivariable logistic regression was used to identify independent predictors of 30-day mortality. Model sensitivity, specificity, and accuracy were evaluated with receiver operating characteristic curves. RESULTS: The 30-day-mortality was 1562 (41.9%). In multivariable analysis, these variables were selected as independent predictors of mortality: age, sex, ICU admission diagnosis, Clinical Frailty Scale, Sequential Organ Failure Score, invasive mechanical ventilation, and renal replacement therapy. The discrimination, accuracy, and calibration of the model were good: the area under the curve for a score of 10 or higher was .80, and the Brier score was .18. At a cut point of 10 or higher (75% of all patients), the model predicts 30-day mortality in 91.1% of all patients who die. CONCLUSION: A predictive model of cumulative events predicts 30-day mortality in patients older than 80 years admitted to ICUs. Future studies should include other potential predictor variables including functional status, presence of advance care plans, and assessment of each patient's decision-making capacity

Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study.

BACKGROUND: The number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival. RESULTS: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81-86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86-1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87-1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7-60.7) vs. 57.1% (95% CI 53.7-60.1), p = 0.85]. CONCLUSIONS: After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival

Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study.

BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)