Height, age at menarche, and risk of epithelial ovarian cancer

Objective: We hypothesized that the hormonal changes of adolescence influence ovarian cancer risk particularly in younger women. We investigated this possibility by examining the relationship between ovarian cancer and adult height and age at menarche as both factors reflect pubertal hormonal levels. Methods: Participants were a population-based sample of women with incident ovarian cancer (n = 794) and control women randomly selected from the Australian Electoral Roll (n = 855). The women provided comprehensive reproductive and lifestyle data during a standard interview. Results: Although neither height nor age at menarche was significantly related to the risk of ovarian cancer overall, increasing height was associated with increasing risk of the subgroup of mucinous borderline ovarian cancer (odds ratio, 5.3; 95% confidence interval, 1.5-19.1 for women 175 cm compared with women < 160 cm, P-trend = 0.02). Similarly, later age at menarche was associated with increasing risk of mucinous borderline cancers (odds ratio, 3.8; 95% confidence interval, 1.3-11.4 for those with age at menarche >= 44 years compared with those < 12 years, P-trend = 0.003). Women with mucinous borderline cancers were significantly younger than the women diagnosed with invasive cancers (mean 44 versus 57 years; P < 0.0001). Conclusions: Development of mucinous borderline ovarian cancers, predominantly diagnosed in women ages under 50 years, seems to be associated with age at menarche and attained adult height. These results are consistent with our original hypothesis that pubertal levels of reproductive hormones and insulin-like growth factor-I influence ovarian cancer risk in younger women.

The influence of dietary sodium chloride, Arginine : Lysine ratio, and methionine source on apparent ileal digestibility of arginine and lysine in acutely heat-stressed broilers

The present study was carried out to determine the ileal digestibility of Arg and Lys in acutely heatstressed broilers using diets varying in Arg:Lys ratio, NaCl concentration, and Met Source. Male broilers were maintained at 22degreesC from 21 to 33 d of age and then at 32degreesC from 33 to 38 d of age. From 28 to 38 d of age, birds were fed a diet with an Arg:Lys ratio of 1.05 and 3 g of supplemental NaCl/kg of diet with or without L-arg free base to increase the Arg:Lys to 1.35, and with or without 3 g/kg of additional NaCl. Methionine was supplied as equimolar amounts of DL-Met or 2-hydroxy-4-(methylthio)-butanoic acid in a 2 x 2 x 2 design. At 38 d of age, digesta were collected from the terminal ileum, and amino acid analyses were conducted on feed and digesta samples and compared with acid-insoluble ash (dietary celite) to calculate the apparent ileal digestibilities of Lys and Arg. Increasing the NaCl concentration and the presence of HMB significantly decreased the digestibility of both Arg and Lys, whereas increasing the Arg:Lys ratio increased the digestibility of only Arg but did increase BW gain (P = 0.08). An interaction between dietary NaCl and Arg:Lys ratio as well as the 3-way interaction suggested that dietary NaCl could affect the apparent ileal digestibility of Arg and Lys at certain Arg:Lys ratios and the response may be influenced by the Met source.

Lifetime suicide risk in major depression: sex and age determinants

Background: Recent work has demonstrated that the lifetime suicide risk for patients with DSM IV Major Depression cannot mathematically approximate the accepted figure of 15%. Gender and age significantly affect both the prevalence of major depression and suicide risk, Methods: Gender and age stratified calculations were made on the entire population of the USA in 1994 using a mathematical algorithm. Sex specific corrections for under-reporting were incorporated into the design. Results: The lifetime suicide risks for men and women were 7% and 1%, respectively. The combined risk was 3.4%. The male:female ratio for suicide risk in major depression was 10:1 for youths under 25, and 5.6:1 for adults. Conclusions: Suicide in major depression is predominantly a male problem, although complacency towards female sufferers is to be avoided. Diagnosis of major depression is of limited help in predicting suicide risk compared to case specific factors. The male experience of depression that leads to suicide is often not identified as a legitimate medical complaint by either sufferers or professionals. Increasing help-accessing by males is a priority. Clinical implications: Patients with a history of hospitalisation; comorbidity, especially for substance abuse; and who are male, require greater vigilance for suicide risk. It may be that for males che threshold for diagnosing and treating major depression needs to be lowered. Limitations: This research is based on a mathematical algorithm to approximate a life-long longitudinal study that identifies community cases of depression. Our findings therefore rely on the validity of the statistics used. Extrapolation is limited to populations with an actual suicide rate of 17/100,000 or less and a lifetime prevalence of major depression of 17% or more. (C) 1999 Elsevier Science B.V. All rights reserved.

2D strain - a new approach to strain and strain rate: the solution to the angle-dependence of tissue Doppler?

Purpose: Tissue Doppler strain rate imaging (SRI) have been validated and applied in various clinical settings, but the clinical use of this modality is still limited due to time-consuming postprocessing, unfavorable signal to noise ratio and major angle dependency of image acquisition. 2D Strain (2DS) measures strain parameters through automated tissue tracking (Lagrangian strain) rather than tissue velocity regression. We sought to compare the accuracy of this technique with SRI and evaluate whether it overcomes the above limitations. Methods: We assessed 26 patients (13 female, age 60±5yrs) at low risk of CAD and with normal DSE at both baseline and peak stress. End systolic strain (ESS), peak systolic strain rate (SR), and timing parameters were measured by two independent observers using SRI and 2D Strain. Myocardial segments were excluded from the analyses if the insonation angle exceeded 30 degrees or if the segments were not visualized; 417 segments were evaluated. Results: Normal ranges for TVI and CEB approaches were comparable for SR (-0.99 ± 0.39 vs -0.88 ± 0.36, p=NS), ESS (-15.1 ± 6.5 vs -14.9 ± 6.3, p=NS), time to end of systole (174 ± 47 vs 174 ± 53, p=NS) and time to peak SR (TTP; 340 ± 34 vs 375 ± 57). The best correlations between the techniques were for time to end systole (rest r=0.6, p

An examination of the relationship between social locations of Chinese immigrants and their ethnic newspaper dependency

This study drew upon media system dependency theory (MSD) and social identity theory to examine the relationship between social locations of Chinese immigrants and their dependency on Chinese ethnic newspapers. Data was obtained from a survey participated by 265 respondents with Chinese origin but currently residing in Australia. Results indicated that among the three indicators of social location, age appeared to be a strong positive predictor of the dependency on ethnic newspapers for information. Respondents who stayed longer in the host country tended to be more frequent readers of ethnic newspapers as well. Education did not appear as a significant predictor of ethnic newspaper dependency. These findings suggested the need for us to further investigate the impact of ethnic print media on ethnic minorities in the age of various information sources offered by new technologies.

The levels of neopterin, biopterin and the neopterin/biopterin ratio in urine from control subjects and patients with Alzheimer’s disease and Down’s syndrome

The levels of neopterin, biopterin and the neopterin/biopterin ratio (N/B) were measured in urine samples taken from normal young and elderly control subjects, exceptionally healthy elderly control subjects classified according to the ‘Senieur’ protocol and patients with Down’s syndrome (DS) or Alzheimer’s disease (AD). The N/B ratio was approximately unity in control groups with the exception of the normal elderly controls. The levels of neopterin and biopterin declined with age in the exceptionally healthy ‘Senieur’ control group. The N/B ratio was elevated in young and old DS patients as a result of the significant increase in neopterin. Neopterin levels were significantly elevated in AD patients compared with the healthy elderly controls, but this did not result in a significant increase in the N/B ratio in these patients. The N/B ratio increased with age in AD patients as a result of a decline in biopterin. These results suggested that there is a cellular immune reponse in DS and AD patients which in DS, may precede the formation of beta-amyloid deposits in the brain. In addition, there may be a deficiency in tetrahydrobiopterin biosynthesis in AD which becomes more marked with age.

Ranibizumab versus Bevacizumab to treat neovascular age-related macular degeneration:one-year findings from the IVAN Randomized Trial

PURPOSE: To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD). DESIGN: Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560). PARTICIPANTS: People >50 years of age with untreated nAMD in the study eye who read =25 letters on the Early Treatment Diabetic Retinopathy Study chart. METHODS: We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review. MAIN OUTCOME MEASURES: The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs. RESULTS: Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval [CI], -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P

Beta-amyloid (beta/A4) deposition in the medial temporal lobe in Down's syndrome: effects of brain region and patient age

The density of diffuse, primitive, classic and compact beta-amyloid (beta/A4) deposits was studied in the medial temporal lobe in 12 cases of Down's syndrome (DS) from 38 to 67 years of age. Total beta/A4 deposit density was greater in the adjacent cortex compared with regions of the hippocampus, and these differences were similar within each age group of patients. The ratio of the primitive to diffuse deposits was greater in the hippocampus than in the adjacent cortex. Total beta/A4 density did not vary significantly with patient age. However, the density of the diffuse deposits exhibited a parabolic, and the primitive, classic and compact deposits an inverted parabolic, response with age. Hence, in DS, (1) beta/A4 density remains relatively constant with age, (2) differences in beta/A4 density between the hippocampus and adjacent cortex are established at an early age, and (3) mature beta/A4 subtype formation depends on brain region and patient age.

Advancing age and bleeding risk are the strongest barriers to anticoagulant prescription in atrial fibrillation

In clinical practice many patients with atrial fibrillation (AF) at high thromboembolic risk fail to receive adequate oral anticoagulation (OAC) [1]. The complex management of anticoagulant therapy [frequent international normalised ratio (INR) monitoring because of narrow therapeutic window, interaction with food and alcohol, concomitant medications and comorbities], the overestimation of bleeding risk and the underestimation of stroke risk, may partially explain physicians' reluctance to prescribe anticoagulation. In the current issue of Age and Ageing, Pugh and Mead [2] report a systematic review on physicians' attitudes concerning anticoagulant treatment among AF patients. Through surveys (questionnaire, clinical vignette and interview) on hypothetical case scenarios, they have identified the barriers to effective anticoagulant prescription, as follows: increasing age, bleeding risk or previous bleeding, fall risk, co-morbidities (e.g. chronic alcoholism or cognitive impairment) and lack of compliance. In particular, advanced age has been reported as the most striking reason for with-holding anticoagulation, while risk of falls and previous bleeding are also disproportionate barriers to warfarin prescription.

Age-related macular degeneration and modification of systemic complement factor H production through liver transplantation

Purpose: To investigate whether modification of liver complement factor H (CFH) production, by alteration of liver CFH Y402H genotype through liver transplantation (LT), influences the development of age-related macular degeneration (AMD). Design: Multicenter, cross-sectional study. Participants: We recruited 223 Western European patients ≥55 years old who had undergone LT ≥5 years previously. Methods: We determined AMD status using a standard grading system. Recipient CFH Y402H genotype was obtained from DNA extracted from recipient blood samples. Donor CFH Y402H genotype was inferred from recipient plasma CFH Y402H protein allotype, measured using enzyme-linked immunosorbent assays. This approach was verified by genotyping donor tissue from a subgroup of patients. Systemic complement activity was ascertained by measuring levels of plasma complement proteins using an enzyme-linked immunosorbent assay, including substrates (C3, C4), activation products (C3a, C4a, and terminal complement complex), and regulators (total CFH, C1 inhibitor). Main Outcome Measures: We evaluated AMD status and recipient and donor CFH Y402H genotype. Results: In LT patients, AMD was associated with recipient CFH Y402H genotype (P = 0.036; odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.4) but not with donor CFH Y402H genotype (P = 0.626), after controlling for age, sex, smoking status, and body mass index. Recipient plasma CFH Y402H protein allotype predicted donor CFH Y402H genotype with 100% accuracy (n = 49). Plasma complement protein or activation product levels were similar in LT patients with and without AMD. Compared with previously reported prevalence figures (Rotterdam Study), LT patients demonstrated a high prevalence of both AMD (64.6% vs 37.1%; OR, 3.09; P<0.001) and the CFH Y402H sequence variation (41.9% vs 36.2%; OR, 1.27; P = 0.014). Conclusions: Presence of AMD is not associated with modification of hepatic CFH production. In addition, AMD is not associated with systemic complement activity in LT patients. These findings suggest that local intraocular complement activity is of greater importance in AMD pathogenesis. The high AMD prevalence observed in LT patients may be associated with the increased frequency of the CFH Y402H sequence variation. © 2013 by the American Academy of Ophthalmology Published by Elsevier Inc.

Systemic circulatory influences on retinal microvascular function in middle-age individuals with low to moderate cardiovascular risk

Purpose: To investigate the relationship between retinal microvascular reactivity, circulatory markers for CVD risk and systemic antioxidative defence capacity in healthy middle-aged individuals with low to moderate risk of CVD. Methods: Retinal vascular reactivity to flickering light was assessed in 102 healthy participants (46-60 years) by means of dynamic retinal vessel analysis (DVA). Other vascular assessments included carotid intima-media thickness (C-IMT) and blood pressure (BP) measurements. Total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and blood glutathione levels in its reduced (GSH) and oxidized (GSSG) forms were also determined for each participant, along with Framingham risk scores (FRS). Results: Retinal arterial baseline diameter fluctuation (BDF) was independently, significantly and negatively influenced by LDL-C levels (β = -0.53, p = 0.027). Moreover, the arterial dilation slope (SlopeAD) was independently, significantly and positively associated with redox index (GSH: GSSG ratio, β = 0.28, p = 0.016), while the arterial constriction slope (SlopeAC) was significantly and negatively influenced by blood GSH levels (β = -0.20, p = 0.042), and positively associated with FRS (β = 0.25, p = 0.009). Venous BDF and dilation amplitude (DA) were also negatively influenced by plasma LDL-C levels (β = -0.83, p = 0.013; and β = -0.22, p = 0.028, respectively). Conclusions: In otherwise healthy individuals with low to moderate cardiovascular risk, retinal microvascular dilation and constriction responses to stress levels are influenced by systemic antioxidant capacity, and circulating markers for cardiovascular risk.

A Case-Only Genome-wide Association Study of Gender- and Age-specific Risk Markers for Childhood Leukemia

Males and age group 1 to 5 years show a much higher risk for childhood acute lymphoblastic leukemia (ALL). We performed a case-only genome-wide association study (GWAS), using the Illumina Infinium HumanCoreExome Chip, to unmask gender- and age-specific risk variants in 240 non-Hispanic white children with ALL recruited at Texas Children’s Cancer Center, Houston, Texas. Besides statistically most significant results, we also considered results that yielded the highest effect sizes. Existing experimental data and bioinformatic predictions were used to complement results, and to examine the biological significance of statistical results. Our study identified novel risk variants for childhood ALL. The SNP, rs4813720 (RASSF2), showed the statistically most significant gender-specific associations (P < 2 x 10-6). Likewise, rs10505918 (SOX5) yielded the lowest P value (P < 1 x 10-5) for age-specific associations, and also showed the statistically most significant association with age-at-onset (P < 1 x 10-4). Two SNPs, rs12722042 and 12722039, from the HLA-DQA1 region yielded the highest effect sizes (odds ratio (OR) = 15.7; P = 0.002) for gender-specific results, and the SNP, rs17109582 (OR = 12.5; P = 0.006), showed the highest effect size for age-specific results. Sex chromosome variants did not appear to be involved in gender-specific associations. The HLA-DQA1 SNPs belong to DQA1*01:07and confirmed previously reported male-specific association with DQA1*01:07. Twenty one of the SNPs identified as risk markers for gender- or age-specific associations were located in the transcription factor binding sites and 56 SNPs were non-synonymous variants, likely to alter protein function. Although bioinformatic analysis did not implicate a particular mechanism for gender- and age-specific associations, RASSF2 has an estrogen receptor-alpha binding site in its promoter. The unknown mechanisms may be due to lack of interest in gender- and age-specificity in associations. These results provide a foundation for further studies to examine the gender- and age-differential in childhood ALL risk. Following replication and mechanistic studies, risk factors for one gender or age group may have a potential to be used as biomarkers for targeted intervention for prevention and maybe also for treatment.

Geochemistry and age models of sediments from the Celtic margin

The sedimentary sections of three cores from the Celtic margin provide high-resolution records of the terrigenous fluxes during the last glacial cycle. A total of 21 14C AMS dates allow us to define age models with a resolution better than 100 yr during critical periods such as Heinrich events 1 and 2. Maximum sedimentary fluxes occurred at the Meriadzek Terrace site during the Last Glacial Maximum (LGM). Detailed X-ray imagery of core MD95-2002 from the Meriadzek Terrace shows no sedimentary structures suggestive of either deposition from high-density turbidity currents or significant erosion. Two paroxysmal terrigenous flux episodes have been identified. The first occurred after the deposition of Heinrich event 2 Canadian ice-rafted debris (IRD) and includes IRD from European sources. We suggest that the second represents an episode of deposition from turbid plumes, which precedes IRD deposition associated with Heinrich event 1. At the end of marine isotopic stage 2 (MIS 2) and the beginning of MIS 1 the highest fluxes are recorded on the Whittard Ridge where they correspond to deposition from turbidity current overflows. Canadian icebergs have rafted debris at the Celtic margin during Heinrich events 1, 2, 4 and 5. The high-resolution records of Heinrich events 1 and 2 show that in both cases the arrival of the Canadian icebergs was preceded by a European ice rafting precursor event, which took place about 1-1.5 kyr before. Two rafting episodes of European IRD also occurred immediately after Heinrich event 2 and just before Heinrich event 1. The terrigenous fluxes recorded in core MD95-2002 during the LGM are the highest reported at hemipelagic sites from the northwestern European margin. The magnitude of the Canadian IRD fluxes at Meriadzek Terrace is similar to those from oceanic sites.

Age determination of sediment cores of the Golf of Lions

Siliciclastic turbidites represent huge volumes of sediments, which are of particular significance for (1) petroleum researchers, interested in their potential as oil reservoirs and (2) sedimentologists, who aim at understanding sediment transport processes from continent to deep-basins. An important challenge when studying marine turbidites has been to establish a reliable chronology for the deposits. Indeed, conventional marine proxies applied to hemipelagic sediments are often unreliable in detrital clays. In siliciclastic turbidites, those proxies can be used only in hemipelagic intervals, providing a poor constraint on their chronology. In this study, we have used sediments from the Rhône Neofan (NW Mediterranean Sea) to demonstrate that pollen grains can provide a high-resolution chronostratigraphical framework for detrital clays in turbidites. Vegetation changes occurring from the end of Marine Isotopic Stage 3 to the end of Marine Isotopic Stage 2 (from ~30 to ~18 ka cal. BP) are clearly recorded where other proxies have failed previously, mainly because the scarcity of foraminifers in these sediments prevented any continuous Sea Surface Temperature (SST) record and radiocarbon dating to be obtained. We show also that the use of palynology in turbidite deposits is able to contribute to oceanographical and sedimentological purposes: (1) Pinus pollen grains can document the timing of sea-level rise, (2) the ratio between pollen grains transported from the continent via rivers and dinoflagellate cysts (elutriating) allows us to distinguish clearly detrital sediments from pelagic clays. Finally, taken together, all these tools show evidence that the Rhône River disconnected from the canyon during the sea-level rise and thus evidence the subsequent rapid starvation of the neofan at 18.5 ka cal. BP. Younger sediments are hemipelagic: the frequency of foraminifers allowed to date sediments with radiocarbon. First results of Sea Surface Temperature obtained on foraminifers are in good agreement with the dinoflagellate cysts climatic signal. Both provide information on the end of the deglaciation and the Holocene.

(Table 1) Age determination of sediment core KY07-04-PC1

Variations in Mg/Ca-based sea surface temperature and oxygen isotope ratio (d18O) of the surface water in the northern East China Sea (ECS) were reconstructed with high resolution during the last 18 kyr using planktic foraminifera. Millennial-scale variations between warmer, more saline surface water and cooler, less saline surface water were recognized during the early deglacial period and the Holocene, suggesting changes in the mixing ratio between the Kuroshio Water and the Changjiang Diluted Water. Stronger East Asian summer monsoon (EASM) precipitation events in south China are identified at 10.5, 8.8, 7.0, 5.3, 4.7, 2.9, 1.7, and 0.5 ka, based on sea surface salinity (SSS) records of the northern ECS. Weaker EASM precipitation events are also detected at 9.3, 8.3, 7.3, 6.0, 3.3, 2.3, 0.7, and 0.4 ka during the Holocene. These events agree with the maxima in d18O records of stalagmites from various parts of the Changjiang (Yangtze) River drainage. This agreement supports that our SSS record properly captures the millennial-scale dry (less EASM precipitation) events over the drainage basin of the Changjiang River during the Holocene. These dry events are also in good agreement with North Atlantic ice-rafted events, suggesting a teleconnection between North Atlantic climate and the EASM during the Holocene.