The interplay between the impact of household's and children's education on the risk of type 2 diabetes and death among older adults: a Danish register-based cohort study.

OBJECTIVES: This study aims to assess the association of household's and children's education on the risk of type 2 diabetes (T2D) and subsequent death. STUDY DESIGN: Danish register-based cohort study. METHODS: In total, 1,021,557 adults were included at their 65th birthday between 2000 and 2018. A multistate survival model was performed to estimate the association of household's and children's education on the transition between the three states: 1) 65th birthday; 2) diagnosis of T2D; and 3) all-cause death. RESULTS: The incidence rates per 1000 person-years were 9.1 for T2D, 18.4 for death without T2D, and 45.0 for death with T2D. Compared to long household's education and children's education, long household's education combined with either short-medium children's education or no children were associated with a 1.49- (95% confidence interval [CI]: 1.44; 1.54] and 1.69-times (95% CI: 1.61;1.78) higher hazard of T2D, respectively. Short-medium household's education combined with either long children's education or no children were associated with 0.64- (95% CI: 0.62; 0.66) and 0.77-times (95% CI: 0.74; 0.79) lower hazard of T2D, respectively. Compared to long household's education and children's education, any other combination of household's and children's education was associated with higher hazards of death both without and with T2D. CONCLUSION: Older adults living in households with long education with no children or children with short-medium education had higher hazards of T2D. Households with short-medium education and no children or children with long education were associated with lower hazards of T2D. Both household's and children's education were associated with higher hazard of death without and with T2D.

C-reactive protein is associated with cognitive performance in a large cohort of euthymic patients with bipolar disorder.

Data support the notion that 40-60% of patients with bipolar disorder (BD) have neurocognitive deficits. It is increasingly accepted that functioning in BD is negatively impacted by these deficits, yet they have not been a successful target for treatment. The biomarkers that predict cognitive deficits in BD are largely unknown, however recent evidence suggests that inflammation may be associated with poorer cognitive outcomes in BD. We measured C-reactive protein (CRP), a marker of systemic inflammation and risk of inflammatory disease, in 222 euthymic BD patients and 52 healthy controls. Within the patient sample, using multivariate analyses of covariance (MANCOVA) we compared cognitive performance of those with high CRP (≥5 mg/L) versus the remaining subjects (<5 mg/L) on a battery of cognitive tests. We evaluated relationships with several other relevant clinical features. We also examined the role of CRP in cognitive decline using a proxy cognitive decline metric, defined as the difference between premorbid and current IQ estimates, in a logistic regression analysis. Approximately 80% of our sample were BD-I, and the remainder were BD-II and 42.6% of our sample had a history of psychosis. We found a statistically significant effect of CRP on cognitive performance on a broad range of tests; participants with CRP ≥ 5 mg/L had worse performance on several measures of executive functioning, MATRICS processing speed and MATRICS reasoning and problem solving relative to those with lower CRP. We also identified CRP as a significant positive predictor of proxy cognitive decline. Our results indicate that elevated CRP is associated with a broad cognitive dysfunction in affectively remitted BD patients. These results may point to a subgroup of patients who might benefit from treatments to reduce inflammation.

Risk factors during pregnancy and birth-related complications in HIV-positive versus HIV-negative women in Denmark, 2002-2014.

OBJECTIVES: We aimed to compare risk factors for adverse pregnancy outcomes in women living with HIV (WLWH) with those in women of the general population (WGP) in Denmark. Further, we estimated risk of pregnancy- or birth-related complications. METHODS: A retrospective cohort study including all WLWH who delivered a live-born child from 2002 to 2014 and WGP, matched by origin, age, year and parity, was carried out. We compared risk factors during pregnancy and estimated risk of pregnancy- and birth-related complications using multivariate logistic regression. RESULTS: A total of 2334 pregnancies in 304 WLWH and 1945 WGP were included in the study. WLWH had more risk factors present than WGP during pregnancy: previous caesarean section (CS) (24.7% versus 16.3%, respectively; P = 0.0001), smoking (14.2% versus 7.5%, respectively; P = 0.0001) and previous perinatal/neonatal death (2.3% versus 0.9%, respectively; P = 0.03). We found no difference between groups regarding gestational diabetes, hypertensive disorders, low birth weights or premature delivery. More children of WLWH had intrauterine growth retardation (IUGR) [adjusted odds ratio (aOR) 1.9; 95% confidence interval (CI) 1.1-3.2; P = 0.02]. Median gestational age and birth weight were lower in children born to WLWH. WLWH had a higher risk of emergency CS (EmCS) (aOR 1.6; 95% CI 1.2-2.1; P = 0.0005) and postpartum haemorrhage (aOR 1.4; 95% CI 1.0-1.9; P = 0.02) but not infection, amniotomy, failure to progress, low activity-pulse-grimace-appearance-respiration (APGAR) score or signs of asphyxia. CONCLUSIONS: WLWH had more risk factors present during pregnancy, similar risks of most pregnancy- and birth-related complications but a higher risk of postpartum haemorrhage and EmCS compared with WGP. Children born to WLWH had lower median birth weights and gestational ages and were at higher risk of IUGR.

Generation and measurement of isolated attosecond pulses with enhanced flux using a two colour synthesized laser field.

We have generated isolated attosecond pulses and performed attosecond streaking measurements using a two-colour synthesized laser field consisting of a strong near-infrared few-cycle pulse and a weaker multi-cycle pulse centred at 400 nm. An actively stabilized interferometer was used to coherently combine the two pulses. Using attosecond streaking we characterised the electric fields of the two pulses and accurately retrieved the spectrum of the multi-cycle pulse. We demonstrated a two-fold increase in the flux of isolated attosecond pulses produced and show that their duration was minimally affected by the presence of the weaker field due to spectral filtering by a multilayer mirror.

Neurocognitive subtypes in patients with bipolar disorder and their unaffected siblings.

BACKGROUND: Our previous work revealed substantial heterogeneity in the cognitive profile of bipolar disorder (BD) due to the presence of three underlying cognitive subgroups characterized as: globally impaired, selectively impaired, or cognitively intact. In an effort to determine whether these subgroups are differentially related to genetic risk for the illness, we investigated whether cognitive deficits were more pronounced in unaffected siblings (UAS) of BD probands within identified clusters. METHODS: Cluster analysis was used to identify cognitive clusters in BD (N = 60). UAS (N = 49) were classified into groups according to their proband sibling's cluster assignment; comparisons were made across all clusters and healthy controls (HCs; N = 71). RESULTS: Three cognitive clusters in BD emerged: a globally impaired (36.7%), a selectively impaired (30%), and a cognitively intact cluster (33.3%). UAS showed a qualitatively similar pattern to their BD siblings; UAS of the globally impaired BD cluster showed verbal memory and general cognitive impairments relative to HCs. In contrast, UAS of the other two clusters did not differ from HCs. CONCLUSIONS: This study corroborates findings from prior work regarding the presence of cognitive heterogeneity in BD. UAS of subjects in the globally impaired BD cluster presented with a qualitatively similar cognitive profile to their siblings and performed worse than all other BD clusters and UAS groups. This suggests that inherited risk factors may be contributing to cognitive deficits more notably in one subgroup of patients with BD, pointing toward differential causes of cognitive deficits in discrete subgroups of patients with the disorder.

Wake and light therapy for moderate-to-severe depression - a randomized controlled trial.

OBJECTIVE: To examine the efficacy of using wake and light therapy as a supplement to standard treatment of hospitalized patients with depression. METHOD: In this randomized, controlled study, 64 patients with moderate-to-severe depression were allocated to standard treatment or to the intervention, which additionally consisted of three wake therapy sessions in one week, 30-min daily light treatment and sleep time stabilization over the entire nine-week study period. RESULTS: Patients in the wake therapy group had a significant decrease in depressive symptoms in week one as measured by HAM-D17 , 17.39 (CI 15.6-19.2) vs. 20.19 (CI 18.3-22.09) (P = 0.04), whereas no statistically significant differences were found between the groups in weeks two to nine. At week nine, the wake therapy group had a significantly larger increase in general self-efficacy (P = 0.001), and waking up during nights was a significantly less frequent problem (1.9 times vs. 3.2) (P = 0.0008). In most weeks, significantly fewer patients in the wake therapy group slept during the daytime, and if they slept, their naps were shorter (week three: 66 min vs. 117 min P = 0.02). CONCLUSION: The antidepressant effect initially achieved could not be maintained during the nine-week study period. However, sleep and general self-efficacy improved.

Solar insolation in springtime influences age of onset of bipolar I disorder.

OBJECTIVE: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. METHOD: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. RESULTS: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). CONCLUSION: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.

Recurrent pregnancy loss: what is the impact of consecutive versus non-consecutive losses?

STUDY QUESTION: Is there a different prognostic impact for consecutive and non-consecutive early pregnancy losses in women with secondary recurrent pregnancy loss (RPL)? SUMMARY ANSWER: Only consecutive early pregnancy losses after the last birth have a statistically significant negative prognostic impact in women with secondary RPL. WHAT IS KNOWN ALREADY: The risk of a new pregnancy loss increases with the number of previous pregnancy losses in patients with RPL. Second trimester losses seem to exhibit a stronger negative impact than early losses. It is unknown whether the sequence of pregnancy losses plays a role for the prognosis in patients with a prior birth. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study of pregnancy outcome in patients with unexplained secondary RPL included in three previously published, Danish double-blinded placebo-controlled trials of intravenous immunoglobulin (IvIg) conducted from 1991 to 2014. No other treatments were given. Patients with documented explained pregnancy losses (ectopic pregnancies and aneuploid miscarriages) were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the 168 patients included in the trials, 127 had secondary RPL and experienced a subsequent live birth or unexplained pregnancy loss in the first pregnancy after giving informed consent to participate in the trials (the index pregnancy). Data analyzed by multivariate analysis included the independent variables age, the number of early pregnancy losses before and after the last birth, respectively and a second trimester pregnancy loss before or after the last birth, respectively. The outcome variable was unexplained loss in the index pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: In patients with secondary RPL, both a late and each early loss before the last birth did not significantly influence the risk of a new pregnancy loss in the index pregnancy: incidence rate ratio (IRR) 1.31 (95% CI 0.62-2.77) and IRR 0.88 (95% CI 0.70-1.11), respectively. In contrast, the impact on risk of pregnancy loss conferred by a late and by each early pregnancy loss occurring after the birth was significant: IRR 2.15 (95% CI 1.57-2.94, P < 0.0001) and IRR 1.14 (95% CI 1.04-1.24, P = 0.002), respectively. LIMITATIONS, REASONS FOR CAUTION: Of the patients, 48% were treated with IvIg, which could influence the results. However, allocation to IvIg was random and prognostic variables were equally distributed in IvIg and placebo-treated patients. WIDER IMPLICATIONS OF THE FINDINGS: A birth in women with secondary RPL eradicates the negative prognostic impact of previous pregnancy losses and this finding is important for our understanding of the pathogenesis. It indicates that only consecutive pregnancy losses should count in the definition of RPL. STUDY FUNDING/COMPETING INTERESTS: There was no particular funding for this study. The authors declare that there is no conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable for two of the included randomized controlled trials. For the last trial: Clinical.Gov NCT00722475.

Returning and staying connected to work after long-term sickness absence.

BACKGROUND: Returning to work (RTW) after long-term sickness absence is a challenge for convalescent workers, co-workers, managers and organizations. Few studies have investigated the post-return phase after long-term sickness absence. AIMS: To investigate the RTW process as experienced by returning workers, co-workers and managers at an emergency care service and a waste disposal company, exploring various perspectives related to early RTW before full recovery and changes in the returning workers' work positions. METHODS: An ethnographic field work design was employed. Returning workers with musculoskeletal disorders, co-workers and managers at two different workplaces participated in individual and group interviews and underwent participant observation over 5 months. These were repeated in a 2-week period after a 4-month interval. Grounded theory analysis was used to identify themes of importance. RESULTS: Four main themes were identified: (1) return before full recovery, (2) changes in work tasks, (3) changes in work position and (4) individual responsibility. CONCLUSIONS: Our results illustrate how returning workers, co-workers and managers at two workplaces experienced the RTW process. The results highlight some of the challenges that occur when returning at an early stage before full recovery is obtained leading to changes in the returning worker's work position.

ANO1 (TMEM16A) in pancreatic ductal adenocarcinoma (PDAC).

Pancreatic ductal adenocarcinoma (PDAC) has one of the worst survival rates of all cancers. ANO1 (TMEM16A) is a recently identified Ca(2+)-activated Cl(-) channel (CaCC) that is upregulated in several tumors. Although ANO1 was subject to extensive studies in the recent years, its pathophysiological function has only been poorly understood. The aim of the present study is to establish the significance of ANO1 in PDAC behavior and demarcate its roles in PDAC from those of the volume-regulated anion channel (VRAC). We performed qPCR and Western blot measurements on different PDAC cell lines (Panc-1, Mia PaCa 2, Capan-1, AsPC-1, BxPC-3) and compared the results to those obtained in a human pancreatic ductal epithelium (HPDE) cell line. All cancer cell lines showed an upregulation of ANO1 on mRNA and protein levels. Whole-cell patch-clamp recordings identified large Ca(2+) and voltage-dependent Cl(-) currents in PDAC cells. Using siRNA knockdown of ANO1 and three ANO1 inhibitors (T16Ainh-A01, CaCCinh-A01, and NS3728), we found that ANO1 is the main constituent of CaCC current in PDAC cells. We further characterized these three inhibitors and found that they had unspecific effects on the free intracellular calcium concentration. Functional studies on PDAC behavior showed that surprisingly inhibition of ANO1 did not influence cellular proliferation. On the other hand, we found ANO1 channel to be pivotal in PDAC cell migration as assessed in wound healing experiments.

Family intentions and personal considerations on postponing childbearing in childless cohabiting and single women aged 35-43 seeking fertility assessment and counselling.

STUDY QUESTION: What characterizes childless women aged 35 years and above seeking fertility assessment and counselling in relation to their reproduction and are there significant differences between single and cohabiting women? SUMMARY ANSWER: Despite the women's advanced age and knowledge of the age-related decline in fecundity, 70% of the single women sought fertility assessment and counselling to gain knowledge regarding the possibility of postponing pregnancy. WHAT IS KNOWN ALREADY: Recent studies have indicated an increasing demand for ovarian reserve testing in women without any known fertility problem to obtain knowledge on their reproductive lifespan and pro-fertility advice. Women postpone their first pregnancy, and maternal age at first birth has increased in western societies over the past two to four decades. Postponed childbearing implies a higher rate of involuntary childlessness, smaller families than desired and declining fertility rates. STUDY DESIGN, SIZE, AND DURATION: Baseline data from a cross-sectional cohort study of 340 women aged 35-43 years examined at the Fertility Assessment and Counselling (FAC) Clinic at Copenhagen University Hospital from 2011 to 2014. The FAC Clinic was initiated to provide individual fertility assessment and counselling. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible women were childless and at least 35 years of age. All completed a web-based questionnaire before and after the consultation including socio-demographic, reproductive, medical, lifestyle and behavioural factors. Consultation by a fertility specialist included transvaginal ultrasound, full reproductive history and AMH measurement. MAIN RESULTS AND THE ROLE OF CHANCE: The study comprised 140 cohabiting and 200 single women. The majority (82%) were well-educated and in employment. Their mean age was 37.4 years. Nonetheless, the main reasons for attending were to obtain knowledge regarding the possibility of postponing pregnancy (63%) and a concern about their fecundity (52%). The majority in both groups (60%) wished for two or more children. The women listed their ideal age at birth of first child and last child as 33 (±4.7) years and 39 (±3.5) years, respectively. Of the single women, 70% would accept use of sperm donation compared with 25% of the cohabiting women (P < 0.001). In general, 45% considered oocyte vitrification for social reasons, yet only 15% were positive towards oocyte donation. The two groups were comparable regarding lifestyle factors, number of previous sexual partners, pregnancies, and ovarian reserve parameters. LIMITATIONS, REASONS FOR CAUTION: The women in the present study were conscious of the risk of infertility with increasing age and attended the FAC Clinic due to a concern about their remaining reproductive lifespan, which in combination with their high educational level could impair the generalizability to the background population. WIDER IMPLICATIONS OF THE FINDINGS: The results indicate that in general women overestimate their own reproductive capacity and underestimate the risk of future childlessness with the continuous postponement of pregnancies.

Ovarian reserve assessment in users of oral contraception seeking fertility advice on their reproductive lifespan.

STUDY QUESTION: To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced? SUMMARY ANSWER: Ovarian reserve parameters defined by anti-Müllerian hormone (AMH), antral follicle count (AFC) and ovarian volume were found to be significantly decreased by 19% (95% CI 9.1-29.3%), 18% (95% CI 11.2-24.8%) and 50% (95% CI 45.1-53.7%) among OC users compared with non-users. WHAT IS KNOWN ALREADY: AMH and AFC have proved to be reliable predictors of ovarian ageing. In women, AMH declines with age and data suggest a relationship with remaining reproductive lifespan and age at menopause. OC may alter parameters related to ovarian reserve assessment but the extent of the reduction is uncertain. STUDY DESIGN, SIZE, DURATION: A cross-sectional study of 887 women aged 19-46 attending the Fertility Assessment and Counselling Clinic (FACC) from 2011 to 2014 comparing ovarian reserve parameters in OC users with non-OC users. PARTICIPANTS/MATERIALS, SETTING, METHODS: The FAC Clinic was initiated to provide individual fertility assessment and counselling. All women were examined on a random cycle day by a fertility specialist. Consultation included; transvaginal ultrasound (AFC, ovarian volume, pathology), a full reproductive history and AMH measurement. Women were grouped into non-users and users of OC (all combinations of estrogen-progestin products and the contraceptive vaginal ring). Non-users included women with an intrauterine device (IUD) or no hormonal contraception. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 887 women, 244 (27.5%) used OC. In a linear regression analyses adjusted for age, ovarian volume was 50% lower (95% CI 45.1-53.7%), AMH was 19% lower (95% CI 9.1-29.3%), and AFC was 18% lower (95% CI 11.2-24.8%) in OC users compared with non-users. Comparison of AMH at values of <10 pmol/l OC was found to have a significant negative influence on AMH (OR 1.6, 95% CI 1.1; 2.4, P = 0.03). Furthermore, we found a significant decrease in antral follicles sized 5-7 mm (P < 0.001) and antral follicles sized 8-10 mm (P < 0.001) but an increase in antral follicles sized 2-4 mm (P = 0.008) among OC users. The two groups (OC users versus non-users) were comparable regarding age, BMI, smoking and maternal age at menopause. LIMITATIONS, REASON FOR CAUTION: The study population comprised women attending the FAC Clinic. Recruitment was based on self-referral, which could imply a potential selection bias. Ovarian reserve was examined at a random cycle day. However, both AMH and AFC can be assessed independently of the menstrual cycle. The accuracy in predicting residual reproductive lifespan is still needed in both users and non-users of OC. WIDER IMPLICATIONS OF THE FINDINGS: OC has a major impact on the ovarian volume, and a moderate impact on AFC and AMH with a shift towards the smaller sized antral follicle subclasses. The most evident reduction occurs in the antral follicles of 5-7 and 8-10 mm with the highest number of AMH secreting granulosa cells. It is essential to be aware of the impact of OC use on ovarian reserve parameters when guiding OC users on their fertility status and reproductive lifespan. STUDY FUNDING/COMPETING INTERESTS: The FAC Clinic was established in 2011 as part of the ReproHigh collaboration. This study received funding through the Capital Region Research Fund and by EU-regional funding. There are no competing interests. TRIAL REGISTRATION NUMBER: The biobank connected to FAC Clinic is approved by the Scientific Ethical Committee (H-1-2011-081).

Use of psychotropic drugs during pregnancy and breast-feeding.

OBJECTIVE: To write clinical guidelines for the use of psychotropic drugs during pregnancy and breast-feeding for daily practice in psychiatry, obstetrics and paediatrics. METHOD: As we wanted a guideline with a high degree of consensus among health professionals treating pregnant women with a psychiatric disease, we asked the Danish Psychiatric Society, the Danish Society of Obstetrics and Gynecology, the Danish Paediatric Society and the Danish Society of Clinical Pharmacology to appoint members for the working group. A comprehensive review of the literature was hereafter conducted. RESULTS: Sertraline and citalopram are first-line treatment among selective serotonin reuptake inhibitor for depression. It is recommended to use lithium for bipolar disorders if an overall assessment finds an indication for mood-stabilizing treatment during pregnancy. Lamotrigine can be used. Valproate and carbamazepin are contraindicated. Olanzapine, risperidone, quetiapine and clozapine can be used for bipolar disorders and schizophrenia. CONCLUSION: It is important that health professionals treating fertile women with a psychiatric disease discuss whether psychotropic drugs are needed during pregnancy and how it has to be administered.

Intravenous immunoglobulin treatment for secondary recurrent miscarriage: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: To determine whether infusions with intravenous immunoglobulin (IVIg) during early pregnancy increase live birth rate in women with secondary recurrent miscarriage compared with placebo. DESIGN: A single-centre, randomised, double-blind, placebo-controlled trial. SETTING: A tertiary centre for recurrent miscarriage in Copenhagen, Denmark. POPULATION: A group of 82 women with unexplained secondary recurrent miscarriage and at least four miscarriages. METHODS: Women were randomly assigned to repeated infusions with IVIg or placebo (albumin) from the time of positive pregnancy test to gestational week 15 or pregnancy loss. MAIN OUTCOME MEASURE: Primary outcome was birth with neonatal survival in all randomised women. RESULTS: In the intention-to-treat analyses, live birth rates were 23/42 (54.8%) in the IVIg and 20/40 (50.0%) in the placebo group, relative risk 1.11 (95% CI 0.70-1.74). In a per protocol analysis, almost identical results were found. The median gestational length at delivery was higher in the IVIg than the placebo group (282 versus 272 days, P = 0.02) but the mean birthweight was not significantly increased. CONCLUSIONS: In this trial, which is the largest so far, IVIg did not increase the live birth rate in patients with secondary recurrent miscarriage and the treatment cannot be recommended in clinical practice.

Relapse Prevention in Major Depressive Disorder After Successful Acute Electroconvulsive Treatment: a 6-month Double-blind Comparison of Three Fixed Dosages of Escitalopram and a Fixed Dose of Nortriptyline - Lessons from a Failed Randomised Trial of the Danish University Antidepressant Group (DUAG-7).

INTRODUCTION: Electroconvulsive treatment (ECT) is an effective treatment for severe depression but carries a risk of relapse in the following months. METHODS: Major depressive disorder patients in a current episode attaining remission from ECT (17-item Hamilton Depression Rating Scale (HAM-D17) score≤9) received randomly escitalopram 10 mg, 20 mg, 30 mg or nortriptyline 100 mg as monotherapies and were followed for 6 months in a multicentre double-blind set-up. Primary endpoint was relapse (HAM-D17≥16). RESULTS: As inclusion rate was low the study was prematurely stopped with only 47 patients randomised (20% of the planned sample size). No statistically significant between-group differences could be detected. When all patients receiving escitalopram were compared with those receiving nortriptyline, a marginal superiority of nortriptyline was found (p=0.08). One third of patients relapsed during the study period, and one third completed. DISCUSSION: Due to small sample size, no valid efficacy inferences could be made. The outcome was poor, probably due to tapering off of non-study psychotropic drugs after randomisation; this has implications for future study designs. ClinicalTrials.gov Identifier: NCT00660062.

T-wave morphology analysis of competitive athletes.

BACKGROUND: T-wave morphology has been shown to be more sensitive than QT and QTc interval to describe repolarization abnormalities. The electrocardiogram (ECG) performed in athletes may manifest abnormalities, including repolarization alterations. The aim of this study was to investigate the characteristics of T-wave morphology features in athletes. METHODS: Eighty male elite athletes, consisting of 40 Tour de France cyclists (age 27±5years), 40 soccer players (age 26±6years) and 40 healthy men (age 27±5years) were included. RESULTS: Sinus bradycardia, left ventricular (LV) hypertrophy, incomplete right bundle branch block and early repolarization were documented in 25 %, 20%, 13% and 14% of athletes, respectively. ECG criteria for LV hypertrophy in 12-lead ECG were more common in cyclists (35%) than in soccer players (5%), P<0.0001. Cyclists and soccer players had significantly longer RR interval, and repolarization features than the control group. CONCLUSIONS: T-wave morphology of athletes is different from non-athletes, depending of the sport. Decreased potassium current in cardiomyocytes associated with LVH may contribute to these changes.

Comparison of Surface Water Quality and Yields from Organically and Conventionally Produced Sweet Corn Plots with Conservation and Conventional Tillage.

Organic agricultural systems are often assumed to be more sustainable than conventional farming, yet there has been little work comparing surface water quality from organic and conventional production, especially under the same cropping sequence. Our objective was to compare nutrient and sediment losses, as well as sweet corn ( L. var. ) yield, from organic and conventional production with conventional and conservation tillage. The experiment was located in the Appalachian Mountains of North Carolina. Four treatments, replicated four times, had been in place for over 18 yr and consisted of conventional tillage (chisel plow and disk) with conventional production (CT/Conven), conservation no-till with conventional production (NT/Conven), conventional tillage with organic production (CT/Org), and conservation no-till with organic production (NT/Org). Water quality (surface flow volume; nitrogen, phosphorus, and sediment concentrations) and sweet corn yield data were collected in 2011 and 2012. Sediment and sediment-attached nutrient losses were influenced by tillage and cropping system in 2011, due to higher rainfall, and tillage in 2012. Soluble nutrients were affected by the nutrient source and rate, which are a function of the cropping system. Sweet corn marketable yields were greater in conventional systems due to high weed competition and reduced total nitrogen availability in organic treatments. When comparing treatment efficiency (yield kg ha /nutrient loss kg ha ), the NT/Conven treatment had the greatest sweet corn yield per unit of nutrient and sediment loss. Other treatment ratios were similar to each other; thus, it appears the most sustainably productive treatment was NT/Conven.

Anoctamin 6 differs from VRAC and VSOAC but is involved in apoptosis and supports volume regulation in the presence of Ca2+.

Anoctamin 6 (ANO6), also known as TMEM16F, has been shown to be a calcium-activated anion channel with delayed calcium activation. The cellular function of ANO6 is under debate, and different groups have come to different conclusions about ANO6's physiological role. Although it is now quite well established that ANO6 is distinct from the volume-regulated anion channel, it is still unclear whether ANO6 or other anoctamins can be activated by cell swelling. In this study, we suggest that ANO1, ANO6, and ANO10 do not contribute to the volume-activated current in ANO-overexpressing HEK293 cells. Furthermore, knock-down of ANO6 in Ehrlich ascites tumor cells (EATC) and Ehrlich-Lettre ascites (ELA) did not decrease but instead significantly increased swelling-activated membrane currents. Knock-down of ANO6 in EATC did not reduce regulatory volume decrease (RVD) in the absence of extracellular calcium, whereas it significantly reduced RVD in the presence of calcium. Interestingly, we found that knock-down of ANO6 in ELA cells resulted in a decrease in cisplatin-induced caspase-3 activity, confirming earlier findings that ANO6 is involved in apoptosis. Finally, knock-down of ANO1 and ANO6 did not affect the volume-sensitive release of taurine in ELA cells. Thus, our data provide evidence that ANO6 cannot be activated directly by cell swelling unless Ca(2+) is present. We also conclude that ANO6 carries a current during RVD, provided extracellular calcium is present. Thus, swelling activation of ANO6 requires the presence of free calcium.

Attosecond pulse walk-off in high-order harmonic generation.

We study the influence of the generation conditions on the group delay of attosecond pulses in high-order harmonic generation in gases. The group delay relative to the fundamental field is found to decrease with increasing gas pressure in the generation cell, reflecting a temporal walk-off due to the dispersive properties of the nonlinear medium. This effect is well reproduced using an on-axis phase-matching model of high-order harmonic generation in an absorbing gas.

Enhanced Risk Stratification for Children and Young Adults with B-Cell Acute Lymphoblastic Leukemia: A Children's Oncology Group Report.

Current strategies to treat pediatric acute lymphoblastic leukemia rely on risk stratification algorithms using categorical data. We investigated whether using continuous variables assigned different weights would improve risk stratification. We developed and validated a multivariable Cox model for relapse-free survival (RFS) using information from 21199 patients. We constructed risk groups by identifying cutoffs of the COG Prognostic Index (PICOG) that maximized discrimination of the predictive model. Patients with higher PICOG have higher predicted relapse risk. The PICOG reliably discriminates patients with low vs. high relapse risk. For those with moderate relapse risk using current COG risk classification, the PICOG identifies subgroups with varying 5-year RFS. Among current COG standard-risk average patients, PICOG identifies low and intermediate risk groups with 96% and 90% RFS, respectively. Similarly, amongst current COG high-risk patients, PICOG identifies four groups ranging from 96% to 66% RFS, providing additional discrimination for future treatment stratification. When coupled with traditional algorithms, the novel PICOG can more accurately risk stratify patients, identifying groups with better outcomes who may benefit from less intensive therapy, and those who have high relapse risk needing innovative approaches for cure.