Parametric pumping at finite frequency

We report on a first principles theory for analyzing the parametric electron pump at a finite frequency. The pump is controlled by two pumping parameters with phase difference $\phi$. In the zero frequency limit, our theory predicts the well known result that the pumped current is proportional to $\sin\phi$. For the more general situation of a finite frequency, our theory predicts a non-vanishing pumped current even when the two driving forces are in phase, in agreement with the recent experimental results. We present the physical mechanism behind the nonzero pumped current at $\phi=0$, which we found to be due to photon-assisted processes

Patterns of variability of retinol levels in a harbour porpoise population from an unpolluted environment

Organochlorine compounds (OC) are known to induce vitamin A (retinoids) deficiency in mammals, which may be associated with impairment of immunocompetence, reproduction and growth. This makes retinoids a potentially useful biomarker of organochlorine impact on marine mammals. However, use of retinoids as a biomarker requires knowledge about its intrapopulation patterns of variation in natural conditions, information which is not currently available. We investigated these patterns in a cetacean population living in an unpolluted environment. 100 harbour porpoises Phocoena phocoena from West Greenland were sampled during the 1995 hunting season. Sex, age, morphometrics, nutritive condition, and retinol (following saponification) and OC levels in blubber were determined for each individual. OC levels found were extremely low and therefore considered unlikely to affect the population adversely: mean blubber concentrations, expressed on an extractable basis, were 2.04 (SD = 1.1) ppm for PCBs and 2.76 (SD = 1.66) ppm for tDDT. The mean blubber retinol concentration for the overall population was 59.66 (SD = 45.26) mu g g(-1). Taking into account the high contribution of blubber to body mass, blubber constitutes a significant body site for retinoid deposition in harbour porpoises. Retinol concentrations did not differ significantly between geographical regions or sexes, but they did correlate significantly (p <0.001) with age. Body condition, measured by determining the lipid content of the blubber, did not have a significant effect on retinol levels but the individuals examined were considered to be in an overall good nutritive condition. It is concluded that measurement of retinol concentrations in blubber samples is feasible and has a potential for use as a biomarker of organochlorine exposure in cetaceans. However, in order to do so, biological information, particularly age, is critical for the correct assessment of physiological impac

Characterization of potential endocrine-related health effects at low-dose levels of exposure to PCBs.

This article addresses issues related to the characterization of endocrine-related health effects resulting from low-level exposures to polychlorinated biphenyls (PCBs). It is not intended to be a comprehensive review of the literature but reflects workshop discussions. "The Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels," workshop provided a forum to discuss the methods and data needed to improve risk assessments of endocrine disruptors. This article contains an overview of endocrine-related (estrogen and thyroid system) interactions and other low-dose effects of PCBs. The data set on endocrine effects includes results obtained from mechanistic methods/ and models (receptor based, metabolism based, and transport protein based), as well as from (italic)in vivo(/italic) models, including studies with experimental animals and wildlife species. Other low-dose effects induced by PCBs, such as neurodevelopmental and reproductive effects and endocrine-sensitive tumors, have been evaluated with respect to a possible causative linkage with PCB-induced alterations in endocrine systems. In addition, studies of low-dose exposure and effects in human populations are presented and critically evaluated. A list of conclusions and recommendations is included

Optimal quantum pump in the presence of a superconducting lead

We investigate the parametric pumping of a hybrid structure consisting of a normal quantum dot, a normal lead and a superconducting lead. Using the time dependent scattering matrix theory, we have derived a general expression for the pumped electric current and heat current. We have also derived the relationship among the instantaneous pumped heat current, electric current, and shot noise. This gives a lower bound for the pumped heat current in the hybrid system similar to that of the normal case obtained by Avron et al

Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: Study protocol of a pragmatic multicentre non-inferiority randomized controlled trial

Background: Approximately 6.2% of women in the USA and 3.7% of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2%. Nonetheless, SSRI use during pregnancy is still controversial. On the one hand SSRIs may be toxic to the intrauterine developing child, while on the other hand relapse or recurrence of depression during pregnancy poses risks for both mother and child. Among patients and professionals there is an urgent need for evidence from randomized studies to make rational decisions regarding continuation or tapering of SSRIs during pregnancy. At present, no such studies exist. Methods/Design: 'Stop or Go' is a pragmatic multicentre randomized non-inferiority trial among 200 pregnant women with a gestational age of less than 16weeks who use SSRIs without clinically relevant depressive symptoms. Women allocated to the intervention group will receive preventive cognitive therapy with gradual, guided discontinuation of SSRIs under medical management (STOP). Women in the control group will continue the use of SSRIs (GO). Primary outcome will be the (cumulative) incidence of relapse or recurrence of maternal depressive disorder (as assessed by the Structured Clinical Inter

Tapering Antidepressants While Receiving Digital Preventive Cognitive Therapy During Pregnancy: An Experience Sampling Methodology Trial

Background: Previous studies indicated that affect fluctuations, the use of antidepressant medication (ADM), as well as depression during pregnancy might have adverse effects on offspring outcomes. The aim of the current proof-of-principle study is to explore the effect of tapering ADM while receiving online preventive cognitive therapy (PCT) on pregnant women and the offspring as compared to pregnant women continuing ADM. Objectives: We sought to compare positive and negative affect fluctuations in pregnant women receiving online PCT while tapering ADM vs. pregnant women continuing ADM, and to investigate if affect fluctuations in early pregnancy were related to offspring birth weight. Method: An experience sampling methodology (ESM)-trial ran alongside a Dutch randomized controlled trial (RCT) and prospective observational cohort of women using ADM at the start of pregnancy. In the ESM-trial fluctuations of positive and negative affect were assessed in the first 8 weeks after inclusion. Recurrences of depression were assessed up to 12 weeks post-partum, and birth records were used to assess offspring birth weight. The RCT has been registered at the Netherlands Trial Register (NTR4694, https://www.trialregister.nl/trial/4551). Results: In total, 19 pregnant women using ADM at start of their pregnancy participated in the ESM-trial. There were no significant differences in positive and negative affect fluctuations, nor recurrence rates between women receiving PCT while tapering ADM vs. women continuing ADM. We found no association between affect fluctuations, pre-natal depressive symptoms, and birth weight (all p > 0.05). Conclusion: This explorative study showed that tapering ADM while receiving online PCT may protect pregnant women against recurrences of depression and affect fluctuations, without affecting birth weight. There is a high need for more controlled studies focusing on tapering ADM with (online) psychological interventions during pregnancy

Dose-effect of maternal serotonin reuptake inhibitor use during pregnancy on birth outcomes: A prospective cohort study

Background: While antidepressant use during pregnancy is increasingly common, there is concern about the possible effects of in-utero antidepressant exposure on the child. Our objective was to examine whether there is a dose-effect of maternal serotonin reuptake inhibitors (SRI) during pregnancy on birth outcomes. Methods: Women between 12 and 16 weeks of gestation, who were using an SRI, were eligible for participation in this nation-wide prospective observational cohort study. Recruitment took place between April 2015 and February 2018 (n = 145). SRI exposure and psychopathology symptoms were assessed throughout pregnancy. Exposure was defined as SRI standardized dose at 36 weeks of gestation and mean SRI standardized dose over total pregnancy. Multivariable linear and logistic regression were used to examine the associations with birth weight, gestational age at birth, and being small for gestational age. Results: Maternal SRI dose at 36 weeks of gestation was significantly associated with birth weight (adjusted ß = -180.7, 95%CI -301.1;-60.2, p-value < 0.01) as was mean SRI standardized dose during total pregnancy (adjusted ß = -187.3, 95%CI -322.0;-52.6, p-value < 0.01). No significant associations between maternal SRI dose and gestational age or being small for gestational age were observed. Limitations: Although prospective, we cannot make full causal inferences given that we did not randomize women to different dosages. Conclusion: These findings suggest that careful dosing of SRI use during pregnancy may prevent a negative impact on birth weight and indicate the need for further investigation of causality

Eligibility for Liver Transplantation in Patients with Perihilar Cholangiocarcinoma

Background: Liver transplantation (LT) has been performed in a select group of patients presenting with unresectable or primary sclerosing cholangitis (PSC)-associated perihilar cholangiocarcinoma (pCCA) in the Mayo Clinic with a reported 5-year overall survival (OS) of 53% on intention-to-treat analysis. The objective of this study was to estimate eligibility for LT in a cohort of pCCA patients in two tertiary referral centers. Methods: Patients diagnosed with pCCA between 2002 and 2014 were included from two tertiary referral centers in the Netherlands. The selection criteria used by the Mayo Clinic were retrospectively applied to determine the proportion of patients that would have been eligible for LT. Results: A total of 732 consecutive patients with pCCA were identified, of whom 24 (4%) had PSC-associated pCCA. Overall, 154 patients had resectable disease on imaging and 335 patients were ineligible for LT because of lymph node or distant metastases. An age limit of 70 years led to the exclusion of 50 patients who would otherwise be eligible for LT. After applying the Mayo Clinic criteria, only 34 patients (5%) were potentially eligible for LT. Median survival from diagnosis for these 34 patients was 13 months (95% CI 3–23). Conclusion: Only 5% of all patients presenting with pCCA were potentially eligible for LT under the Mayo criteria. Without transplantation, a median OS of about 1 year was observed