The brominated flame retardants (BFRs) hexabromocyclododecane (HBCDD), eight polybrominated diphenyl ethers (PBDEs), and decabromodiphenyl ethane (DBDPE) were measured in 16 pools of human milk from ...Ireland. Concentrations of BDEs-47, -99, −100, −153, and HBCDD were significantly lower (p < 0.05) than those in Irish human milk collected in 2011. In contrast, concentrations of BDE-209 in our study exceeded those in 2011, and while decabromodiphenyl ethane (DBDPE) was not detected in 2011 it was detected in 3 of our samples. This suggests increased use of DBDPE and that while restrictions on the Penta- and Octa-BDE formulations are reducing human exposure, those on Deca-BDE use have yet to reduce body burdens. Estimated exposures for nursing infants to all target BFRs do not suggest a health concern. A one compartment pharmacokinetic model was used to predict body burdens arising from BFR intakes via air, dust and diet. While for most targeted BFRs, predicted and observed body burdens derived from our human milk data compared reasonably well; predicted BDE-209 and DBDPE values were substantially lower than observed. This suggests exposure pathways not included in the model like dermal uptake from fabrics may be important, and highlights knowledge gaps about the human half-lives and bioavailability of these contaminants.
•Significant decline since 2011 of BDEs 47, 99, 100, 153 and HBCDD in Irish human milk.•BDE-209 and DBDPE concentrations and detection frequency higher than in 2011.•Estimated exposures of Irish nursing infants to BFRs do not suggest a health concern.
Policy makers are increasingly looking to a portfolio of options including hydrogen fuel cell technology to simultaneously lower criteria pollutant emissions, greenhouse gas emissions, and petroleum ...consumption in medium and heavy duty vehicles (MHDVs). However, the feasibility of introducing large numbers of fuel cell electric trucks, buses, and vans to the roads remains unclear, in part because the MHDV market is highly diverse in terms of vehicle size, use, and vocation. This paper attempts to answer the question: will hydrogen fuel cell MHDVs be space or weight constrained given their range of operation? The results suggest that most MHDVs have sufficient space for hydrogen storage tanks under the side rails, behind the cab, and/or under the chassis to accommodate 90 percent of each vehicle segment’s daily range of operation, although identifying a standard size, design, and placement of these components may be challenging.
We continue our deep optical imaging survey of the Virgo cluster using the CWRU Burrell Schmidt telescope by presenting B-band surface photometry of the core of the Virgo cluster in order to study ...the cluster's intracluster light (ICL). We find ICL features down to {mu}{sub B} {approx}29 mag arcsec{sup -2}, confirming the results of Mihos et al., who saw a vast web of low surface brightness streams, arcs, plumes, and diffuse light in the Virgo cluster core using V-band imaging. By combining these two data sets, we are able to measure the optical colors of many of the cluster's low surface brightness features. While much of our imaging area is contaminated by galactic cirrus, the cluster core near the cD galaxy, M87, is unobscured. We trace the color profile of M87 out to over 2000'', and find a blueing trend with radius, continuing out to the largest radii. Moreover, we have measured the colors of several ICL features which extend beyond M87's outermost reaches and find that they have similar colors to the M87's halo itself, B - V {approx}0.8. The common colors of these features suggest that the extended outer envelopes of cD galaxies, such as M87, may be formed from similar streams, created by tidal interactions within the cluster, that have since dissolved into a smooth background in the cluster potential.
Exposure to moisture and elevated temperatures usually results in significant degradation of organic thin film transistor (OTFT) performance. Typical observations include reduced mobility, unstable ...threshold voltage and the appearance of hysteresis in electrical characteristics. In this contribution we investigate the effects of environmental conditions on OTFTs based on DNTT, a high-mobility, small-molecule, organic semiconductor, with polystyrene (PS) as the gate insulator. Device characteristics were measured after consecutive 30-min exposures to a relative humidity (RH) that was gradually increased from 20% to 80% with temperature fixed at 20 °C and for temperatures increasing from 20 °C to 90 °C with RH held at 10%. Despite significant negative shifts in turn-on and threshold voltages, only slight changes in the hole mobility were observed at the highest RH and temperature. The DNTT density of states (DoS) extracted from transfer characteristics in the linear regime using the Grünewald approach showed little change with environmental conditions. In all cases, the DoS decreased from ∼1 × 1020 down to ∼1 × 1017 cm−3 eV−1 in the 0.45 eV energy range above the hole mobility edge. Some evidence was obtained for a weak trap feature between ∼0.25 and 0.35 eV above the mobility edge. These results confirm the high stability of DNTT as a semiconducting material and that OTFT instability observed here is associated almost entirely with a flatband voltage shift caused by hole trapping in the polystyrene gate dielectric or at the polystyrene/DNTT interface.
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•Effect of relative humidity and temperature on DNTT transistors.•Grünewald approach used to determine DNTT Density of States (DoS).•DoS insensitive to relative humidity.•Slight increase in DoS ∼0.3 eV above mobility edge with increasing temperature.•Instability in VON and VT associated with hole trapping in the gate insulator.
Suicidal ideation or behavior (SIB) is a symptom of major depressive disorder (MDD). This study evaluated health care resource utilization (HRU) and costs of commercially insured adults who had ...diagnosed MDD with acute SIB (MDSI).
Adults with MDSI (index date: first SIB claim) and controls without MDD or suicide-related claims (random index date) were identified using
,
codes in the OptumHealth Care Solutions, Inc. database (October 2014 to March 2017). Adults with < 12 months of plan enrollment pre-index and/or selected psychiatric comorbidities were excluded. MDSI and control cohorts were matched 1:1 on demographics and comorbidities. HRU and costs were compared between matched cohorts during up to 1 and 12 months post-index (inclusive) using regressions adjusted for baseline costs.
Among patients with MDSI (n = 1,576, mean age = 34 years, 55.6% female), most index events occurred in emergency department (ED; 50.7%) and inpatient (45.2%) settings. The MDSI cohort, compared with the control cohort within 1 and 12 months post-index, respectively, had 157.7 and 28.0 times more inpatient admissions, 16.4 and 5.4 times more ED visits, and 4.9 and 3.2 times more outpatient visits (all
< .01). Incremental health care costs per patient per month in the MDSI compared with the control cohort within 1 and 12 months were $7,839 and $2,757, respectively (both
values < .01). Inpatient and ED costs constituted 70.6% and 16.5% of the total incremental costs, respectively, within the first month of follow-up.
Among commercially insured adults, MDSI was associated with significant economic burden; inpatient and ED services drove incremental costs of the condition. Further assessment of treatment options for this vulnerable patient population is warranted.
The purpose of this study was to investigate the effects of leptin on human uterine contractility in vitro.
Biopsies of human myometrium were obtained at elective cesarean section (n = 18). Dissected ...myometrial strips suspended under isometric conditions, undergoing spontaneous and oxytocin-induced contractions, were exposed to cumulative additions of leptin in the concentration range of 1 nmol/L to 1 μmol/L. Control strips were run simultaneously. Integrals of contractile activity were measured using the PowerLab hardware unit and Chart v3.6 software.
Leptin exerted a potent and cumulative inhibitory effect on spontaneous and oxytocin-induced contractions compared to control strips. The mean maximal inhibition values were as follows: 46.794 ± 5.133% (n = 6;
P < .001) for spontaneous contractions and 42.323 ± 3.692% (n = 6;
P < .001) for oxytocin-induced contractions. There was an apparent reduction in both frequency and amplitude of contractions.
This physiologic inhibitory effect of leptin on uterine contractility may play a role in the dysfunctional labor process associated with maternal obesity, and the resultant high cesarean section rates.
The aim of this study was to compare the effects of oxytocin and ergometrine on the intrinsic contractile parameters of human uterine smooth muscle at term between primiparous and multiparous women.
...Myometrial biopsies were obtained from women undergoing planned caesarean section at term. The biopsies were dissected into eight uniform strips and mounted in tissue baths for isometric recording. The strips were challenged with increasing concentrations of oxytocin and ergometrine. Parameters of contractile activity, including mean contractile force (MCF) and maximum amplitude of contractions (MAMP) were recorded and analysed. Results were compared between primiparous (Group 1) and multiparous (Group 2) women.
Myometrial biopsies were obtained from n = 11 donors (88 tissue strips), of which n = 5 were Group 1 and n = 6 were Group 2. In relation to oxytocin, the MAMP value observed was significantly greater in Group 2 than in Group 1 (151 ± 18mN vs 67 ± 14mN, P < 0.01). Regarding ergometrine, the MCF response was greater in Group 2 samples (24 ± 10 mN) than that in Group 1 (18 ± 2mN) (P < 0.05).
Our findings highlight that women in a first pregnancy have a decreased response to both oxytocin and ergometrine in an in vitro setting when compared with women in a subsequent pregnancy, and this may have clinical implications regarding the management of postpartum haemorrhage in this cohort.
RAD51 is a critical recombinase that functions in concert with auxiliary mediator proteins to direct the homologous recombination (HR) DNA repair pathway. We show that Cys319 RAD51 possesses ...nucleophilic characteristics and is important for irradiation-induced RAD51 foci formation and resistance to inhibitors of poly (ADP-ribose) polymerase (PARP). We have previously identified that cysteine (Cys) oxidation of proteins can be important for activity and modulated via binding to peroxiredoxin 1 (PRDX1). PRDX1 reduces peroxides and coordinates the signaling actions of protein binding partners. Loss of PRDX1 inhibits irradiation-induced RAD51 foci formation and represses HR DNA repair. PRDX1-deficient human breast cancer cells and mouse embryonic fibroblasts display disrupted RAD51 foci formation and decreased HR, resulting in increased DNA damage and sensitization of cells to irradiation. Following irradiation cells deficient in PRDX1 had increased incorporation of the sulfenylation probe DAz-2 in RAD51 Cys319, a functionally-significant, thiol that PRDX1 is critical for maintaining in a reduced state. Molecular dynamics (MD) simulations of dT-DNA bound to a non-oxidized RAD51 protein showed tight binding throughout the simulation, while dT-DNA dissociated from an oxidized Cys319 RAD51 filament. These novel data establish RAD51 Cys319 as a functionally-significant site for the redox regulation of HR and cellular responses to IR.
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•A functionally-significant Cys319 was identified in RAD51 that possesses nucleophilic characteristics.•RAD51 Cys319 plays a central role in RAD51-mediated repair of DNA double strand breaks (DSB).•Loss of peroxiredoxin 1 (PRDX1) impairs DNA DSB repair by homologous recombination and results in DNA damage.•PRDX1 is critical for maintaining RAD51 Cys319 in a reduced state.•Molecular dynamic (MD) simulations suggest ssDNA to dissociate from sulfenylated and not reduced RAD51 Cys319.
This study assessed the healthcare resource utilization (HRU) and cost burden of patients with major depressive disorder (MDD) and acute suicidal ideation or behavior (SIB; MDSI) versus those with ...MDD without SIB and those without MDD.
Adults were selected from the MarketScan® Databases (10/2015–02/2020). The MDSI cohort received an MDD diagnosis within 6 months of a claim for acute SIB (index date). The index date was a random MDD claim in the MDD without SIB cohort and a random date in the non-MDD cohort. Patients had continuous eligibility ≥12 months pre- and ≥1 month post-index. HRU and costs were compared during 1- and 12-month post-index periods between MDSI and control cohorts matched 1:1 on demographics.
The MDSI cohort included 73,242 patients (mean age 35 years, 60.6% female, 37.2% Medicaid coverage). At 1 month post-index, the MDSI cohort versus the MDD without SIB/non-MDD cohorts had 12.8/67.2 times more inpatient admissions and 3.3/8.9 times more emergency department visits; they had 2.9 times more outpatient visits versus the non-MDD cohort (all p < 0.001). The MDSI cohort had incremental mean healthcare costs of $5255 and $6674 per-patient-month versus the MDD without SIB and non-MDD cohorts (all p < 0.001); inpatient costs drove up to 89.5% of incremental costs. At 12 months post-index, HRU and costs remained higher in MDSI versus control cohorts.
SIB are underreported in claims; unobserved confounders may cause bias.
MDSI is associated with substantial excess healthcare costs driven by inpatient costs, concentrated in the first month post-index, and persisting during the following year.
•Excess healthcare resource use and costs of depression with acute suicidal ideation or behavior in the US were estimated•The burden is substantial and concentrated in the provision of acute care•Early interventions and coordination to facilitate routine care may preclude the need for acute treatment
•Increased severity status was associated with incremental burden in patients with TRD.•Inpatient admissions and outpatient visits were key drivers of incremental costs.•Pharmacotherapy use was ...similar across the severity cohorts.
Among patients with major depressive disorder (MDD), those with treatment-resistant depression (TRD) have a higher economic burden. However, the healthcare resource utilization (HRU) and costs may vary by severity status in TRD patients. This study quantified the incremental economic burden of severity status in TRD patients.
In a US database of privately insured employees and dependents (07/01/2009–03/31/2015), a claims-based algorithm identified adult TRD patients who were stratified into mild, moderate, and severe cohorts based on the information in the last observed MDD ICD-9-CM code. HRU and costs of moderate and severe cohorts were compared to those of the mild cohort during the 2-year follow-up after the first antidepressant claim.
Among 6411 TRD patients, 455 (7.1%) were identified as mild, 2153 (33.6%) as moderate, and 1455 (22.7%) as severe. Moderate and severe patients compared to mild had 45% and 150% more inpatient admissions, 65% and 164% more inpatient days, 18% and 54% more emergency department visits and 8% and 10% more outpatient visits per-patient-per-year (PPPY), respectively (all-cause; all p < 0.05). Mean all-cause direct total healthcare costs were $12,123, $16,885, and $18,911 PPPY in mild, moderate, and severe patients, respectively. The all-cause total healthcare cost differences adjusted for baseline characteristics amounted to $3455 in moderate and $5150 in severe versus mild patients, respectively (PPPY; all p < 0.05).
Not all TRD patients had a severity specifier; the severity specifier was not cross-validated against a depression scale.
Increased severity status is associated with incremental economic burden in TRD patients.
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