Prenatal detection and evaluation of differences of sex development: A qualitative interview study of parental perspectives and unmet needs.

OBJECTIVES: Prenatal diagnoses of differences of sex development (DSD) are increasing due to availability of cell-free DNA screening (cell-free DNA screening (cfDNA)). This study explores first-hand experiences of parents whose children had prenatal findings of DSD. METHODS: Eligible parents were identified through chart review at a pediatric center and interviewed about their prenatal evaluation, decision making, informational sources, and support systems. Interviews were coded using a combined inductive and deductive thematic analysis. Parents also completed quantitative measures of decisional regret. RESULTS: Seventeen parents (13 mothers; 4 fathers) of 13 children (with 7 DSD diagnoses) were recruited. Four children had discordance between sex predicted by cfDNA versus prenatal ultrasound, and 2 had non-binary appearing (atypical) genitalia on prenatal ultrasound. Of these 6, 3 were not offered additional prenatal testing or counseling. Most parents described tension between obtaining support through disclosure of their child's diagnosis and preserving their child's autonomy/privacy, highlighting the need for mental health support. CONCLUSION: This is the first study to gather qualitative data from parents whose children had prenatal findings of DSD. We identified multiple targets for intervention to improve care for patients with DSD across the lifespan, including improvements in clinician education, pre- and post-test counseling, and patient education materials.

Cloud condensation nucleation activities of calcium carbonate and its atmospheric ageing products.

Aerosol particles can serve as cloud condensation nuclei (CCN) to form cloud droplets, and its composition is a main factor governing whether an aerosol particle is an effective CCN. Pure mineral dust particles are poor CCN; however, changes in chemical composition of mineral dust aerosol particles, due to heterogeneous reactions with reactive trace gases in the troposphere, can modify their CCN properties. In this study we investigated the CCN activities of CaCO3 (as a surrogate for mineral dust) and its six atmospheric ageing products: Ca(NO3)2, CaCl2, CaSO4, Ca(CH3SO3)2, Ca(HCOO)2, and Ca(CH3COO)2. CaCO3 has a very low CCN activity with a hygroscopicity parameter (κ) of 0.001-0.003. The CCN activities of its potential atmospheric ageing products are significantly higher. For example, we determined that Ca(NO3)2, CaCl2 and Ca(HCOO)2 have κ values of ∼0.50, similar to that of (NH4)2SO4. Ca(CH3COO)2 has slightly lower CCN activity with a κ value of ∼0.40, and the κ value of CaSO4 is around 0.02. We further show that exposure of CaCO3 particles to N2O5 at 0% relative humidity (RH) significantly enhances their CCN activity, with κ values increasing to around 0.02-0.04. Within the experimental uncertainties, it appears that the variation in exposure to N2O5 from ∼550 to 15,000 ppbv s does not change the CCN activities of aged CaCO3 particles. This observation indicates that the CaCO3 surface may be already saturated at the shortest exposure. We also discussed the atmospheric implications of our study, and suggested that the rate of change in CCN activities of mineral dust particles in the troposphere is important to determine their roles in cloud formation.

Remediation of dichloromethane (CH2Cl2) using non-thermal, atmospheric pressure plasma generated in a packed-bed reactor.

This work describes the application of a non-thermal plasma generated in a dielectric barrier packed-bed plasma reactor for the remediation of dichloromethane (CH2Cl2, DCM). The overall aim of this investigation is to identify the role of key process parameters and chemical mechanisms on the removal efficiency of DCM in plasma. The influence of process parameters, such as oxygen concentration, concentration of initial volatile organic compounds (VOCs), energy density, plasma residence time, and background gas, on the removal efficiency of 500 ppm DCM was investigated. Results showed a maximum removal efficiency with the addition of 2-4% oxygen into a nitrogen plasma. It is thought that oxygen concentrations in excess of 4% decreased the decomposition of chlorinated VOCs as a result of ozone and nitrogen oxide formation. Increasing the residence time and the energy density resulted in increasing the removal efficiency of chlorinated VOCs in plasma. A chemical kinetic model has been developed on the basis of the proposed reaction scheme, and the calculation of end product concentrations are in general good agreement with the observed values. With the understanding of the effect of the key parameters, it has been possible to optimize the remediation process.

Dichloroacetate inhibits aerobic glycolysis in multiple myeloma cells and increases sensitivity to bortezomib.

BACKGROUND: Dichloroacetate (DCA), through the inhibition of aerobic glycolysis (the 'Warburg effect') and promotion of pyruvate oxidation, induces growth reduction in many tumours and is now undergoing several clinical trials. If aerobic glycolysis is active in multiple myeloma (MM) cells, it can be potentially targeted by DCA to induce myeloma growth inhibition. METHODS: Representative multiple myeloma cell lines and a myeloma-bearing mice were treated with DCA, alone and in combination with bortezomib. RESULTS: We found that aerobic glycolysis occurs in approximately half of MM cell lines examined, producing on average 1.86-fold more lactate than phorbol myristate acetate stimulated-peripheral blood mononuclear cells and is associated with low-oxidative capacity. Lower doses of DCA (5-10 mM) suppressed aerobic glycolysis and improved cellular respiration that was associated with activation of the pyruvate dehydrogenase complex. Higher doses of DCA (10-25 mM) induced superoxide production, apoptosis, suppressed proliferation with a G0/1 and G2M phase arrest in MM cell lines. In addition, DCA increased MM cell line sensitivity to bortezomib, and combinatorial treatment of both agents improved the survival of myeloma-bearing mice. CONCLUSION: Myeloma cells display aerobic glycolysis and DCA may complement clinically used MM therapies to inhibit disease progression.

Gas purification by nonthermal plasma: a case study of ethylene.

The destruction of ethylene in a dielectric barrier discharge plasma is investigated by the combination of kinetic modeling and experiments, as a case study for plasma-based gas purification. The influence of the specific energy deposition on the removal efficiency and the selectivity toward CO and CO2 is studied for different concentrations of ethylene. The model allows the identification of the destruction pathway in dry and humid air. The latter is found to be mainly initiated by metastable N2 molecules, but the further destruction steps are dominated by O atoms and OH radicals. Upon increasing air humidity, the removal efficiency drops by ± 15% (from 85% to 70%), but the selectivity toward CO and CO2 stays more or less constant at 60% and 22%, respectively. Beside CO and CO2, we also identified acetylene, formaldehyde, and water as byproducts of the destruction process, with concentrations of 1606 ppm, 15033 ppm, and 185 ppm in humid air (with 20% RH), respectively. Finally, we investigated the byproducts generated by the humid air discharge itself, which are the greenhouse gases O3, N2O, and the toxic gas NO2.

Workflow for Management of Gonadal Neoplasm in 2 Patients with Differences of Sex Development Enrolled in an Experimental Gonadal Tissue Cryopreservation Protocol.

OBJECTIVE: To outline our experimental gonadal tissue cryopreservation (GTC) protocol that does not disrupt the standard of care in medically-indicated gonadectomy for patients with differences of sex development, including highlighting the multidisciplinary collaborative protocol for when neoplasm is discovered in these cases. METHODS: Two patients with complete gonadal dysgenesis who were undergoing medically-indicated prophylactic bilateral gonadectomy elected to pursue GTC. Both were found to have germ cell neoplasia in situ on initial pathologic analysis, requiring recall of the gonadal tissue, which had been cryopreserved. RESULTS: Cryopreserved gonadal tissue was successfully thawed and transferred to pathology for complete analysis. No germ cells were identified in either patient nor were found to have malignancy, so further treatment beyond gonadectomy was not indicated. Pathologic information was communicated to each family, including that long-term GTC was no longer possible. CONCLUSION: Organizational planning and coordination between the clinical care teams, GTC laboratory, and pathology were key to handling these cases with neoplasia. Processes that anticipated the possibility of discovering neoplasia within tissue sent to pathology and the potential need to recall GTC tissue to complete staging included (1) documenting the orientation and anatomical position of tissue processed for GTC, (2) defining parameters in which tissue will be recalled, (3) efficiently thawing and transferring GTC tissue to pathology, and (4) coordinating release of pathology results with verbal communication from the clinician to provide context. GTC is desired by many families and at the time of gonadectomy and is (1) feasible for patients with DSD, and (2) did not inhibit patient care in 2 patients with GCNIS.

A-TAPER: A Framework for Deprescribing Medications effectively.

Inappropriate medication use creates avoidable safety issues for older adults. Deprescribing medications that are high risk and/or of minimal benefit is important for reducing morbidity and adverse effects, especially in this population. A variety of deprescribing resources and algorithms are available, but a singular framework to effectively approach and implement the deprescribing of unnecessary medications in practice does not exist. An interprofessional team of pharmacists, geriatricians, and researchers developed a framework to guide providers in deprescribing medications. This framework is represented by the acronym A-TAPER, which stands for Assess medication use, Talk about risks versus benefits, select Alternatives, Plan next steps, Engage patient, and Reduce dose. Within this framework, comprehensive, medication-specific deprescribing toolkits can be created.

Signalling through the insulin receptor.

The insulin receptor substrates function at the heart of the insulin signalling network. It has recently become apparent that the intracellular localisation of these molecules is regulated in a precise manner that is critical for both the generation and the termination of the insulin signal. Some insulin receptor substrate isoforms appear to be associated with an insoluble matrix that resembles the cytoskeleton. When inappropriately dissociated from this matrix the signalling network collapses concomitant with loss of insulin sensitivity.

Synergistic effects of ascorbic acid and thiazolidinedione on secretion of high molecular weight adiponectin from human adipocytes.

AIM: To test the hypothesis that ascorbic acid (AA) and thiazolidinedione (TZD) would have additive effects on HMW adiponectin secretion by virtue of different modes of action. METHODS: We determined the effects of supplementation of AA and/or TZD on expression and secretion of total and HMW adiponectin from human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes in the absence or presence of the proinflammatory cytokine TNFα. RESULTS: AA supplementation significantly increased secretion of HMW adiponectin (1.7-fold) without altering adiponectin expression or total adiponectin secretion. TZD significantly increased expression (3-fold) and secretion of total (1.4-fold) but not HMW adiponectin. Combined supplementation resulted in a significant increase in expression (3-fold) and secretion of total (1.8-fold) and HMW (5-fold) adiponectin. Similar results were seen in cells co-treated with TNFα. CONCLUSIONS: These data show that AA and TZD have synergistic rather than simple additive effects on secretion of HMW adiponectin from human adipocytes and raise the possibility that differences in AA levels may contribute to the variability in adiponectin multimer profiles and efficacy of TZD in humans. Our results also provide a rationale for longitudinal clinical trials investigating the effects of AA supplementation with or without TZD on adiponectin and metabolic profiles.

Chemical vapour deposition of graphene on copper-nickel alloys: the simulation of a thermodynamic and kinetic approach.

Chemical vapour deposition (CVD) of graphene on transition metals is generally believed to be the fabrication route best suited for the production of high-quality large-area graphene sheets. The mechanism of CVD graphene growth is governed by interactions in both the gas phase and at the surface. Here we present a simulation of the CVD graphene growth mechanism which includes thermodynamics, gas phase kinetics and the surface reaction in a sequential manner. The thermodynamic simulation shows that the deposition driving force is the greatest for high carbon to hydrogen ratios and reaches a maximum at around 850 °C. No graphene growth is observed below this temperature. The surface kinetic model also shows that below this temperature, the carbon surface concentration is less than the solubility limit, thus no film can grow. The effect of the reaction chamber geometry on the product concentrations was clear from the gas phase decomposition reactions. The gas residence times studied here (around 0.07 s) show that the optimum gas phase composition is far from that expected at thermodynamic equilibrium. The surface kinetics of CH4 reactions on Ni, Cu and Cu-Ni surfaces shows good agreement with the experimental results for different growth pressures (0.1 to 0.7 mbar), temperatures (600 to 1200 °C) and different Ni thicknesses (25-500 µm). Also, the model works well when substrates with various C solubilities are used. The thermodynamic and kinetic models described here can be used for the design of improved reactors to optimise the production of graphene with differing qualities, either single or multi-layer and sizes. More importantly, the transfer to a continuous process with a moving substrate should also be possible using the model if it is extended from 2D to 3D.

Sediment metal enrichment and ecological risk assessment of ten ports and estuaries in the World Harbours Project.

Ten global harbours were assessed for sediment quality by quantifying the magnitude of anthropogenic change and ecological risk. Anthropogenic change (enrichment) was high for Derwent River and Sydney estuary, moderate for Santander Harbour, Rio de Janeiro and Dublin Port, slight for Hong Kong, minimal for Darwin. All 10 enrichment indices used showed similar results. Derwent River sediment was rated at high ecological risk, followed by Sydney and Santander estuaries with moderate risk. Auckland and Darwin sediments exhibited minimal ecological risk and sediment in the remaining harbours (Dublin, Hong Kong, Ravenna, Ria de Vigo and Rio de Janeiro) were assessed at slight ecological risk. The extraordinary variety of environments and types/quantities/qualities of data investigated resulted in as much a critique and development of methodology, as an assessment of human impact, including unique techniques for elemental normalisation and contaminant classification. Recommendations for an improved technical framework for sediment quality assessment are provided.

Moving flame experiment with liquid mercury: possible implications for the venus atmosphere.

A bunsen flame rotated under a cylindrical annulus filled with liquid mercury forces the liquid mercury to rotate in a direction counter to that of the rotating flame. The rate of rotation of the liquid is several times greater than that of the flame. This observation may provide an explanation for the high velocities of apparent cloud formations in the upper atmosphere of Venus.

Mantle plumes and entrainment: isotopic evidence.

Many oceanic island basalts show sublinear subparallel arrays in Sr-Nd-Pb isotopic space. The depleted upper mantle is rarely a mixing end-member of these arrays, as would be expected if mantle plumes originated at a 670-kilometer boundary layer and entrained upper mantle during ascent. Instead, the arrays are fan-shaped and appear to converge on a volume in isotopic space characterized by low (87)Sr/(86)Sr and high (143)Nd/(144)Nd, (206)Pb/(204)Pb, and (3)He/(4)He ratios. This new isotopic component may be the lower mantle, entrained into plumes originating from the core-mantle boundary layer.

Seasat altimeter calibration: initial results.

Preliminary analysis of radar altimeter data indicates that the instrument has met its specifications for measuring spacecraft height above the ocean surface (+/- 10 centimeters) and significant wave height (+/- 0.5 meter). There is ample evidence that the radar altimeter, having undergone development through three earth orbit missions [Skylab, Geodynamics Experimental Ocean Satellite 3 (GEOS-3), and Seasat], has reached a level of precision that now makes possible its use for important quantitative oceanographic investigations and practical applications.

Consultation activities of clinical ethics committees in the United Kingdom: an empirical study and wake-up call.

OBJECTIVE: To identify the consultation activities of clinical ethics committees (CECs) in the UK and the views of CEC chairpersons regarding such activities. METHODS: An anonymous, password-protected online questionnaire was sent by e-mail to 70 CEC chairpersons. The questionnaire contained 14 items. RESULTS: Of the 70 CECs contacted, 30 responded (a response rate of 43%). There has been an almost fourfold increase in the number of CECs in the past 7 years. Over half of the CECs that responded had considered three or fewer active cases and three or fewer retrospective cases in the preceding year. Eighty percent of chairpersons felt that the number of active cases considered by their committee was too low. Seventy percent of CECs had rapid response teams. Aside from low consultation caseloads, chairpersons identified a number of concerns, including education and training of members, composition of CECs, low profile and lack of funding and support. Although most respondents believed there is a need for clinical ethics support in the NHS, many noted the limited use of the services, even after efforts to increase the visibility of their CEC. CONCLUSION: Despite a sharp increase in the absolute numbers of CECs across the UK, the number of cases considered by the majority of CECs is low. The findings presented here suggest we must reflect on the reasons for such low caseloads and pause to consider whether the committee model is most appropriate for the UK context.

Effects of captan on Apis mellifera brood development under field conditions in California almond orchards.

Three almond field trials were conducted during 2003 and 2004 at two locations in central (Fresno County) and northern (Yolo County) California to evaluate the potential effects of commercial applications of Captan on honey bees, Apis mellifera L. Captan was applied at 5.0 kg (AI)/ha during bloom. Hives were evaluated for hive health and brood development parameters for approximately 2 mo after application. This study showed that the application of Captan was not harmful to foraging honey bees or their brood. No treatment-related effects were noted on hive weights, dead bee deformity, number of dead bees, survival of individual larvae, weight of individual emerging adults, and other hive health parameters.

Enhancement of the destruction of propane in a low-temperature plasma by the addition of unsaturated hydrocarbons: experiment and modeling.

The oxidative destruction of propane at low temperature ( approximately 150 degrees C) in a nonthermal, atmospheric pressure plasma can be significantly enhanced without the use of a catalyst by the simple addition of an unsaturated alkene. An enhancement in the destruction of propane of up to 45% can be achieved by the addition of propene. Propene acts as a supply of OH radicals, which accelerate the breakdown of the propane. Ethene also enhances the destruction of propane but to a more limited extent. The experimental results are interpreted by chemical modeling, which is used to elucidate the reaction mechanisms.

Decomposition of hydrofluorocarbons in a dielectric-packed plasma reactor.

This study investigated the decomposition of hydrofluorocarbons (HFCs) having high global warming potentials by using a dielectric-packed-bed nonthermal plasma reactor with barium titanate beads as the packing material. The target HFCs were 1,1,1,2-tetrafluoroethane (HFC-134a) and 1,1-difluoroethene (HFC-132a). The effects of several parameters such as reaction temperature, oxygen content, and initial concentration on the HFC decomposition efficiency were evaluated. There was essentially no temperature dependence of the HFC decomposition efficiency in the range 150-250 degrees C. The optimum oxygen content for HFC decomposition was found to be about 0.5 vol %. Variations in the initial concentration did not affect the decomposition efficiency. The decomposition products were analyzed, and some decomposition pathways were elucidated. The energy requirements for the decomposition of HFC-134a and HFC-132a were found to be 0.038 and 0.062 mol MJ-1, respectively, based on the initial concentrations of 200 and 120 ppm (parts per million, volumetric).

The destruction of atmospheric pressure propane and propene using a surface discharge plasma reactor.

Surface discharge plasma reactors (SDRs) have been shown to be effective in removing a wide range of pollutants. In this study, the effectiveness of a SDR for the removal of propane and propene from an atmospheric pressure air stream was investigated. For an input energy of 100 J L-1, the conversions were found to be 16% and 68% for propane and propene, respectively. The total carbon recovery was found to increase with increasing specific input energy (SIE) for both hydrocarbons. FTIR analysis showed that CO and CO2 are the major end-products, and GC-MS identified formic acid as a significant byproduct. The effect of initial propane concentration was also investigated. The reaction chemistry involved in the oxidative plasma conversion of propane and propene is discussed.

Glycosyltransferases in human blood.I. Galactosyltransferase in human serum and erythrocyte membranes.

Human serum and hemoglobin-free erythrocyte membranes were found to contain a galactosyltransferase which catalyzes the transfer of galactose from UDP-galactose to specific large and small molecular weight acceptors. The requirements for enzyme activity were found to be similar for the enzymes from both sources. However, the membrane-bound enzyme depended on a detergent for maximal activity. Mn(++) was an absolute requirement for transfer and uridine nucleoside phosphates were inhibitors. The most effective acceptor for galactose was a glycoprotein containing N-acetylglucosamine residues in the terminal position of its oligosaccharide side chains, N-acetylglucosamine was also an acceptor. While the presence of alpha-lactalbumin in the incubation medium resulted in a significant decrease in the transfer of galactose to N-acetylglucosamine, glucose, which was not an acceptor for galactose in the absence of alpha-lactalbumin, became an excellent acceptor. The serum enzyme catalyzed the transfer of 54 nmoles of galactose per milliliter of serum per hour and its apparent K(m) for UDP-galactose was 7.5 x 10(-6)M. The membrane enzyme had a similar apparent K(m). Using a quantitative assay system the enzyme was found to be present in all individuals studied, regardless of their blood type, secretor status, or sex.