An ab Initio Investigation of the Stabilization of Selected β-substituted Ethyl Cations and α-substituted Methyl Cations

In this study, we calculate the stabilization of β-substituted ethyl cations (R = H, Li, BeH, BH_2, CH_3, NH_2, OH, F, Na, MgH, AlH_2, SiH_3, PH_2, SH, Cl) and α-substituted methyl cations (R = H, Li, CH_3, NH_2, OH, F, Na, SiH_3, PH_2, SH, Cl) in order to obtain a relationship between the nature of the substituent and the degree of stabilization of the cation. Results show that the stabilization energy is related to the electronegativity of the β substituents, but not the α substituents. The rotational barrier of the β-substituted ethyl cation is linearly related to the Mulliken population of the 2p(C+) orbital. We found that the stabilization energy is linearly related to the ionization potential of the α- and PLA β-substituted radicals, and the HOMO energies of the PLA β-substituted radical are linearly related to the corresponding ionization potentials. Trends in the stabilization by second- and third-row substituents are discussed

Women’s knowledge, attitudes and views of preconception health and intervention delivery methods:a cross-sectional survey

Background: Several preconception exposures have been associated with adverse pregnancy, birth and postpartum outcomes. However, few studies have investigated women’s knowledge of and attitudes towards preconception health, and the acceptability of potential intervention methods. Methods: Seven primary care centres in the West of England posted questionnaires to 4330 female patients aged 18 to 48 years. Without providing examples, we asked women to list maternal preconception exposures that might affect infant and maternal outcomes, and assessed their knowledge of nine literature-derived risk factors. Attitudes towards preconception health (interest, intentions, self-efficacy and perceived awareness and importance) and the acceptability of intervention delivery methods were also assessed. Multivariable multilevel regression examined participant characteristics associated with these outcomes. Results: Of those who received questionnaires, 835 (19.3%) responded. Women were most aware of the preconception risk factors of diet (86.0%) and physical activity (79.2%). Few were aware of weight (40.1%), folic acid (32.9%), abuse (6.3%), advanced age (5.9%) and interpregnancy intervals (0.2%), and none mentioned interpregnancy weight change or excess iron intake. After adjusting for demographic and reproductive covariates, women aged 18–24-years (compared to 40–48-year-olds) and nulligravid women were less aware of the benefit of preconception folic acid supplementation (adjusted odds ratios (aOR) for age: 4.30 [2.10–8.80], gravidity: aOR 2.48 [1.70–3.62]). Younger women were more interested in learning more about preconception health (aOR 0.37 [0.21–0.63]) but nulligravid women were less interested in this (aOR 1.79 [1.30–2.46]). Women with the lowest household incomes (versus the highest) were less aware of preconception weight as a risk factor (aOR: 3.11 [1.65–5.84]) and rated the importance of preconception health lower (aOR 3.38 [1.90–6.00]). The most acceptable information delivery methods were websites/apps (99.5%), printed healthcare materials (98.6%), family/partners (96.3%), schools (94.4%), television (91.9%), pregnancy tests (91.0%) and doctors, midwives and nurses (86.8–97.0%). Dentists (23.9%) and hairdressers/beauticians (18.1%) were the least acceptable. Conclusions: Our findings demonstrate a need to promote awareness of preconception risk factors and motivation for preconception health changes, particularly amongst younger and nulligravid women and women with lower incomes. Interventions to improve preconception health should focus on communication from healthcare professionals, schools, family members, and digital media

Preconception exposures and adverse pregnancy, birth and postpartum outcomes:Umbrella review of systematic reviews

Background Preconception exposures have been associated with adverse pregnancy, birth and postpartum outcomes. However, the reports, statements and guidelines of national and international health organisations vary in what they recommend individuals should monitor, avoid, reduce or practise in the preconception period. Objectives To synthesise and evaluate the evidence across systematic reviews for associations between exposures before conception and adverse pregnancy, birth and postpartum outcomes. Data sources MEDLINE, Embase, Epistemonikos (to May 2020) and reference lists of included reviews, without language or date restrictions. Study selection, data extraction and synthesis Systematic literature reviews of observational and/or interventional studies reporting associations between preconception exposures in women and/or men of reproductive age and pregnancy, birth or postpartum health outcomes were included. The methodological quality of reviews and the certainty of the evidence underlying each exposure-outcome association were assessed using AMSTAR 2 and the GRADE approach. Results We identified 53 eligible reviews reporting 205 unique exposure-outcome associations. Methodological quality was generally low with only two reviews rated as ‘high’ quality and two as ‘moderate’. We found high-certainty, randomised trial evidence that maternal folate supplementation reduces the risk of neural tube defects and anomaly-related terminations. Moderate-certainty, observational evidence was found that maternal physical activity is associated with reduced risk of pre-eclampsia and gestational diabetes, and that paternal age of ≥40 years and maternal body mass index (BMI) and interpregnancy weight gain are associated with increased risk of various adverse pregnancy and birth outcomes. Low- and very low-certainty evidence was found for other associations. Conclusions Clinicians and policymakers can be confident that maternal folate supplementation should be encouraged during the preconception period. There is moderate certainty in the evidence base that maternal physical activity, BMI and interpregnancy weight gain and advanced paternal age are important preconception considerations. High-quality research is required to better understand other exposure-outcome associations

Dust and the Infrared Kinematic Properties of Early-Type Galaxies

We have obtained spectra and measured the stellar kinematics in a sample of 25 nearby early-type galaxies (with velocity dispersions from less than 100 km/s to over 300 km/s) using the near-infrared CO absorption bandhead at 2.29 microns. Our median uncertainty for the dispersions is ~10%. We examine the effects of dust on existing optical kinematic measurements. We find that the near-infrared velocity dispersions are in general smaller than optical velocity dispersions, with differences as large as 30%. The median difference is 11% smaller, and the effect is of greater magnitude for higher dispersion galaxies. The lenticular galaxies (18 out of 25) appear to be causing the shift to lower dispersions while the classical ellipticals (7 out of 25) are consistent between the two wavelength regimes. If uniformly distributed dust causes these differences, we would expect to find a correlation between the relative amount of dust in a galaxy and the fractional change in dispersion, but we do not find such a correlation. We do see correlations both between velocity dispersion and CO bandhead equivalent width, and velocity dispersion and Mg2 index. The differences in dispersion are not well explained by current models of dust absorption. The lack of correlation between the relative amount of dust and shift in dispersion possibly suggets that dust does not have a similar distribution from galaxy to galaxy. The CO equivalent widths of these galaxies are quite high (>10 angstroms for almost all), requiring the light at these wavelengths to be dominated by very cool stars.Comment: 17 pages, 14 figures, accepted to The Astronomical Journa

The power of quantum systems on a line

We study the computational strength of quantum particles (each of finite dimensionality) arranged on a line. First, we prove that it is possible to perform universal adiabatic quantum computation using a one-dimensional quantum system (with 9 states per particle). This might have practical implications for experimentalists interested in constructing an adiabatic quantum computer. Building on the same construction, but with some additional technical effort and 12 states per particle, we show that the problem of approximating the ground state energy of a system composed of a line of quantum particles is QMA-complete; QMA is a quantum analogue of NP. This is in striking contrast to the fact that the analogous classical problem, namely, one-dimensional MAX-2-SAT with nearest neighbor constraints, is in P. The proof of the QMA-completeness result requires an additional idea beyond the usual techniques in the area: Not all illegal configurations can be ruled out by local checks, so instead we rule out such illegal configurations because they would, in the future, evolve into a state which can be seen locally to be illegal. Our construction implies (assuming the quantum Church-Turing thesis and that quantum computers cannot efficiently solve QMA-complete problems) that there are one-dimensional systems which take an exponential time to relax to their ground states at any temperature, making them candidates for being one-dimensional spin glasses.Comment: 21 pages. v2 has numerous corrections and clarifications, and most importantly a new author, merged from arXiv:0705.4067. v3 is the published version, with additional clarifications, publisher's version available at http://www.springerlink.co

Conditional Deletion of Murine Fgf23: Interruption of the Normal Skeletal Responses to Phosphate Challenge and Rescue of Genetic Hypophosphatemia

The transgenic and knockout (KO) animals involving Fgf23 have been highly informative in defining novel aspects of mineral metabolism, but are limited by shortened lifespan, inability of spatial/temporal FGF23 control, and infertility of the global KO. To more finely test the role of systemic and genetic influences in FGF23 production, a mouse was developed that carried a floxed ("f")-Fgf23 allele (exon 2 floxed) which demonstrated in vivo recombination when bred to global-Cre transgenic mice (eIIa-cre). Mice homozygous for the recombined allele ("Δ") had undetectable serum intact FGF23, elevated serum phosphate (p < 0.05), and increased kidney Cyp27b1 mRNA (p < 0.05), similar to global Fgf23-KO mice. To isolate cellular FGF23 responses during phosphate challenge, Fgf23(Δ/f) mice were mated with early osteoblast type Iα1 collagen 2.3-kb promoter-cre mice (Col2.3-cre) and the late osteoblast/early osteocyte Dentin matrix protein-1-cre (Dmp1-cre). Fgf23(Δ/f) /Col2.3-cre(+) and Fgf23(Δ/f) /Dmp1-cre(+) exhibited reduced baseline serum intact FGF23 versus controls. After challenge with high-phosphate diet Cre(-) mice had 2.1-fold to 2.5-fold increased serum FGF23 (p < 0.01), but Col2.3-cre(+) mice had no significant increase, and Dmp1-cre(+) mice had only a 37% increase (p < 0.01) despite prevailing hyperphosphatemia in both models. The Fgf23(Δ/f) /Col2.3-cre was bred onto the Hyp (murine X-linked hypophosphatemia [XLH] model) genetic background to test the contribution of osteoblasts and osteocytes to elevated FGF23 and Hyp disease phenotypes. Whereas Hyp mice maintained inappropriately elevated FGF23 considering their marked hypophosphatemia, Hyp/Fgf23(Δ/f) /Col2.3-cre(+) mice had serum FGF23 <4% of Hyp (p < 0.01), and this targeted restriction normalized serum phosphorus and ricketic bone disease. In summary, deleting FGF23 within early osteoblasts and osteocytes demonstrated that both cell types contribute to baseline circulating FGF23 concentrations, and that targeting osteoblasts/osteocytes for FGF23 production can modify systemic responses to changes in serum phosphate concentrations and rescue the Hyp genetic syndrome

A Mechanistic Analysis of Phase Evolution and Hydrogen Storage Behavior in Nanocrystalline Mg(BH4)2 within Reduced Graphene Oxide.

Magnesium borohydride (Mg(BH4)2, abbreviated here MBH) has received tremendous attention as a promising onboard hydrogen storage medium due to its excellent gravimetric and volumetric hydrogen storage capacities. While the polymorphs of MBH-alpha (α), beta (β), and gamma (γ)-have distinct properties, their synthetic homogeneity can be difficult to control, mainly due to their structural complexity and similar thermodynamic properties. Here, we describe an effective approach for obtaining pure polymorphic phases of MBH nanomaterials within a reduced graphene oxide support (abbreviated MBHg) under mild conditions (60-190 °C under mild vacuum, 2 Torr), starting from two distinct samples initially dried under Ar and vacuum. Specifically, we selectively synthesize the thermodynamically stable α phase and metastable β phase from the γ-phase within the temperature range of 150-180 °C. The relevant underlying phase evolution mechanism is elucidated by theoretical thermodynamics and kinetic nucleation modeling. The resulting MBHg composites exhibit structural stability, resistance to oxidation, and partially reversible formation of diverse [BH4]- species during de- and rehydrogenation processes, rendering them intriguing candidates for further optimization toward hydrogen storage applications

NRG Oncology-Radiation Therapy Oncology Group Study 1014: 1-Year Toxicity Report From a Phase 2 Study of Repeat Breast-Preserving Surgery and 3-Dimensional Conformal Partial-Breast Reirradiation for In-Breast Recurrence.

PURPOSE: To determine the associated toxicity, tolerance, and safety of partial-breast reirradiation. METHODS AND MATERIALS: Eligibility criteria included in-breast recurrence occurring \u3e1 year after whole-breast irradiation, \u3c3 \u3ecm, unifocal, and resected with negative margins. Partial-breast reirradiation was targeted to the surgical cavity plus 1.5 cm; a prescription dose of 45 Gy in 1.5 Gy twice daily for 30 treatments was used. The primary objective was to evaluate the rate of grade ≥3 treatment-related skin, fibrosis, and/or breast pain adverse events (AEs), occurring ≤1 year from re-treatment completion. A rate of ≥13% for these AEs in a cohort of 55 patients was determined to be unacceptable (86% power, 1-sided α = 0.07). RESULTS: Between 2010 and 2013, 65 patients were accrued, and the first 55 eligible and with 1 year follow-up were analyzed. Median age was 68 years. Twenty-two patients had ductal carcinoma in situ, and 33 had invasive disease: 19 ≤1 cm, 13 \u3e1 to ≤2 cm, and 1 \u3e2 cm. All patients were clinically node negative. Systemic therapy was delivered in 51%. All treatment plans underwent quality review for contouring accuracy and dosimetric compliance. All treatment plans scored acceptable for tumor volume contouring and tumor volume dose-volume analysis. Only 4 (7%) scored unacceptable for organs at risk contouring and organs at risk dose-volume analysis. Treatment-related skin, fibrosis, and/or breast pain AEs were recorded as grade 1 in 64% and grade 2 in 7%, with only 1 ( CONCLUSION: Partial-breast reirradiation with 3-dimensional conformal radiation therapy after second lumpectomy for patients experiencing in-breast failures after whole-breast irradiation is safe and feasible, with acceptable treatment quality achieved. Skin, fibrosis, and breast pain toxicity was acceptable, and grade 3 toxicity was rare

Increased FGF23 protects against detrimental cardio-renal consequences during elevated blood phosphate in CKD

The phosphaturic hormone FGF23 is elevated in chronic kidney disease (CKD). The risk of premature death is substantially higher in the CKD patient population, with cardiovascular disease (CVD) as the leading mortality cause at all stages of CKD. Elevated FGF23 in CKD has been associated with increased odds for all-cause mortality; however, whether FGF23 is associated with positive adaptation in CKD is unknown. To test the role of FGF23 in CKD phenotypes, a late osteoblast/osteocyte conditional flox-Fgf23 mouse (Fgf23fl/fl/Dmp1-Cre+/-) was placed on an adenine-containing diet to induce CKD. Serum analysis showed casein-fed Cre+ mice had significantly higher serum phosphate and blood urea nitrogen (BUN) versus casein diet and Cre- genotype controls. Adenine significantly induced serum intact FGF23 in the Cre- mice over casein-fed mice, whereas Cre+ mice on adenine had 90% reduction in serum intact FGF23 and C-terminal FGF23 as well as bone Fgf23 mRNA. Parathyroid hormone was significantly elevated in mice fed adenine diet regardless of genotype, which significantly enhanced midshaft cortical porosity. Echocardiographs of the adenine-fed Cre+ hearts revealed profound aortic calcification and cardiac hypertrophy versus diet and genotype controls. Thus, these studies demonstrate that increased bone FGF23, although associated with poor outcomes in CKD, is necessary to protect against the cardio-renal consequences of elevated tissue phosphate