Ionic and Electronic Conduction in TiNb2O7 Griffith, Kent J; Seymour, Ieuan D; Hope, Michael A ...
Journal of the American Chemical Society,
10/2019, Letnik:
141, Številka:
42
Journal Article
Recenzirano
Odprti dostop
TiNb2O7 is a Wadsley–Roth phase with a crystallographic shear structure and is a promising candidate for high-rate lithium ion energy storage. The fundamental aspects of the lithium insertion ...mechanism and conduction in TiNb2O7, however, are not well-characterized. Herein, experimental and computational insights are combined to understand the inherent properties of bulk TiNb2O7. The results show an increase in electronic conductivity of seven orders of magnitude upon lithiation and indicate that electrons exhibit both localized and delocalized character, with a maximum Curie constant and Li NMR paramagnetic shift near a composition of Li0.60TiNb2O7. Square-planar or distorted-five-coordinate lithium sites are calculated to invert between thermodynamic minima or transition states. Lithium diffusion in the single-redox region (i.e., x ≤ 3 in Li x TiNb2O7) is rapid with low activation barriers from NMR and D Li = 10–11 m2 s–1 at the temperature of the observed T 1 minima of 525–650 K for x ≥ 0.75. DFT calculations predict that ionic diffusion, like electronic conduction, is anisotropic with activation barriers for lithium hopping of 100–200 meV down the tunnels but ca. 700–1000 meV across the blocks. Lithium mobility is hindered in the multiredox region (i.e., x > 3 in Li x TiNb2O7), related to a transition from interstitial-mediated to vacancy-mediated diffusion. Overall, lithium insertion leads to effective n-type self-doping of TiNb2O7 and high-rate conduction, while ionic motion is eventually hindered at high lithiation. Transition-state searching with beyond Li chemistries (Na+, K+, Mg2+) in TiNb2O7 reveals high diffusion barriers of 1–3 eV, indicating that this structure is specifically suited to Li+ mobility.
The hedgehog (HH) signaling pathway is a key regulator in tumorigenesis of pancreatic adenocarcinoma and is upregulated in pancreatic adenocarcinoma cancer stem cells (CSCs). GDC-0449 is an oral ...small-molecule inhibitor of the HH pathway. This study assessed the effect of GDC-0449-mediated HH inhibition in paired biopsies, followed by combined treatment with gemcitabine, in patients with metastatic pancreatic adenocarcinoma.
Twenty-five patients were enrolled of which 23 underwent core biopsies at baseline and following 3 weeks of GDC-0449. On day 29, 23 patients started weekly gemcitabine while continuing GDC-0449. We evaluated GLI1 and PTCH1 inhibition, change in CSCs, Ki-67, fibrosis, and assessed tumor response, survival and toxicity.
On pretreatment biopsy, 75% of patients had elevated sonic hedgehog (SHH) expression. On posttreatment biopsy, GLI1 and PTCH1 decreased in 95.6% and 82.6% of 23 patients, fibrosis decreased in 45.4% of 22, and Ki-67 in 52.9% of 17 evaluable patients. No significant changes were detected in CSCs pre- and postbiopsy. The median progression-free and overall survival for all treated patients were 2.8 and 5.3 months. The response and disease control rate was 21.7% and 65.2%. No significant correlation was noted between CSCs, fibrosis, SHH, Ki-67, GLI1, PTCH1 (baseline values or relative change on posttreatment biopsy), and survival. Grade ≥ 3 adverse events were noted in 56% of patients.
We show that GDC-0449 for 3 weeks leads to downmodulation of GLI1 and PTCH1, without significant changes in CSCs compared with baseline. GDC-0449 and gemcitabine were not superior to gemcitabine alone in the treatment of metastatic pancreatic cancer.
Establishing structure-property correlations is of paramount importance to materials research. The ability to selectively detect observable magnetization from transitions between quantized spin ...states of nuclei makes nuclear magnetic resonance (NMR) spectroscopy a powerful probe to characterize solids at the atomic level. In this article, we review recent advances in NMR techniques in six areas: spectral resolution, sensitivity, atomic correlations, ion dynamics, materials imaging, and hardware innovation. In particular, we focus on the applications of these techniques to materials research. Specific examples are given following the general introduction of each topic and technique to illustrate how they are applied. In conclusion, we suggest future directions for advanced solid-state NMR spectroscopy and imaging in interdisciplinary research.
Within the multidisciplinary management of breast cancer, variations exist in the reconstructive options offered and care provided. The authors evaluated plastic surgeon perspectives on important ...issues related to breast cancer management and reconstruction and provide some insight into factors that influence these perspectives.
Women diagnosed with early-stage breast cancer (stages 0 to II) between July of 2013 and September of 2014 were identified through the Georgia and Los Angeles Surveillance, Epidemiology, and End Results registries. These women were surveyed and identified their treating plastic surgeons. Surveys were sent to the identified plastic surgeons to collect data on specific reconstruction practices.
Responses from 134 plastic surgeons (74.4 percent response rate) were received. Immediate reconstruction (79.7 percent) was the most common approach to timing, and expander/implant reconstruction (72.6 percent) was the most common technique reported. Nearly one-third of respondents (32.1 percent) reported that reimbursement influenced the proportion of autologous reconstructions performed. Most (82.8 percent) reported that discussions about contralateral prophylactic mastectomy were initiated by patients. Most surgeons (81.3 to 84.3 percent) felt that good symmetry is achieved with unilateral autologous reconstruction with contralateral symmetry procedures in patients with small or large breasts; a less pronounced majority (62.7 percent) favored unilateral implant reconstructions in patients with large breasts. In patients requiring postmastectomy radiation therapy, one-fourth of the surgeons (27.6 percent) reported that they seldom recommend delayed reconstruction, and 64.9 percent reported recommending immediate expander/implant reconstruction.
Reconstructive practices in a modern cohort of plastic surgeons suggest that immediate and implant reconstructions are performed preferentially. Respondents perceived a number of factors, including surgeon training, time spent in the operating room, and insurance reimbursement, to negatively influence the performance of autologous reconstruction.
This phase 1/2 study in patients with newly diagnosed multiple myeloma (N = 53) assessed CRd—carfilzomib (20, 27, or 36 mg/m2, days 1, 2, 8, 9, 15, 16 and 1, 2, 15, 16 after cycle 8), lenalidomide ...(25 mg/d, days 1-21), and weekly dexamethasone (40/20 mg cycles 1-4/5+)—in 28-day cycles. After cycle 4, transplantation-eligible candidates underwent stem cell collection (SCC) then continued CRd with the option of transplantation. The maximum planned dose level (carfilzomib 36 mg/m2) was expanded in phase 2 (n = 36). Thirty-five patients underwent SCC, 7 proceeded to transplantation, and the remainder resumed CRd. Grade 3/4 toxicities included hypophosphatemia (25%), hyperglycemia (23%), anemia (21%), thrombocytopenia (17%), and neutropenia (17%); peripheral neuropathy was limited to grade 1/2 (23%). Most patients did not require dose modifications. After a median of 12 cycles (range, 1-25), 62% (N = 53) achieved at least near-complete response (CR) and 42% stringent CR. Responses were rapid and improved during treatment. In 36 patients completing 8 or more cycles, 78% reached at least near CR and 61% stringent CR. With median follow-up of 13 months (range, 4-25 months), 24-month progression-free survival estimate was 92%. CRd was well tolerated with exceptional response rates. This study is registered at http://www.clinicaltrials.gov as NCT01029054.
To evaluate the financial experiences of a racially and ethnically diverse cohort of long-term breast cancer survivors (17% African American, 40% Latina) identified through population-based ...registries.
Longitudinal study of women diagnosed with nonmetastatic breast cancer in 2005 to 2007 and reported to the SEER registries of metropolitan Los Angeles and Detroit. We surveyed 3,133 women approximately 9 months after diagnosis and 4 years later. Multivariable models evaluated correlates of self-reported decline in financial status attributed to breast cancer and of experiencing at least one type of privation (economically motivated treatment nonadherence and broader hardships related to medical expenses).
Among 1,502 patients responding to both surveys, median out-of-pocket expenses were ≤ $2,000; 17% of respondents reported spending > $5,000; 12% reported having medical debt 4 years postdiagnosis. Debt varied significantly by race: 9% of whites, 15% of blacks, 17% of English-speaking Latinas, and 10% of Spanish-speaking Latinas reported debt (P = .03). Overall, 25% of women experienced financial decline at least partly attributed to breast cancer; Spanish-speaking Latinas had significantly increased odds of this decline relative to whites (odds ratio OR, 2.76; P = .006). At least one privation was experienced by 18% of the sample; blacks (OR, 2.6; P < .001) and English-speaking Latinas (OR, 2.2; P = .02) were significantly more likely to have experienced privation than whites.
Racial and ethnic minority patients appear most vulnerable to privations and financial decline attributable to breast cancer, even after adjustment for income, education, and employment. These findings should motivate efforts to control costs and ensure communication between patients and providers regarding financial distress, particularly for vulnerable subgroups.
To report interim cosmetic results and toxicity from a prospective study evaluating accelerated partial-breast irradiation (APBI) administered using a highly conformal external beam approach.
We ...enrolled breast cancer patients in an institutional review board-approved prospective study of APBI using beamlet intensity-modulated radiotherapy (IMRT) at deep-inspiration breath-hold. Patients received 38.5 Gy in 3.85 Gy fractions twice daily. Dosimetric parameters in patients who maintained acceptable cosmesis were compared with those in patients developing unacceptable cosmesis in follow-up, using t-tests.
Thirty-four patients were enrolled; 2 were excluded from analysis because of fair baseline cosmesis. With a median follow-up of 2.5 years, new unacceptable cosmesis developed in 7 patients, leading to early study closure. We compared patients with new unacceptable cosmesis with those with consistently acceptable cosmesis. Retrospective analysis demonstrated that all but one plan adhered to the dosimetric requirements of the national APBI trial. The mean proportion of a whole-breast reference volume receiving 19.25 Gy (V50) was lower in patients with acceptable cosmesis than in those with unacceptable cosmesis (34.6% vs. 46.1%; p = 0.02). The mean percentage of this reference volume receiving 38.5 Gy (V100) was also lower in patients with acceptable cosmesis (15.5% vs. 23.0%; p = 0.02).
The hypofractionated schedule and parameters commonly used for external beam APBI and prescribed by the ongoing national trial may be suboptimal, at least when highly conformal techniques such as IMRT with management of breathing motion are used. The V50 and V100 of the breast reference volume seem correlated with cosmetic outcome, and stricter limits may be appropriate in this setting.
Contralateral prophylactic mastectomy (CPM) use is increasing among women with unilateral breast cancer, but little is known about treatment decision making or physician interactions in diverse ...patient populations.
To evaluate patient motivations, knowledge, and decisions, as well as the impact of surgeon recommendations, in a large, diverse sample of patients who underwent recent treatment for breast cancer.
A survey was sent to 3631 women with newly diagnosed, unilateral stage 0, I, or II breast cancer between July 2013 and September 2014. Women were identified through the population-based Surveillance Epidemiology and End Results registries of Los Angeles County and Georgia. Data on surgical decisions, motivations for those decisions, and knowledge were included in the analysis. Logistic and multinomial logistic regression of the data were conducted to identify factors associated with (1) CPM vs all other treatments combined, (2) CPM vs unilateral mastectomy (UM), and (3) CPM vs breast-conserving surgery (BCS). Associations between CPM receipt and surgeon recommendations were also evaluated. All statistical models and summary estimates were weighted to be representative of the target population.
Receipt of CPM was the primary dependent variable for analysis and was measured by a woman's self-report of her treatment.
Of the 3631 women selected to receive the survey, 2578 (71.0%) responded and 2402 of these respondents who did not have bilateral disease and for whom surgery type was known constituted the final analytic sample. The mean (SD) age was 61.8 (12) years at the time of the survey. Overall, 1301 (43.9%) patients considered CPM (601 24.8% considered it very strongly or strongly); only 395 (38.1%) of them knew that CPM does not improve survival for all women with breast cancer. Ultimately, 1466 women (61.6%) received BCS, 508 (21.2%) underwent UM, and 428 (17.3%) received CPM. On multivariable analysis, factors associated with CPM included younger age (per 5-year increase: odds ratio OR, 0.71; 95% CI, 0.65-0.77), white race (black vs white: OR, 0.50; 95% CI, 0.34-0.74), higher educational level (OR, 1.69; 95% CI, 1.20-2.40), family history (OR, 1.63; 95% CI, 1.22-2.17), and private insurance (Medicaid vs private insurance: OR, 0.47; 95% CI, 0.28-0.79). Among 1569 patients (65.5%) without high genetic risk or an identified mutation, 598 (39.3%) reported a surgeon recommendation against CPM, of whom only 12 (1.9%) underwent CPM, but among the 746 (46.8%) of these women who received no recommendation for or against CPM from a surgeon, 148 (19.0%) underwent CPM.
Many patients consider CPM, but knowledge about the procedure is low and discussions with surgeons appear to be incomplete. Contralateral prophylactic mastectomy use is substantial among patients without clinical indications but is low when patients report that their surgeon recommended against it. More effective physician-patient communication about CPM is needed to reduce potential overtreatment.
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