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An empirical model for investigating the behaviour of CaCO3 polymorphs incorporating a shell model for oxygen has been created. The model was constructed by fitting to: the structure of aragonite and calcite; their elastic, static and high-frequency dielectric constants; phonon frequencies at the wave vectors [½ 0 2] and [0 0 0] of calcite; and vibrational frequencies of the carbonate deformation modes of calcite. The high-pressure phase transition between calcite I and II is observed. The potentials for the CO3 group were transferred to other carbonates, by refitting the interaction between CO3 and the cation to both the experimental structures and their bulk modulus, creating a set of potentials for calculating the properties of a wide range of carbonate materials. Defect energies of substitutional cation defects were analyzed for calcite and aragonite phases. The results were rationalized by studying the structure of calcite and aragonite in greater detail.

29Si nuclear magnetic resonance (NMR) spectroscopy was used to characterize the silica phases in a moderately-shocked Coconino sandstone from Meteor Crater, Arizona. The spectra were recorded using direct polarization, magic-angle spinning, and variable delay times in a saturation recovery pulse sequence. Resonances observed at -97.3, -107.1, -113.9 and -191.2 ppm were assigned to a densified hydrous form of amorphous silica (D phase), quartz, coesite and stishovite phases, respectively. The relative percentages were estimated as 1.7, 80.6, 16.4 and 1.3% for the D, quartz, coesite, and stishovite phases. The power-law recoveries of the magnetization for the quartz and coesite phases can be interpreted in terms of their phase geometries.

Magnesium self-diffusion coefficients were determined experimentally for diffusion parallel to each of the three crystallographic directions in natural orthoenstatite (En88Fs12). Experiments were conducted at 1 atm in CO-CO2 gas mixing furnaces, which provided oxygen fugacities equivalent to the iron-wustite buffer.

Molecular simulation is a practical method of obtaining structural and dynamical information about clay minerals and their aqueous interfaces, especially given the difficulty in characterizing the atomic dispositions and crystal structures using experimental methods. This chapter provides a brief introduction to the basics of classical simulations as well as a review of force field development specific to clay minerals. Several applications are also provided, including clay mineral swelling, interlayer structure and dynamics, and solute adsorption.

Key Points In this Analysis, we explore the possibility that commonly inherited genetic variants in the p53 pathway play a significant part in susceptibility to a broad range of cancers. We use genome-wide datasets of genetic variation, cancer susceptibility loci derived from hundreds of genome-wide association studies conducted in a broad range of cancers, and expression quantitative trait loci (eQTLs) from eQTL databases from many different tissue types. Our results demonstrate that p53 pathway genes are more significantly enriched in cancer susceptibility loci compared with other signalling pathways. We did not find p53 pathway genes to be significantly enriched in susceptibility loci for any other major disease groupings. We observe strong similarities between the causal, somatic mutations and the inherited, cancer-associated single nucleotide polymorphisms of the p53 pathway, in which both classes of genetic variant are found to occur in a high proportion of p53 pathway genes in multiple cancer types, and in similar genes. Our results enable insights into p53-mediated tumour suppression in humans and into p53 pathway-based cancer surveillance and treatment strategies. Using genomic data, this Analysis demonstrates that commonly inherited single nucleotide polymorphisms (SNPs) occurring in genes of the p53 pathway affect the incidence of a broad range of cancers, more so than SNPs in other pathways. This has implications for p53-mediated tumour suppression in humans. Decades of research have shown that mutations in the p53 stress response pathway affect the incidence of diverse cancers more than mutations in other pathways. However, most evidence is limited to somatic mutations and rare inherited mutations. Using newly abundant genomic data, we demonstrate that commonly inherited genetic variants in the p53 pathway also affect the incidence of a broad range of cancers more than variants in other pathways. The cancer-associated single nucleotide polymorphisms (SNPs) of the p53 pathway have strikingly similar genetic characteristics to well-studied p53 pathway cancer-causing somatic mutations. Our results enable insights into p53-mediated tumour suppression in humans and into p53 pathway-based cancer surveillance and treatment strategies.

BackgroundPatients with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) have a significant need for effective treatment options. Odronextamab is an Fc-silenced, human, CD20×CD3 bispecific antibody that targets CD20-expressing cells via T-cell-mediated cytotoxicity independent of T-cell/major histocompatibility complex interaction. Phase I results in patients with R/R B-NHL demonstrated that odronextamab monotherapy could achieve deep and durable responses with a generally manageable safety profile (ELM-1; NCT02290951). As part of a biomarker analysis of the same study, we investigated potential biomarkers and mechanisms of resistance to odronextamab.MethodsPatients with R/R B-NHL enrolled in ELM-1 received one time per week doses of intravenous odronextamab for 4×21 day cycles, then doses every 2 weeks thereafter. Patient tumor biopsies were obtained at baseline, on-treatment, and at progression. Immune cell markers were analyzed by immunohistochemistry, flow cytometry, single-cell RNA sequencing, and whole genome sequencing.ResultsBaseline tumor biopsies showed that almost all patients had high proportions of B cells that expressed the CD20 target antigen, whereas expression of other B-cell surface antigens (CD19, CD22, CD79b) was more variable. Responses to odronextamab in patients with diffuse large B-cell lymphoma were not related to the relative level of baseline CD20 expression, cell of origin, or high-risk molecular subtype. A potential link was observed between greater tumor programmed cell death-ligand 1 expression and increased likelihood of response to odronextamab. Similarly, a trend was observed between clinical response and increased levels of CD8 T cells and regulatory T cells at baseline. We also identified an on-treatment pharmacodynamic shift in intratumoral immune cell subsets. Finally, loss of CD20 expression through inactivating gene mutations was identified as a potential mechanism of resistance in patients who were treated with odronextamab until progression, as highlighted in two detailed patient cases reported here.ConclusionsThis biomarker analysis expands on clinical findings of odronextamab in patients with R/R B-NHL, providing verification of the suitability of CD20 as a therapeutic target, as well as evidence for potential mechanisms of action and resistance.

The lesbian, gay, bisexual, transgender, and queer (LGBTQ+) adolescent population experiences health disparities due to barriers to care, including lack of access to culturally competent health care providers. The purpose of this quality improvement project was to increase access to culturally competent care through continuing education, a physical makeover of clinic space, and a social marketing campaign. The impact of the project on the number of LGBTQ+ adolescent patients at the clinic and the rate of documentation of sexual orientation and gender identity data was evaluated via a chart audit. Changes in nurses' and health care providers' knowledge as a result of the continuing education were evaluated with a pretest and a posttest. The number of LGBTQ+ patients and provider knowledge increased following the continuing education. Sexual orientation and gender identity data were documented during 87.5% of visits. The participants' knowledge increased by 4.7% following the continuing education. Further, five physical changes to the clinic were completed and a social marketing campaign was launched. This quality improvement project demonstrates that continuing education can be an effective way to increase cultural competence for the care of LGBTQ+ individuals. [J Contin Educ Nurs. 2022;53(8):348–354.]

The total mass density of the Universe appears to be dominated by dark matter. However, beyond its gravitational interactions at the galactic scale, little is known about its nature 1 . Several proposals have been advanced in recent years for the detection of dark matter 2 – 4 . In particular, a network of atomic clocks could be used to search for transient indicators of hypothetical dark matter 5 in the form of stable topological defects; for example, monopoles, strings or domain walls 6 . The clocks become desynchronized when a dark-matter object sweeps through the network. This pioneering approach 5 requires a comparison between at least two distant optical atomic clocks 7 – 9 . Here, by exploiting differences in the susceptibilities of the atoms and the cavity to the fine-structure constant 10 , 11 , we show that a single optical atomic clock 12 is already sensitive to dark-matter events. This implies that existing optical atomic clocks 13 , 14 can serve as a global topological-defect dark-matter observatory, without any further developments in experimental apparatus or the need for long phase-noise-compensated optical-fibre links 15 . Using optical atomic clocks, we explored a new dimension of astrophysical observations by constraining the strength of atomic coupling to hypothetical dark-matter cosmic objects. Under the conditions of our experiments, the degree of constraint was found to exceed the previously reported limits 16 by more than three orders of magnitude. An experimental apparatus using a single optical atomic clock to detect dark matter topological defects (like strings) is proposed. Tests show it can constrain the dark matter–Standard Model coupling strength ~3 orders of magnitude better than previous limits.

Background Impaired orienting to social stimuli is one of the core early symptoms of autism spectrum disorder (ASD). However, in contrast to faces, name processing has rarely been studied in individuals with ASD. Here, we investigated brain activity and functional connectivity associated with recognition of names in the high-functioning ASD group and in the control group. Methods EEG was recorded in 15 young males with ASD and 15 matched one-to-one control individuals. EEG data were analyzed with the event-related potential (ERP), event-related desynchronization and event-related synchronization (ERD/S), as well as coherence and direct transfer function (DTF) methods. Four categories of names were presented visually: one’s own, close-other’s, famous, and unknown. Results Differences between the ASD and control groups were found for ERP, coherence, and DTF. In individuals with ASD, P300 (a positive ERP component) to own-name and to a close-other’s name were similar whereas in control participants, P300 to own-name was enhanced when compared to all other names. Analysis of coherence and DTF revealed disruption of fronto-posterior task-related connectivity in individuals with ASD within the beta range frequencies. Moreover, DTF indicated the directionality of those impaired connections—they were going from parieto-occipital to frontal regions. DTF also showed inter-group differences in short-range connectivity: weaker connections within the frontal region and stronger connections within the occipital region in the ASD group in comparison to the control group. Conclusions Our findings suggest a lack of the self-preference effect and impaired functioning of the attentional network during recognition of visually presented names in individuals with ASD.