High sensitivity of 17O NMR to p-d hybridization in transition metal perovskites: first principles calculations of large anisotropic chemical shielding

A first principles embedded cluster approach is used to calculate O chemical shielding tensors, sigma, in prototypical transition metal oxide ABO_3 perovskite crystals. Our principal findings are 1) a large anisotropy of sigma between deshielded sigma_x ~ sigma_y and shielded sigma_z components (z along the Ti-O bond); 2) a nearly linear variation, across all the systems studied, of the isotropic sigma_iso and uniaxial sigma_ax components, as a function of the B-O-B bond asymmetry. We show that the anisotropy and linear variation arise from large paramagnetic contributions to sigma_x and sigma_y due to virtual transitions between O(2p) and unoccupied B(nd) states. The calculated isotropic delta_iso and uniaxial delta_ax chemical shifts are in good agreement with recent BaTiO_3 and SrTiO_3 single crystal 17O NMR measurements. In PbTiO_3 and PbZrO_3, calculated delta_iso are also in good agreement with NMR powder spectrum measurements. In PbZrO_3, delta_iso calculations of the five chemically distinct sites indicate a correction of the experimental assignments. The strong dependence of sigma on covalent O(2p)-B(nd) interactions seen in our calculations indicates that 17O NMR spectroscopy, coupled with first principles calculations, can be an especially useful tool to study the local structure in complex perovskite alloys.Comment: 12 pages, 3 figures, and 3 Table

Non-equilibrium phase transitions in biomolecular signal transduction

We study a mechanism for reliable switching in biomolecular signal-transduction cascades. Steady bistable states are created by system-size cooperative effects in populations of proteins, in spite of the fact that the phosphorylation-state transitions of any molecule, by means of which the switch is implemented, are highly stochastic. The emergence of switching is a nonequilibrium phase transition in an energetically driven, dissipative system described by a master equation. We use operator and functional integral methods from reaction-diffusion theory to solve for the phase structure, noise spectrum, and escape trajectories and first-passage times of a class of minimal models of switches, showing how all critical properties for switch behavior can be computed within a unified framework

Essential package of palliative care for women with cervical cancer: Responding to the suffering of a highly vulnerable population

Women with cervical cancer, especially those with advanced disease, appear to experience suffering that is more prevalent, complex, and severe than that caused by other cancers and serious illnesses, and approximately 85% live in low- and middle-income countries where palliative care is rarely accessible. To respond to the highly prevalent and extreme suffering in this vulnerable population, we convened a group of experienced experts in all aspects of care for women with cervical cancer, and from countries of all income levels, to create an essential package of palliative care for cervical cancer (EPPCCC). The EPPCCC consists of a set of interventions, medicines, simple equipment, social supports, and human resources, and is designed to be safe and effective for preventing and relieving all types of suffering associated with cervical cancer. It includes only inexpensive and readily available medicines and equipment, and its use requires only basic training. Thus, the EPPCCC can and should be made accessible everywhere, including for the rural poor. We provide guidance for integrating the EPPCCC into gynecologic and oncologic care at all levels of health care systems, and into primary care, in countries of all income levels

Augmented package of palliative care for women with cervical cancer: Responding to refractory suffering

The essential package of palliative care for cervical cancer (EPPCCC), described elsewhere, is designed to be safe and effective for preventing and relieving most suffering associated with cervical cancer and universally accessible. However, it appears that women with cervical cancer, more frequently than patients with other cancers, experience various types of suffering that are refractory to basic palliative care such as what can be provided with the EPPCCC. In particular, relief of refractory pain, vomiting because of bowel obstruction, bleeding, and psychosocial suffering may require additional expertise, medicines, or equipment. Therefore, we convened a group of experienced experts in all aspects of care for women with cervical cancer, and from countries of all income levels, to create an augmented package of palliative care for cervical cancer with which even suffering refractory to the EPPCCC often can be relieved. The package consists of medicines, radiotherapy, surgical procedures, and psycho-oncologic therapies that require advanced or specialized training. Each item in this package should be made accessible whenever the necessary resources and expertise are available

Assessing and Responding to Palliative Care Needs in Rural Sub-Saharan Africa: Results from a Model Intervention and Situation Analysis in Malawi

Introduction: Palliative care is rarely accessible in rural sub-Saharan Africa. Partners In Health and the Malawi government established the Neno Palliative Care Program (NPCP) to provide palliative care in rural Neno district. We conducted a situation analysis to evaluate early NPCP outcomes and better understand palliative care needs, knowledge, and preferences. Methods: Employing rapid evaluation methodology, we collected data from 3 sources: 1) chart review of all adult patients from the NPCP’s first 9 months; 2) structured interviews with patients and caregivers; 3) semi-structured interviews with key stakeholders. Results: The NPCP enrolled 63 patients in its first 9 months. Frequent diagnoses were cancer (n = 50, 79%) and HIV/AIDS (n = 37 of 61, 61%). Nearly all (n = 31, 84%) patients with HIV/AIDS were on antiretroviral therapy. Providers registered 112 patient encounters, including 22 (20%) home visits. Most (n = 43, 68%) patients had documented pain at baseline, of whom 23 (53%) were treated with morphine. A majority (n = 35, 56%) had ≥1 follow-up encounter. Mean African Palliative Outcome Scale pain score decreased non-significantly between baseline and follow-up (3.0 vs. 2.7, p = 0.5) for patients with baseline pain and complete pain assessment documentation. Providers referred 48 (76%) patients for psychosocial services, including community health worker support, socioeconomic assistance, or both. We interviewed 36 patients referred to the NPCP after the chart review period. Most had cancer (n = 19, 53%) or HIV/AIDS (n = 10, 28%). Patients frequently reported needing income (n = 24, 67%) or food (n = 22, 61%). Stakeholders cited a need to make integrated palliative care widely available. Conclusions: We identified a high prevalence of pain and psychosocial needs among patients with serious chronic illnesses in rural Malawi. Early NPCP results suggest that comprehensive palliative care can be provided in rural Africa by integrating disease-modifying treatment and palliative care, linking hospital, clinic, and home-based services, and providing psychosocial support that includes socioeconomic assistance

Cervical cancer-associated suffering: Estimating the palliative care needs of a highly vulnerable population

Purpose: To enable design of optimum palliative care for women with cervical cancer, we studied the most common types of suffering and their severity, prevalence, and duration.Methods: We first reviewed the literature on the major types, severity, prevalence, and duration of suffering associated with cervical cancer. We then conducted a modified Delphi process with experts in cervical cancer care to supplement the literature. For each type of suffering, we distinguished between decedents (those who die from cervical cancer in a given year) and nondecedents (those who have cervical cancer in a given year but do not die). By applying the suffering prevalence and duration estimates to the number of decedents, nondecedents, and family caregivers in 2017, we were able to estimate their palliative care needs and the intensity of palliative care needed to respond adequately to this suffering.Results: There is a high prevalence among decedents of moderate or severe pain (84%), vaginal discharge (66%), vaginal bleeding (61%), and loss of faith (31%). Among both decedents and nondecedents, there is a high prevalence of clinically significant anxiety (63% and 50%, respectively), depressed mood (52% and 38%, respectively), and sexual dysfunction (87% and 83%, respectively). Moderate or severe financial distress is prevalent among decedents, nondecedents, and family caregivers (84%, 74%, and 66%, respectively). More than 40% of decedents and nondecedents are abandoned by their intimate partners. Most patients experience some combination of moderate or severe physical, psychological, social, and spiritual suffering. In total, 258,649 decedents and 2,558,857 nondecedents needed palliative care in 2017, approximately 85% of whom were in low- and middle-income countries where palliative care is rarely accessible.Conclusion: Among women with advanced cervical cancer, suffering is highly prevalent and often severe and multifaceted

Targeted plasma multi-omics propose glutathione, glycine and serine as biomarkers for abdominal aortic aneurysm growth on serial CT scanning

Background and aims: Abdominal aortic aneurysm (AAA) patients undergo uniform imaging surveillance until reaching the surgical threshold. In spite of the ongoing exploration of AAA pathophysiology, biomarkers for personalized surveillance are lacking. This study aims to identify potential circulating biomarkers for AAA growth on serial CT scans. Methods: Patients with an AAA (maximal diameter ≥40 mm) were included in this multicentre, prospective cohort study. Participants underwent baseline blood sampling and yearly CT-imaging to determine AAA diameter and volume. Proteins and metabolites were measured using proximity extension assay (Olink Cardiovascular III) or separate ELISA panels, and mass-spectrometry (LC-TQMS), respectively. Linear mixed-effects, orthogonal partial least squares, and Cox regression were used to explore biomarker associations with AAA volume growth rate and the risk of surpassing the surgical threshold, as formulated by current guidelines. Results: 271 biomarkers (95 proteins, 176 metabolites) were measured in 109 (90.8 % male) patients with mean age 72. Median baseline maximal AAA diameter was 47.8 mm, volume 109 mL. Mean annual AAA volume growth rate was 11.5 %, 95 % confidence interval (CI) (10.4, 12.7). Median follow-up time was 23.2 months, 49 patients reached the surgical threshold. Patients with one standard deviation (SD) higher glutathione and glycine levels at baseline had an AAA volume growth rate that respectively was 1.97 %, 95%CI (0.97, 2.97) and 1.74 %, 95%CI (0.78, 2.71) larger, relative to the actual aneurysm size. Serine was associated with the risk of reaching the surgical threshold, independent of age and baseline AAA size (cause-specific hazard ratio per SD difference 1.78, 95%CI (1.30, 2.44)). Conclusions: Among multiple intertwined biomarkers related to AAA pathophysiology and progression, glutathione, glycine and serine were most promising.</p

Stratification of co-evolving genomic groups using ranked phylogenetic profiles

<p>Abstract</p> <p>Background</p> <p>Previous methods of detecting the taxonomic origins of arbitrary sequence collections, with a significant impact to genome analysis and in particular metagenomics, have primarily focused on compositional features of genomes. The evolutionary patterns of phylogenetic distribution of genes or proteins, represented by phylogenetic profiles, provide an alternative approach for the detection of taxonomic origins, but typically suffer from low accuracy. Herein, we present <it>rank-BLAST</it>, a novel approach for the assignment of protein sequences into genomic groups of the same taxonomic origin, based on the ranking order of phylogenetic profiles of target genes or proteins across the reference database.</p> <p>Results</p> <p>The rank-BLAST approach is validated by computing the phylogenetic profiles of all sequences for five distinct microbial species of varying degrees of phylogenetic proximity, against a reference database of 243 fully sequenced genomes. The approach - a combination of sequence searches, statistical estimation and clustering - analyses the degree of sequence divergence between sets of protein sequences and allows the classification of protein sequences according to the species of origin with high accuracy, allowing taxonomic classification of 64% of the proteins studied. In most cases, a main cluster is detected, representing the corresponding species. Secondary, functionally distinct and species-specific clusters exhibit different patterns of phylogenetic distribution, thus flagging gene groups of interest. Detailed analyses of such cases are provided as examples.</p> <p>Conclusion</p> <p>Our results indicate that the rank-BLAST approach can capture the taxonomic origins of sequence collections in an accurate and efficient manner. The approach can be useful both for the analysis of genome evolution and the detection of species groups in metagenomics samples.</p