Integration of epidemiological and blood biomarker analysis links haem iron intake to increased type 2 diabetes risk.

Dietary haem iron intake is linked to an increased risk of type 2 diabetes (T2D), but the underlying plasma biomarkers are not well understood. We analysed data from 204,615 participants (79% females) in three large US cohorts over up to 36 years, examining the associations between iron intake and T2D risk. We also assessed plasma metabolic biomarkers and metabolomic profiles in subsets of 37,544 (82% females) and 9,024 (84% females) participants, respectively. Here we show that haem iron intake but not non-haem iron is associated with a higher T2D risk, with a multivariable-adjusted hazard ratio of 1.26 (95% confidence interval 1.20-1.33; P for trend <0.001) comparing the highest to the lowest quintiles. Haem iron accounts for significant proportions of the T2D risk linked to unprocessed red meat and specific dietary patterns. Increased haem iron intake correlates with unfavourable plasma profiles of insulinaemia, lipids, inflammation and T2D-linked metabolites. We also identify metabolites, including L-valine and uric acid, potentially mediating the haem iron-T2D relationship, highlighting their pivotal role in T2D pathogenesis.

Planetary Health Diet Index and risk of total and cause-specific mortality in three prospective cohorts.

BACKGROUND: In 2019, the EAT-Lancet Commission proposed a healthy dietary pattern that, along with reductions in food waste and improved agricultural practices, could feed the increasing global population sustainably. We developed a Planetary Health Diet Index (PHDI) to quantify adherence to the EAT-Lancet reference diet. OBJECTIVES: We aimed to assess associations between PHDI and total and cause-specific mortality in 3 prospective cohorts of males and females in the United States. METHODS: We followed 66,692 females from the Nurses' Health Study (1986-2019), 92,438 females from the Nurses' Health Study II (1989-2019), and 47,274 males from the Health Professionals Follow-up Study (1986-2018) who were free of cancer, diabetes, and major cardiovascular diseases at baseline. The PHDI was calculated every 4 y using a semiquantitative food frequency questionnaire. Hazard ratios (HRs) were calculated using multivariable proportional-hazards models. RESULTS: During follow-up, we documented 31,330 deaths among females and 23,206 among males. When comparing the highest with the lowest quintile of PHDI, the pooled multivariable-adjusted HRs were 0.77 [95% confidence interval (CI): 0.75, 0.80] for all-cause mortality (P-trend < 0.0001). The PHDI was associated with lower risk of deaths from cardiovascular diseases (HR: 0.86; 95% CI: 0.81, 0.91), cancer (HR: 0.90; 95% CI: 0.85, 0.95), respiratory diseases (HR: 0.53; 95% CI: 0.48, 0.59), and neurodegenerative diseases (HR: 0.72; 95% CI: 0.67, 0.78). In females, but not males, the PHDI was also significantly associated with a lower risk of deaths from infectious diseases (HR: 0.62; 95% CI: 0.51, 0.76). PHDI scores were also associated inversely with greenhouse gas emissions and other environmental impacts. CONCLUSIONS: In 3 large United States-based prospective cohorts of males and females with up to 34 y of follow-up, a higher PHDI was associated with lower risk of total and cause-specific mortality and environment impacts.

MEASURING PERFORMANCE FOR END-OF-LIFE CARE.

Although not without controversy, readmission is entrenched as a hospital quality metric with statistical analyses generally based on fitting a logistic-Normal generalized linear mixed model. Such analyses, however, ignore death as a competing risk, although doing so for clinical conditions with high mortality can have profound effects; a hospital's seemingly good performance for readmission may be an artifact of it having poor performance for mortality. in this paper we propose novel multivariate hospital-level performance measures for readmission and mortality that derive from framing the analysis as one of cluster-correlated semi-competing risks data. We also consider a number of profiling-related goals, including the identification of extreme performers and a bivariate classification of whether the hospital has higher-/lower-than-expected readmission and mortality rates via a Bayesian decision-theoretic approach that characterizes hospitals on the basis of minimizing the posterior expected loss for an appropriate loss function. in some settings, particularly if the number of hospitals is large, the computational burden may be prohibitive. To resolve this, we propose a series of analysis strategies that will be useful in practice. Throughout, the methods are illustrated with data from CMS on N = 17,685 patients diagnosed with pancreatic cancer between 2000-2012 at one of J = 264 hospitals in California.

Enhancing Physicochemical Properties and Single Cell Performance of Sulfonated Poly(arylene ether) (SPAE) Membrane by Incorporation of Phosphotungstic Acid and Graphene Oxide: A Potential Electrolyte for Proton Exchange Membrane Fuel Cells.

The development of potential and novel proton exchange membranes (PEMs) is imperative for the further commercialization of PEM fuel cells (PEMFCs). In this work, phosphotungstic acid (PWA) and graphene oxide (GO) were integrated into sulfonated poly(arylene ether) (SPAE) through a solution casting approach to create a potential composite membrane for PEMFC applications. Thermal stability of membranes was observed using thermogravimetric analysis (TGA), and the SPAE/GO/PWA membranes exhibited high thermal stability compared to pristine SPAE membranes, owing to the interaction between SPAEK, GO, and PWA. By using a scanning electron microscope (SEM) and atomic force microscope (AFM), we observed that GO and PWA were evenly distributed throughout the SPAE matrix. The SPAE/GO/PWA composite membrane comprising 0.7 wt% GO and 36 wt% PWA exhibited a maximum proton conductivity of 186.3 mS cm-1 at 90 °C under 100% relative humidity (RH). As a result, SPAE/GO/PWA composite membrane exhibited 193.3 mW cm-2 of the maximum power density at 70 °C under 100% RH in PEMFCs.

Ameliorated Performance of Sulfonated Poly(Arylene Ether Sulfone) Block Copolymers with Increased Hydrophilic Oligomer Ratio in Proton-Exchange Membrane Fuel Cells Operating at 80% Relative Humidity.

We designed and synthesized a series of sulfonated poly(arylene ether sulfone) (SPES) with different hydrophilic or hydrophobic oligomer ratios using poly-condensation strategy. Afterward, we fabricated the corresponding membranes via a solution-casting approach. We verified the SPES membrane chemical structure using nuclear magnetic resonance (1H NMR) and confirmed the resulting oligomer ratio. Field-emission scanning electron microscope (FE-SEM) and atomic force microscope (AFM) results revealed that we effectively attained phase separation of the SPES membrane along with an increased hydrophilic oligomer ratio. Thermal stability, glass transition temperature (Tg) and membrane elongation increased with the ratio of hydrophilic oligomers. SPES membranes with higher hydrophilic oligomer ratios exhibited superior water uptake, ion-exchange capacity, contact angle and water sorption, while retaining reasonable swelling degree. The proton conductivity results showed that SPES containing higher amounts of hydrophilic oligomers provided a 74.7 mS cm-1 proton conductivity at 90 °C, which is better than other SPES membranes, but slightly lower than that of Nafion-117 membrane. When integrating SPES membranes with proton-exchange membrane fuel cells (PEMFCs) at 60 °C and 80% relative humidity (RH), the PEMFC power density exhibited a similar increment-pattern like proton conductivity pattern.

Unjamming and collective migration in MCF10A breast cancer cell lines.

Each cell comprising an intact, healthy, confluent epithelial layer ordinarily remains sedentary, firmly adherent to and caged by its neighbors, and thus defines an elemental constituent of a solid-like cellular collective [1,2]. After malignant transformation, however, the cellular collective can become fluid-like and migratory, as evidenced by collective motions that arise in characteristic swirls, strands, ducts, sheets, or clusters [3,4]. To transition from a solid-like to a fluid-like phase and thereafter to migrate collectively, it has been recently argued that cells comprising the disordered but confluent epithelial collective can undergo changes of cell shape so as to overcome geometric constraints attributable to the newly discovered phenomenon of cell jamming and the associated unjamming transition (UJT) [1,2,5-9]. Relevance of the jamming concept to carcinoma cells lines of graded degrees of invasive potential has never been investigated, however. Using classical in vitro cultures of six breast cancer model systems, here we investigate structural and dynamical signatures of cell jamming, and the relationship between them [1,2,10,11]. In order of roughly increasing invasive potential as previously reported, model systems examined included MCF10A, MCF10A.Vector; MCF10A.14-3-3ζ; MCF10.ErbB2, MCF10AT; and MCF10CA1a [12-15]. Migratory speed depended on the particular cell line. Unsurprisingly, for example, the MCF10CA1a cell line exhibited much faster migratory speed relative to the others. But unexpectedly, across different cell lines higher speeds were associated with enhanced size of cooperative cell packs in a manner reminiscent of a peloton [9]. Nevertheless, within each of the cell lines evaluated, cell shape and shape variability from cell-to-cell conformed with predicted structural signatures of cell layer unjamming [1]. Moreover, both structure and migratory dynamics were compatible with previous theoretical descriptions of the cell jamming mechanism [2,10,11,16,17]. As such, these findings demonstrate the richness of the cell jamming mechanism, which is now seen to apply across these cancer cell lines but remains poorly understood.

Variation in zygotic CRISPR/Cas9 gene editing outcomes generates novel reporter and deletion alleles at the Gdf11 locus.

Recent advances in CRISPR/Cas gene editing technology have significantly expanded the possibilities and accelerated the pace of creating genetically engineered animal models. However, CRISPR/Cas-based strategies designed to precisely edit the genome can often yield unintended outcomes. Here, we report the use of zygotic CRISPR/Cas9 injections to generate a knock-in GFP reporter mouse at the Gdf11 locus. Phenotypic and genomic characterization of founder animals from these injections revealed a subset that contained the correct targeting event and exhibited GFP expression that, within the hematopoietic system, was restricted predominantly to lymphoid cells. Yet, in another subset of founder mice, we detected aberrant integration events at the target site that dramatically and inaccurately shifted hematopoietic GFP expression from the lymphoid to the myeloid lineage. Additionally, we recovered multiple Gdf11 deletion alleles that modified the C-terminus of the GDF11 protein. When bred to homozygosity, most of these alleles recapitulated skeletal phenotypes reported previously for Gdf11 knockout mice, suggesting that these represent null alleles. However, we also recovered one Gdf11 deletion allele that encodes a novel GDF11 variant protein ("GDF11-WE") predicted to contain two additional amino acids (tryptophan (W) and glutamic acid (E)) at the C-terminus of the mature ligand. Unlike the other Gdf11 deletion alleles recovered in this study, homozygosity for the Gdf11WE allele did not phenocopy Gdf11 knockout skeletal phenotypes. Further investigation using in vivo and in vitro approaches demonstrated that GDF11-WE retains substantial physiological function, indicating that GDF11 can tolerate at least some modifications of its C-terminus and providing unexpected insights into its biochemical activities. Altogether, our study confirms that one-step zygotic injections of CRISPR/Cas gene editing complexes provide a quick and powerful tool to generate gene-modified mouse models. Moreover, our findings underscore the critical importance of thorough characterization and validation of any modified alleles generated by CRISPR, as unintended on-target effects that fail to be detected by simple PCR screening can produce substantially altered phenotypic readouts.

Outcome of early dental implant placement versus other dental implant placement protocols: A systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis was to compare the clinical efficacy of the early dental implant placement protocol with immediate and delayed dental implant placement protocols. METHODS: An electronic and manual search of literature was made to identify clinical studies comparing early implant placement with immediate or delayed placement. Data from the included studies were pooled and quantitative analyses were performed for the implant outcomes reported as the number of failed implants (primary outcome variable) and for changes in peri-implant marginal bone level, peri-implant probing depth, and peri-implant soft tissue level (secondary outcome variables). RESULTS: Twelve studies met the inclusion criteria. Significant difference in risk of implant failure was found neither between the early and immediate placement protocols (risk difference = -0.018; 95% confidence interval [CI] = -0.06, 0.025; P = 0.416) nor between early and delayed placement protocols (risk difference = -0.008; 95% CI = -0.044, 0.028; P = 0.670). Pooled data of changes in peri-implant marginal bone level demonstrated significantly less marginal bone loss for implants placed using the early placement protocol compared with those placed in fresh extraction sockets (P = 0.001; weighted mean difference = -0.14 mm; 95% CI = -0.22, -0.05). No significant differences were found between the protocols for the other variables. CONCLUSIONS: The available evidence supports the clinical efficacy of the early implant placement protocol. Present findings indicate that the early implant placement protocol results in implant outcomes similar to immediate and delayed placement protocols and a superior stability of peri-implant hard tissue compared with immediate implant placement.

Geometric constraints during epithelial jamming.

As an injury heals, an embryo develops, or a carcinoma spreads, epithelial cells systematically change their shape. In each of these processes cell shape is studied extensively whereas variability of shape from cell-to-cell is regarded most often as biological noise. But where do cell shape and its variability come from? Here we report that cell shape and shape variability are mutually constrained through a relationship that is purely geometrical. That relationship is shown to govern processes as diverse as maturation of the pseudostratified bronchial epithelial layer cultured from non-asthmatic or asthmatic donors, and formation of the ventral furrow in the Drosophila embryo. Across these and other epithelial systems, shape variability collapses to a family of distributions that is common to all. That distribution, in turn, is accounted for by a mechanistic theory of cell-cell interaction showing that cell shape becomes progressively less elongated and less variable as the layer becomes progressively more jammed. These findings suggest a connection between jamming and geometry that spans living organisms and inert jammed systems, and thus transcends system details. Although molecular events are needed for any complete theory of cell shape and cell packing, observations point to the hypothesis that jamming behavior at larger scales of organization sets overriding geometrical constraints.

Enhanced Performance of a Sulfonated Poly(arylene ether ketone) Block Copolymer Bearing Pendant Sulfonic Acid Groups for Polymer Electrolyte Membrane Fuel Cells Operating at 80% Relative Humidity.

The series of sulfonated poly(arylene ether ketone) (SPAEK) block copolymers with controlled F-oligomer length bearing pendant diphenyl unit were synthesized via a polycondensation reaction. Sulfonation was verified by 1H NMR analysis to introduce sulfonic acid group selectively and intensively on the pendant diphenyl unit of polymer backbones. The SPAEK membranes fabricated by the solution casting approach were very transparent and flexible with the thickness of ∼50 µm. These membranes with different F-oligomer lengths were investigated to the physiochemical properties such as water absorption, dimensional stability, ion exchange capacity, and proton conductivity. As a result, the SPAEK membranes (X4.8Y8.8, X7.5Y8.8, and X9.1Y8.8) in accordance to increasing the length of hydrophilic oligomer showed excellent proton conductivity in range of 131-154 mS cm-1 compared to Nafion-115 (131 mS cm-1) at 90 °C under 100% relative humidity (RH). Among the SPAEK membranes, proton conductivity of SPAEK X9.1Y8.8 (140.7 mS cm-1) is higher than that of Nafion-115 (102 mS cm-1) at 90 °C under 80% RH. The atomic force microscopy image demonstrated that number of ion transport channels is increased with increase in the length of hydrophilic oligomer in the main chains, and the morphology is proved to be related to the proton conductivity. The synthesized SPAEK membrane exhibited a maximum power density of 324 mW cm-2, which is higher than that of Nafion-115 (291 mW cm-2) at 60 °C under 100% RH.

Improved Physicochemical Stability and High Ion Transportation of Poly(Arylene Ether Sulfone) Blocks Containing a Fluorinated Hydrophobic Part for Anion Exchange Membrane Applications.

A series of anion exchange membranes composed of partially fluorinated poly(arylene ether sulfone)s (PAESs) multiblock copolymers bearing quaternary ammonium groups were synthesized with controlled lengths of the hydrophilic precursor and hydrophobic oligomer via direct polycondensation. The chloromethylation and quaternization proceeded well by optimizing the reaction conditions to improve hydroxide conductivity and physical stability, and the fabricated membranes were very flexible and transparent. Atomic force microscope images of quaternized PAES (QN-PAES) membranes showed excellent hydrophilic/hydrophobic phase separation and distinct ion transition channels. An extended architecture of phase separation was observed by increasing the hydrophilic oligomer length, which resulted in significant improvements in the water uptake, ion exchange capacity, and hydroxide conductivity. Furthermore, the open circuit voltage (OCV) of QN-PAES X10Y23 and X10Y13 was found to be above 0.9 V, and the maximum power density of QN-PAES X10Y13 was 131.7 mW cm-2 at 60 °C under 100% RH.

Regional differences in infection control conditions in a sample of primary health care services in Brazil / Diferenças regionais nas condições de controle de infecções em uma amostra de serviços de atenção primária no Brasil / Diferencias regionales en las condiciones del control de infecciones en una muestra de servicios de atención primaria en Brasil

International guidelines have pointed out the importance of the physical environment of health care facilities in preventing and controlling infection. We aimed to describe the physical environment of dental care facilities in Brazil in 2014, focusing on characteristics designed to control infections. Exactly 16,202 dental offices in the Brazilian Unified National Health System (SUS) participated in this survey. Trained researchers extracted information about the infection control characteristics of health facilities by using a structured instrument. We used data from 12 dichotomous questions that evaluated the wall, floor, sink and tap conditions, and the presence and condition of sterilization equipment. We calculated a score by summing the number of characteristics handled appropriately for infection control, which could range from 0 to 12. Hierarchical cluster analyses were developed. None of the 12 criteria were met by all the oral health teams. Only 208 (1.3%) dental offices correctly performed all 12-infection control practices. Two clusters, with different frequencies of structure for infection control in dental offices, were identified. South and Southeast regions had the highest frequencies for Cluster 1, with better structure of infection control in dental offices. Dental care facilities of oral health teams were not typically meeting the infection control guidelines regarding clinic design and equipment. Adherence to the guidelines varied among the Brazilian geographic regions.

As diretrizes internacionais destacam a importância do ambiente físico dos serviços de saúde para prevenir e controlar as infecções. Procuramos descrever o ambiente físico em serviços de saúde bucal no Brasil em 2014, com enfoque nas características programadas para controlar as infecções. Precisamente 16.202 consultórios odontológicos no Sistema Único de Saúde (SUS) participaram na pesquisa. Pesquisadores treinados coletaram informações sobre as características do controle de infecções nesses serviços de saúde, utilizando um instrumento padronizado. Utilizamos dados de 12 perguntas dicotômicas que avaliavam as condições das paredes, piso, pia e torneira e a presença e as condições do equipamento de esterilização. Calculamos um escore pela soma do número de características administradas adequadamente para o controle de infecções, variando de 0 a 12. Foram desenvolvidas análises hierárquicas de clusters. Nenhum dos 12 critérios foi atendido por todas as equipes de saúde bucal. Apenas 208 (1,3%) dos consultórios odontológicos realizavam todas as 12 práticas de controle de infecções. Foram identificados dois clusters com distintas frequências de estruturas para controle de infecções nos consultórios odontológicos. As regiões Sul e Sudeste mostraram as maiores frequências no Cluster 1, com melhor estrutura de controle de infecções nos consultórios odontológicos. De maneira geral os serviços de saúde bucal não atendiam as diretrizes para o controle de infecções, referentes à planta física e equipamento dos consultórios. A aderência às diretrizes variava de acordo com a região do país.

Las directrices internacionales destacan la importancia del ambiente físico de los servicios de salud para prevenir y controlar infecciones. Procuramos describir el ambiente físico en servicios de salud bucal en Brasil en 2014, centrándonos en las características programadas para controlar las infecciones. Precisamente 16.202 consultorios odontológicos del Sistema Único de Salud (SUS) participaron en la investigación. Investigadores entrenados recogieron información sobre las características del control de infecciones en esos servicios de salud, utilizando un instrumento estandarizado. Utilizamos los datos procedentes de 12 preguntas dicotómicas que evaluaban las condiciones de las paredes, suelo, fregadero y grifo, además de la existencia y condiciones del equipamiento de esterilización. Calculamos una puntuación para la suma del número de características administradas adecuadamente para el control de infecciones, variando de 0 a 12. Se desarrollaron análisis jerárquicos de clúster. Ninguno de los 12 criterios fue observado por todos los equipos de salud bucal. Solamente 208 (1,3%) de los consultorios odontológicos realizaban las 12 prácticas de control de infecciones al completo. Se identificaron dos clústeres con distintas frecuencias de estructuras para el control de infecciones en los consultorios odontológicos. Las regiones Sur y Sudeste mostraron las mayores frecuencias en el Clúster 1, con una mejor estructura de control de infecciones en los consultorios odontológicos. De manera general, los servicios de salud bucal no atendían a las directrices para el control de infecciones, referentes a las instalaciones físicas y equipamiento de los consultorios. La adherencia a las directrices variaba de acuerdo con la región del país.

Multivariate Bayesian variable selection exploiting dependence structure among outcomes: Application to air pollution effects on DNA methylation.

The analysis of multiple outcomes is becoming increasingly common in modern biomedical studies. It is well-known that joint statistical models for multiple outcomes are more flexible and more powerful than fitting a separate model for each outcome; they yield more powerful tests of exposure or treatment effects by taking into account the dependence among outcomes and pooling evidence across outcomes. It is, however, unlikely that all outcomes are related to the same subset of covariates. Therefore, there is interest in identifying exposures or treatments associated with particular outcomes, which we term outcome-specific variable selection. In this work, we propose a variable selection approach for multivariate normal responses that incorporates not only information on the mean model, but also information on the variance-covariance structure of the outcomes. The approach effectively leverages evidence from all correlated outcomes to estimate the effect of a particular covariate on a given outcome. To implement this strategy, we develop a Bayesian method that builds a multivariate prior for the variable selection indicators based on the variance-covariance of the outcomes. We show via simulation that the proposed variable selection strategy can boost power to detect subtle effects without increasing the probability of false discoveries. We apply the approach to the Normative Aging Study (NAS) epigenetic data and identify a subset of five genes in the asthma pathway for which gene-specific DNA methylations are associated with exposures to either black carbon, a marker of traffic pollution, or sulfate, a marker of particles generated by power plants.

Hierarchical models for semi-competing risks data with application to quality of end-of-life care for pancreatic cancer.

Readmission following discharge from an initial hospitalization is a key marker of quality of health care in the United States. For the most part, readmission has been studied among patients with 'acute' health conditions, such as pneumonia and heart failure, with analyses based on a logistic-Normal generalized linear mixed model (Normand et al., 1997). Naïve application of this model to the study of readmission among patients with 'advanced' health conditions such as pancreatic cancer, however, is problematic because it ignores death as a competing risk. A more appropriate analysis is to imbed such a study within the semi-competing risks framework. To our knowledge, however, no comprehensive statistical methods have been developed for cluster-correlated semi-competing risks data. To resolve this gap in the literature we propose a novel hierarchical modeling framework for the analysis of cluster-correlated semi-competing risks data that permits parametric or non-parametric specifications for a range of components giving analysts substantial flexibility as they consider their own analyses. Estimation and inference is performed within the Bayesian paradigm since it facilitates the straightforward characterization of (posterior) uncertainty for all model parameters, including hospital-specific random effects. Model comparison and choice is performed via the deviance information criterion and the log-pseudo marginal likelihood statistic, both of which are based on a partially marginalized likelihood. An efficient computational scheme, based on the Metropolis-Hastings-Green algorithm, is developed and had been implemented in the SemiCompRisks R package. A comprehensive simulation study shows that the proposed framework performs very well in a range of data scenarios, and outperforms competitor analysis strategies. The proposed framework is motivated by and illustrated with an on-going study of the risk of readmission among Medicare beneficiaries diagnosed with pancreatic cancer. Using data on n=5,298 patients at J=112 hospitals in the six New England states between 2000-2009, key scientific questions we consider include the role of patient-level risk factors on the risk of readmission and the extent of variation in risk across hospitals not explained by differences in patient case-mix.

Bayesian Semi-parametric Analysis of Semi-competing Risks Data: Investigating Hospital Readmission after a Pancreatic Cancer Diagnosis.

In the U.S., the Centers for Medicare and Medicaid Services uses 30-day readmission, following hospitalization, as a proxy outcome to monitor quality of care. These efforts generally focus on treatable health conditions, such as pneumonia and heart failure. Expanding quality of care systems to monitor conditions for which treatment options are limited or non-existent, such as pancreatic cancer, is challenging because of the non-trivial force of mortality; 30-day mortality for pancreatic cancer is approximately 30%. In the statistical literature, data that arise when the observation of the time to some non-terminal event is subject to some terminal event are referred to as 'semi-competing risks data'. Given such data, scientific interest may lie in at least one of three areas: (i) estimation/inference for regression parameters, (ii) characterization of dependence between the two events, and (iii) prediction given a covariate profile. Existing statistical methods focus almost exclusively on the first of these; methods are sparse or non-existent, however, when interest lies with understanding dependence and performing prediction. In this paper we propose a Bayesian semi-parametric regression framework for analyzing semi-competing risks data that permits the simultaneous investigation of all three of the aforementioned scientific goals. Characterization of the induced posterior and posterior predictive distributions is achieved via an efficient Metropolis-Hastings-Green algorithm, which has been implemented in an R package. The proposed framework is applied to data on 16,051 individuals diagnosed with pancreatic cancer between 2005-2008, obtained from Medicare Part A. We found that increased risk for readmission is associated with a high comorbidity index, a long hospital stay at initial hospitalization, non-white race, male, and discharge to home care.

A new flavonol glycoside from Hylomecon vernalis.

Purification of a MeOH extract from the aerial parts of Hylomecon vernalis Maxim. (Papaveraceae) using column chromatography furnished a new acetylated flavonol glycoside (1), together with twenty known phenolic compounds (2-21). Structural elucidation of 1 was based on 1D- and 2D-NMR spectroscopy data analysis to be quercetin 3-O-[4‴-O-acetyl-α-L-arabinopyranosyl]-(1‴→6″)-ß-D-galactopyranoside (1). The structures of compounds 2-21 were elucidated by spectroscopy and confirmed by comparison with reported data; quercetin 3-O-[2‴-O-acetyl-α-L-arabinopyranosyl]-(1‴→6″)-ß -D-galactopyranoside (2), quercetin 3-O-α-L-arabinopyranosyl-(1‴→6″)-ß-D-galactopyranoside (3), quercetin 3-O-ß -D-galactopyranoside (4), kaempferol 3,7-O-α-L-dirhamnopyranoside (5), diosmetin 7-O-ß -D-glucopyranoside (6), diosmetin 7-O-ß -D-xylopyranosyl-(1‴→6″)-ß-D-glucopyranoside (7), p-hydroxybenzoic acid (8), protocatechuic acid (9), caffeic acid (10), 6-hydroxy-3,4-dihydro-1-oxo-ß -carboline (11), (Z)-3-hexenyl-ß -D-glucopyranoside (12), (E)-2-hexenyl-ß -D-glucopyranoside (13), (Z)-3-hexenyl-α-Larabinopyranosyl-(1″→6')-ß-D-glucopyranoside (14), oct-1-en-3-yl-α-L-arabinopyranosyl-(1″→6')-ß-D-glucopyranoside (15), benzyl-ß-D-apiofuranosyl-(1″→6')-ß-D-glucopyranoside (16), benzyl-α-L-arabinopyranosyl-(1″→6')-ß-D-glucopyranoside (17), benzyl-ß-D-xylopyranosyl-(1″→6')-ß-Dglucopyranoside (18), 2-phenylethyl-α-L-arabinopyranosyl-(1″→6')-ß-D-glucopyranoside (19), 2-phenylethyl-ß-D-apiofuranosyl-(1″→6')-ß-D-glucopyranoside (20), and aryl-ß-D-glucopyranoside (21). Compounds 2-21 were isolated for the first time from this plant. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using a Sulforhodamin B bioassay.

Terpene and phenolic constituents of Lactuca indica L.

We isolated seven terpenes and five phenolic constituents from the aerial parts of Lactuca indica L. using column chromatographic separation of its MeOH extract. Their structures were determined by spectroscopic methods to be trans-phytol (1), 3beta-hydroxyglutin-5-ene (2), 5,6-epoxy-3-hydroxy-7-megastigmen-9-one (3), 11beta-13-dihydrolactucin (4), 2-phenylethyl beta-D-glucopyranoside (5), cichorioside B (6), 1-hydroxylinaloyl-6-O-beta-D-glucopyranoside (7), (6S,9S)-roseoside (8), benzyl-beta-D-glucopyranoside (9), 2-(3'-O-beta-D-glucopyranosyl-4'-hydroxyphenyl)-ethanol (10), 3-(beta-D-glucopyranosyloxymethyl)-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-7-methoxy-dihydrobenzofuran (11), and (+)-taraxafolin-B (12). Compounds 1-3, 5, and 7-12 were isolated for the first time from this plant source. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using a Sulforhodamin B bioassay.

A new phenolic amide from the roots of Paris verticillata.

A new phenolic amide 8, together with the nine known phenolic compounds 1-7, 9 and 10 were isolated from the MeOH extract of the roots of Paris verticillata. The structure of the new compound 8 was determined to be 1-N-feruloylaminobutyl-4-rho-hydroxybenzamide by spectroscopic methods. The isolated compounds were tested for cytotoxicity against four human tumor cell lines using the SRB assay.

Two new phenolic constituents of Humulus japonicus and their cytotoxicity test in vitro.

Two new phenolic constituents (4 and 6), together with four known constituents, methyl ferulate (1), eugenyl-beta-D-glucopyranoside (2), apigenin-7-O-beta-D-glucopyranoside (3), and (E)-resveratrol-3-O-beta-D-glucopyranoside (5) were isolated from the MeOH extract of the aerial part sof Humulus japonicus. The structures of the new compounds were determined by spectroscopic methods to be divarin-3-O-beta-glucopyranoside (4), and lariciresinol-9-O-beta-xylopyranoside (6). Compounds 1 and 3 exhibited moderate cytotoxicity against two human cancer cell lines (SK-OV-3 and HCT15) with ED50 values ranging from 8.84 to 8.79 microM.

Lignan and terpene constituents from the aerial parts of Saussurea pulchella.

Chromatographic separation of the MeOH extract from the aerial parts of Saussurea pulchella led to the isolation of seven terpenes (1-4, 11-13), and eight phenolics (5-10, 14-15). Their structures were determined by spectroscopic means to be (3S)-3-O-(3',4'-diangeloyl-beta-D-glucopyranosyloxy)-3,7-trimethylocta-1,6-diene (1), 7delta-methoxy- 4(14)- oppositen-1beta-ol (2) 4(15)- eudesmene-1beta, 6alpha-diol (3), 3alpha-hydroxy-5, 6-epoxy-7-megastigmen-9-one (4), (+)-syringaresinol (5), (7S, 8R, 8'R)-5,5'-dimethoxylariciresinol (6), 8alpha-hydroxypinoresinol (7), (7'R, 8'R)-2,2'- dimethoxy-4- (3-hydroxyl-propenyl)-4'-(1,2,3-trihydroxypropyl)-biphenyl ether (8), 4-allyl-2,6- dimethoxyphenyl glucoside (9), 2-methoxy-4-(2-propenyl)phenyl beta-D-glucoside (10), (-)-oplopan-4-one- 10alpha-O-beta-D-glucoside (11), linalyl-O-beta-D-glucoside (12), amarantholidoside IV (13), (+)-1-hydroxypinoresinol 1-O-beta-D-glucoside (14), and syringin (15). Compounds 1-3 and 8-13 were first isolated from the genus Saussurea. The isolated compounds were examined for cytotoxic activity against four human cancer cell lines in vitro using the sulforhodamin B bio assay method.