MILFM: Multiple index latent factor model based on high-dimensional features.

The aim of this article is to develop a multiple-index latent factor modeling (MILFM) framework to build an accurate prediction model for clinical outcomes based on a massive number of features. We develop a three-stage estimation procedure to build the prediction model. MILFM uses an independent screening method to select a set of informative features, which may have a complex nonlinear relationship with the outcome variables. Moreover, we develop a latent factor model to project all informative predictors onto a small number of local subspaces, which lead to a few key features that capture reliable and informative covariate information. Finally, we fit the regularized empirical estimate to those key features in order to accurately predict clinical outcomes. We systematically investigate the theoretical properties of MILFM, such as risk bounds and selection consistency. Our simulation results and real data analysis show that MILFM outperforms many state-of-the-art methods in terms of prediction accuracy.

Stigma, self-blame, and satisfaction with care among patients with lung cancer.

OBJECTIVE: We sought to understand the experiences of patients with lung cancer and to see if attitudes varied by demographic factors. METHODS: We administered a 63-question survey by phone or online among 174 patients with lung cancer. Factor analysis was used to identify two groups of questions with a conceptual relationship and high Cronbach's alphas, stigma and satisfaction with care. We used a multivariable analysis to identify predictors of self-blame and the factors of stigma and satisfaction with care. RESULTS: Patients were satisfied with the quality of their care and treatment choices but did not feel that there is enough public support for or research in lung cancer. Predictors of lower satisfaction with care were never being a smoker, lack of college education, not living in a rural location, refusing to report income, and not knowing/not being sure of stage. Self-blame was modest; in multivariable analysis, predictors of self-blame were believing that smoking was a cause of their lung cancer, younger age, male sex, living in a suburban location, and not knowing/not being sure of the stage of the cancer. Reported stigma was low and the only predictor for stigma was being married. Despite low scores on their personal experience of stigma, patients reported a high degree of stigmatization of lung cancer in general. Smoking was a significant predictor of personal stigma. CONCLUSION: Despite satisfaction with their treatment and care, lung cancer patients feel that society stigmatizes them as a general population. Patients who smoke are more likely to report that they have personally experienced stigma.

Spike-and-slab type variable selection in the Cox proportional hazards model for high-dimensional features.

In this paper, we develop a variable selection framework with the spike-and-slab prior distribution via the hazard function of the Cox model. Specifically, we consider the transformation of the score and information functions for the partial likelihood function evaluated at the given data from the parameter space into the space generated by the logarithm of the hazard ratio. Thereby, we reduce the nonlinear complexity of the estimation equation for the Cox model and allow the utilization of a wider variety of stable variable selection methods. Then, we use a stochastic variable search Gibbs sampling approach via the spike-and-slab prior distribution to obtain the sparsity structure of the covariates associated with the survival outcome. Additionally, we conduct numerical simulations to evaluate the finite-sample performance of our proposed method. Finally, we apply this novel framework on lung adenocarcinoma data to find important genes associated with decreased survival in subjects with the disease.

Copper(I) coordination polymers of N,N'-bis[3-(methylthio)propyl]pyromellitic diimide: crystal transformation and solvatochromism by halogen-π interactions.

Four copper(I) coordination polymers with ligand N,N'-bis[3-(methylthio)propyl]pyromellitic diimide (L), [Cu(2)I(2)L(2)](n) (1), [Cu(2)I(2)L(2)](n) (2), [Cu(2)I(2)L](n) (3), and {[Cu(2)I(2)L(2)]·CH(2)Cl(2)}(n) (4), have been successfully synthesized and structurally characterized by single-crystal X-ray diffraction. Structural transformations between the polymers were controlled by the appropriate solvent composition, mole ratio, or temperature. When a 1:1 CuI/L ratio was employed, dimorphic products, 1 and 2, based on a rhomboid Cu(2)I(2) cluster were obtained from an acetonitrile solution and from a dichloromethane/acetonitrile solution with ultrasonication, respectively. When a 1:2 CuI/L ratio was employed, polymer 3 based on infinite stair-step polymer (CuI)(∞) was crystallized. Crystalline product 4 was obtained by the transformation of 1 in a mixed-solvent system with a 1:5 acetonitrile/dichloromethane ratio. Polymers 1-4 were transformed into polymer 3 at 197 °C. X-ray structures of 2-4 show short distances (3.406-3.667 Å) between halogens (I(-) and Cl) and aromatic rings. 1 and 4 show solvatochromism; upon inclusion of the colorless electron donor CH(2)Cl(2), the red color changes as a result of the formation of a chloride-π charge-transfer complex 4 of a pale-colored electron acceptor, 1. Therefore, the origin of the red color from 2 and 3 is also assigned as iodide-to-electron-deficient aromatic π charge transfer.

Acrinathrin: (S)-cyano-(3-phen-oxy-phenyl)methyl (Z)-(1R,3S)-2,2-dimethyl-3-{2-[2,2,2-trifluoro-1-(trifluoro-methyl)eth-oxy-carbon-yl]vin-yl}cyclo-propane-1-carboxyl-ate.

In the title compound, C(26)H(21)F(6)NO(5), the dihedral angle between the cyclo-propane ring plane and the vinyl group plane is 79.3 (3)°. The dihedral angle between the benzene and phenyl ring planes in the phen-oxy-benzyl group is 82.7 (1)°. In the crystal structure, weak inter-molecular C-H⋯π inter-actions and C-H⋯F hydrogen bonds contribute to the stabilization of the packing.

Weighted functional linear Cox regression model.

The aim of this paper is to develop a weighted functional linear Cox regression model that accounts for the association between a failure time and a set of functional and scalar covariates. We formulate the weighted functional linear Cox regression by incorporating a comprehensive three-stage estimation procedure as a unified methodology. Specifically, the weighted functional linear Cox regression uses a functional principal component analysis to represent the functional covariates and a high-dimensional Cox regression model to capture the joint effects of both scalar and functional covariates on the failure time data. Then, we consider an uncensored probability for each subject by estimating the important parameter of a censoring distribution. Finally, we use such a weight to construct the pseudo-likelihood function and maximize it to acquire an estimator. We also show our estimation and testing procedures through simulations and an analysis of real data from the Alzheimer's Disease Neuroimaging Initiative.

Alternative splicing of the murine receptor for advanced glycation end-products (RAGE) gene.

The alternative splicing of pre-mRNAs is a critical mechanism in genomic complexity, disease, and development. Studies of the receptor for advanced glycation end-products (RAGE) indicate that this gene undergoes a variety of splice events in humans. However, no studies have extensively analyzed the tissue distribution in other species or compared evolutionary differences of RAGE isoforms. Because the majority of studies probing RAGE function have been performed in murine models, we therefore performed studies to identify and characterize the splice variants of the murine RAGE gene, and we compared these to human isoforms. Here, using mouse tissues, we identified numerous splice variants including changes in the extracellular domain or the removal of the transmembrane and cytoplasmic domains, which produce soluble splice isoforms. Comparison of splice variants between humans and mice revealed homologous regions in the RAGE gene that undergo splicing as well as key species-specific mechanisms of splicing. Further analysis of tissue splice variant distribution in mice revealed major differences between lung, kidney, heart, and brain. To probe the potential impact of disease-like pathological states, we studied diabetic mice and report that RAGE splice variation changed dramatically, resulting in an increase in production of soluble RAGE (sRAGE) splice variants, which were not associated with detectable levels of sRAGE in murine plasma. In conclusion, we have determined that the murine RAGE gene undergoes extensive splicing with distinct splice isoforms being uniquely distributed in different tissues. These differences in RAGE splicing in both physiological and pathogenic states further expand our understanding of the biological repertoire of this receptor in health and disease.

Bis(benzyl-sulfan-yl)methane.

In the title compound, C(15)H(16)S(2), the structure of the dithioalkyl chain is a helix with an all-cis conformation. The dihedral angle between the mean planes of the terminal aromatic rings is 74.60 (4)°. In the crystal structure, weak C-H⋯π inter-actions contribute to the stabilization of the packing.

Flutolanil [N-(3-isopropoxyphen-yl)-2-(trifluoro-meth-yl)benzamide].

The title compound, C(17)H(16)F(3)NO(2), crystallizes with two independent mol-ecules in the asymmetric unit. The dihedral angles between the isopropoxyphenyl and trifluoro-methyl-phenyl rings are 85.78 (5) and 63.15 (6)° in the two mol-ecules. In the crystal structure, inter-molecular N-H⋯O and C-H⋯π inter-actions are observed.

Pirimicarb: 2-dimethylamino-5,6-dimethylpyrimidin-4-yl dimethyl-carbamate.

In the title compound, C(11)H(18)N(4)O(2) (systematic name: 2-dimethyl-amino-5,6-dimethyl-pyrimidin-4-yl N,N-dimethyl-carb-amate), the pyrimidine ring and dimethyl-amino group are almost in the same plane, making a dihedral angle of 1.6 (1)°. The dihedral angle between the mean plane of the pyrimidine ring and that of the dimethyl-carbamate group is 83.42 (5)°. In the crystal structure, inter-molecular C-H⋯O hydrogen bonds contribute to the stabilization of the packing.

Phosmet: O,O-dimethyl S-phthalimidomethyl phospho-rodithio-ate.

In the title compound, C(11)H(12)NO(4)PS(2), the dihedral angle between the phthalimidyl ring plane and the PS(2) plane of the phospho-rodithio-ate group is 60.41 (3)°. In the crystal structure, weak inter-molecular C-H⋯O hydrogen bonds and S⋯S inter-actions [3.3825 (9) Å] contribute to the stabilization of the packing.

Quantile Function on Scalar Regression Analysis for Distributional Data.

Radiomics involves the study of tumor images to identify quantitative markers explaining cancer heterogeneity. The predominant approach is to extract hundreds to thousands of image features, including histogram features comprised of summaries of the marginal distribution of pixel intensities, which leads to multiple testing problems and can miss out on insights not contained in the selected features. In this paper, we present methods to model the entire marginal distribution of pixel intensities via the quantile function as functional data, regressed on a set of demographic, clinical, and genetic predictors to investigate their effects of imaging-based cancer heterogeneity. We call this approach quantile functional regression, regressing subject-specific marginal distributions across repeated measurements on a set of covariates, allowing us to assess which covariates are associated with the distribution in a global sense, as well as to identify distributional features characterizing these differences, including mean, variance, skewness, heavy-tailedness, and various upper and lower quantiles. To account for smoothness in the quantile functions, account for intrafunctional correlation, and gain statistical power, we introduce custom basis functions we call quantlets that are sparse, regularized, near-lossless, and empirically defined, adapting to the features of a given data set and containing a Gaussian subspace so non-Gaussianness can be assessed. We fit this model using a Bayesian framework that uses nonlinear shrinkage of quantlet coefficients to regularize the functional regression coefficients and provides fully Bayesian inference after fitting a Markov chain Monte Carlo. We demonstrate the benefit of the basis space modeling through simulation studies, and apply the method to Magnetic resonance imaging (MRI) based radiomic dataset from Glioblastoma Multiforme to relate imaging-based quantile functions to various demographic, clinical, and genetic predictors, finding specific differences in tumor pixel intensity distribution between males and females and between tumors with and without DDIT3 mutations.

Identification, classification, and expression of RAGE gene splice variants.

The receptor for advanced glycation end-products (RAGE) is a single-transmembrane, multiligand receptor of the immunoglobulin superfamily. RAGE up-regulation is implicated in numerous pathological states including vascular disease, diabetes, cancer, and neurodegeneration. The understanding of the regulation of RAGE is important in both disease pathogenesis and normal homeostasis. Here, we demonstrate the characterization and identification of human RAGE splice variants by analysis of RAGE cDNA from tissue and cells. We identified a vast range of splice forms that lead to changes in the protein coding region of RAGE, which we have classified according to the Human Gene Nomenclature Committee (HGNC). These resulted in protein changes in the ligand-binding domain of RAGE or the removal of the transmembrane domain and cytosolic tail. Analysis of splice variants for premature termination codons reveals approximately 50% of identified variants are targeted to the nonsense-mediated mRNA decay pathway. Expression analysis revealed the RAGE_v1 variant to be the primary secreted soluble isoform of RAGE. Taken together, identification of functional splice variants of RAGE underscores the biological diversity of the RAGE gene and will aid in the understanding of the gene in the normal and pathological state.

Impacts of Surgery on Symptom Burden and Quality of Life in Pituitary Tumor Patients in the Subacute Post-operative Period.

Background: Pituitary tumors are rare but are associated with significant symptoms that impact patients' quality of life (QOL). Surgery remains one of the most effective treatment options for long term disease control and symptom benefit, but symptom, and quality of life recovery in the subacute period has not been previously reported. This study aimed to better understand the impact of surgery on patients' symptom burden and QOL in the subacute post-surgical period. Methods: Twenty-three adult patients with pituitary tumors undergoing surgical resection at University of North Carolina Cancer Hospital were enrolled in this study. M.D. Anderson Symptom Inventory Brain Tumor Module, European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BN20 questionnaires were collected pre- and 1-month post- surgical resection and differences were analyzed for individual and groups of symptoms and QOL using Wilcoxon signed-rank tests. Results: Twenty adult patients had both pre-operation and post-operation follow-up visits; 60% had functional pituitary adenomas. Seven symptoms including fatigue, memory, vision, numbness, speaking, appearance, and weakness were significantly improved at the 1-month post-operation visit while one symptom, sleep, worsened. Global Health Status/QOL measurements was improved minimally from 63 (SD 25) at pre-operation to 67 (SD 22) at 1-month post-operation without statistical significance. Conclusions: This study demonstrated a rapid improvement of many symptoms in the subacute post-operative period in pituitary tumor patients. Disturbed sleep was identified as the only symptom to worsen post-operatively, encouraging potential prospective interventions to improve sleep, and subsequently improve the QOL in pituitary tumor patients following surgical intervention.

Traffic accident severity analysis with rain-related factors using structural equation modeling - A case study of Seoul City.

Weather conditions are strongly correlated with traffic accident severity. In particular, rain-related factors are an important cause of traffic accidents due to the poor visibility and reduced friction resulting from slippery road conditions. This paper presents a systematic approach to analyze the extent to which the rainfall intensity and level of water depth are responsible for traffic accidents using Seoul City, Korea, as a case study. The rainfall and traffic accident data over a nine-year period (from 2007 to 2015) for Seoul were analyzed through Structural Equation Modeling to identify the relationships among variables by handling endogenous and exogenous variables simultaneously. In the model, four latent variables, namely those representing the road; traffic, environmental, and human factors; and rain and water depth factors, were defined and the coefficients of the latent, endogenous, and exogenous variables were estimated to obtain the level of accident severity. Furthermore, a statistical goodness of fit index was suggested for model fitting. In conclusion, traffic, environmental, and human factors; rain and water depth factors; and road factors are mutually correlated with the level of accident severity. Compact cars, young drivers, female drivers, heavy rain, deep water, and roads with a long drainage length are more likely to be associated with an increase in the level of accident severity, as are features like a tangent, down slope, right-hand curve, and shorter curve length.

Healthcare satisfaction in older and younger patients with cancer.

OBJECTIVE: Although older patients represent the most rapidly growing segment of the oncology population, clinical care is guided by very little data on patient-reported outcomes, particularly satisfaction with healthcare. Using a large cancer center registry, we sought to describe factors associated with satisfaction with care for older and younger oncology patients. METHODS: Data were collected through the University of North Carolina Health Registry Cancer Survivorship Cohort. Satisfaction was measured with the Patient Satisfaction Questionnaire Short Form. Quality of life (QOL) measures included were the Promis Global short form and the Functional Assessment of Cancer Therapy General (FACT-G). RESULTS: A total of 2385 patients were included. 460 (20%) were aged 70 and above (older group). Older patients reported significantly higher levels of satisfaction in domains of time spent with doctor (scores 3.84 versus 3.73 p=0.03) and financial aspects (scores 4.03 versus 3.44 p<0.001) compared to younger patients. In multivariable analysis, higher QOL scores and higher self-reported ECOG performance status were associated with higher satisfaction scores. African American race was associated with lower satisfaction scores in all age groups. QOL was more closely correlated with satisfaction in older patients compared to younger patients. CONCLUSIONS: Older patients with cancer report higher levels of satisfaction with care, in part due to lesser financial burden of care. Better QOL is associated with satisfaction with care in older patients. Use of patient-reported outcomes such as patient satisfaction may help improve patient-centered geriatric oncology care.

Single-Institution Experience with Robotic Partial Nephrectomy for Renal Masses Greater Than 4 cm.

PURPOSE: To review our institution's experience with robotic partial nephrectomy (RPN) for T1b and greater renal masses (>4 cm [T1b+]) in terms of perioperative and oncologic outcomes relative to a contemporary cohort of patients with T1a renal masses (<4 cm). PATIENTS AND METHODS: 232 patients underwent RPN at our institution between 2008 and 2014. Demographics, R.E.N.A.L. nephrometry score, and operative, pathologic, and renal function outcomes, as well as complications, were compared between the two groups (T1a vs T1b+). RESULTS: A total of 168 and 64 patients underwent RPN for T1a and T1b+ renal masses, respectively. T1b+ patients had a higher mean nephrometry score (8.2 vs 6.9), median pathologic tumor size (4.8 vs 2.6 cm), median blood loss (200 vs 100 mL), median warm ischemia time (23 vs 21 minutes), rate of conversion to radical nephrectomy (7.8% vs 1.2%), and rate of Clavien grade III or higher complications (14% vs 4.2%) compared with T1a patients. One patient was found to have disease recurrence in the T1a group, and no patients experienced recurrence in the T1b+ group. No patient died from the disease. CONCLUSIONS: The current series represents the largest single-institutional report of RPN for tumors >4 cm. The higher complexity of tumors resected in this series did not preclude a safe and oncologically efficacious operation; however, Clavien grade III complications were more common in patients with tumors >4 cm, likely from a higher rate of pseudoaneurysm. These data should be considered in preoperative counseling with patients before RPN for tumors >4 cm.

A pilot study of a home-based motivational exercise program for African American breast cancer survivors: clinical and quality-of-life outcomes.

INTRODUCTION: African American breast cancer survivors engage in less physical activity compared with their Caucasian counterparts. There is a need for exercise intervention research that focuses on improving the overall health and long-term survivorship of African American breast cancer survivors, especially because they often have worse outcomes than Caucasian survivors. Study objectives were to determine whether African American participants increase physical activity and explore whether exercise had a positive impact on fitness and health. METHODS: African American breast cancer survivors, stage 0 to IIIA, within 2 years of completing primary cancer treatments were recruited for a 16-week home-based aerobic and resistance training exercise pilot study. Outcome measures assessed at baseline and postintervention included physical activity questionnaires and accelerometry, cardiopulmonary function (VO2peak) with gas exchange, muscle strength, Selective Functional Movement Assessment, and dual energy X-ray absorptiometry scans for body composition analysis. Assessments for fatigue and quality of life (QOL) were also completed at baseline and postintervention. Motivational interviewing was utilized to determine goals and explore exercise facilitators/barriers. Participants completed weekly exercise logs and received weekly phone calls. Wilcoxon signed rank tests were used to detect significant changes in physical activity and also changes in fitness/health parameters, fatigue, and QOL. Spearman correlation coefficients were used to examine relationships between physical activity and health measures. RESULTS: A total of 17 women enrolled; 13 completed the intervention (76%). Mean age of the participants was 51 years. There was a significant increase in total minutes of weekly physical activity postintervention ( : = 271 minutes, S: = 151; : = .001). Significant improvements were found in cardiopulmonary fitness as measured by VO2peak with a mean increase of 2.03 mL/kg/min ( : = .01). Several strength measures significantly increased and also functional movement ( : = .005). Positive correlations existed between physical activity and several physical measures, with significant relationships between functional movement and some strength measures (eg, left arm extension: RS : = 0.61, : = .002). Total QOL and fatigue scores improved, but neither was significant. CONCLUSIONS: The intervention led to increased physical activity. As a result of increased levels of physical activity, improvements on several fitness/health parameters occurred.

Practice patterns in the perioperative treatment of patients undergoing septorhinoplasty: a survey of facial plastic surgeons.

IMPORTANCE The common practices used in the perioperative care of patients undergoing septorhinoplasty are diverse and controversial. A consensus statement on the preferred clinical pathway in the perioperative treatment of patients undergoing septorhinoplasty has yet to be approached formally. OBJECTIVES To investigate the perioperative treatment of patients undergoing septorhinoplasty and to identify common practice patterns based on the preferences of leading facial plastic surgeons. DESIGN, SETTING, AND PARTICIPANTS We distributed an online survey to members of the American Academy of Facial Plastic and Reconstructive Surgery. Specifically, fellowship directors and academic contact members were anonymously polled and stratified by the number of septorhinoplasties performed annually. MAIN OUTCOME AND MEASURE A cohesive clinical guide to perioperative treatment after rhinoplasty. RESULTS Of the 92 members surveyed, 67 (73%) successfully completed the survey. The distribution of respondents included 43 academicians (64%) and 24 physicians in private practice (36%). Twenty-eight surgeons (42%) performed fewer than 50 rhinoplasties a year and 39 (58%), more than 50, representing 3510 to 4549 septorhinoplasties in total among respondents. Forty-four surgeons (66%) refrained from using any packing, and 41 (61%) used intranasal splints, with polymeric silicone splints the most popular of these (n = 24 [59%]). Sixty-six surgeons (99%) used external nasal splints, including 49 (74%) who used a thermoplastic splint and 49 (74%) who left the external nasal splint in place for 7 days or longer. The most common postoperative interventions to reduce edema and ecchymosis were elevation of the head of bed by 62 (93%), ice packs by 50 (75%), and Arnica montana by 33 (49%). Only 12 surgeons (18%) used postoperative corticosteroids to reduce edema. Fifty-six respondents (84%) prohibited participation in contact sports until at least 6 weeks after surgery. CONCLUSIONS AND RELEVANCE Perioperative care and practices after nasal surgery vary among the most highly trained and leading rhinoplasty surgeons. No published communication or consensus on perioperative practices has been disseminated in this setting. Given the results from those surgeons performing the most rhinoplasties in our field, some surgeons may choose to vary their practices to coincide with those of experienced surgeons. These guidelines could facilitate future studies of patient outcomes.