Large Cluster Asymptotics for GEE: Working Correlation Models

This paper presents large cluster asymptotic results for generalized estimating equations. The complexity of working correlation model is characterized in terms of the number of working correlation components to be estimated. When the cluster size is relatively large, we may encounter a situation where a high-dimensional working correlation matrix is modeled and estimated from the data. In the present asymptotic setting, the cluster size and the complexity of working correlation model grow with the number of independent clusters. We show the existence, weak consistency and asymptotic normality of marginal regression parameter estimators using the results of empirical process theory and the work of Xie and Yang (2003). We also show the weak consistency of the sandwich variance estimator. Lastly, we present sufficient conditions for the increasing complexity of working correlation models using maximal inequalities

Intonational Cues to Segmental Contrasts in the Native Language Facilitate the Processing of Intonational Cues to Lexical Stress in the Second Language

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.This study examines whether second language (L2) learners' processing of an intonationally cued lexical contrast is facilitated when intonational cues signal a segmental contrast in the native language (L1). It does so by investigating Seoul Korean and French listeners' processing of intonationally cued lexical-stress contrasts in English. Neither Seoul Korean nor French has lexical stress; instead, the two languages have similar intonational systems where prominence is realized at the level of the Accentual Phrase. A critical difference between the two systems is that French has only one tonal pattern underlying the realization of the Accentual Phrase, whereas Korean has two underlying tonal patterns that depend on the laryngeal feature of the phrase-initial segment. The L and H tonal cues thus serve to distinguish segments at the lexical level in Korean but not in French; Seoul Korean listeners are thus hypothesized to outperform French listeners when processing English lexical stress realized only with (only) tonal cues (H* on the stressed syllable). Seoul Korean and French listeners completed a sequence-recall task with four-item sequences of English words that differed in intonationally cued lexical stress (experimental condition) or in word-initial segment (control condition). The results showed higher accuracy for Seoul Korean listeners than for French listeners only when processing English lexical stress, suggesting that the processing of an intonationally cued lexical contrast in the L2 is facilitated when intonational cues signal a segmental contrast in the L1. These results are interpreted within the scope of the cue-based transfer approach to L2 prosodic processing

A Study on the Transition of Power Dressing in Contemporary Fashion

The purpose of this study is to examine changes of power dressing from 1930s to present. I believe this study will help predict future changes of power dressing by reinterpreting trends in modern fashion based on history and investigating power dressing of women as a barometer of women\u27s social power

Žarnyno mikroorganizmų įtaka jungties nesandarumui po storosios žarnos operacijų

Introduction. One of the most common and serious complications of near-postoperative surgery after colon resection with anastomosis is intestinal leakage with a frequency of 1 to 24%. Therefore, it is very important to evaluate the factors that may determine the development of this complication. One of the etiological factors behind the development of this complication is the intestinal microbiota, which is playing an increasingly important role in this process. Nevertheless, there is still a lack of comprehensive clinical evidence on the influence of the intestinal microbiota on postoperative complications such as anastomotic leakage. Purpose. To evaluate the influence of intestinal microorganisms on anastomotic leakage after elective intestines surgery. Methods. A prospective study was performed at the Lithuanian University of Health Sciences Hospital, Kaunas Clinics, Clinic of Surgery. There were included patients who underwent colon surgery (right hemicolectomy, left hemicolectomy, sigmoid resection and closure of ileostomy). Intestinal mucosal biopsy performed before restoring intestinal integrity and sent for microbiological and antibiotic examination. Patients were also observed postoperatively for anastomotic leakage. Results. The majority of patients were treated for colon cancer – 46 (92.0%). In 19 patients crop (38.0%) grown one microorganism, in 12 (24.0%) – 2 microorganisms, in 5 (10.0%) – 3 microorganisms, in 1 (2.0%) – 4 types of bacteria. In the most of the crops were observed growth by E. coli – 30 (60.0%), Enterococcus spp. – 12 (24.0%), Bacteroides spp. – 4 (8.0%), Klebsiella oxytoca – 2 (4.0%), Beta hemolytic streptococcus – 2 (4.0%) patients. Citrobacter fundii, Citrobacter brakii, Parabacteroides distasonis, Proteus mirabilis, Klebsiella pneumoniae, Enterobacteriaceae daacea grew only in 1 (2.0%) patients crop. Postoperative anastomotic leakage diagnosed in 2 (4.0%) patients. Conclusions. The major microorganisms that grown were E. coli. Due to the small sample, tendency can not be predicted, but microorganisms that promote small blood vessels thrombosis may be one of the factors that cause anastomotic leakage.Įžanga. Po rezekcinių storosios žarnos operacijų, kai formuojama jungtis, viena iš dažniausių ir pavojingiausių artimojo po­operacinio laikotarpio komplikacijų yra žarnų jungties nesandarumas (dažnis – 1–24 proc.), todėl labai svarbu įvertinti veiksnius, galinčius lemti šios komplikacijos vystymąsi. Vienas iš etiologinių veiksnių šiai komplikacijai išsivystyti yra žarnyno mikrobiota. Pastaraisiais metais jai skiriama vis daugiau dėmesio, tačiau vis dar trūksta išsamių klinikinių tyrimų apie žarnyno mikrobiotos įtaką pooperaciniam žarnų jungties nesandarumui. Tikslas. Įvertinti žarnyno mikroorganizmų įtaką jungčių nesandarumui po planinių žarnų operacijų. Metodika. Lietuvos sveikatos mokslų universiteto ligoninės Kauno klinikos (LSMUL KK) Chirurgijos klinikoje atliktas perspektyvusis tyrimas. Atrinkti pacientai, kuriems atliktos storosios žarnos operacijos: dešinioji hemikolektomija, kairioji hemikolektomija, riestinės žarnos rezekcija ir ileostomos uždarymas. Tyrimo dalyviams, prieš atkuriant žarnyno vientisumą, paimti žarnos gleivinės bioptatai, jie išsiųsti mikrobiologiniams tyrimams ir antibiotikogramai atlikti. Pacientai stebėti ir po operacijos, vertintas jungties nesandarumas. Rezultatai. Didžioji dalis pacientų stacionarizuoti ir operuoti dėl storosios žarnos vėžio (46 pacientai, 92,0 %). Devyniolikai pacientų (38,0 %) išauginta viena bakterija, dviem pacientams (24,0 %) – dvi, penkiems (10,0 %) – trys, vienam (2,0 %) – keturios skirtingos bakterijos. Didžiojoje dalyje išaugintų pasėlių rasta E. coli bakterija (30 pacientų, 60,0 %), dvylikai pacientų (24,0 %) – Enterococcus spp., 4 (8,0 %) – Bacteroides spp., dviem (4,0 %) – Klebsiella oxytoca, dviem (4,0 %) – Beta hemolitinis streptokokas. Vienam pacientui (2,0 %) išauginta: Citrobacter fundii, Citrobacter brakii, Parabacteroides distasonis, Proteus mirabilis, Klebsiella pneumoniae, Enterobacteriaceae daacea. Ankstyvasis jungties nesandarumas nustatytas dviem atvejais (4,0 %). Išvados. Dažniausiai nustatyta E. coli bakterija. Dėl nedidelės tyrimo apimties negalima numatyti tolesnių tendencijų, tačiau mikroorganizmai, skatinantys smulkiųjų kraujagyslių trombozę, gali būti vienas iš veiksnių, lemiančių jungties nesandarumą

Requirements for Trustworthy Artificial Intelligence and its Application in Healthcare

Objectives Artificial intelligence (AI) technologies are developing very rapidly in the medical field, but have yet to be actively used in actual clinical settings. Ensuring reliability is essential to disseminating technologies, necessitating a wide range of research and subsequent social consensus on requirements for trustworthy AI. Methods This review divided the requirements for trustworthy medical AI into explainability, fairness, privacy protection, and robustness, investigated research trends in the literature on AI in healthcare, and explored the criteria for trustworthy AI in the medical field. Results Explainability provides a basis for determining whether healthcare providers would refer to the output of an AI model, which requires the further development of explainable AI technology, evaluation methods, and user interfaces. For AI fairness, the primary task is to identify evaluation metrics optimized for the medical field. As for privacy and robustness, further development of technologies is needed, especially in defending training data or AI algorithms against adversarial attacks. Conclusions In the future, detailed standards need to be established according to the issues that medical AI would solve or the clinical field where medical AI would be used. Furthermore, these criteria should be reflected in AI-related regulations, such as AI development guidelines and approval processes for medical devices

Solving Continual Combinatorial Selection via Deep Reinforcement Learning

We consider the Markov Decision Process (MDP) of selecting a subset of items at each step, termed the Select-MDP (S-MDP). The large state and action spaces of S-MDPs make them intractable to solve with typical reinforcement learning (RL) algorithms especially when the number of items is huge. In this paper, we present a deep RL algorithm to solve this issue by adopting the following key ideas. First, we convert the original S-MDP into an Iterative Select-MDP (IS-MDP), which is equivalent to the S-MDP in terms of optimal actions. IS-MDP decomposes a joint action of selecting K items simultaneously into K iterative selections resulting in the decrease of actions at the expense of an exponential increase of states. Second, we overcome this state space explo-sion by exploiting a special symmetry in IS-MDPs with novel weight shared Q-networks, which prov-ably maintain sufficient expressive power. Various experiments demonstrate that our approach works well even when the item space is large and that it scales to environments with item spaces different from those used in training.Comment: Accepted to IJCAI 2019,14 pages,8 figure

Infliximab Does Not Promote the Presence of Collagenolytic Bacteria in a Mouse Model of Colorectal Anastomosis

BACKGROUND: Previous work from our group has suggested a pivotal role for collagenolytic bacteria in the development of anastomotic complications. Tumor necrosis factor antagonists are a mainstay of treatment for patients with inflammatory bowel disease. The reported impact of these agents on key surgical outcomes such as anastomotic leak has been inconsistent. The objective of this study is to assess the impact of infliximab on the anastomotic microbiome in a mouse model of colon resection. DESIGN: BALB/c mice underwent colon resection with primary anastomosis. Mice were randomly assigned to receive either an intraperitoneal dose of saline (control) or 10 mg/kg of infliximab for 8 weeks prior to surgery. On postoperative day 7, the animals were sacrificed. Anastomotic tissues were analyzed by histology with TUNNEL staining as a marker of epithelial apoptosis. In order to assess compositional and functional changes of the local microbiome, anastomotic tissues were further analyzed by 16S rRNA V4 region sequencing and for the presence of collagenolytic strains that may impair anastomotic healing. The main outcome measures were microbiome community structure and the presence of collagenolytic bacteria. RESULTS: Infliximab-treated mice demonstrated an increase in epithelial apoptosis, consistent with the expected drug effect. Although infliximab modified the perianastomotic microbiome, no increase in the presence of collagenolytic bacteria was observed. CONCLUSIONS: Infliximab did not promote the emergence of collagenolytic bacteria or demonstrably impair anastomotic healing in a mouse model of colon resection and anastomosis

Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity.

Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression

Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts

Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard antibiotics used for prophylaxis. Risk factors identified in such cases include obesity and antibiotic exposure. To study the combined effect of obesity and antibiotic exposure on postoperative infection, mice were allowed to gain weight on an obesogenic Western-type diet (WD), administered antibiotics and then subjected to an otherwise recoverable sterile surgical injury (30% hepatectomy). The feeding of a WD alone resulted in a major imbalance of the cecal microbiota characterized by a decrease in diversity, loss of Bacteroidetes, a bloom in Proteobacteria, and the emergence of antibiotic-resistant organisms among the cecal microbiota. When WD-fed mice were administered antibiotics and subjected to 30% liver resection, lethal sepsis, characterized by multiple-organ damage, developed. Notable was the emergence and systemic dissemination of multidrug-resistant (MDR) pathobionts, including carbapenem-resistant, extended-spectrum β-lactamase-producing Serratia marcescens, which expressed a virulent and immunosuppressive phenotype. Analysis of the distribution of exact sequence variants belonging to the genus Serratia suggested that these strains originated from the cecal mucosa. No mortality or MDR pathogens were observed in identically treated mice fed a standard chow diet. Taken together, these results suggest that consumption of a Western diet and exposure to certain antibiotics may predispose to life-threating postoperative infection associated with MDR organisms present among the gut microbiota. IMPORTANCE Obesity remains a prevalent and independent risk factor for life-threatening infection following major surgery. Here, we demonstrate that when mice are fed an obesogenic Western diet (WD), they become susceptible to lethal sepsis with multiple organ damage after exposure to antibiotics and an otherwise-recoverable surgical injury. Analysis of the gut microbiota in this model demonstrates that WD alone leads to loss of Bacteroidetes, a bloom of Proteobacteria, and evidence of antibiotic resistance development even before antibiotics are administered. After antibiotics and surgery, lethal sepsis with organ damage developed in in mice fed a WD with the appearance of multidrug-resistant pathogens in the liver, spleen, and blood. The importance of these findings lies in exposing how the selective pressures of diet, antibiotic exposure, and surgical injury can converge on the microbiome, resulting in lethal sepsis and organ damage without the introduction of an exogenous pathogen

Impact of Fatty Liver on Acute Pancreatitis Severity

Aim. Acute pancreatitis is typically a mild disease, but some patients develop severe courses. Fatty liver changes are seen in patients with acute pancreatitis, but its clinical significance has not been well-studied. We aimed to investigate the relationship between fatty liver and the severity of acute pancreatitis. Methods. Unenhanced CT images of patients with acute pancreatitis were retrospectively reviewed by a radiologist, and mean hepatic and splenic attenuation was measured in Hounsfield units (HU). Fatty liver was defined as mean hepatic/splenic HU<1. Results. Among 200 patients, fatty liver was found in 67 (33.5%) and nonfatty liver in 133 (66.5%). Compared with patients without fatty liver, the severity of pancreatitis and levels of serum C-reactive protein were higher in fatty liver patients. The prevalence of local complications, persistent organ failure, and mortality were also higher in patients with fatty liver. Even after adjusting for age, sex, body mass index, and cause of pancreatitis, fatty liver was significantly associated with moderately severe or severe acute pancreatitis. Conclusions. Fatty liver may play a prognostic role in acute pancreatitis. Fatty liver could be incorporated into future predictive scoring models