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Despite the introduction of multiple factors, multidimensional approaches cannot represent the complexity of the objective determinants of well-being (ODW). This paper proposes an alternative OWD model that adds a systemic approach, by using Bayesian networks algorithms to discover a directed two level network of variables nested in subnetworks of determinants. The network was inferred by using subsamples of the 2013 version of the American Community Survey. Network analysis methods applied to the model provided new insights concerning single ODW relevance and the roles that are useful to focus selective welfare interventions; they also offered a big picture that is fundamental to reason about the unpremeditated universal character of the selective US welfare policies.

BackgroundThe accurate prediction of surgical risk is important to patients and physicians. Logistic regression (LR) models are typically used to estimate these risks. However, in the fields of data mining and machine-learning, many alternative classification and prediction algorithms have been developed. This study aimed to compare the performance of LR to several data mining algorithms for predicting 30-day surgical morbidity in children. MethodsWe used the 2012 National Surgical Quality Improvement Program-Pediatric dataset to compare the performance of (1) a LR model that assumed linearity and additivity (simple LR model) (2) a LR model incorporating restricted cubic splines and interactions (flexible LR model) (3) a support vector machine, (4) a random forest and (5) boosted classification trees for predicting surgical morbidity. ResultsThe ensemble-based methods showed significantly higher accuracy, sensitivity, specificity, PPV, and NPV than the simple LR model. However, none of the models performed better than the flexible LR model in terms of the aforementioned measures or in model calibration or discrimination. ConclusionSupport vector machines, random forests, and boosted classification trees do not show better performance than LR for predicting pediatric surgical morbidity. After further validation, the flexible LR model derived in this study could be used to assist with clinical decision-making based on patient-specific surgical risks. We aimed to predict pediatric surgical morbidity using preoperative characteristics.We compared logistic regression models to data mining algorithms.The data mining algorithms performed as well as a simple logistic regression model.A flexible logistic regression model performed best on most model fit criteria.

This phase II single-arm trial of docetaxel and capecitabine in previously untreated non-small cell lung cancer (NSCLC) patients was designed to evaluate response rate of this regimen based on promising efficacy data from phase II testing in pre-treated NSCLC patients. The trial also evaluated the correlation between peripheral blood dihydropyrimidine dehydrogenase (DPD) expression and efficacy/toxicity.Patients with advanced NSCLC (metastatic, including malignant pleural effusion) without prior chemotherapy were enrolled. Baseline DPD screening was performed; patients with baseline DPD level0.07 nmol/min/mg protein were considered ineligible for the study. Treatment included a 28-day cycle of docetaxel 36 mg/m(2) on days 1, 8, 15 and capecitabine 1250 mg/m(2)/day in divided doses on days 5-18. Overall response rate (RR) was the primary endpoint with a target RR of 50%. Correlative studies included evaluation of DPD activity levels in peripheral blood and correlation with clinical responses.Twenty-eight patients received 86 cycles of treatment (median 3 cycles) and were evaluable for response. The RR was 18% (5 patients); RR did not meet the pre-specified efficacy endpoint and the trial was stopped. 14 patients had stable disease (SD - 50%) and 4 patients had SD12 weeks. Median time to progression was 3.3 months (95% CI 1.5-4.6 months). Median overall survival was 10.5 months (95% CI: 3.2-15 months). Main toxicities included fatigue, stomatitis and leukopenia. DPD levels ranged from 0.06 to 0.26 nmol/min/mg. The majority of responders (4/5) had DPD levels ≤0.1 nmol/min/mg. Most of the responders (4/5) experienced grade 3 toxicities including leukopenia, dehydration, fatigue, and diarrhea. None of the patients (0/4) with higher DPD levels (0.2 nmol/min/mg) had a response.The response rate for the regimen did not demonstrate sufficient activity and further study of this regimen in this setting is not indicated. Interestingly, the results suggest that low DPD expression may be associated with response to capecitabine but also with increased toxicity.

Bisphosphonates have been associated with osteonecrosis of the jaw. The purpose of this study was to examine the effect of a potent bisphosphonate, zoledronic acid (ZA) on osteocyte viability and bone formation. Ten experimental C57BL/6 mice were administered ZA (0.1 mg/kg-i.p.) weekly for 9 weeks while four control mice did not receive the drug. A pair of calcein (30 mg/kg) labels was administered 10 and 3 days prior to sacrifice of the 34-week-old mice. Fresh mandibular and femoral sections were obtained to evaluate osteocyte viability using a lactate dehydrogenase (LDH) assay. In addition, sections from the femur, mandible and maxilla were prepared for standard histomorphometry. The operator was blinded for data collection to eliminate bias. Data on necrotic area/total bone area from the LDH sections were collected. In addition, standard histomorphometric variables including bone formation rate were calculated. Mixed models were used to analyse data. The osteocytes were overwhelmingly viable and no necrotic areas were detected in the mandible and femur of both groups. ZA was not directly cytotoxic to the mouse osteocytes. There was suppression in indices of bone formation at all skeletal sites of the ZA group compared to the control group. While ZA administration in mice does not produce necrotic osteocytes, it severely suppresses bone formation. Such reductions can have a profound effect on bone healing.

Interferon-gamma (IFN-gamma) has been shown to enhance anti-tumor immunity and inhibit the formation of bone-resorbing osteoclasts. We evaluated the role of IFN-gamma in bone metastases, tumor-associated bone destruction, and hypercalcemia in human T cell lymphotrophic virus type 1-Tax transgenic mice. Compared with Tax(+)IFN-gamma(+/+) mice, Tax(+)IFN-gamma(-/-) mice developed increased osteolytic bone lesions and soft tissue tumors, as well as increased osteoclast formation and activity. In vivo administration of IFN-gamma to tumor-bearing Tax(+)IFN-gamma(-/-) mice prevented new tumor development and resulted in decreased bromodeoxyuridine uptake by established tumors. In vitro, IFN-gamma directly decreased the viability of Tax(+) tumor cells through inhibition of proliferation, suppression of ERK phosphorylation, and induction of apoptosis and caspase 3 cleavage. IFN-gamma also inhibited macrophage colonystimulating factor-mediated proliferation and survival of osteoclast progenitors in vitro. Administration of IFN-gamma to C57BL/6 mice decreased Tax(+) tumor growth and prevented tumor-associated bone loss and hypercalcemia. In contrast, IFN-gamma treatment failed to protect IFN-gammaR1(-/-) mice from Tax(+) tumor-induced skeletal complications, despite decreasing tumor growth. These data demonstrate that IFN-gamma suppressed tumor-induced bone loss and hypercalcemia in Tax(+) mice by inhibiting both Tax(+) tumor cell growth and host-induced osteolysis. These data suggest a protective role for IFN-gamma in patients with bone metastases and hypercalcemia of malignancy.

Two anthrax toxin receptors have been identified, tumor endothelial marker 8 (TEM8) and capillary morphogenesis protein 2 (CMG2). Both receptors have been shown to be capable of facilitating the entry of Bacillus anthracis exotoxins into the cytosol of susceptible cells. The levels of TEM8 and CMG2 RNA transcripts present in human primary macrophages derived from multiple unrelated donors and primary mouse macrophages have not been well described. In this communication, we examined the expression of mRNA transcripts of TEM8 and CMG2 in primary human and mouse macrophages and mouse tissues by standard and quantitative real-time RT-PCR. Our results indicate that CMG2 transcripts are preferentially expressed over TEM8 transcripts in primary human and mouse macrophages as compared to immortalized cell lines.

In order to delineate the role of proteoglycans in muscle development, the immunohistological localization of glycosaminoglycans and proteoglycan core proteins was studied in embryonic chick leg at Hamburger-Hamilton stages (St.) 36, 39, 43, and 46, and at 2 weeks posthatching. A specific anatomical landmark was chosen (the junction between the pars pelvica and the pars accessoria of the flexor cruris lateralis muscle) in order to ensure the study of anatomically equivalent sites. Frozen cross sections were immunostained with monoclonal antibodies to chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, and keratan sulfate glycosaminoglycans; to the core proteins of muscle/mesenchymal chondroitin sulfate proteoglycan, dermatan sulfate proteoglycan, and basement membrane heparan sulfate proteoglycan; and to laminin and tenascin. Extracellular matrix zones corresponding to the endomysium, perimysium, epimysium, basement membrane, and myotendinous junction each show characteristic immunostaining patterns from St. 36 to St. 46 and have unique matrix compositions by St. 46. In some cases, there is a sequential or coordinate expression of epitopes, first in the epimysium, then the perimysium, and last in the endomysium. Dermatan sulfate proteoglycan is detected in the epimysium at St. 36, in the perimysium at St. 39 (there is no perimysium structure at St. 36), and is not detected in the endomysium until St. 43. A putative mesenchymal proteoglycan core protein (reactive to the monoclonal antibody MY-174) is detected at St. 39 in both epimysium and perimysium, but is not detected in the endomysium until St. 43. Keratan sulfate antibody immunostains epimysium at St. 39 and perimysium at St. 46, but is never detected in the endomysium. Some epitopes are expressed independently in each of the extracellular matrix zones: antibody to tenascin stains only a subset of the epimysium, at the myotendinous junction; and heparan sulfate proteoglycan and laminin are detected only in the endomysium. Between St. 36 and St. 39, the muscle/MY-174-reactive proteoglycan core protein staining decreases in intensity in the endomysium and becomes positive in the epimysium and perimysium. An inverse relationship is found between (1) the disappearance of muscle/MY-174-reactive proteoglycan core protein staining at the surface of myotubes from St. 36 to St. 39 and (2) the infiltration of laminin and heparan sulfate proteoglycan staining encompassing groups of myotubes (St. 36) to circumferential staining of all myotubes (St. 39).(ABSTRACT TRUNCATED AT 400 WORDS)

technique with mesna submucosal injection greatly reduced procedural challenges associated with gastric ESD, although the difference of TSD between the groups was not significant and the benefit couldn’t completely negate all relevant factors. The results of this study warrant further evaluation with larger sample sizes and multi-centric design. References: 1. Sumiyama K, et al. Chemically assisted endoscopic mechanical submucosal dissection. Gastrointest Endosc. 2008; 67: 534-8. 2. Sumiyama K, et al. Chemically assisted submucosal injection facilitates endoscopic submucosal dissection of gastric neoplasms. Endoscopy 2010;42:627-32

Background: Serotonin (5-HT) plays a major role in gastrointestinal (GI) functions. Of several subtypes of 5-HT receptors, 5-HT3 and 5-HT4 are involved in GI motility and pain. 5-HT4 receptor agonist tegaserod (TEG) has been shown to modulate visceral pain in both humans and animals. However, its underlying mechanism of action remains unknown. Aim: The objective of the present study is to examine the site of action of this drug in colorectal distension (CRD)-induced visceral pain in naive and post-inflamed sensitized rats. Methods: In each of 47 male Sprague-Dawley rats under fully anesthetized state, a bipolar electrode was implanted surgically into the external oblique muscle of the abdomen to measure the visceromotor response (VMR) represented as electrical activity (EMG) of the muscle to graded CRD (10-80mmHg). VMR was recorded in fully awake rats 72 hours following the surgery. To induce colonic inflammation, 0.5ml of tri-nitrobenzene sulfonic acid (TNBS) in 50% ethanol was infused into the colon under the influence of anesthesia and rats were tested 7days after TNBS injection. Drugs were injected either intraperitoneally (ip), intravenously (iv) or subcutaneously (sc). Electrophysiological recordings were made from the S1 sacral dorsal root receiving pelvic nerve innervating the colon. Responses of pelvic afferents to CRD were recorded before and after TEG injection. Results: Rats exhibited linear increasing VMR to graded CRD. TNBS-treated rats exhibited significantly (p