P-values and confidence intervals of linear rank tests for left-truncated data under truncated binomial design.

The paper provides computations comparing the accuracy of the saddlepoint approximation approach and the normal approximation method in approximating the mid-p-value of Wilcoxon and log-rank tests for the left-truncated data using a truncated binomial design. The paper uses real data examples to apply the comparison, along with some simulated studies. Confidence intervals are provided by the inversion of the tests under consideration.

Saddlepoint p-values for a class of location-scale tests.

The main idea of this paper is to approximate the exact p-value of a class of non-parametric, two-sample location-scale tests. In this paper, the most famous non-parametric two-sample location-scale tests are formulated in a class of linear rank tests. The permutation distribution of this class is derived from a random allocation design. This allows us to approximate the exact p-value of the non-parametric two-sample location-scale tests of the considered class using the saddlepoint approximation method. The proposed method shows high accuracy in approximating the exact p-value compared to the normal approximation method. Moreover, the proposed method only requires a few calculations and time, as in the case of the simulated method. The procedures of the proposed method are clarified through four sets of real data that represent applications for a number of different fields. In addition, a simulation study compares the proposed method with the traditional methods to approximate the exact p-value of the specified class of the non-parametric two-sample location-scale tests.

Weighted log-rank tests for censored data under Wei's urn design: saddlepoint approximation and confidence intervals.

The randomization designs in clinical trials provide probabilistic basis for the statistical inference of the permutation tests. One of the widely used designs to avoid the problems of imbalance and selection bias for one of the treatments is Wei's urn design. In this article, the saddlepoint approximation is suggested to approximate the p-values of the weighted log-rank class of two-sample tests under Wei's urn design. To show the accuracy of the proposed method and to clarify its procedure, two sets of real data are analyzed, and a simulation study is conducted using different sample sizes and three different life time distributions. Through the illustrative examples and simulation study, a comparison is made between the proposed method and the traditional method, which is the normal approximation method. All of these procedures confirmed that the proposed method is more accurate and efficient than the normal approximation method in approximating the exact p-value of the considered class of tests. As a result, the nominal 95% confidence intervals for the treatment effect are determined.

Weighted log-rank tests for left-truncated data under Wei's urn design: saddlepoint p-values and confidence intervals.

Left-truncated data are constructed from the time of an initial event and the time of the event of interest. That is to say, each individual represented by such data is exposed to an event prior to the event of interest, and both times are recorded. Weighted log-rank testing is commonly used for such data. In this paper, a saddlepoint approximation method is provided for computing p-values of the permutation distribution of tests from the weighted log-rank testing in the presence of left-truncated data and Wei's urn design. A simulation study is used to assess the efficiency of the saddlepoint approximation. The accuracy of the saddlepoint approximation in comparison to the normal approximation enables us to compute accurate confidence intervals for the treatment effect.

Log-rank tests for censored clustered data under generalized randomized block design: Saddlepoint approximation.

The weighted log-rank class is the common and widely used class of two-sample tests for clustered data. Clustered data with censored failure times often arise in tumorigenicity investigations and clinical trials. The randomized block design is a significant design that reduces both unintentional bias and selection bias. Accordingly, the p-values of the null permutation distribution of weighted log-rank class for clustered data are approximated using the double saddlepoint approximation technique. Comprehensive simulation studies are carried out to appraise the accuracy of the saddlepoint approximation. This approximation exhibits a significant improvement in precision over the asymptotic approximation. This precision motivates us to determine the approximated confidence intervals for the treatment impact.

Antiapoptotic and antioxidant effects of carvedilol and vitamin E protect against diabetic nephropathy and cardiomyopathy in diabetic Wistar albino rats.

Carvedilol is a novel ß-adrenoreceptor blocker, with antioxidant properties inhibiting lipid peroxidation and preventing the depletion of endogenous antioxidants. Moreover, carvedilol was reported to enhance the expression of Bcl-2 gene, which has antioxidant and antiapoptotic effects. There are few researches testing the protective effect of carvedilol on the development of diabetic cardiomyopathy and nephropathy. In this study, we induced diabetes mellitus in male Wistar albino rats. We investigated carvedilol, as well as vitamin E, administrated in healthy and diabetic rats for 6 weeks to compare their effects on biochemical parameters and the expression of Bcl-2 protein in both myocardial and renal tissues by immunohistochemistry. The study showed that the diabetic rats not only had renal dysfunction and more myocardial damage, but also showed lower expression of Bcl-2 protein. Carvedilol and vitamin E treatments were associated with better renal function and less myocardial damage, lower blood glucose, and lipid peroxidation, higher antioxidant capacity, better serum lipids, and higher expression of Bcl-2 protein in diabetic rats. These results indicate that carvedilol and vitamin E treatments partly protect against myocardial and renal damage probably via their antioxidant and antiapoptotic properties in diabetic rats.

Saddlepoint p-values for a class of location-scale tests under randomized block design.

This paper deals with a class of nonparametric two-sample location-scale tests. The purpose of this paper is to approximate the exact p-value of the considered class under a randomized block design. The exact p-value of the considered class is approximated by the saddlepoint approximation method, also by the traditional method which is the normal approximation method. The saddlepoint approximation method is more accurate than the normal approximation method in approximating the exact p-value, and does not take a lot of time like the simulation method. This accuracy is proved by applying the mentioned methods to two real data sets and a simulation study.

A new approach for approximating the p-value of a class of bivariate sign tests.

Bivariate data are frequently encountered in many applied fields, including econometrics, engineering, physiology, biology, and medicine. For bivariate analysis, a wide range of non-parametric and parametric techniques can be applied. There are fewer requirements needed for non-parametric procedures than for parametric ones. In this paper, the saddlepoint approximation method is used to approximate the exact p-values of some non-parametric bivariate tests. The saddlepoint approximation is an approximation method used to approximate the mass or density function and the cumulative distribution function of a random variable based on its moment generating function. The saddlepoint approximation method is proposed in this article as an alternative to the asymptotic normal approximation. A comparison between the proposed method and the normal asymptotic approximation method is performed by conducting Monte Carlo simulation study and analyzing three numerical examples representing bivariate real data sets. In general, the results of the simulation study show the superiority of the proposed method over the asymptotic normal approximation method.

Lemon peel essential oil and its nano-formulation to control Agrotis ipsilon (Lepidoptera: Noctuidae).

Due to excessive use of synthetic pesticides the pest resistance developed along with pesticide residues accumulation in crops. Therefore, many nations are switching from chemical-based agriculture to "green" agriculture for pest control. The destructive pest black cutworm, Agrotis ipsilon (Hufnagel) (Lepidoptera: Noctuidae), is a polyphagous species that economically lead to extensive loss of a broad range of crops including corn, cotton, wheat, and many vegetables through the damage of foliar and roots. In this study, lemon peel essential oil (LPEO) was subjected to nano-formulation using polyethylene glycol as nanocarrier. The lethal activity of LPEO and its nano-form (LPEO-NPs) were tested against A. ipsilon second larval instar using feeding bioassay at different concentrations. Growth and developmental parameters, including larval and pupal duration, larval and pupal mortality, malformations % and adult emergence were evaluated. Results showed that LPEO exhibited insecticidal activity and causes different levels of effects on the development of A. ipsilon according to its concentration and formulation. In addition, at 75 mg/ml LPEO and LPEO-NPs significantly increased the larval mortality to 80.00% and 90.00%, respectively. The overall data revealed that insecticidal toxicity of LPEO was increased by nano-formulation.

Weighted log-rank tests for clustered censored data: Saddlepoint p-values and confidence intervals.

Clustered data with censored failure times frequently arise in clinical trials and tumorigenicity studies. For such data, the common and extensively used class of two-sample tests is the weighted log-rank tests. In this article, a double saddlepoint approximation is used to calculate the p-values of the null permutation distribution of these tests. This technique is demonstrated using three real clustered data sets. Comprehensive simulation studies are conducted to appraise the efficiency of the saddlepoint approximation. This approximation is far superior to the asymptotic normal approximation. This precision allows us to determine almost exact confidence intervals for the treatment impact.

Evaluating Disaster Damages and Operational Status of Health-Care Facilities During the Emergency Response Phase of Hurricane Maria in Puerto Rico.

On September 20, 2017, Hurricane Maria made landfall on Puerto Rico as a category 4 storm, resulting in serious widespread impact across the island, including communication and power outages, water systems impairment, and damage to life-saving infrastructure. In collaboration with the Puerto Rico Department of Health, the Public Health Branch (PHB), operating under the Department of Health and Human Services Incident Response Coordination Team, was tasked with completing assessments of health-care facilities in Puerto Rico to determine infrastructure capabilities and post-hurricane capacity. Additionally, in response to significant data entry and presentation needs, the PHB leadership worked with the Puerto Rico Planning Board to develop and test a new app-based infrastructure capacity assessment tool. Assessments of hospitals were initiated September 28, 2017, and completed November 10, 2017 (n = 64 hospitals, 97%). Assessments of health-care centers were initiated on October 7, 2017, with 186 health-care centers (87%) assessed through November 18, 2017. All hospitals had working communications; however, 9% (n = 17) of health-care centers reported no communication capabilities. For the health-care centers, 114 (61%) reported they were operational but had sustainment needs. In conclusion, health-care facility assessments indicated structural damage issues and operational capacity decreases, while health-care centers reported loss of communication capabilities post-Hurricane Maria.

Mucocele of appendix with an elevated carcinoembryonic antigen: A case report.

Mucocele of the appendix is an uncommon disease in which there is cystic dilatation of the appendix caused by mucus secretion and usually associated with benign or malignant causes. Preoperative diagnosis is difficult as the patient presents with non-specific clinical symptoms. We report a case of mucocele of the appendix with elevated serum carcinoembryonic antigen (CEA) - a condition sparsely reported in literature. Patient presented with pain in the right iliac fossa for 7 months. On exploration, a cystic mass of the appendix without perforation was found in right iliac fossa. There was no lymph nodes enlargement. Appendicectomy was performed with subsequent normalization of CEA level and histopathology confirmed the diagnosis of mucinous neoplasm of the appendix. Patient is feeling well after one year of follow up.

The use of experimental design in the optimization of risperidone biodegradable nanoparticles: in vitro and in vivo study.

The aim of this study was optimization of risperidone (model drug) biodegradable nanoparticles utilizing emulsion-solvent evaporation technique. Box-Behnken design was adopted to optimize the preparation process. Optimized nanoparticles were characterized for surface morphology using scanning electron microscope. Pharmacokinetic parameters were compared with the marketed tablets. Results revealed that the optimized formula showed 297.37 nm, 85.12%, and 59.79% for Y1, Y2, and Y3, respectively. Optimized formula showed significant improved bioavailability compared with marketed tablets. Successful achievement of prolonged risperidone release with improved bioavailability is expected to maximize patients' adherence to their antipsychotic drug therapy and to minimize risk of relapse during maintenance therapy.

Enhancement of 5-fluoro-2'-deoxyuridine antitumor efficacy by the uridine phosphorylase inhibitor 5-(benzyloxybenzyl)barbituric acid acyclonucleoside.

5-(Benzyloxybenzyl)barbituric acid acyclonucleoside (BBBA) was recently synthesized as a potent and specific inhibitor of uridine phosphorylase (EC 2.4.2.3), the enzyme responsible for the catabolism of 5-fluoro-2'-deoxyuridine (FdUrd) in many types of tumors that are deficient or have little thymidine phosphorylase (EC 2.4.2.4) activity. The effect of BBBA on modulating the antitumor efficacy of FdUrd was evaluated in vitro, against the human colon carcinomas DLD-1 and HCT-15 grown in culture, and in vivo, against DLD-1 grown as xenografts in anti-thymocyte serum immunosuppressed mice. The concentrations of FdUrd that produced 50% growth inhibition after a 3-h exposure were 88 and 340 nM for HCT-15 and DLD-1, respectively. BBBA alone, at all concentrations tested, had no significant effect on the growth of DLD-1 and HCT-15 in culture. However, BBBA at 5, 10, 20, and 40 nM potentiated (P < 0.05) the cytotoxicity of FdUrd (340 nM; 3 h) against DLD-1 in culture by 20, 33, 55, and 63%, respectively. Similarly, BBBA at 10 and 20 nM potentiated the cytotoxicity of FdUrd (88 nM; 3 h) against HCT-15 in culture by 37 and 45%, respectively. In soft agar, BBBA (10 nM) also enhanced the cytocidal effect of FdUrd (10 and 32 nM) against DLD-1 by 41 and 55%, respectively, and against HCT-15 by 6 and 31%, respectively. Increasing BBBA dose to 20 nM enhanced further the FdUrd (10 and 32 nM) cytotoxicity against DLD-1 by 76 and 77%, respectively, and HCT-15 by 31 and 48%, respectively. BBBA also potentiated the chemotherapeutic efficacy of FdUrd in anti-thymocyte serum immunosuppressed mice bearing DLD-1 xenografts with no apparent host toxicity. At a low tumor burden (2.5 x 10(6) cells/mouse), 2 days treatment with FdUrd alone (50 mg/kg/day x 2) did not result in significant reduction in tumor volume. Coadministration of BBBA at 5 and 10 mg/kg/day x 2 did not potentiate the efficacy of FdUrd over that achieved by FdUrd alone, but it significantly reduced the tumor volume by 27 and 32%, respectively, when compared with untreated controls. FdUrd alone at 150 mg/kg/day x 2 reduced the tumor volume by 29%. This reduction in tumor volume was enhanced 1.8-fold by coadministration of BBBA (10 mg/kg/day x 2). At a higher tumor burden (5 x 10(6) cells/mouse) and 4 days treatment, BBBA at 10 and 30 mg/kg/day x 4 reduced further the tumor volume produced by FdUrd alone (200 mg/kg/day x 4) by 1.2- and 1.4-fold, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Intramedullary spinal cord metastases (ISCM) and non-small cell lung carcinoma (NSCLC): clinical patterns, diagnosis and therapeutic considerations.

Intramedullary spinal cord metastasis (ISCM) is an unusual occurrence in systemic cancer, occurring in as few as 2% of autopsy cases and also represents 8.5% of all cases of central nervous system metastases. Although ISCM from small cell lung carcinoma is well documented, ISCM from non-small cell lung carcinoma of the lung is rarely diagnosed prior to the patients' demise and very little data regarding outcomes exists in such patients. We present the results of our observational case series to better delineate the presentation and clinical course of this uncommon entity which shows that ISCM may present atypically and should be considered in any patient with a previous history of bronchogenic carcinoma and neurologic symptoms.

Second-line chemotherapy for small-cell lung cancer: a review.

Small-cell lung cancer (SCLC) is an aggressive malignancy, and only a minority of patients survive 2 years. Although this cancer is sensitive to both chemotherapy and radiotherapy, the majority of patients relapse, and second-line treatment is an option for many. Currently in the United States, the combination of cisplatin/etoposide is the standard first-line therapy in SCLC. At this time, topotecan is the only Food and Drug Administration-approved chemotherapeutic agent for second-line treatment of SCLC. In this paper, we review studies of second-line chemotherapy for SCLC.

Rectosigmoid bilharzioma causing intestinal obstruction.

Schistosomiasis is an infection caused by flukes (trematodes) of any species of the genus Schistosoma whereas bilharzioma implies a localized mass of fibrous and inflammatory tissue, which usually contains many eggs, frequently involving serosa and mesentery. Bilharziomas are probably caused by a reaction to numerous eggs produced by one or more pair of worms in a single site, although altered host reactivity may also be a factor. Bilharziomas, even in endemic areas are quite uncommon lesions in adults. So far they have not been reported to cause intestinal obstruction in children. Herein we present a case masquerading as large bowel malignancy in a child. Management and follow up are also mentioned.

Analysis of indoor concentrations of benzene using an air-quality model.

We performed measurements to determine indoor benzene levels in 26 residential houses in Kuwait, located in zones of different activity levels. Pumped (or active) sampling was conducted via use of 12 sampling tubes over a period of 24 hr for both indoor and outdoor concentrations simultaneously. Time-average indoor concentration varied linearly with time-average outdoor concentration in accordance with a mass-balance-based indoor air-quality model in which source and sink terms were incorporated. We used regression analysis to determine benzene adsorption rates, which appear in the removal and source terms of the model. The removal rate parameter varied between 0.12/hr and 2.16/hr, whereas source term parameter varied between 0.60 mg/hr and 76.07 mg/hr. Houses were then divided into three groups according to their benzene source strengths (i.e., < 1.0 mg/hr, 1-10 mg/hr, and 10-50 mg/hr). Qualitatively, these levels depended on the characteristics of occupants (e.g., smoking and gas cooker use, number of cars, and parking area) and location of the building.

Living conditions in Iraq: 10 years after the US-led invasion.

In the early 1980s, Iraq was a middle-income and rapidly developing country with a well-developed health system. A few decades later - after wars, sanctions and a violent sectarian upsurge - child and maternal health indicators have deteriorated, its poverty headcount index is at 22.9% and diseases such as cholera have remerged. Today Iraq is beset by chronic political deadlock and a complexity of economic challenges; accordingly, all aspects of life are suffering, including health. Irrespective of the monumental investment to improve components of the health system, via national and international efforts, the health status of the population can only advance through resounding and synergistic effort in other aspects of life affecting health: the social determinants of health.