We consider estimation and goodness–of–fit tests in GARCH models with innovations following a heavy–tailed and possibly asymmetric distribution. Although the method is fairly general and applies to GARCH models with arbitrary innovation distribution, we consider as special instances the stable Paretian, the variance gamma and the normal inverse Gaussian distribution. Exploiting the simple structure of the characteristic function of these distributions we propose minimum distance estimation based on the empirical characteristic function of properly standardized GARCH–residuals. The finite–sample results presented facilitate comparison with existing methods, while the new procedures are also applied to real data from the financial market.
The objectives of this autopsy-based audit of firearm-related fatalities were to acquire data to inform policy decisions and to assess the probability of the injured arriving alive at a hospital and receiving definitive care. Evaluated variables Demographics; co-morbidities; location and intention of the injury; toxicology; types of firearms; Abbreviated Injury Scale; Injury Severity Score (ISS); transfer means and time; and location of death. Results Of a total of 370 fatalities, 85.7% were male. The median age was 38 (9–95) years. Suicides (47%) and assaults (45.1%) were the most common underlying intentions. The most seriously injured regions were the head (44.5%), thorax (25.7%), abdomen (10.7%), and spine (5.7%). Of the 370 total subjects, 4.9% had an İSS\} < 16 and 59.5% had an İSS\} ≤ 74; both groups were classified as potentially preventable deaths. The majority (84%) died at the scene, and only 9.8% left the emergency department alive for further treatment. Multivariate analyses documented that postmortem İSS\} is an independent factor that predicts the probability of the injured reaching a hospital alive and receiving definitive care. Individuals injured in greater Athens and those most seriously injured in the face, abdomen or spine had significantly greater chances of reaching a hospital alive and receiving definitive care, whereas those injured by a shotgun and the positive toxicology group were significantly less likely to. In conclusion, this study provides data to inform policy decisions, calls for a surveillance network and establishes a baseline for estimating the probability regarding the location of firearm-related deaths.
Knowledge, research, and innovation are of crucial importance for the competitiveness of an economy and a recipe for economic development not only for developed and developing countries, but also for entities surviving a political abnormality, such as the Palestinian territories. As Palestinians are currently planning for their future viable state, the policy and decision makers should formulate relevant science, technology, and innovation policies that encourage the different national sectors to utilize the available innovation potentials and the experience and support of other countries, for developing a competitive economy. Conducting and analyzing a community innovation survey on two major Palestinian industrial sectors, namely quarrying and stone fabrication and the food and beverages sector, brought about very promising indicators and showed high innovative potentials in both sectors. Employment, export, and revenues are clearly improved in innovative enterprises. Lack of cooperation between the industrial sector and the higher education and research and development institutions is found to be a major problem that should be tackled in order to strengthen the enterprises’ ability to innovate.
Summary: A phase-I study was conducted to examine the safety, pharmacokinetics, and activity of combination 2',3'-dideoxyinosine (ddI) and ribavirin against human immunodeficiency virus type 1 (HIV-1)-positive individuals with CD4+ cell counts of ≤500/μl. Nineteen patients were enrolled into the study in which ddI monotherapy (200 mg p.o. b.i.d.) was administered for the first 4 weeks, followed by the coadministration of ribavirin (600 mg p.o. q.d.) and ddI (200 mg p.o. b.i.d.) for 8 or 20 additional weeks. The combination regimen was safe and well tolerated. Three patients did not complete 12 weeks of the study because of adverse events or voluntary withdrawal. The pharmacokinetic studies performed at weeks 4, 6, and 12 on specimens collected from the 15 individuals who completed 12 weeks of therapy revealed no pharmacokinetic interaction between ddI and ribavirin. A significant decline from baseline in HIV-1 titer as measured by quantitative HIV-1 culture was detected both during the ddI-monotherapy phase (week 4, p < 0.001) and during the combination-therapy ddI + ribavirin phase (week 12, p < 0.001); the median drop observed was 0.90 log10 at week 4 and 0.92 log10 at week 12. While the addition of ribavirin did not result in further reductions in viremia in the following weeks on study treatment, 13 (81%) of the 16 patients had at least a -0.5 log10 change in viral titer at week 12. The median decline in plasma viral RNA was 0.68 log10 at week 4 (p < 0.001) and 0.67 log10 at week 12 (p = 0.005). CD4+ cell counts increased above baseline significantly during the ddI-monotherapy phase of the study (p = 0.0038). The median increase was +26 cells/mm3 at week 4 and +11 cells/mm3 at week 12; for patients who remained on treatment through 24 weeks, the median CD4+ cell count increase was +10 cells/mm3. The L74V ddI resistance-conferring HIV-1 reverse-transcriptase mutation emerged in 53% of the patients. Patients with non-syncytiuminducing HIV variants demonstrated greater responses to treatment with larger decreases in virus load and greater increases in CD4+ cell count. Our results reveal that the combination of ddI and ribavirin in HIV-positive patients is safe, well tolerated, without adverse pharmacologic interaction, and associated with significant and sustained declines in virus load over 12 weeks of therapy.
Ro 24-7429, a Tat antagonist, dosed at 75, 150, or 300 mg/day, was compared with nucleoside analogue (zidovudine or didanosine) for 12 weeks in 96 human immunodeficiency virus (HIV)-infected patients to assess safety and activity. The primary adverse effect of Ro 24-7429 was rash, which necessitated treatment discontinuation in 6 of 71 patients. Nucleoside analogue treatment produced an average increase in CD4 cell count of 28 cells/mm3 at week 8 versus a decrease of 27 cells/mm3 in recipients of Ro 24-7429 (P < .001). Serum HIV p24 antigen levels decreased by an average of 111 pg/mL in nucleoside recipients at week 8 compared with an increase of 41 pg/mL in recipients of Ro 24-7429 (P = .007). Nucleoside-treated patients had a mean 0.66 log10 reduction in infectious peripheral blood mononuclear cells, while Ro 24-7429 recipients had a mean 0.02 log10 reduction (P = .02). No dose-response relationships were observed in the Ro 24-7429 groups. In this study, Ro 24-7429 treatment showed no evidence of antiviral activity.
AIDS patients with newly diagnosed cytomegalovirus (CMV) retinitis who had just completed a 14-day course of ganciclovir induction therapy were randomly assigned to an alternating or concurrent combination regimen of chronic ganciclovir-foscarnet therapy for CMV retinitis. Each regimen used lower weekly cumulative doses of each drug than standard monotherapy maintenance treatment regimens. Dose-limiting toxicity attributable to foscarnet occurred in only 2 (7%) of29 evaluatable patients, and no patients experienced dose-limiting nephrotoxicity. Although absolute neutrophil counts <500 cells/µL occurred in 11 (38%) of 29 patients, all who subsequently used adjunctive granulocyte colony-stimulating factor had severe neutropenia prevented. Severe toxicity of any type and neutropenia, in particular, occurred significantly more frequently in patients assigned to the concurrent treatment regimen. CMV was isolated from none of 21 patients who had urine cultured and from only 1 of 24 who had blood cultured while being treated during the study (median evaluation, 12 weeks). This suggests that combination therapy provides better in vivo antiviral activity in suppressing CMV replication than previously reported with monotherapy regimens.
The estimation of the treatment effect in the two-sample problem with right censoring is of interest in survival analysis. In this article we consider both the location shift model and the scale change model. We establish the large-sample properties of a generalized Hodges-Lehmann type estimator. The strong consistency is established under the minimal possible conditions. The asymptotic normality is also obtained without imposing any conditions on the censoring mechanisms. As a by-product, we also establish a result for the oscillation behavior of the Kaplan-Meier process, which extends the Bahadur result for the empirical process to the censored case.
A generalized Hodges-Lehmann type estimator for the treatment effect in the two-sample problem with right censoring, is proposed based on an inverse-quantile-type idea using truncated versions of the Kaplan-Meier estimators over the subspace where they are consistent. Its strong consistency and asymptotic normality can be obtained, under no conditions on the uninformative censorings, and the resulting variance is easily estimable from the data. In simulation studies the proposed estimator is superior to existing procedures in the presence of heavy unequal censoring.
▪ Objective: To evaluate the safety and immunologic and antiviral effects of combination therapy with zidovudine and dideoxycytidine (ddC) in patients with advanced human immunodeficiency virus type 1 (HIV) infection.
▪ Design: A phase I/II open-label, dose-ranging study.
▪ Setting: Two AIDS Clinical Trials Group units.
▪ Patients: Patients (56) with advanced HIV disease.
▪ Interventions: Patients were randomly assigned to one of three paired regimens of zidovudine and ddC. We evaluated six dosing regimens, each involving oral administration of the study drugs at 8-hour intervals.
▪ Measurements: Pharmacokinetics, toxicity, CD4 counts, p24 antigenemia and clinical end points.
▪ Main Results: The median follow-up period was 40.6 weeks (range, 0.3 to 70 weeks). Neither drug affected the pharmacokinetic profile of the other. Episodes of serious hematologic toxicity were infrequent, occurring in only 17.9% of patients, and did not differ among the regimens (P = 0.15). Severe sensory peripheral neuropathy occurred in two patients (one patient each in regimens 1 and 4). One patient receiving regimen 4 died.
The mean maximal increase in CD4 counts exceeded 109 cells/mm3, and 69% of patients receiving combinations containing 300 or 600 mg of zidovudine daily had an increase in CD4 counts of 50 cells/mm3 or greater. Regimens containing 600 mg of zidovudine daily (regimens 2 and 5) were also more likely to result in persistent increases in CD4 counts above pretreatment values than were the two lowest dose regimens (P = 0.003). The decline in CD4 counts was more rapid, and the suppression of the p24 antigenemia was less rapid and less sustained in patients receiving the lowest zidovudine dose alone (regimen 6). The addition of ddC to regimen 6 (regimen 3) resulted in a slower decline in the CD4 counts (P = 0.06).
▪ Conclusions: Combination therapy with zidovudine and ddC at the doses tested was well tolerated and did not result in toxicity. A daily oral dose of 150 mg of zidovudine appeared to produce a suboptimal effect on p24 antigenemia and CD4 counts. Combination therapy with ddC and higher doses of zidovudine produced greater and more persistent effects in patients with advanced HIV infection compared with other study regimens and with the results of previous trials of zidovudine monotherapy.
National and Kapodistrian University of Athens (+30) 210-3689491 Sofokleous 1 & Aristeidou - Grypareio Megaro, 6th floor, room 604, Athens, ZipCode 10559 firstname.lastname@example.org