New Results Concerning Probability Distributions with Increasing Generalized Failure Rates

The generalized failure rate of a continuous random variable has demonstrable importance in operations management. If the valuation distribution of a product has an increasing generalized failure rate (that is, the distribution is IGFR), then the associated revenue function is unimodal, and when the generalized failure rate is strictly increasing, the global maximum is uniquely specified. The assumption that the distribution is IGFR is thus useful and frequently held in recent pricing, revenue, and supply chain management literature. This note contributes to the IGFR literature in several ways. First, it investigates the prevalence of the IGFR property for the left and right truncations of valuation distributions. Second, we extend the IGFR notion to discrete distributions and contrast it with the continuous distribution case. The note also addresses two errors in the previous IGFR literature. Finally, for future reference, we analyze all common (continuous and discrete) distributions for the prevalence of the IGFR property, and derive and tabulate their generalized failure rates.

Rates of disease progression according to initial highly active antiretroviral therapy regimen: a collaborative analysis of 12 prospective cohort studies

BACKGROUND: No large clinical end-point trials have been conducted comparing regimens among human immunodeficiency virus type 1-positive persons starting antiretroviral therapy. We examined clinical progression according to initial regimen in the Antiretroviral Therapy Cohort Collaboration, which is based on 12 European and North American cohort studies. METHODS: We analyzed progression to death from any cause and to AIDS or death (AIDS/death), comparing efavirenz (EFV), nevirapine (NVP), nelfinavir, idinavir, ritonavir (RTV), RTV-boosted protease inhibitors (PIs), saquinavir, and abacavir. We also compared nucleoside reverse-transcriptase inhibitor pairs: zidovudine/lamivudine (AZT/3TC), stavudine (D4T)/3TC, D4T/didanosine (DDI), and others. RESULTS: A total of 17,666 treatment-naive patients, 55,622 person-years at risk, 1,617 new AIDS events, and 895 deaths were analyzed. Compared with EFV, the adjusted hazard ratio (HR) for AIDS/death was 1.28 (95% confidence interval [CI], 1.03-1.60) for NVP, 1.31 (95% CI, 1.01-1.71) for RTV, and 1.45 (95% CI, 1.15-1.81) for RTV-boosted PIs. For death, the adjusted HR for NVP was 1.65 (95% CI, 1.16-2.36). The adjusted HR for death for D4T/3TC was 1.35 (95% CI, 1.14-1.59), compared with AZT/3TC. CONCLUSIONS: Outcomes may vary across initial regimens. Results are observational and may have been affected by bias due to unmeasured or residual confounding. There is a need for large, randomized, clinical end-point trials.

Tenofovir use is associated with a reduction in calculated glomerular filtration rates in the Swiss HIV Cohort Study

BACKGROUND: A growing number of case reports have described tenofovir (TDF)-related proximal renal tubulopathy and impaired calculated glomerular filtration rates (cGFR). We assessed TDF-associated changes in cGFR in a large observational HIV cohort. METHODS: We compared treatment-naive patients or patients with treatment interruptions > or = 12 months starting either a TDF-based combination antiretroviral therapy (cART) (n = 363) or a TDF-sparing regime (n = 715). The predefined primary endpoint was the time to a 10 ml/min reduction in cGFR, based on the Cockcroft-Gault equation, confirmed by a follow-up measurement at least 1 month later. In sensitivity analyses, secondary endpoints including calculations based on the modified diet in renal disease (MDRD) formula were considered. Endpoints were modelled using pre-specified covariates in a multiple Cox proportional hazards model. RESULTS: Two-year event-free probabilities were 0.65 (95% confidence interval [CI] 0.58-0.72) and 0.80 (95% CI 0.76-0.83) for patients starting TDF-containing or TDF-sparing cART, respectively. In the multiple Cox model, diabetes mellitus (hazard ratio [HR] = 2.34 [95% CI 1.24-4.42]), higher baseline cGFR (HR = 1.03 [95% CI 1.02-1.04] by 10 ml/min), TDF use (HR = 1.84 [95% CI 1.35-2.51]) and boosted protease inhibitor use (HR = 1.71 [95% CI 1.30-2.24]) significantly increased the risk for reaching the primary endpoint. Sensitivity analyses showed high consistency. CONCLUSION: There is consistent evidence for a significant reduction in cGFR associated with TDF use in HIV-infected patients. Our findings call for a strict monitoring of renal function in long-term TDF users with tests that distinguish between glomerular dysfunction and proximal renal tubulopathy, a known adverse effect of TDF.

Comparison of drug retention rates and causes of drug discontinuation between anti-tumor necrosis factor agents in rheumatoid arthritis

OBJECTIVE: Tumor necrosis factor (TNF) inhibitors have revolutionized the treatment of severe rheumatoid arthritis (RA), yet drug discontinuation is common. The aim of this study was to compare treatment retention rates and specific causes of anti-TNF discontinuation in a population-based RA cohort. METHODS: All patients treated with etanercept, infliximab, or adalimumab within the Swiss Clinical Quality Management RA cohort between 1997 and 2006 were included in the study. Causes of treatment discontinuation were broadly categorized as adverse events (AEs) or nontoxic causes, and further subdivided into specific categories. Specific causes of treatment interruption were analyzed using a Cox proportional hazards model and adjusted for potential confounders. RESULTS: A total of 2,364 anti-TNF treatment courses met the inclusion criteria. Treatment discontinuation was reported 803 times: 309 with etanercept, 249 with infliximab, and 245 with adalimumab. Drug inefficacy represented the largest single cause of treatment discontinuation (55.8% of cases). The median time of receiving anti-TNF therapy was 37 months, but discontinuation rates differed between the 3 anti-TNF agents (P < 0.001), with shorter retention rates for infliximab (hazard ratio [HR] 1.24, 99% confidence interval [99% CI] 1.01-1.51). The specific causes of treatment discontinuation revealed an increased risk of AEs with infliximab (HR 1.4, 99% CI 1.003-1.96), mostly due to an increased risk of infusion or allergic reactions (HR 2.11, 99% CI 1.23-3.62). Other discontinuation causes were equally distributed between the anti-TNF agents. CONCLUSION: In this population, infliximab was associated with higher overall discontinuation rates compared with etanercept and adalimumab, which is mainly due to an increased risk of infusion or allergic reactions.

Animal Guts as Ideal Chemical Reactors: Maximizing Absorption Rates

I solved equations that describe coupled hydrolysis in and absorption from a continuously stirred tank reactor (CSTR), a plug flow reactor (PFR), and a batch reactor (BR) for the rate of ingestion and/or the throughput time that maximizes the rate of absorption (=gross rate of gain from digestion). Predictions are that foods requiring a single hydrolytic step (e.g., disaccharides) yield ingestion rates that vary inversely with the concentration of food substrate ingested, whereas foods that require multiple hydrolytic and absorptive reactions proceeding in parallel (e.g., proteins) yield maximal ingestion rates at intermediate substrate concentrations. Counterintuitively, then, animals acting to maximize their absorption rates should show compensatory ingestion (more rapid feeding on food of lower concentration), except for the lower range of diet quality fur complex diets and except for animals that show purely linear (passive) uptake. At their respective maxima in absorption rates, the PFR and BR yield only modestly higher rates of gain than the CSTR but do so at substantially lower rates of ingestion. All three ideal reactors show milder than linear reduction in rate of absorption when throughput or holding time in the gut is increased (e.g., by scarcity or predation hazard); higher efficiency of hydrolysis and extraction offset lower intake. Hence adding feeding costs and hazards of predation is likely to slow ingestion rates and raise absorption efficiencies substantially over the cost-free optima found here.

Seawater carbonate chemistry, clearance rates, respiration rates, condition index and cellular turnover (RNA: DNA) of Juvenile King Scallop, Pecten maximus in a laboratory experiment

The decline in ocean water pH and changes in carbonate saturation states through anthropogenically mediated increases in atmospheric CO2 levels may pose a hazard to marine organisms. This may be particularly acute for those species reliant on calcareous structures like shells and exoskeletons. This is of particular concern in the case of valuable commercially exploited species such as the king scallop, Pecten maximus. In this study we investigated the effects on oxygen consumption, clearance rates and cellular turnover in juvenile P. maximus following 3 months laboratory exposure to four pCO2 treatments (290, 380, 750 and 1140 µatm). None of the exposure levels were found to have significant effect on the clearance rates, respiration rates, condition index or cellular turnover (RNA: DNA) of individuals. While it is clear that some life stages of marine bivalves appear susceptible to future levels of ocean acidification, particularly under food limiting conditions, the results from this study suggest that where food is in abundance, bivalves like juvenile P. maximus may display a tolerance to limited changes in seawater chemistry.

Seismic Activity Rates in the Iberian Peninsula

Evaluating the seismic hazard requires establishing a distribution of the seismic activity rate, irrespective of the methodology used in the evaluation. In practice, how that activity rate is established tends to be the main difference between the various evaluation methods. The traditional procedure relies on a seismogenic zonation and the Gutenberg-Richter (GR) hypothesis. Competing zonations are often compared looking only at the geometry of the zones, but the resulting activity rate is affected by both geometry and the values assigned to the GR parameters. Contour plots can be used for conducting more meaningful comparisons, providing the GR parameters are suitably normalised. More recent approaches for establishing the seismic activity rate forego the use of zones and GR statistics and special attention is paid here to such procedures. The paper presents comparisons between the local activity rates that result for the complete Iberian Peninsula using kernel estimators as well as two seismogenic zonations. It is concluded that the smooth variation of the seismic activity rate produced by zoneless methods is more realistic than the stepwise changes associated with zoned approaches; moreover, the choice of zonation often has a stronger influence on the results than its fairly subjective origin would warrant. It is also observed that the activity rate derived from the kernel approach, related with the GR parameter “a”, is qualitatively consistent with the epicentres in the catalogue. Finally, when comparing alternative zonations it is not just their geometry but the distribution of activity rate that should be compared.

Lung cancer rates in men and women with comparable histories of smoking

Background: Recent case-control studies suggest that, given equal smoking exposure, women may have a higher relative risk of developing lung cancer than men. Despite prospective data that conflict with this hypothesis, mechanistic studies to find a biologic basis for a sex difference continue. Methods: We addressed the hypothesis directly by analyzing prospective data from former and current smokers in two large cohorts-the Nurses' Health Study of women and the Health Professionals Follow-up Study of men. We calculated incidence rates and hazard ratios of lung cancer in women compared with men, adjusting for age, number of cigarettes smoked per day, age at start of smoking, and time since quitting, using Cox proportional hazards models. We also reviewed published results from prospective analyses. Results: From 1986 through 2000, 955 and 311 primary lung cancers were identified among 60 296 women and 25 397 men, respectively, who ranged in age from 40 to 79 years. Incidence rates per 100 000 person-years for women and men were 253 and 232, respectively, among current smokers and 81 and 73, respectively, among former smokers. The hazard ratio in women ever smokers compared with men was 1.11 (95% confidence interval = 0.95 to 1.31). Six published prospective cohort studies allowed assessment of comparative susceptibility to lung cancer by sex. None supported an excess risk of lung cancer for women. Conclusions: Women do not appear to have a greater susceptibility to lung cancer than men, given equal smoking exposure. Research should be focused on enhancing preventive interventions for all.

Does the Pareto Distribution of Hurricane Damage Inherit its Fat Tail from a Zipf Distribution of Assets at Hazard?

Tropical Cyclones are a continuing threat to life and property. Willoughby (2012) found that a Pareto (power-law) cumulative distribution fitted to the most damaging 10% of US hurricane seasons fit their impacts well. Here, we find that damage follows a Pareto distribution because the assets at hazard follow a Zipf distribution, which can be thought of as a Pareto distribution with exponent 1. The Z-CAT model is an idealized hurricane catastrophe model that represents a coastline where populated places with Zipf- distributed assets are randomly scattered and damaged by virtual hurricanes with sizes and intensities generated through a Monte-Carlo process. Results produce realistic Pareto exponents. The ability of the Z-CAT model to simulate different climate scenarios allowed testing of sensitivities to Maximum Potential Intensity, landfall rates and building structure vulnerability. The Z-CAT model results demonstrate that a statistical significant difference in damage is found when only changes in the parameters create a doubling of damage.

Oral cancer incidence and survival rates in the Republic of Ireland, 1994-2009

Background: Oral cancer is a significant public health problem world-wide and exerts high economic, social, psychological, and physical burdens on patients, their families, and on their primary care providers. We set out to describe the changing trends in incidence and survival rates of oral cancer in Ireland between 1994 and 2009. Methods: National data on incident oral cancers [ICD 10 codes C01-C06] were obtained from the National Cancer Registry Ireland from 1994 to 2009. We estimated annual percentage change (APC) in oral cancer incidence during 1994–2009 using joinpoint regression software (version 4.2.0.2). The lifetime risk of oral cancer to age 79 was estimated using Irish incidence and population data from 2007 to 2009. Survival rates were also examined using Kaplan-Meier curves and Cox proportional hazard models to explore the influence of several demographic/lifestyle covariates with follow-up to end 2012. Results: Data were obtained on 2,147 oral cancer incident cases. Men accounted for two-thirds of oral cancer cases (n = 1,430). Annual rates in men decreased significantly during 1994–2001 (APC = -4.8 %, 95 % CI: −8.7 to −0.7) and then increased moderately (APC = 2.3 %, 95 % CI: −0.9 to 5.6). In contrast, annual incidence increased significantly in women throughout the study period (APC = 3.2 %, 95 % CI: 1.9 to 4.6). There was an elevated risk of death among oral cancer patients who were: older than 60 years of age; smokers; unemployed or retired; those living in the most deprived areas; and those whose tumour was sited in the base of the tongue. Being married and diagnosed in more recent years were associated with reduced risk of death. Conclusion: Oral cancer increased significantly in both sexes between 1999 and 2009 in Ireland. Our analyses demonstrate the influence of measured factors such as smoking, time of diagnosis and age on observed trends. Unmeasured factors such as alcohol use, HPV and dietary factors may also be contributing to increased trends. Several of these are modifiable risk factors which are crucial for informing public health policies, and thus more research is needed.

Brazilian multicentre study of common mental disorders in primary care: rates and related social and demographic factors

Mental health problems are common in primary health care, particularly anxiety and depression. This study aims to estimate the prevalence of common mental disorders and their associations with socio-demographic characteristics in primary care in Brazil (Family Health Strategy). It involved a multicenter cross-sectional study with patients from Rio de Janeiro, São Paulo, Fortaleza (Ceará State) and Porto Alegre (Rio Grande do Sul State), assessed using the General Health Questionnaire (GHQ-12) and the Hospital Anxiety and Depression Scale (HAD). The rate of mental disorders in patients from Rio de Janeiro, São Paulo, Fortaleza and Porto Alegre were found to be, respectively, 51.9%, 53.3%, 64.3% and 57.7% with significant differences between Porto Alegre and Fortaleza compared to Rio de Janeiro after adjusting for confounders. Prevalence proportions of mental problems were especially common for females, the unemployed, those with less education and those with lower incomes. In the context of the Brazilian government's moves towards developing primary health care and reorganizing mental health policies it is relevant to consider common mental disorders as a priority alongside other chronic health conditions.

Melatonin in maturation media fails to improve oocyte maturation, embryo development rates and DNA damage of bovine embryos

Melatonin (MEL) acts as a powerful scavenger of free radicals and direct gonadal responses to melatonin have been reported in the literature. Few studies, however, have evaluated the effect of MEL during in vitro maturation (IVM) on bovine embryos. This study tested the addition of MEL to maturation medium (MM) with no gonadotropins on nuclear maturation and embryo development rates and the incidence of DNA damage in resulting embryos. Cumulus-oocyte complexes were aspirated from abattoir ovaries and cultured in MM (TCM-199 medium supplemented with 10% fetal calf serum - FCS) at 39ºC and 5% CO2 in air. After 24 hours of culture in MM with 0.5 µg mL-1 FSH and 5.0 µg mL-1 LH; 10-9 M MEL) or 10-9 M MEL, 0.5 µg mL-1 FSH and 5.0 µg mL-1 LH, the oocytes were stained with Hoechst 33342 to evaluate nuclear maturation rate. After in vitro fertilization and embryo culture, development rates were evaluated and the blastocysts were assessed for DNA damage by Comet assay. There was no effect of melatonin added to the MM, alone or in combination with gonadotropins, on nuclear maturation, cleavage and blastocyst rates. These rates ranged between 88% to 90%, 85% to 88% and 42% to 46%, respectively. The extent of DNA damage in embryos was also not affected by MEL supplementation during IVM. The addition of 10-9 M MEL to the MM failed to improve nuclear maturation and embryo development rates and the incidence of DNA damage in resulting embryos, but was able to properly substitute for gonadotropins during IVM.

Deleterious effect of TRIS buffer on growth rates and pigment content of Gracilaria birdiae Plastino & E.C. Oliveira (Gracilariales, Rhodophyta)

This work evaluated the effects of Tris (hydroxymethyl)-aminomethane (TRIS) buffer and its interaction with nutrient concentration on the development of Gracilaria birdie, a common species on the Brazilian coast that has been exploited for agar production. Responses to different conditions were assessed through growth rates and pigment content (chlorophyll a, phycoerythrin, phycocyanin and allophycocyanin). Provasoli's nutrient solution with and without TRIS addition was tested at concentrations of 12.5, 25 and 50%. The pH was also monitored. G. birdiae grew better in the absence of TRIS and at low nutrient concentrations, 12.5 and 25% (growth rates of 10.8-11.3%.day-1). Higher contents of phycoerythrin and chlorophyll a were observed without TRIS at 12.5 and 25% (Phycoerythrin, 649.6-698.0 μg g-1 fresh biomass; Chlorophyll a, 156.0-168.6 μg g-1 fresh biomass). These findings highlight the deleterious effect of TRIS on growth and phycoerythrin and chlorophyll a content. They also demonstrate the importance of appropriate nutrient concentration for laboratory cultures, depending on the intrinsic characteristics of each species.

Effects of temperature and salinity on the survival rates of coxicerberus ramosae (Albuquerque, 1978), an interstitial isopod of a Sandy Beach on the coast of Brazil

The tolerance to the combined effects of temperature and salinity was investigated in the interstitial isopod Coxicerberus ramosae (Albuquerque, 1978), a species of intertidal zone of sandy beaches in Rio de Janeiro, Brazil. The animals were collected on Praia Vermelha Beach. The experiments lasted 24 h and nine salinities and seven temperatures were used for a total of 63 combinations. Thirty animals were tested in each combination. The species showed high survival in most of the combinations. The temperature of 35 ºC was lethal and at 5 ºC, the animals tolerated only a narrow range of salinities. The statistical analyses showed that the effects of temperature and salinity were significant on the survival, which confirmed the euryhalinity and eurythermy of this species.

Rates of antimicrobial resistance in latin america (2004-2007) and in vitro activity of the glycylcycline tigecycline and of other antibiotics

As a part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.), Gram-positive and Gram-negative bacterial isolates were collected from 33 centers in Latin America (centers in Argentina, Brazil, Chile, Colombia, Guatemala, Honduras, Jamaica, Mexico, Panama, Puerto Rico, and Venezuela) from January 2004 to September 2007. Argentina and Mexico were the greatest contributors of isolates to this study. Susceptibilities were determined according to Clinical Laboratory Standards Institute guidelines. Resistance levels were high for most key organisms across Latin America: 48.3% of Staphylococcus aureus isolates were methicillin-resistant while 21.4% of Acinetobacter spp. isolates were imipenem-resistant. Extended-spectrum β-lactamase were reported in 36.7% of Klebsiella pneumoniae and 20.8% of E. coli isolates. Tigecycline was the most active agent against Gram-positive isolates. Tigecycline was also highly active against all Gram-negative organisms, with the exception of Pseuodomonas aeruginosa, against which piperacillin-tazobactam was the most active agent tested (79.3% of isolates susceptible). The in vitro activity of tigecycline against both Gram-positive and Gram-negative isolates indicates that it may be an useful tool for the treatment of nosocomial infections, even those caused by organisms that are resistant to other antibacterial agents.