Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2.

BackgroundIn the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR(+)) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study.Patients and methodsPatients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations.ResultsThe safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class-effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).ConclusionsMost EVE-associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.Trial registration numberNCT00863655

Behavior of reinforced concrete short columns exposed to fire

AbstractFire could dramatically reduce strength of reinforced concrete columns. The objective of this work is to study columns exposed to fire under axial load and to evaluate reduction in column compressive capacity after fire. The first part of this research is experimental investigation of fifteen-column specimens (15×15×100)cm exposed except one specimen to (600°C) fire. The second part is a theoretical analysis performed using three-dimensional nonlinear finite element program. The main studied parameters were concrete strength, fire duration, level of applied loads, longitudinal reinforcement yield strength, percentage of longitudinal reinforcement, and bar diameters.Comparison between experimental results and theoretical analysis indicated that for columns not exposed to fire, the first crack appeared at 80% of column failure load while the first crack occurred at 50% of column failure load for columns exposed to fire. Columns with the same reinforcement percentage but with smaller bar diameters gained less lateral strain and smaller vertical displacement than columns with bigger bar diameters. Using high-grade steel as main reinforcement showed failure load higher by 55% than that of column reinforced by mild steel. Cooling column by jet water resulted in 17% reduction in failure load than columns cooling gradually in room temperature

Factors modifying the risk of IDDM in offspring of an IDDM parent

Offspring of mothers with insulin-dependent diabetes mellitus (IDDM) have a much lower risk of IDDM than do offspring of diabetic fathers, and this risk is particularly low for offspring born to diabetic mothers over the age of 25 years. To determine whether increasing maternal age also protects the offspring of IDDM fathers from IDDM, we surveyed 367 IDDM fathers (IDDM onset before age 35) who first came to the Joslin Clinic (Boston, MA) between 1945 and 1969. Of the 840 offspring of these men, IDDM developed in 28 before the age of 20, giving a cumulative risk of 5.1 +/- 1.0% (means +/- SE). Because this is similar to the result of our earlier study of IDDM fathers, the two groups were combined to give 1,084 offspring, 39 having IDDM (cumulative risk of IDDM 5.4 +/- 0.9% by age 20), for comparison with our cohort of 1,391 offspring of 739 IDDM mothers. In that cohort, IDDM developed in 20 offspring before the age of 20 years, giving a cumulative risk of 2.1 +/- 0.5%. The risk of diabetes in offspring was higher if the parent's IDDM was diagnosed before age 11 than if it was diagnosed later: 9.3 compared with 4.0% (P = 0.006) for the offspring of IDDM fathers and 2.7 compared with 1.8% for the offspring of IDDM mothers (P = 0.06). In the families in which the father's IDDM was diagnosed after age 11, a protective effect of maternal age > or = 25, similar to that in families of IDDM mothers, seems to be present.(ABSTRACT TRUNCATED AT 250 WORDS

Enhancement of punching shear strength of flat slabs using shear-band reinforcement

Flat-slab system is widely used nowadays. Major and critical problem of this system is its sudden brittle failure is called punching shear failure. To overcome the punching failure problem, there are many ways to increase the punching shear strength of concrete slabs, increasing slab thickness in the area adjacent to the column, increasing column thickness which is against the architectural desire, and finally providing slab with shear reinforcement. Shear reinforcement is more advanced from both the structural and economical point of view.An experimental program includes seven full scale square flat slab interior column specimens tested under gravity loads. All slabs have same dimensions of 1700 mm × 1700 mm with thickness 160 mm and reinforcement ratio of 1.2%. Column was square of 200 mm length and 250 mm height. Elongated steel strips of 25 mm width and 1.5 mm thickness undulated into the slab in different ways to investigate punching shear resistance.The program is divided into five groups. First group investigates the effect of installing the shear-band reinforcement (hanged up on top mesh, knit the top and bottom mesh together). The second group investigates the effect of inclination of shear reinforcement (shear band with vertical leg, with bended leg 45°). The third group investigates the effect of concentrating the shear reinforcement by increasing the quantity around the column. The fourth group investigates effect of radial distribution of shear-band system around the column. Finally, the fifth group investigates the effect of box distribution of shear-band system around the column. Keywords: Flat slab, Shear band, Punching shear, Failure loa