A randomised sham controlled trial of vertebroplasty for painful acute osteoporotic vertebral fractures (VERTOS IV)

Background

Combination of erlotinib and bevacizumab is a promising regimen in advanced non-squamous non-small-cell lung cancer (NSCLC). We are conducting a single arm phase II trial which aims to evaluate the efficacy and safety of this regime as a second- or third-line chemotherapy.

Methods

Key eligibility criteria were histologically or cytologically confirmed non-squamous NSCLC, stage III/IV or recurrent NSCLC not indicated radical chemoradiation, prior one or two regimen of chemotherapy, age 20 years or more, and performance status of two or less. The primary endpoint is objective response rate. The secondary endpoints include overall survival, progression-free survival, disease control rate and incidence of adverse events. This trial plans to accrue 80 patients based on a two-stage design employing a binomial distribution with an alternative hypothesis response rate of 35% and a null hypothesis threshold response rate of 20%. A subset analysis according to EGFR mutation status is planned.

Discussion

We have presented the design of a single arm phase II trial to evaluate the efficacy and safety of combination of bevacizumab and erlotinib in advanced non-squamous NSCLC patients. In particular we are interested in determining the merit of further development of this regimen and whether prospective patient selection using EGFR gene is necessary in future trials.

Trial registration

This trial was registered at the UMIN Clinical Trials Registry as UMIN000004255 (http://www.umin.ac.jp/ctr/index.htm).     

Thermal parameters and locomotor performance in juvenile of Pleurodema nebulosum (Anura: Leptodactylidae) from the Monte Desert

We studied a combination of thermal parameters (critical thermal maximum, selected body temperature, and field body temperature) and locomotor performance capacities (laboratory and field conditions) of juveniles of Pleurodema nebulosum. We found that field body temperature was determined largely by the temperature of the micro-environment. Field body temperatures of juveniles of P. nebulosum were below selected body temperature. The locomotor performance curve was maximized and reaches a plateau between 30 and 35 °C, with 35 °C being the temperature at which maximum performance was obtained for analyzed individuals. The plateau values were close to the selected body temperature (T_sel) obtained for the studied frogs. In field conditions the locomotor performance was determinated by the substrate temperature. Apparently, juveniles of P. nebulosum show thermal coadaptation because the selected body temperature and the optimum temperature for locomotion had close values. We believe that the temperatures prevailing during the early hours of activity would allow frogs to explore the micro-environment, covering larger areas in search of food.     

Spatial serial conditioning maintained with minimal temporal contingency

Two experiments used a spatial serial conditioning paradigm to assess the effectiveness of spatially informative conditioned stimuli in eliciting tracking behavior in pigeons. The experimental paradigm consisted of the simultaneous presentation of 2 key lights (CS2 and CTRL), followed by another key light (CS1), followed by food (the unconditioned stimulus or US). CS2 and CTRL were presented in 2 of 3 possible locations, randomly assigned; CS1 was always presented in the same location as CS2. CS2 was designed to signal the spatial, but not the temporal locus of CS1; CS1 signaled the temporal locus of the US. In experiment 1, differential pecking on CS2 was observed even when CS2 was present throughout the interval between consecutive presentations of CS1, but only in a minority of pigeons; prevalence of differential pecking was enhanced when CS2 duration was halved. A control condition verified that pecking on CS2 was not due to temporal proximity between CS2 and US. Experiment 2 demonstrated the reversibility of spatial conditioning between CS2 and CTRL. Asymptotic performance never involved tracking CTRL more than CS2 for any of 16 pigeons. It is inferred that pigeons learned the spatial association between CS2 and CS1, and that temporal contingency facilitated its expression as tracking behavior.     

Identification of candidate genes in rice for resistance to sheath blight disease by whole genome sequencing

Recent advances in whole genome sequencing (WGS) have allowed identification of genes for disease susceptibility in humans. The objective of our research was to exploit whole genome sequences of 13 rice (Oryza sativa L.) inbred lines to identify non-synonymous SNPs (nsSNPs) and candidate genes for resistance to sheath blight, a disease of worldwide significance. WGS by the Illumina GA IIx platform produced an average 5× coverage with ~700 K variants detected per line when compared to the Nipponbare reference genome. Two filtering strategies were developed to identify nsSNPs between two groups of known resistant and susceptible lines. A total of 333 nsSNPs detected in the resistant lines were absent in the susceptible group. Selected variants associated with resistance were found in 11 of 12 chromosomes. More than 200 genes with selected nsSNPs were assigned to 42 categories based on gene family/gene ontology. Several candidate genes belonged to families reported in previous studies, and three new regions with novel candidates were also identified. A subset of 24 nsSNPs detected in 23 genes was selected for further study. Individual alleles of the 24 nsSNPs were evaluated by PCR whose presence or absence corresponded to known resistant or susceptible phenotypes of nine additional lines. Sanger sequencing confirmed presence of 12 selected nsSNPs in two lines. “Resistant” nsSNP alleles were detected in two accessions of O. nivara that suggests sources for resistance occur in additional Oryza sp. Results from this study provide a foundation for future basic research and marker-assisted breeding of rice for sheath blight resistance.     

Biological studies of Oligonychus punicae (Acari: Tetranychidae) on grapevine cultivars

Life cycle, fecundity and longevity of the avocado brown mite, Oligonychus punicae (Hirst), were studied on six grapevine cultivars (Tucupita, Villanueva, Red Globe, Sirah, Sauvignon and Chenin Blanc), under laboratory conditions at 27 +/- 2 degrees C, 80 +/- 10% RH, and L12:D12 photoperiod. Mite-infested leaves were collected from vineyards, placed in paper bags and taken to the laboratory. A laboratory mite culture was established using the grape cultivar Criolla Negra as host plant. To elucidate potential effects on avocado brown mite parameters, we assessed levels of secondary metabolites, such as alkaloids, flavonoids, tannins and polyphenols, of leaves of the six grape cultivars, as well as the thickness of the adaxial cuticle-epidermis. The life cycle of O. punicae differed among cultivars with average values ranging between 8.2 days on Tucupita leaves and 9.1 days on Sirah. Relatively high fecundity was found on Tucupita leaves (2.8 eggs/female/day) during 11.4 oviposition days, while low fecundity values occurred on Sirah and Villanueva leaves, with 0.9 and 1.8 eggs/female/day during 7.9 and 6.7 days, respectively. Average longevity of O. punicae females ranged from 8.1 to 17.5 days on Sirah and Sauvignon leaves, respectively. Intrinsic rate of increase (r (m)) was highest on Sauvignon (0.292) and Tucupita (0.261), and lowest on Sirah (0.146) and Villanueva (0.135). Although significant differences in cuticle-epidermis thickness were detected among the six cultivars, it seemed not to affect mite parameters. Secondary metabolite content also varied between the cultivars. Generally, increasing flavonoid content coincided with decreasing reproductive parameters. The natural plant resistance observed in this study could be useful in the development of an integrated pest management program for mite pests in grape production.     

Potential risk of biologic pollution associated to the introduction of <i>Pinus radiata</i> in grassland areas

Afforestation is a recommended practice to mitigate global warming. However, their implementation may generate undesirable impacts, mostly if exotic species are used. Plantations of Pinus radiata D Don in Ventania (Bs. As., Argentina) soils showed notorious increments of extractable P (Pe), which could affect the dynamic of this element as well as the degree of phosphorus saturation (GSP_Bray). The objectives of this study were: i) to quantify the GSP_Bray in Mollisols afforested with P. radiata comparing the results with those coming from adjacent, natural grassland areas (base line); ii) to evaluate the potential environmental risk induced by afforestation through the identification of a change point (PC) in the GSP_Bray indicative of a phosphate leaching increment. Treatments included mature stands of P. radiata (TB) and adjacent areas with natural grassland vegetation (TP). Samples were taken at 0-15; 15-30 and 30-45 cm soil depth, and texture, pH, total organic carbon (COT), Pe, soluble reactive phosphorus (PSR), phosphorus sorption index (ISP) and GSP_Bray were determined. The results showed a significant acidification in TB and an increase in the COT stock, indicating an additional atmospheric CO₂ sequestration by the trees. The Pe and PSR values were notoriously higher in TB, and they were reflected in a significant increment in the GSP_Bray with respect to TP. The detection of a significant PC in the GSP_Bray-PSR regression indicates higher chances of phosphate leaching in the forest stands, which could reach water courses, lakes and artificial reservoirs promoting their eutrophication. Because of the potential environmental pollution risk of biologic origin derived from the afforestation with P. radiata in Mollisols areas, their inclusion in clean development practices must be reconsidered.     

Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine

Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day) or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin-norepinephrine reuptake inhibitors, especially considering the lower reproductive efficiency of humans compared to males of other species.     

From Sub- to Super-Citizenship: Sex Hormones and the Body Politic in Brazil

Sex hormones in Brazil are mobilised as modes of regulatory control and to discipline subjectivites. Their packaging effectively differentiates between two forms of citizenship. The first, available to those with private health, is founded on notions of personal autonomy, individual choice and self-enhancement, while the second frames decisions in terms of the individual's moral responsibility to the wider collectivity. Here, technical and biomedical interventions on middle-class bodies have personalising tendencies, while those effected on the bodies of the urban poor can be read as modes of inclusion through standardisation. Personalisation, in the Brazilian sense, concerns the attribution of privileges which place a person above the undifferentiated mass of individuals. The paper critically engages with approaches to bio-citizenships developed in contexts where biological inclusion is predicated on patient activism and shows how, in Brazil, complying with medical regimes is an integral part of constituting oneself as a citizen