High efficacy and low toxicity of weekly docetaxel given as first-line treatment for metastatic breast cancer

Background: Docetaxel is one of the most effective antitumor agents currently available for the treatment of metastatic breast cancer (MBC). This phase II multicenter study prospectively analyzed the efficacy and toxicity of docetaxel given on a weekly schedule as first-line treatment of metastatic breast cancer. Patients and Methods: All patients received docetaxel, 35 mg/m(2) weekly for 6 weeks, followed by 2 weeks of rest. Subsequent cycles ( 3 weeks of treatment, 2 weeks of rest) were given until a maximum of 5 cycles or disease progression. Premedication consisted of 8 mg dexamethasone intravenously 30 min prior to the infusion of docetaxel. Results: Fifty-four patients at a median age of 58 years with previously untreated MBC were included in the study. A median of 10 doses ( median cumulative dose 339 mg/m(2)) was administered ( range: 2 - 18). The overall response rate was 48.1% ( 95% CI: 34 - 61%, intent-to-treat). Median survival was 15.8 months and median time to progression was 5.9 months ( intent-to-treat). Hematological toxicity was mild with absence of neutropenia-related complications. Grade 3 neutropenia was observed in 3.7% of patients and grade 3 and 4 anemia was observed in 5.6 and 1.9% of patients, respectively. Conclusion: The weekly administration of docetaxel is highly efficient and safe as first-line treatment for MBC and may serve as an important treatment option specifically in elderly patients and patients with a reduced performance status. Copyright (C) 2005 S. Karger AG, Basel

Improvements in vision-related quality of life in blind patients implanted with the Argus II Epiretinal Prosthesis

Background: The purpose of this analysis is to report the change in quality of life (QoL) after treatment with the Argus II Epiretinal Prosthesis in patients with end-stage retinitis pigmentosa. Methods: The Vision and Quality of Life Index (VisQoL) was used to assess changes in QoL dimensions and overall utility score in a prospective 30-patient single-arm clinical study. VisQoL is a multi-attribute instrument consisting of six dimensions (injury, life, roles, assistance, activity and friendship) that may be affected by visual impairment. Within each dimension, patients were divided into two groups based on how much their QoL was affected by their blindness at baseline (moderate/severe or minimal). Outcomes were compared within each dimension sub-group between baseline and the combined follow-up periods using the Friedman test. In addition, data from the six dimensions were combined into a single utility score, with baseline data compared to the combined follow-up periods. Results: Overall, 80 per cent of the patients reported difficulty in one or more dimensions preimplant. Composite VisQoL utility scores at follow-up showed no statistically significant change from baseline; however, in three of the six VisQoL dimensions (injury, life and roles), patients with baseline deficits showed significant and lasting improvement after implantation with Argus II. In two of the three remaining dimensions (assistance and activity), data trended toward an improvement. In the final VisQoL dimension (friendship), none of the patients reported baseline deficits, suggesting that patients had largely adjusted to this attribute. Conclusion: Patients whose vision negatively affected them with respect to three VisQoL dimensions (that is, getting injured, coping with the demands of their life and fulfilling their life roles) reported significant improvement in QoL after implantation of the Argus II retinal prosthesis. Furthermore, the benefit did not deteriorate at any point during the 36-month follow-up, suggesting a long-term, durable improvement

Triatoma dimidiata Infestation in Chagas Disease Endemic Regions of Guatemala: Comparison of Random and Targeted Cross-Sectional Surveys

Chagas disease is a vector-borne parasitic zoonosis endemic throughout South and Central America and Mexico. Guatemala is engaged in the Central America Initiative to interrupt Chagas disease transmission. A major strategy is the reduction of Triatoma dimidiata domiciliary infestations through indoor application of residual insecticides. Successful control of T. dimidiata will depend on accurate identification of areas at greatest risk for infestation. Initial efforts focused primarily on targeted surveys of presumed risk factors and suspected infestation to define intervention areas. This policy has not been evaluated and might not maximize the effectiveness of limited resources if high prevalence villages are missed or low prevalence villages are visited unnecessarily. We compare findings from the targeted surveys to concurrent random surveys in two primary foci of Chagas disease transmission in Guatemala to evaluate the performance of the targeted surveys. Our results indicate that random surveys performed better than targeted surveys and should be considered over targeted surveys when reliability of risk factors has not been evaluated, identify useful environmental factors to predict infestation, and indicate that infestation risk varies locally. These findings are useful for decision-makers at national Chagas Disease control programs in Central America, institutions supporting development efforts, and funding agencies

Early-Time Energy Loss in a Strongly-Coupled SYM Plasma

We carry out an analytic study of the early-time motion of a quark in a strongly-coupled maximally-supersymmetric Yang-Mills plasma, using the AdS/CFT correspondence. Our approach extracts the first thermal effects as a small perturbation of the known quark dynamics in vacuum, using a double expansion that is valid for early times and for (moderately) ultrarelativistic quark velocities. The quark is found to lose energy at a rate that differs significantly from the previously derived stationary/late-time result: it scales like T^4 instead of T^2, and is associated with a friction coefficient that is not independent of the quark momentum. Under conditions representative of the quark-gluon plasma as obtained at RHIC, the early energy loss rate is a few times smaller than its late-time counterpart. Our analysis additionally leads to thermally-corrected expressions for the intrinsic energy and momentum of the quark, in which the previously discovered limiting velocity of the quark is found to appear naturally.Comment: 39 pages, no figures. v2: Minor corrections and clarifications. References added. Version to be published in JHE

TESS Reveals a Short-period Sub-Neptune Sibling (HD 86226c) to a Known Long-period Giant Planet

The Transiting Exoplanet Survey Satellite mission was designed to find transiting planets around bright, nearby stars. Here, we present the detection and mass measurement of a small, short-period (≈4 days) transiting planet around the bright (V = 7.9), solar-type star HD 86226 (TOI-652, TIC 22221375), previously known to host a long-period (~1600 days) giant planet. HD 86226c (TOI-652.01) has a radius of 2.16 ± 0.08 R⊕ and a mass of ${7.25}_{-1.12}^{+1.19}$ M⊕, based on archival and new radial velocity data. We also update the parameters of the longer-period, not-known-to-transit planet, and find it to be less eccentric and less massive than previously reported. The density of the transiting planet is 3.97 g cm−3, which is low enough to suggest that the planet has at least a small volatile envelope, but the mass fractions of rock, iron, and water are not well-constrained. Given the host star brightness, planet period, and location of the planet near both the "radius gap" and the "hot Neptune desert," HD 86226c is an interesting candidate for transmission spectroscopy to further refine its composition

Performance of real-world functional vision tasks by blind subjects improves after implantation with the Argus (R) II retinal prosthesis system

Background: The main objective of this study was to test Argus II subjects on three real‐world functional vision tasks. / Design: The study was designed to be randomized and prospective. Testing was conducted in a hospital/research laboratory setting at the various participating centres. / Participants: Twenty eight Argus II subjects, all profoundly blind, participated in this study. / Methods: Subjects were tested on the three real‐world functional vision tasks: Sock Sorting, Sidewalk Tracking and Walking Direction Discrimination task. / Main Outcome Measures: For the Sock Sorting task, percentage correct was computed based on how accurately subjects sorted the piles on a cloth‐covered table and on a bare table. In the Sidewalk Tracking task, an ‘out of bounds’ count was recorded, signifying how often the subject veered away from the test course. During the Walking Direction Discrimination task, subjects were tested on the number of times they correctly identified the direction of testers walking across their field of view. / Results: The mean percentage correct OFF versus ON for the Sock Sorting task was found to be significantly different for both testing conditions (t‐test, P < 0.01). On the Sidewalk Tracking task, subjects performed significantly better with the system ON than they did with the system OFF (t‐test, P < 0.05). Eighteen (18) of 27 subjects (67%) performed above chance with the system ON, and 6 (22%) did so with system OFF on the Walking Direction Discrimination task. / Conclusions: Argus II subjects performed better on all three tasks with their systems ON than they did with their systems OFF

Multiple interactions between the alpha2C- and beta1-adrenergic receptors influence heart failure survival

<p>Abstract</p> <p>Background</p> <p>Persistent stimulation of cardiac β₁-adrenergic receptors by endogenous norepinephrine promotes heart failure progression. Polymorphisms of this gene are known to alter receptor function or expression, as are polymorphisms of the α_2C-adrenergic receptor, which regulates norepinephrine release from cardiac presynaptic nerves. The purpose of this study was to investigate possible synergistic effects of polymorphisms of these two intronless genes (<it>ADRB1 </it>and <it>ADRA2C</it>, respectively) on the risk of death/transplant in heart failure patients.</p> <p>Methods</p> <p>Sixteen sequence variations in <it>ADRA2C </it>and 17 sequence variations in <it>ADRB1 </it>were genotyped in a longitudinal study of 655 white heart failure patients. Eleven sequence variations in each gene were polymorphic in the heart failure cohort. Cox proportional hazards modeling was used to identify polymorphisms and potential intra- or intergenic interactions that influenced risk of death or cardiac transplant. A leave-one-out cross-validation method was utilized for internal validation.</p> <p>Results</p> <p>Three polymorphisms in <it>ADRA2C </it>and five polymorphisms in <it>ADRB1 </it>were involved in eight cross-validated epistatic interactions identifying several two-locus genotype classes with significant relative risks ranging from 3.02 to 9.23. There was no evidence of intragenic epistasis. Combining high risk genotype classes across epistatic pairs to take into account linkage disequilibrium, the relative risk of death or transplant was 3.35 (1.82, 6.18) relative to all other genotype classes.</p> <p>Conclusion</p> <p>Multiple polymorphisms act synergistically between the <it>ADRA2C </it>and <it>ADRB1 </it>genes to increase risk of death or cardiac transplant in heart failure patients.</p

Differential regulation of diacylglycerol kinase isoform in human failing hearts

Evidence from several studies indicates the importance of Gαq protein-coupled receptor (GPCR) signaling pathway, which includes diacylglycerol (DAG), and protein kinase C, in the development of heart failure. DAG kinase (DGK) acts as an endogenous regulator of GPCR signaling pathway by catalyzing and regulating DAG. Expressions of DGK isoforms α, ε, and ζ in rodent hearts have been detected; however, the expression and alteration of DGK isoforms in a failing human heart has not yet been examined. In this study, we detected mRNA expressions of DGK isoforms γ, η, ε, and ζ in failing human heart samples obtained from patients undergoing cardiovascular surgery with cardiopulmonary bypass. Furthermore, we investigated modulation of DGK isoform expression in these hearts. We found that expressions of DGKη and DGKζ were increased and decreased, respectively, whereas those of DGKγ and DGKε remained unchanged. This is the first report that describes the differential regulation of DGK isoforms in normal and failing human hearts

An Unprecedented Role Reversal: Ground Beetle Larvae (Coleoptera: Carabidae) Lure Amphibians and Prey upon Them

Amphibians often feed on beetle larvae, including those of ground beetles (Carabidae). Preliminary reports have detailed an unusual trophic interaction in which, in contrast, larvae of the ground beetle Epomis prey upon juvenile and adult amphibians. While it is known that these larvae feed exclusively on amphibians, how the predator-prey encounter occurs to the advantage of the beetle larvae had been unknown to date. Using laboratory observations and controlled experiments, we recorded the feeding behavior of Epomis larvae, as well as the behavior of their amphibian prey. Here we reveal that larvae of two species of Epomis (E. circumscriptus and E. dejeani) lure their potential predator, taking advantage of the amphibian's predation behavior. The Epomis larva combines a sit-and-wait strategy with unique movements of its antennae and mandibles to draw the attention of the amphibian to the presence of a potential prey. The intensity of this enticement increases with decreasing distance between the larva and the amphibian. When the amphibian attacks, the larva almost always manages to avoid the predator's protracted tongue, exploiting the opportunity to attach itself to the amphibian's body and initiate feeding. Our findings suggest that the trophic interaction between Epomis larvae and amphibians is one of the only natural cases of obligatory predator-prey role reversal. Moreover, this interaction involves a small insect larva that successfully lures and preys on a larger vertebrate. Such role reversal is exceptional in the animal world, extending our perspective of co-evolution in the arms race between predator and prey, and suggesting that counterattack defense behavior has evolved into predator-prey role reversal