Ambiguity-Free Method for Fast and Precise GNSS Differential Positioning

Methods based on integer ambiguity determination, such as the least-squares ambiguity decorrelation adjustment (LAMBDA) method, are currently used for precise global navigation satellite system (GNSS) differential positioning. In the present paper, the author proposes an ambiguity-free method based on a dedicated mixed (stochastic/deterministic) optimization algorithm that, unlike the LAMBDA method, is capable of providing reliable and accurate results using few observation epochs (e.g., 1-cm accuracy with just two epochs), having the additional advantages of insensitivity to cycle slips and impossibility of wrong ambiguity fixation. In addition, it is demonstrated that the application of the linear (deterministic) part of this algorithm yields the correct baseline results much more easily and quickly than methods requiring integer ambiguity determination, provided the initial approximate coordinates are accurate to a few centimeters. However, the use of ambiguity-free methods requires that the integer character of the ambiguities be preserved so that they can be eliminated; therefore no ionosphere-free combination can be computed and the methods are valid only for short baselines (e.g., less than 10 km).Baselga Moreno, S. (2014). Ambiguity-Free Method for Fast and Precise GNSS Differential Positioning. Journal of Surveying Engineering. 140(1):22-27. doi:10.1061/(ASCE)SU.1943-5428.0000111S2227140

Genetic selection of maternal lines and digestive efficiency in rabbits: long term selection for litter size at weaning versus hyper selection for reproductive longevity

The objective of the present paper is to evaluate how long-term selection for litter size at weaning or short-term hyper selection for reproductive longevity, affect the digestive utilisation of growing and lactating rabbits. A digestibility trial was carried out during the 3rd week of lactation with a total of 27 multiparous does: 14 females came from a line selected for litter size at weaning over 32 generations (V), and 13 from a recently constituted, long lived-productive line (LP). Another digestibility trial was performed during the growing period with a total of 48 growing rabbits (24 from each line). After a 7 d adaptation period, faeces were collected individually for 4 d (from 13 to 16 d of lactation or from 49 to 53 d of age, respectively). Daily feed intake and weight gain recorded during the experimental growing period were similar for both lines (137 g of dry matter (DM)/d and 48 g/d, respectively). Growing rabbits from the V-line showed greater values for the digestibility of the DM and OM (+1 percentage point; P<0.10) and signifi cantly higher values for the acid detergent fi bre (+3 percentage points; P=0.03) than animals from the LP line. No signifi cant differences for the apparent digestibility coeffi cients of crude protein, neutral detergent fi bre, crude fi bre and gross energy were observed between lines, these being on average 65.7, 23.0, 10.7 and 52.6%, respectively. Females from the LP line were initially heavier (+258 g of live weight; P=0.06), and presented a signifi cantly greater daily feed intake (+22 g DM/d; P=0.04) and milk yield (+37 g/d; P=0.01) during the pre-experimental and faeces collection phases (from 6 to 16 d of lactation). V-line lactating does displayed greater values for digestibility for all those nutrients evaluated (from +0.9 and +3.7 percentage points for the crude protein and acid detergent fi bre) compared to the LP line females, although these were only signifi cant for the DM, organic matter and gross energy (+2.3, +2.5, +2.1 percentage points; P<0.05). In conclusion, rabbits selected for litter size at weaning seem to have greater effi ciency for digestive utilisation than those hyper selected for reproductive longevity.This study has been supported by the Spanish CICYT project AGL 2004-02710/GAN.Pascual Amorós, JJ.; Ródenas, L.; Martínez, E.; Cervera, C.; Blas, E.; Baselga, M. (2008). Genetic selection of maternal lines and digestive efficiency in rabbits: long term selection for litter size at weaning versus hyper selection for reproductive longevity. World Rabbit Science. 16(3). doi:10.4995/wrs.2008.62516

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

Pten loss promotes MAPK pathway dependency in HER2/neu breast carcinomas

Loss of the tumor suppressor gene PTEN is implicated in breast cancer progression and resistance to targeted therapies, and is thought to promote tumorigenesis by activating PI3K signaling. In a transgenic model of breast cancer, Pten suppression using a tetracycline-regulatable short hairpin (sh)RNA cooperates with human epidermal growth factor receptor 2 (HER2/neu), leading to aggressive and metastatic disease with elevated signaling through PI3K and, surprisingly, the mitogen-activated protein kinase (MAPK) pathway. Restoring Pten function is sufficient to down-regulate both PI3K and MAPK signaling and triggers dramatic tumor regression. Pharmacologic inhibition of MAPK signaling produces similar effects to Pten restoration, suggesting that the MAPK pathway contributes to the maintenance of advanced breast cancers harboring Pten loss

Genomic characterization of a novel group A lamb rotavirus isolated in Zaragoza, Spain

An ovine rotavirus (OVR) strain, 762, was isolated from a 30-day-old lamb affected with severe gastroenteritis, in Zaragoza, Spain, and the VP4, VP7, VP6, NSP4, and NSP5/NSP6 genes were subsequently characterized molecularly. Strain OVR762 was classified as a P[14] rotavirus, as the VP4 and VP8* trypsin-cleavage product of the VP4 protein revealed the highest amino acid (aa) identity (94% and 97%, respectively) with that of the P11[14] human rotavirus (HRV) strain PA169, isolated in Italy. Analysis of the VP7 gene product revealed that OVR762 possessed G8 serotype specificity, a type common in ruminants, with the highest degree of aa identity(95–98%) shared with serotype G8 HRV, bovine rotavirus, and guanaco (Lama guanicoe) rotavirus strains. Moreover, strain OVR762 displayed a bovine-like NSP4 (genotype E2) and NSP5/NSP6 (genotype H3), and a VP6 genotype I2, as well as a long electropherotype pattern. This is the first report of a lamb rotavirus with P[14] and G8 specificities, providing additional evidence for the wide genetic and antigenic diversity of group A rotaviruses

An implantable microdevice to perform high-throughput in vivo drug sensitivity testing in tumors

Current anticancer chemotherapy relies on a limited set of in vitro or indirect prognostic markers of tumor response to available drugs. A more accurate analysis of drug sensitivity would involve studying tumor response in vivo. To this end, we have developed an implantable device that can perform drug sensitivity testing of several anticancer agents simultaneously inside the living tumor. The device contained reservoirs that released microdoses of single agents or drug combinations into spatially distinct regions of the tumor. The local drug concentrations were chosen to be representative of concentrations achieved during systemic treatment. Local efficacy and drug concentration profiles were evaluated for each drug or drug combination on the device, and the local efficacy was confirmed to be a predictor of systemic efficacy in vivo for multiple drugs and tumor models. Currently, up to 16 individual drugs or combinations can be assessed independently, without systemic drug exposure, through minimally invasive biopsy of a small region of a single tumor. This assay takes into consideration physiologic effects that contribute to drug response by allowing drugs to interact with the living tumor in its native microenvironment. Because these effects are crucial to predicting drug response, we envision that these devices will help identify optimal drug therapy before systemic treatment is initiated and could improve drug response prediction beyond the biomarkers and in vitro and ex vivo studies used today. These devices may also be used in clinical drug development to safely gather efficacy data on new compounds before pharmacological optimization.National Cancer Institute (U.S.) (Innovative Molecular Analysis Technologies Program R21-CA177391)Kibur Medical, Inc