Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

Gaussian process for interpreting pulsed eddy current signals for ferromagnetic pipe profiling

© 2014 IEEE. This paper describes a Gaussian Process based machine learning technique to estimate the remaining volume of cast iron in ageing water pipes. The method utilizes time domain signals produced by a commercially available pulsed Eddy current sensor. Data produced by the sensor are used to train a Gaussian Process model and perform inference of the remaining metal volume. The Gaussian Process model was learned using sensor data obtained from cast iron calibration plates of various thicknesses. Results produced by the Gaussian Process model were validated against the remaining wall thickness acquired using a high resolution laser scanner after the pipes were sandblasted to remove corrosion. The evaluation shows agreement between model outputs and ground truth. The paper concludes by discussing the implications or results and how the proposed method can potentially advance the current technological setup by facilitating real time pipe profiling

Drag Reduction by Polymers in Wall Bounded Turbulence

We address the mechanism of drag reduction by polymers in turbulent wall bounded flows. On the basis of the equations of fluid mechanics we present a quantitative derivation of the "maximum drag reduction (MDR) asymptote" which is the maximum drag reduction attained by polymers. Based on Newtonian information only we prove the existence of drag reduction, and with one experimental parameter we reach a quantitative agreement with the experimental measurements.Comment: 4 pages, 1 fig., included, PRL, submitte

Rethinking place and the social work office in the delivery of children's social work services

Limited attention has been given to the concept of place in social work research and practice. This paper draws on the national evaluation of social work practices (SWPs) in England undertaken between 2009 and 2012. SWPs were pilot organisations providing independent social work services for children in out-of-home care in five sites. One factor distinguishing some of these pilots was their attention to place. The evaluation employed a mixed methods approach and we use data from interviews with 121 children and young people in out-of-home care, 19 birth parents and 31 interviews with SWP staff which explored their views and experiences of the SWP offices. Children and young people were alert to the stigma which could attach to social work premises and appreciated offices which were planned and furnished to appear less institutional and more ‘normal’. Daily interactions with staff which conveyed a sense of recognition and value to service users also contributed to a view of some SWP offices as accessible and welcoming places. Both children and parents appreciated offices that provided fun activities that positioned them as active rather than passive. Staff valued opportunities for influencing planning decisions about offices and place was seen to confer a value on them as well as on service users. However, not all the SWPs were able to achieve these aspects of place, and engaging children and families in place was less likely when the service user population was widely dispersed. Recognising the importance of place and how place is constructed through relationships between people as well as through the physical environment appeared to be key to creating offices that combated the stigma attached to out-of-home care. Those leading and managing children’s services should explore ways of involving local communities in planning social work offices and turn attention to making these offices accessible, welcoming, places

Pulmonary Dysfunction in Patients with Femoral Shaft Fracture Treated with Intramedullary Nailing

Background: This study was undertaken to determine whether alveolar dead space increases during intramedullary nailing of femoral shaft fractures and whether alveolar dead space predicts postoperative pulmonary dysfunction in patients undergoing intramedullary nailing of a femoral shaft fracture. Methods: All patients with a femoral shaft fracture were prospectively enrolled in the study unless there was evidence of acute myocardial infarction, shock, or heart failure. Arterial blood gases were measured at three consecutive time-periods after induction of general anesthesia: before intramedullary nailing and ten and thirty minutes after intramedullary nailing. The end-tidal carbon-dioxide level, minute ventilation, positive end‐expiratory pressure, and percent of inspired and expired inhalation agent were recorded simultaneously with the blood-gas measurement. Postoperatively, all subjects were monitored for evidence of pulmonary dysfunction, defined as the need for mechanical ventilation or supplemental oxygen (at a fraction of inspired oxygen of >40%) in the presence of clinical signs of a respiratory rate of >20 breaths/min or the use of accessory muscles of respiration. Results: Seventy‐four patients with a total of eighty femoral shaft fractures completed the study. Fifty fractures (62.5%) underwent nailing after reaming, and thirty fractures (37.5%) underwent nailing with minimal or no reaming. The mean alveolar dead-space measurements before canal opening and at ten and thirty minutes after canal opening were 14.5%, 15.8%, and 15.2% in the total series of seventy‐four patients (general linear model, p = 0.2) and 20.5%, 22.7%, and 24.2% in the twenty patients with postoperative pulmonary dysfunction (general linear model, p = 0.05). Of the twenty‐one patients with an alveolar dead-space measurement of >20% thirty minutes after nailing, sixteen had postoperative pulmonary dysfunction. According to univariate and multivariate analysis, the alveolar dead-space measurement was strongly associated with postoperative pulmonary dysfunction. Conclusions: According to our data, intramedullary nailing of femoral shaft fractures did not significantly increase alveolar dead space, and the amount of alveolar dead space can predict which patients will have pulmonary dysfunction postoperatively

Dynamic of a non homogeneously coarse grained system

To study materials phenomena simultaneously at various length scales, descriptions in which matter can be coarse grained to arbitrary levels, are necessary. Attempts to do this in the static regime (i.e. zero temperature) have already been developed. In this letter, we present an approach that leads to a dynamics for such coarse-grained models. This allows us to obtain temperature-dependent and transport properties. Renormalization group theory is used to create new local potentials model between nodes, within the approximation of local thermodynamical equilibrium. Assuming that these potentials give an averaged description of node dynamics, we calculate thermal and mechanical properties. If this method can be sufficiently generalized it may form the basis of a Molecular Dynamics method with time and spatial coarse-graining.Comment: 4 pages, 4 figure

Elevated Rates of Sister Chromatid Exchange at Chromosome Ends

Chromosome ends are known hotspots of meiotic recombination and double-strand breaks. We monitored mitotic sister chromatid exchange (SCE) in telomeres and subtelomeres and found that 17% of all SCE occurs in the terminal 0.1% of the chromosome. Telomeres and subtelomeres are significantly enriched for SCEs, exhibiting rates of SCE per basepair that are at least 1,600 and 160 times greater, respectively, than elsewhere in the genome