A phase 1 trial dose-escalation study of tipifarnib on a week-on, week-off schedule in relapsed, refractory or high-risk myeloid leukemia.

Inhibition of farnesyltransferase (FT) activity has been associated with in vitro and in vivo anti-leukemia activity. We report the results of a phase 1 dose-escalation study of tipifarnib, an oral FT inhibitor, in patients with relapsed, refractory or newly diagnosed (if over age 70) acute myelogenous leukemia (AML), on a week-on, week-off schedule. Forty-four patients were enrolled, two patients were newly diagnosed, and the rest were relapsed or refractory to previous treatment, with a median age of 61 (range 33-79). The maximum tolerated dose was determined to be 1200 mg given orally twice daily (b.i.d.) on this schedule. Cycle 1 dose-limiting toxicities were hepatic and renal. There were three complete remissions seen, two at the 1200 mg b.i.d. dose and one at the 1000 mg b.i.d. dose, with minor responses seen at the 1400 mg b.i.d. dose level. Pharmacokinetic studies performed at doses of 1400 mg b.i.d. showed linear behavior with minimal accumulation between days 1-5. Tipifarnib administered on a week-on, week-off schedule shows activity at higher doses, and represents an option for future clinical trials in AML

Estimating instantaneous sea-ice dynamics from space using the bi-static radar measurements of Earth Explorer 10 candidate Harmony

This article describes the observation techniques and suggests processing methods to estimate dynamical sea-ice parameters from data of the Earth Explorer 10 candidate Harmony. The two Harmony satellites will fly in a reconfigurable formation with Sentinel-1D. Both will be equipped with a multi-angle thermal infrared sensor and a passive radar receiver, which receives the reflected Sentinel-1D signals using two antennas. During the lifetime of the mission, two different formations will be flown. In the stereo formation, the Harmony satellites will fly approximately 300 km in front and behind Sentinel-1, which allows for the estimation of instantaneous sea-ice drift vectors. We demonstrate that the addition of instantaneous sea-ice drift estimates on top of the daily integrated values from feature tracking have benefits in terms of interpretation, sampling and resolution. The wide-swath instantaneous drift observations of Harmony also help to put high-temporal-resolution instantaneous buoy observations into a spatial context. Additionally, it allows for the extraction of deformation parameters, such as shear and divergence. As a result, Harmony's data will help to improve sea-ice statistics and parametrizations to constrain sea-ice models. In the cross-track interferometry (XTI) mode, Harmony's satellites will fly in close formation with an XTI baseline to be able to estimate surface elevations. This will allow for improved estimates of sea-ice volume and also enables the retrieval of full, two-dimensional swell-wave spectra in sea-ice-covered regions without any gaps. In stereo formation, the line-of-sight diversity allows the inference of swell properties in both directions using traditional velocity bunching approaches. In XTI mode, Harmony's phase differences are only sensitive to the ground-range direction swell. To fully recover two-dimensional swell-wave spectra, a synergy between XTI height spectra and intensity spectra is required. If selected, the Harmony mission will be launched in 2028

Equal Graph Partitioning on Estimated Infection Network as an Effective Epidemic Mitigation Measure

Controlling severe outbreaks remains the most important problem in infectious disease area. With time, this problem will only become more severe as population density in urban centers grows. Social interactions play a very important role in determining how infectious diseases spread, and organization of people along social lines gives rise to non-spatial networks in which the infections spread. Infection networks are different for diseases with different transmission modes, but are likely to be identical or highly similar for diseases that spread the same way. Hence, infection networks estimated from common infections can be useful to contain epidemics of a more severe disease with the same transmission mode. Here we present a proof-of-concept study demonstrating the effectiveness of epidemic mitigation based on such estimated infection networks. We first generate artificial social networks of different sizes and average degrees, but with roughly the same clustering characteristic. We then start SIR epidemics on these networks, censor the simulated incidences, and use them to reconstruct the infection network. We then efficiently fragment the estimated network by removing the smallest number of nodes identified by a graph partitioning algorithm. Finally, we demonstrate the effectiveness of this targeted strategy, by comparing it against traditional untargeted strategies, in slowing down and reducing the size of advancing epidemics

Cloaked Facebook pages: Exploring fake Islamist propaganda in social media

This research analyses cloaked Facebook pages that are created to spread political propaganda by cloaking a user profile and imitating the identity of a political opponent in order to spark hateful and aggressive reactions. This inquiry is pursued through a multi-sited online ethnographic case study of Danish Facebook pages disguised as radical Islamist pages, which provoked racist and anti-Muslim reactions as well as negative sentiments towards refugees and immigrants in Denmark in general. Drawing on Jessie Daniels’ critical insights into cloaked websites, this research furthermore analyses the epistemological, methodological and conceptual challenges of online propaganda. It enhances our understanding of disinformation and propaganda in an increasingly interactive social media environment and contributes to a critical inquiry into social media and subversive politics

The combined diabetes and renal control trial (C-DIRECT) - a feasibility randomised controlled trial to evaluate outcomes in multi-morbid patients with diabetes and on dialysis using a mixed methods approach

Background: This cluster randomised controlled trial set out to investigate the feasibility and acceptability of the “Combined Diabetes and Renal Control Trial” (C-DIRECT) intervention, a nurse-led intervention based on motivational interviewing and self-management in patients with coexisting end stage renal diseases and diabetes mellitus (DM ESRD). Its efficacy to improve glycaemic control, as well as psychosocial and self-care outcomes were also evaluated as secondary outcomes. Methods: An assessor-blinded, clustered randomised-controlled trial was conducted with 44 haemodialysis patients with DM ESRD and ≥ 8% glycated haemoglobin (HbA1c), in dialysis centres across Singapore. Patients were randomised according to dialysis shifts. 20 patients were assigned to intervention and 24 were in usual care. The C-DIRECT intervention consisted of three weekly chair-side sessions delivered by diabetes specialist nurses. Data on recruitment, randomisation, and retention, and secondary outcomes such as clinical endpoints, emotional distress, adherence, and self-management skills measures were obtained at baseline and at 12 weeks follow-up. A qualitative evaluation using interviews was conducted at the end of the trial. Results: Of the 44 recruited at baseline, 42 patients were evaluated at follow-up. One patient died, and one discontinued the study due to deteriorating health. Recruitment, retention, and acceptability rates of C-DIRECT were generally satisfactory HbA1c levels decreased in both groups, but C-DIRECT had more participants with HbA1c < 8% at follow up compared to usual care. Significant improvements in role limitations due to physical health were noted for C-DIRECT whereas levels remained stable in usual care. No statistically significant differences between groups were observed for other clinical markers and other patient-reported outcomes. There were no adverse effects. Conclusions: The trial demonstrated satisfactory feasibility. A brief intervention delivered on bedside as part of routine dialysis care showed some benefits in glycaemic control and on QOL domain compared with usual care, although no effect was observed in other secondary outcomes. Further research is needed to design and assess interventions to promote diabetes self-management in socially vulnerable patients

Why Are Male Social Relationships Complex in the Doubtful Sound Bottlenose Dolphin Population?

Copyright 2008 Elsevier B.V., All rights reserved.Peer reviewedPublisher PD

Prevalence of Malaria and Anaemia among HIV Infected Pregnant women Receiving Co-trimoxazole Prophylaxis in Tanzania: A Cross Sectional Study in Kinondoni Municipality.

HIV-infected pregnant women are particularly more susceptible to the deleterious effects of malaria infection particularly anaemia. In order to prevent opportunistic infections and malaria, a policy of daily co-trimoxazole prophylaxis without the standard Suphadoxine-Pyrimethamine intermittent preventive treatment (SP-IPT) was introduced to all HIV infected pregnant women in the year 2011. However, there is limited information about the effectiveness of this policy. This was a cross sectional study conducted among HIV-infected pregnant women receiving co-trimoxazole prophylaxis in eight public health facilities in Kinondoni Municipality from February to April 2013. Blood was tested for malaria infection and anaemia (haemoglobin <11 g/dl). Data were collected on the adherence to co-trimoxazole prophylaxis and other risk factors for malaria infection and anaemia. Pearson chi-square test, Fischer's exact test and multivariate logistic regression were used in the statistical analysis. This study enrolled 420 HIV infected pregnant women. The prevalence of malaria infection was 4.5%, while that of anaemia was 54%. The proportion of subjects with poor adherence to co-trimoxazole was 50.5%. As compared to HIV infected pregnant women with good adherence to co-trimoxazole prophylaxis, the poor adherents were more likely to have a malaria infection (Adjusted Odds Ratio, AOR = 6.81, 95%CI = 1.35-34.43, P = 0.02) or anaemia (AOR = 1.75, 95%CI = 1.03-2.98, P = 0.039). Other risk factors associated with anaemia were advanced WHO clinical stages, current malaria infection and history of episodes of malaria illness during the index pregnancy. The prevalence of malaria was low; however, a significant proportion of subjects had anaemia. Good adherence to co-trimoxazole prophylaxis was associated with reduction of both malaria infection and anaemia among HIV infected pregnant women

A Rapid Assessment of the Quality of Neonatal Healthcare in Kilimanjaro Region, Northeast Tanzania.

While child mortality is declining in Africa there has been no evidence of a comparable reduction in neonatal mortality. The quality of inpatient neonatal care is likely a contributing factor but data from resource limited settings are few. The objective of this study was to assess the quality of neonatal care in the district hospitals of the Kilimanjaro region of Tanzania. Clinical records were reviewed for ill or premature neonates admitted to 13 inpatient health facilities in the Kilimanjaro region; staffing and equipment levels were also assessed. Among the 82 neonates reviewed, key health information was missing from a substantial proportion of records: on maternal antenatal cards, blood group was recorded for 52 (63.4%) mothers, Rhesus (Rh) factor for 39 (47.6%), VDRL for 59 (71.9%) and HIV status for 77 (93.1%). From neonatal clinical records, heart rate was recorded for3 (3.7%) neonates, respiratory rate in 14, (17.1%) and temperature in 33 (40.2%). None of 13 facilities had a functioning premature unit despite calculated gestational age <36 weeks in 45.6% of evaluated neonates. Intravenous fluids and oxygen were available in 9 out of 13 of facilities, while antibiotics and essential basic equipment were available in more than two thirds. Medication dosing errors were common; under-dosage for ampicillin, gentamicin and cloxacillin was found in 44.0%, 37.9% and 50% of cases, respectively, while over-dosage was found in 20.0%, 24.2% and 19.9%, respectively. Physician or assistant physician staffing levels by the WHO indicator levels (WISN) were generally low. Key aspects of neonatal care were found to be poorly documented or incorrectly implemented in this appraisal of neonatal care in Kilimanjaro. Efforts towards quality assurance and enhanced motivation of staff may improve outcomes for this vulnerable group

REDSHIFT MEASUREMENT and SPECTRAL CLASSIFICATION for eBOSS GALAXIES with the REDMONSTER SOFTWARE

We describe the redmonster automated redshift measurement and spectral classification software designed for the extended Baryon Oscillation Spectroscopic Survey (eBOSS) of the Sloan Digital Sky Survey IV (SDSS-IV). We describe the algorithms, the template standard and requirements, and the newly developed galaxy templates to be used on eBOSS spectra. We present results from testing on early data from eBOSS, where we have found a 90.5% automated redshift and spectral classification success rate for the luminous red galaxy sample (redshifts 0.6 ≲ z ≲ 1.0). The redmonster performance meets the eBOSS cosmology requirements for redshift classification and catastrophic failures and represents a significant improvement over the previous pipeline. We describe the empirical processes used to determine the optimum number of additive polynomial terms in our models and an acceptable δX2rthreshold for declaring statistical confidence. Statistical errors on redshift measurement due to photon shot noise are assessed, and we find typical values of a few tens of km s-1. An investigation of redshift differences in repeat observations scaled by error estimates yields a distribution with a Gaussian mean and standard deviation of μ ∼ 0.01 and σ ∼ 0.65, respectively, suggesting the reported statistical redshift uncertainties are over-estimated by ∼54%. We assess the effects of object magnitude, signal-to-noise ratio, fiber number, and fiber head location on the pipeline's redshift success rate. Finally, we describe directions of ongoing development

Astrocytic Ion Dynamics: Implications for Potassium Buffering and Liquid Flow

We review modeling of astrocyte ion dynamics with a specific focus on the implications of so-called spatial potassium buffering, where excess potassium in the extracellular space (ECS) is transported away to prevent pathological neural spiking. The recently introduced Kirchoff-Nernst-Planck (KNP) scheme for modeling ion dynamics in astrocytes (and brain tissue in general) is outlined and used to study such spatial buffering. We next describe how the ion dynamics of astrocytes may regulate microscopic liquid flow by osmotic effects and how such microscopic flow can be linked to whole-brain macroscopic flow. We thus include the key elements in a putative multiscale theory with astrocytes linking neural activity on a microscopic scale to macroscopic fluid flow.Comment: 27 pages, 7 figure