Results from a Phase 1 Study of Sodium Selenite in Combination with Palliative Radiation Therapy in Patients with Metastatic Cancer.

In preclinical studies, selenite had single agent activity and radiosensitized tumors in vivo. Here we report results from a Phase 1 trial in 15 patients with metastatic cancer treated with selenite (5.5 to 49.5 mg) orally as a single dose 2 hours before each radiation therapy (RT) treatment. Patients received RT regimens that were standard of care. The primary objective of the study was to assess the safety of this combination therapy. Secondary objectives included measurement of pharmacokinetics (PK) and evaluation of efficacy. Endpoints included assessment of PK, toxicity, tumor response, and pain before and after treatment. The half-life of selenite was 18.5 hours. There were no adverse events attributable to selenite until the 33 mg dose level, at which the primary toxicities were grade 1 GI side effects. One patient treated with 49.5 mg had grade 2 GI toxicity. Although this was not a DLT, it was felt that the highest acceptable dose in this patient population was 33 mg. Most patients had stabilization of disease within the RT fields, with some demonstrating objective evidence of tumor regression. Most patients had a marked improvement in pain and seven out of nine patients with prostate cancer had a decrease in PSA ranging from 11-78%. Doses up to 33 mg selenite were well tolerated in combination with RT. A randomized, well controlled study is needed at the 33 mg dose level to determine if selenite results in clinically meaningful improvements in the response to palliative RT

Estimating rainfall and water balance over the Okavango River Basin for hydrological applications

A historical database for use in rainfall-runoff modeling of the Okavango River Basin in Southwest Africa is presented. The work has relevance for similar data-sparse regions. The parameters of main concern are rainfall and catchment water balance which are key variables for subsequent studies of the hydrological impacts of development and climate change. Rainfall estimates are based on a combination of in-situ gauges and satellite sources. Rain gauge measurements are most extensive from 1955 to 1972, after which they are drastically reduced due to the Angolan civil war. The sensitivity of the rainfall fields to spatial interpolation techniques and the density of gauges was evaluated. Satellite based rainfall estimates for the basin are developed for the period from 1991 onwards, based on the Tropical Rainfall Measuring Mission (TRMM) and Special Sensor Microwave Imager (SSM/I) data sets. The consistency between the gauges and satellite estimates was considered. A methodology was developed to allow calibration of the rainfall-runoff hydrological model against rain gauge data from 1960-1972, with the prerequisite that the model should be driven by satellite derived rainfall products for the 1990s onwards. With the rain gauge data, addition of a single rainfall station (Longa) in regions where stations earlier were lacking was more important than the chosen interpolation method. Comparison of satellite and gauge rainfall outside the basin indicated that the satellite overestimates rainfall by 20%. A non-linear correction was derived used by fitting the rainfall frequency characteristics to those of the historical rainfall data. This satellite rainfall dataset was found satisfactory when using the Pitman rainfall-runoff model (Hughes et al., this issue). Intensive monitoring in the region is recommended to increase accuracy of the comprehensive satellite rainfall estimate calibration procedur

Attitudes to a male contraceptive pill in a group of contraceptive users in the UK

BACKGROUND. Small scale trials of male hormonal contraception have produced encouraging results. Attitudes to and beliefs about a proposed male pill may affect uptake. METHODS. This paper examines attitudes towards a proposed ‘male contraceptive pill’ among a self selected sample of 54 men and 134 women, living in a non-metropolitan centre in the East of England, United Kingdom who were already users of contraception. Thirty four respondents were also interviewed and their views on the male pill were qualitatively analysed. RESULTS. The acceptability of a male pill was high with just under half (49.5%) of respondents indicating that they would use it. Gender, length of relationship, age and educational achievement did not affect the reported acceptability. 42% of respondents expressed concerns that men would forget to take a male pill. Women were significantly more likely to express this concern than men. 26% of respondents expressed health concerns. Willingness to take a male pill was associated with expressing the view that increased protection against pregnancy would be an advantage of such a method. Those unwilling or undecided were more likely to express concerns about the effect of a pill on future fertility. CONCLUSIONS. A male pill was accepted as a potential aid to increased fertility control by a large proportion of a convenience sample of contraceptive users in the East of England. If a male pill were to be marketed in the UK this study suggests that concerns about effects on future fertility and health risks may need to be addressed

Emergence of Hemagglutinin Mutations during the Course of Influenza Infection

Influenza remains a significant cause of disease mortality. The ongoing threat of influenza infection is partly attributable to the emergence of new mutations in the influenza genome. Among the influenza viral gene products, the hemagglutinin (HA) glycoprotein plays a critical role in influenza pathogenesis, is the target for vaccines and accumulates new mutations that may alter the efficacy of immunization. To study the emergence of HA mutations during the course of infection, we employed a deep-targeted sequencing method. We used samples from 17 patients with active H1N1 or H3N2 influenza infections. These patients were not treated with antivirals. In addition, we had samples from five patients who were analyzed longitudinally. Thus, we determined the quantitative changes in the fractional representation of HA mutations during the course of infection. Across individuals in the study, a series of novel HA mutations directly altered the HA coding sequence were identified. Serial viral sampling revealed HA mutations that either were stable, expanded or were reduced in representation during the course of the infection. Overall, we demonstrated the emergence of unique mutations specific to an infected individual and temporal genetic variation during infection

Chapter Globally Optimised Energy-Efficient Data Centres

A great deal of energy in Information and Communication Technology (ICT) systems can be wasted by software, regardless of how energy-efficient the underlying hardware is. To avoid such waste, programmers need to understand the energy consumption of programs during the development process rather than waiting to measure energy after deployment. Such understanding is hindered by the large conceptual gap from hardware, where energy is consumed, to high-level languages and programming abstractions. The approaches described in this chapter involve two main topics: energy modelling and energy analysis. The purpose of modelling is to attribute energy values to programming constructs, whether at the level of machine instructions, intermediate code or source code. Energy analysis involves inferring the energy consumption of a program from the program semantics along with an energy model. Finally, the chapter discusses how energy analysis and modelling techniques can be incorporated in software engineering tools, including existing compilers, to assist the energy-aware programmer to optimise the energy consumption of code

University Chorale and Women\u27s Choir with Cantori, Creekview High School, Spring Shall Bloom

KSU School of Music presents University Chorale and Women\u27s Choir with Cantori, Creekview High School, Spring Shall Bloom.https://digitalcommons.kennesaw.edu/musicprograms/1215/thumbnail.jp

Globally Optimised Energy-Efficient Data Centres

Data centres are part of today\u27s critical information and communication infrastructure, and the majority of business transactions as well as much of our digital life now depend on them. At the same time, data centres are large primary energy consumers, with energy consumed by IT and server room air conditioning equipment and also by general building facilities. In many data centres, IT equipment energy and cooling energy requirements are not always coordinated, so energy consumption is not optimised. Most data centres lack an integrated energy management system that jointly optimises and controls all its energy consuming equipments in order to reduce energy consumption and increase the usage of local renewable energy sources. In this chapter, the authors discuss the challenges of coordinated energy management in data centres and present a novel scalable, integrated energy management system architecture for data centre wide optimisation. A prototype of the system has been implemented, including joint workload and thermal management algorithms. The control algorithms are evaluated in an accurate simulation‐based model of a real data centre. Results show significant energy savings potential, in some cases up to 40%, by integrating workload and thermal management

Phenotypic plasticity in normal breast derived epithelial cells

Background Normal, healthy human breast tissue from a variety of volunteer donors has become available for research thanks to the establishment of the Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center (KTB). Multiple epithelial (K-HME) and stromal cells (K-HMS) were established from the donated tissue. Explant culture was utilized to isolate the cells from pieces of breast tissue. Selective media and trypsinization were employed to select either epithelial cells or stromal cells. The primary, non-transformed epithelial cells, the focus of this study, were characterized by immunohistochemistry, flow cytometry, and in vitro cell culture. Results All of the primary, non-transformed epithelial cells tested have the ability to differentiate in vitro into a variety of cell types when plated in or on biologic matrices. Cells identified include stratified squamous epithelial, osteoclasts, chondrocytes, adipocytes, neural progenitors/neurons, immature muscle and melanocytes. The cells also express markers of embryonic stem cells. Conclusions The cell culture conditions employed select an epithelial cell that is pluri/multipotent. The plasticity of the epithelial cells developed mimics that seen in metaplastic carcinoma of the breast (MCB), a subtype of triple negative breast cancer; and may provide clues to the origin of this particularly aggressive type of breast cancer. The KTB is a unique biorepository, and the normal breast epithelial cells isolated from donated tissue have significant potential as new research tools