Cooling is hotting up in the UK

The cooling of buildings is currently responsible for about 20% of total electricity use worldwide. It is estimated that the electricity needed for cooling will more than triple by 2050. Despite this concerning outlook, little attention has been paid to cooling demand in policy and research in the United Kingdom (UK). The demand for space cooling in the UK’s domestic and non-domestic buildings is currently small—about 10% of total electricity use. However, this has the potential to increase as the climate warms and expectations of comfort grow. This paper reviews UK cooling demand and how this has been considered in energy policy. Following a thorough review of the existing literature using a cooling decarbonisation framework (Avoid, Improve and Shift), it is clear there is a limited understanding of the future UK cooling demand for domestic buildings in a warmer future as well as how policy makers and households should act. More importantly, this sector appears under-represented in the UK research and policy landscape compared to heating despite obvious technological crossovers associated with electrification. Several policy and research recommendations have been made based on these findings

Recent Advances in the Molecular Characterization of Circulating Tumor Cells

Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch((R)) system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs hold for oncology lies at the level of molecular characterization. Clinical treatment decisions may be more effective if they are based on molecular characteristics of metastatic cells rather than on those of the primary tumor alone. Molecular characterization of CTCs (which can be repeatedly isolated in a minimally invasive fashion) provides the opportunity for a. real-time liquid biopsy that allows assessment of genetic drift, investigation of molecular disease evolution, and identification of actionable genomic characteristics. This review focuses on recent advances in this area, including approaches involving immunophenotyping, fluorescence in situ hybridization (FISH), multiplex RT-PCR, microarray, and genomic sequencing

Exploring Body Mass Index Changes in Left Ventricular Assist Device Patients

Background: Current treatment options for end-stage heart failure, such as transplantation, can be limited by obesity guidelines. Mechanical devices such as Left Ventricular Assistive Devices (LVAD) can bridge heart failure patients to transplantation, however, after implantation; some patients may experience weight gain that precludes them from transplantation. Therefore, the objective of this study was to evaluate weight changes after the implantation of an LVAD. Methods: A retrospective review of 130 patients receiving an LVAD were divided into two groups based on BMI at the time of implantation: obese (\u3e30 kg/m2) and non-obese (/m2). Patients were evaluated at three time points post LVAD implantation: 3, 6, and 12 months for changes in weight and BMI. Results: The mean BMI of the overall cohort at the time of LVAD implantation was 30.3 kg/m2. Patients who were not classified as obese at the time of LVAD implementation had a significant increase in BMI (2.1 kg/m2, p\u3c0.001) Conclusion: Weight gain after LVAD implementation is more likely in patients who are non-obese at the time of LVAD evaluation; however, obese subjects remained unlikely to lose weight one year post implantation

Circulating Tumor Cell Analysis in Preclinical Mouse Models of Metastasis

The majority of cancer deaths occur because of metastasis since current therapies are largely non-curative in the metastatic setting. The use of in vivo preclinical mouse models for assessing metastasis is, therefore, critical for developing effective new cancer biomarkers and therapies. Although a number of quantitative tools have been previously developed to study in vivo metastasis, the detection and quantification of rare metastatic events has remained challenging. This review will discuss the use of circulating tumor cell (CTC) analysis as an effective means of tracking and characterizing metastatic disease progression in preclinical mouse models of breast and prostate cancer and the resulting lessons learned about CTC and metastasis biology. We will also discuss how the use of clinically-relevant CTC technologies such as the CellSearch((R)) and Parsortix platforms for preclinical CTC studies can serve to enhance the study of cancer biology, new biomarkers, and novel therapies from the bench to the bedside

Adaptation of Semiautomated Circulating Tumor Cell (CTC) Assays for Clinical and Preclinical Research Applications

The majority of cancer-related deaths occur subsequent to the development of metastatic disease. This highly lethal disease stage is associated with the presence of circulating tumor cells (CTCs). These rare cells have been demonstrated to be of clinical significance in metastatic breast, prostate, and colorectal cancers. The current gold standard in clinical CTC detection and enumeration is the FDA-cleared CellSearch system (CSS). This manuscript outlines the standard protocol utilized by this platform as well as two additional adapted protocols that describe the detailed process of user-defined marker optimization for protein characterization of patient CTCs and a comparable protocol for CTC capture in very low volumes of blood, using standard CSS reagents, for studying in vivo preclinical mouse models of metastasis. In addition, differences in CTC quality between healthy donor blood spiked with cells from tissue culture versus patient blood samples are highlighted. Finally, several commonly discrepant items that can lead to CTC misclassification errors are outlined. Taken together, these protocols will provide a useful resource for users of this platform interested in preclinical and clinical research pertaining to metastasis and CTCs

The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat

The effect of Pgp induction in rats by pregnenolone 16α-carbonitrile (PCN) (3 days, 35 mg/kg/d, p.o.) on digoxin pharmacokinetics and intestinal transport has been assessed. After intravenous or oral digoxin dosing the arterial and hepatic portal vein (oral) AUC(0-24h) were significantly reduced by PCN pre-treatment. Biliary digoxin clearance increased 2-fold following PCN treatment. PCN significantly increased net digoxin secretion (2.05- and 4.5-fold respectively) in ileum and colon but not in duodenum or jejunum. This increased secretion correlated with increased Pgp protein expression in ileum and colon. Both intestinal and biliary excretion therefore contribute to altered digoxin disposition following PCN

Differential Effects of MitoVitE, α-Tocopherol and Trolox on Oxidative Stress, Mitochondrial Function and Inflammatory Signalling Pathways in Endothelial Cells Cultured under Conditions Mimicking Sepsis

Funding: This research was funded by The British Journal of Anaesthesia/Royal College of Anaesthetists (PhD studentship to Beverley Minter). Acknowledgments: We are very grateful to Professor M.P. Murphy, MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge, UK for the generous gift of MitoVitE used in all the experiments, without which this work would not have been possible.Peer reviewedPublisher PD

Impact of Bi-directional Loading on the Seismic Performance of C-shaped Piers of Core Walls

Reinforced concrete structural walls are commonly used as the primary lateral load resisting system in modern buildings constructed in high seismic regions. Most walls in high-rise buildings are C-shaped to accommodate elevators or other architectural features. C-shaped walls have complex loading and response including: (1) symmetric response in the direction of the web, (2) asymmetric response in the direction of the flange and (3) high compression and shear demands when used as a pier in a coupled-wall configuration. A research study was conducted on C-shaped walls tested under (1) uni-directional and (2) bi-directional loading of an isolated walls and (3) bi-directional loading of a c-shaped pier in a coupled wall system. Each of the walls failed in flexure with strength loss resulting from low-cycle fatigue of the boundary element longitudinal reinforcement with buckling followed by fracture. The damage progression was as follows: (1) cracking at the wall-foundation interface, (2) concrete spalling in the web, (3) buckling and fracture of web reinforcement, (4) spalling in the flanges, (5) buckling and fracture of the bars in the boundary elements. Concrete spalling and steel bar damage occurred at lower strong-axis drift levels for the bi-directionally loaded, resulting in lower drift capacities for these loading protocols. However, for the strong-axis direction, bi-directional loading does not reduce flexural or shear effective stiffness values suggesting that current values are appropriate for design and evaluation of buildings with c-shaped walls

Epithelial-to-mesenchymal transition leads to disease-stage differences in circulating tumor cell detection and metastasis in pre-clinical models of prostate cancer

Metastasis is the cause of most prostate cancer (PCa) deaths and has been associated with circulating tumor cells (CTCs). The presence of \u3e= 5 CTCs/7.5mL of blood is a poor prognosis indicator in metastatic PCa when assessed by the CellSearch (R) system, the gold standard clinical platform. However, similar to 35% of metastatic PCa patients assessed by CellSearch (R) have undetectable CTCs. We hypothesize that this is due to epithelial-to-mesenchymal transition (EMT) and subsequent loss of necessary CTC detection markers, with important implications for PCa metastasis. Two pre-clinical assays were developed to assess human CTCs in xenograft models; one comparable to CellSearch (R) (EpCAM-based) and one detecting CTCs semi-independent of EMT status via combined staining with EpCAM/HLA (human leukocyte antigen). In vivo differences in CTC generation, kinetics, metastasis and EMT status were determined using 4 PCa models with progressive epithelial (LNCaP, LNCaP-C42B) to mesenchymal (PC-3, PC-3M) phenotypes. Assay validation demonstrated that the CellSearch (R)-based assay failed to detect a significant number (similar to 40-50%) of mesenchymal CTCs. In vivo, PCa with an increasingly mesenchymal phenotype shed greater numbers of CTCs more quickly and with greater metastatic capacity than PCa with an epithelial phenotype. Notably, the CellSearch (R)-based assay captured the majority of CTCs shed during early-stage disease in vivo, and only after establishment of metastases were a significant number of undetectable CTCs present. This study provides important insight into the influence of EMT on CTC generation and subsequent metastasis, and highlights that novel technologies aimed at capturing mesenchymal CTCs may only be useful in the setting of advanced metastatic disease

Western Province: text summaries, maps, code lists and village identification

The major purpose of the Papua New Guinea Agricultural Systems Project is to produce information on small holder (subsistence) agriculture at provincial and national levels (Allen et al 1995). Information was collected by field observation, interviews with villagers and reference to published and unpublished documents. Methods are described by Bourke et al. (1993). This Working Paper contains a written summary of the information on the Agricultural Systems in this Province, maps of the location of agriculture systems, a complete listing of all information in the database in coded form, and lists of villages with National Population Census codes, indexed by agricultural systems. This information is available as a map-linked database (GIS) suitable for use on a personal computer in ESRI and MapInfo formats. An Agricultural System is identified when a set of similar agricultural crops and practices occur within a defined area. Six criteria are used to distinguish one system from another: 1. Fallow type (the vegetation which is cleared from a garden site before cultivation). 2. Fallow period (the length of time a garden site is left unused between cultivations). 3. Cultivation intensity (the number of consecutive crops planted before fallow). 4. The staple, or most important, crops. 5. Garden and crop segregation (the extent to which crops are planted in separate gardens; in separate areas within a garden; or are planted sequentially). 6. Soil fertility maintenance techniques (other than natural regrowth fallows). Where one or more of these factors differs significantly and the differences can be mapped, then a separate system is distinguished. Where variation occurs, but is not able to be mapped at 1:500 000 scale because the areas in which the variation occurs are too small or are widely dispersed within the larger system, a subsystem is identified. Subsystems within an Agricultural System are allocated a separate record in the database, identified by the Agricultural System number and a subsystem number. Sago is a widespread staple food in lowland Papua New Guinea. Sago is produced from palms which are not grown in gardens. Most of the criteria above cannot be applied. In this case, systems are differentiated on the basis of the staple crops only. The Papua New Guinea Resource Information System (PNGRIS) is a GIS which contains information on the natural resources of PNG (Bellamy 1986). PNGRIS contains no information on agricultural practices, other than an assessment of land use intensity based on air photograph interpretation by Saunders (1993. The Agricultural Systems Project is designed to provide detailed information on agricultural practices and cropping patterns as part of an upgraded PNGRIS geographical information system. For this reason the Agricultural Systems database contains almost no information on the environmental settings of the systems, except for altitude and slope. The layout of the text descriptions, the database code files and the village lists are similar to PNGRIS formats (Cuddy 1987). The mapping of Agricultural Systems has been carried out on the same map base and scale as PNGRIS (Tactical Pilotage Charts, 1:500 000). Agricultural Systems were mapped within the areas of agricultural land use established by Saunders (1993) from aerial photography. Except where specifically noted, Agricultural Systems boundaries have been mapped without reference to PNGRIS Resource Mapping Unit (RMU) boundaries. Agricultural Systems are defined at the level of the Province (following PNGRIS) but their wider distribution is recognised in the database by cross-referencing systems which cross provincial borders. A preliminary view of the relationships between PNGRIS RMUs and the Agricultural Systems in this Province can be obtained from the listing of villages by Agricultural System, where RMU numbers are appended. Allen, B. J., R. M. Bourke and R. L. Hide 1995. The sustainability of Papua New Guinea agricultural systems: the conceptual background. Global Environmental Change 5(4): 297-312. Bourke, R. M., R. L. Hide, B. J. Allen, R. Grau, G. S. Humphreys and H. C. Brookfield 1993. Mapping agricultural systems in Papua New Guinea. Population Family Health and Development. T. Taufa and C. Bass. University of Papua New Guinea Press, Port Moresby: 205-224. Bellamy, J. A. and J. R. McAlpine 1995. Papua New Guinea Inventory of Natural Resources, Population Distribution and Land Use Handbook. Commonwealth Scientific and Industrial Research Organisation for the Australian Agency for International Development. PNGRIS Publication No. 6, Canberra. Cuddy, S. M. 1987. Papua New Guinea Inventory of Natural Resources, Population Distribution and Land Use: Code Files Part 1 Natural Resources. Division of Water and Land Resources, Commonwealth Scientific and Industrial Research Organisation and Land Utilization Section, Department of Primary Industry, Papua New Guinea, Canberra