MS-based clinical proteomics: biomarker discovery in men’s cancer

Importance of biomarker discovery in men’s cancer diagnosis and prognosis Each year around 10,000 men in the UK die as a result of prostate cancer (PCa) making it the 3rd most common cancer behind lung and breast cancer; worldwide more than 670,000 men are diagnosed every year with the disease [1]. Current methods of diagnosis of PCa mainly rely on the detection of elevated prostate-specific antigen (PSA) levels in serum and/or physical examination by a doctor for the detection of an abnormal prostate. PSA is a glycoprotein produced almost exclusively by the epithelial cells of the prostate gland [2]. Its role is not fully understood, although it is known that it forms part of the ejaculate and its function is to solubilise the sperm to give them the mobility to swim. Raised PSA levels in serum are thought to be due to both an increased production of PSA from the proliferated prostate cells, and a diminished architecture of affected cells, allowing an easier distribution of PSA into the wider circulatory system.

Adapting to climate change impacts on water resources in England - an assessment of draft Water Resources Management Plans

Climate change is expected to produce reductions in water availability in England, potentially necessitating adaptive action by the water industry to maintain supplies. As part of Ofwat's fifth Periodic Review (PR09), water companies recently released their draft Water Resources Management Plans, setting out how each company intends to maintain the balance between the supply and demand for water over the next 25 years, following Environment Agency guidelines. This paper reviews these plans to determine company estimates of the impact of climate change on water supply relative to other resource pressures. The approaches adopted for incorporating the impact in the plans and the proposed management solutions are also identified. Climate change impacts for individual resource zones range from no reductions in deployable output to greater than 50% over the planning period. The estimated national aggregated loss of deployable output under a “core” climate scenario is ~520 Ml/d (3% of deployable output) by 2034/35, the equivalent of the supply of one entire water company (South West Water). Climate change is the largest single driver of change in water supplies over the planning period. Over half of the climate change impact is concentrated in southern England. In extreme cases, climate change uncertainty is of the same magnitude as the change under the core scenario (up to a loss of ~475 Ml/d). 44 of the 68 resource zones with available data are estimated to have a climate change impact. In 35 of these climate change has the greatest impact although in 10 zones sustainability reductions have a greater impact. Of the overall change in downward pressure on the supply-demand balance over the planning period, ~56% is accounted for by increased demand (620 Ml/d) and supply side climate change accounts for ~37% (407 Ml/d). Climate change impacts have a cumulative impact in concert with other changing supply side reducing components increasing the national pressure on the supply-demand balance. Whilst the magnitude of climate change appears to justify its explicit consideration, it is rare that adaptation options are planned solely in response to climate change but as a suite of options to provide a resilient supply to a range of pressures (including significant demand side pressures). Supply-side measures still tend to be considered by water companies to be more reliable than demand-side measures.

Adapting to the effects of climate change on water supply reliability

This paper presents preliminary results from an assessment of the barriers to adaptation to water supply shortage in a case study catchment in south east England with multiple supply companies. The investigation applies a conceptual framework, which distinguishes between generic barriers affecting the ability of supply companies to make adaptation decisions, and specific barriers to the implementation of each option. The preliminary analysis suggests that whilst there is a widespread awareness of the challenge of climate change, and a conceptual understanding of the need for adaptation, some of the generic barriers that will affect detailed evaluations and actual adaptation decisions have yet to be approached. The analysis also shows that different individual adaptation options are assessed differently by different stakeholders, and that there are differences in the barriers to adoption between supply-side and demand-side measures. First, however, the paper develops the general conceptual framework for the characterisation of the barriers to adaptation used in the study.

The relationship between convection and sea surface temperature on intraseasonal timescales

The relationship between tropical convection, surface fluxes, and sea surface temperature (SST) on intraseasonal timescales has been examined as part of an investigation of the possibility that the intraseasonal oscillation is a coupled atmosphere–ocean phenomenon. The unique feature of this study is that 15 yr of data and the whole region from the Indian Ocean to the Pacific Ocean have been analyzed using lag-correlation analysis and compositing techniques. A coherent relationship between convection, surface fluxes, and SST has been found on intraseasonal timescales in the Indian Ocean, Maritime Continent, and west Pacific regions of the Tropics. Prior to the maximum in convection, there are positive shortwave and latent heat flux anomalies into the surface, followed by warm SST anomalies about 10 days before the convective maximum. Coincident with the convective maximum, there is a minimum in the shortwave flux, followed by a cooling due to increased evaporation associated with enhanced westerly wind stress, leading to negative SST anomalies about 10 days after the convection. The relationships are robust from year to year, including both phases of the El Niño–Southern Oscillation (ENSO) although the eastward extent of the region over which the relationship holds varies with the phase of ENSO, consistent with the variations in the eastward extent of the warm pool and westerly winds. The spatial scale of the anomalies is about 60° longitude, consistent with the scale of the intraseasonal oscillation. The spatial and temporal characteristics of the surface flux and SST perturbations are consistent with the surface flux variations forcing the ocean, and the magnitudes of the anomalies are consistent with mixed-layer depths appropriate to the Indian Ocean and west Pacific

Understanding construction competitiveness: the contribution of system dynamics

Purpose – Construction sector competitiveness has been a subject of interest for many years. Research too often focuses on the means of overcoming the “barriers to change” as if such barriers were static entities. There has been little attempt to understand the dynamic inter-relationship between the differing factors which impinge upon construction sector competitiveness. The purpose of this paper is to outline the benefits of taking a systems approach to construction competitiveness research. Design/methodology/approach – The system dynamics (SD) modelling methodology is described. This can provide practitioners with “microworlds” within which they can explore the dynamic effects of different policy decisions. The data underpinning the use of SD was provided by interviews and case study research which allowed an understanding of the context within which practitioners operate. Findings – The over-riding conclusion is that the SD methodology has been shown to be capable of providing a means to assess the forces which shape the sustained competitiveness of construction firms. As such, it takes the assessment of strategic policy analysis in the construction sector onto a higher plane. The need to collect data and make retrospective assessments of competitiveness and strategic performance at the statistical level is not now the only modus operandi available. Originality/value – The paper describes a novel research methodology which points towards an alternative research agenda for construction competitiveness research.

Design and development of a haptic dental training system - hapTEL

This paper presents a novel design of a virtual dental training system (hapTEL) using haptic technology. The system allows dental students to learn and practice procedures such as dental drilling, caries removal and cavity preparation for tooth restoration. This paper focuses on the hardware design, development and evaluation aspects in relation to the dental training and educational requirements. Detailed discussions on how the system offers dental students a natural operational position are documented. An innovative design of measuring and connecting the dental tools to the haptic device is also shown. Evaluation of the impact on teaching and learning is discussed.

Genome expansion and gene loss in powdery mildew fungi reveal tradeoffs in extreme parasitism

Powdery mildews are phytopathogens whose growth and reproduction are entirely dependent on living plant cells. The molecular basis of this life-style, obligate biotrophy, remains unknown. We present the genome analysis of barley powdery mildew, Blumeria graminis f.sp. hordei (Blumeria), as well as a comparison with the analysis of two powdery mildews pathogenic on dicotyledonous plants. These genomes display massive retrotransposon proliferation, genome-size expansion, and gene losses. The missing genes encode enzymes of primary and secondary metabolism, carbohydrate-active enzymes, and transporters, probably reflecting their redundancy in an exclusively biotrophic life-style. Among the 248 candidate effectors of pathogenesis identified in the Blumeria genome, very few (less than 10) define a core set conserved in all three mildews, suggesting thatmost effectors represent species-specific adaptations.

Activation of lower back muscles via FES for pressure sores prevention in paraplegia: a case study

The aim of this paper is to show the feasibility of the use of functional electrical stimulation (FES) applied to the lower back muscles for pressure sores prevention in paraplegia. The hypothesis under study is that FES induces a change in the pressure distribution on the contact area during sitting. Tests were conducted on a paraplegic subject (T5), sitting on a standard wheelchair and cushion. Trunk extensors (mainly the erector spinae) were stimulated using surface electrodes placed on the skin. A pressure mapping system was used to measure the pressure on the sitting surface in four situations: (a) no stimulation; (b) stimulation on one side of the spine only; (c) stimulation on both sides, at different levels; and (d) stimulation at the same level on both sides, during pressure-relief manoeuvres. A session of prolonged stimulation was also conducted. The experimental results show that the stimulation of the erector spinae on one side of the spine can induce a trunk rotation on the sagittal plane, which causes a change in the pressure distribution. A decrease of pressure on the side opposite to the stimulation was recorded. The phenomenon is intensified when different levels of stimulation are applied to the two sides, and such change can be sustained for a considerable time (around 5 minutes). The stimulation did not induce changes during pressure-relief manoeuvres. Finally, from this research we can conclude that the stimulation of the trunk extensors can be a useful tool for pressure sores prevention, and can potentially be used in a routine for pressure sores prevention based on periodical weight shifts.

Syntheses, structures, some reactions, and electrochemical oxidation of ferrocenylethynyl complexes of iron, ruthenium, and osmium

The syntheses and characterizations of several complexes containing ferrocenylethynyl and ferrocene-1,1'-bis(ethynyl) groups attached to M(PP)Cp'[M = Fe, Ru, PP = dppe, Cp'= Cp*; M = Ru, Os, PP = (PPh3)(2), dppe, Cp' = Cp] are described. Reactions with tetracyanoethene have given either tetracyanobuta-1,3-dienyl or eta(3)-allylic derivatives, while addition of Me+ afforded the corresponding vinylidene derivatives. Some electrochemical measurements are discussed in terms of electronic communication between the redox-active M(PP)Cp' groups through the ferrocene nucleus. The molecular structures of 14 of these complexes have been determined by crystallographic methods.

Baroclinic waves with parameterized effects of moisture interpreted using Rossby wave components

A theoretical framework is developed for the evolution of baroclinic waves with latent heat release parameterized in terms of vertical velocity. Both wave–conditional instability of the second kind (CISK) and large-scale rain approaches are included. The new quasigeostrophic framework covers evolution from general initial conditions on zonal flows with vertical shear, planetary vorticity gradient, a lower boundary, and a tropopause. The formulation is given completely in terms of potential vorticity, enabling the partition of perturbations into Rossby wave components, just as for the dry problem. Both modal and nonmodal development can be understood to a good approximation in terms of propagation and interaction between these components alone. The key change with moisture is that growing normal modes are described in terms of four counterpropagating Rossby wave (CRW) components rather than two. Moist CRWs exist above and below the maximum in latent heating, in addition to the upper- and lower-level CRWs of dry theory. Four classifications of baroclinic development are defined by quantifying the strength of interaction between the four components and identifying the dominant pairs, which range from essentially dry instability to instability in the limit of strong heating far from boundaries, with type-C cyclogenesis and diabatic Rossby waves being intermediate types. General initial conditions must also include passively advected residual PV, as in the dry problem.

The advection of high-resolution tracers by low-resolution winds

The usefulness of any simulation of atmospheric tracers using low-resolution winds relies on both the dominance of large spatial scales in the strain and time dependence that results in a cascade in tracer scales. Here, a quantitative study on the accuracy of such tracer studies is made using the contour advection technique. It is shown that, although contour stretching rates are very insensitive to the spatial truncation of the wind field, the displacement errors in filament position are sensitive. A knowledge of displacement characteristics is essential if Lagrangian simulations are to be used for the inference of airmass origin. A quantitative lower estimate is obtained for the tracer scale factor (TSF): the ratio of the smallest resolved scale in the advecting wind field to the smallest “trustworthy” scale in the tracer field. For a baroclinic wave life cycle the TSF = 6.1 ± 0.3 while for the Northern Hemisphere wintertime lower stratosphere the TSF = 5.5 ± 0.5, when using the most stringent definition of the trustworthy scale. The similarity in the TSF for the two flows is striking and an explanation is discussed in terms of the activity of potential vorticity (PV) filaments. Uncertainty in contour initialization is investigated for the stratospheric case. The effect of smoothing initial contours is to introduce a spinup time, after which wind field truncation errors take over from initialization errors (2–3 days). It is also shown that false detail from the proliferation of finescale filaments limits the useful lifetime of such contour advection simulations to 3σ−1 days, where σ is the filament thinning rate, unless filaments narrower than the trustworthy scale are removed by contour surgery. In addition, PV analysis error and diabatic effects are so strong that only PV filaments wider than 50 km are at all believable, even for very high-resolution winds. The minimum wind field resolution required to accurately simulate filaments down to the erosion scale in the stratosphere (given an initial contour) is estimated and the implications for the modeling of atmospheric chemistry are briefly discussed.

The restoration of phytophagous beetles in species-rich chalk grasslands

This study focuses on the restoration of chalk grasslands over a 6-year period and tests the efficacy of two management practices, hay spreading and soil disturbance, in promoting this process for phytophagous beetles. Restoration success for the beetles, measured as similarity to target species-rich chalk grassland, was not found to be influenced by either management practice. In contrast, restoration success for the plants did increase in response to hay spreading management. Although the presence of suitable host plants was considered to dictate the earliest point at which phytophagous beetles could successfully colonized, few beetle species colonized as soon as their host plants became established. Morphological characteristics and feeding habits of 27 phytophagous beetle species were therefore tested to identify factors that limited their colonization and persistence. The lag time between host plant establishment and colonization was greatest for flightless beetles. Beetles with foliage-feeding larvae both colonized at slower rates than seed-, stem-, or root-feeding species and persisted within the swards for shorter periods. Although the use of hay spreading may benefit plant communities during chalk grassland restoration, it did not directly benefit phytophagous beetles. Without techniques for overcoming colonization limitation for invertebrate taxa, short-term success of restoration may be limited to the plants only.