Comparing a discrete and continuum model of the intestinal crypt

The integration of processes at different scales is a key problem in the modelling of cell populations. Owing to increased computational resources and the accumulation of data at the cellular and subcellular scales, the use of discrete, cell-level models, which are typically solved using numerical simulations, has become prominent. One of the merits of this approach is that important biological factors, such as cell heterogeneity and noise, can be easily incorporated. However, it can be difficult to efficiently draw generalizations from the simulation results, as, often, many simulation runs are required to investigate model behaviour in typically large parameter spaces. In some cases, discrete cell-level models can be coarse-grained, yielding continuum models whose analysis can lead to the development of insight into the underlying simulations. In this paper we apply such an approach to the case of a discrete model of cell dynamics in the intestinal crypt. An analysis of the resulting continuum model demonstrates that there is a limited region of parameter space within which steady-state (and hence biologically realistic) solutions exist. Continuum model predictions show good agreement with corresponding results from the underlying simulations and experimental data taken from murine intestinal crypts.

Evidence-based psychological therapies: from bench to bedside

Patients with mental health difficulties do not always receive appropriate and recommended psychological treatment for their difficulties, and clinicians are not always appropriately trained to deliver them. This paper considers why this might be the case and provides an overview of the Charlie Waller Institute, a not-for-profit organisation funded by the NHS, University of Reading, and the Charlie Waller Memorial Trust. The Institute seeks to address this problem by training clinicians in wide variety of evidence-based therapies and assessing the impact of this training on clinician knowledge and skill.

Therapeutic and cytotoxic effects of the novel antipsoriasis codrug, naproxyl-dithranol, on HaCaT cells

A novel topical codrug, naproxyl–dithranol (Nap-DTH), in which dithranol and naproxen are linked via an ester in a 1:1 ratio to form a single chemical entity, was synthesized. The antiproliferative, anti-inflammatory and toxic effects of Nap-DTH were assessed, at the cellular level, using various in vitro methods. Cultured HaCaT keratinocytes were treated with Nap-DTH, and the cellular effects were compared with those of the parent compounds, individually and as a 1:1 mixture of naproxen:dithranol to mimic 1:1 in situ liberation from Nap-DTH. The results demonstrate that Nap-DTH did not modify proliferation and only exhibited slight toxic effects after 24 h at concentrations >21 μM. At a lower concentration (3.4 μM), Nap-DTH did not alter cell proliferation or inflammation, which suggests that the codrug is therapeutically inert. Relating to this, the 1:1 mixture of naproxen:dithranol exhibited the lowest toxic effect and the highest antiproliferative effect on HaCaT keratinocytes compared to dithranol at the same concentration. Moreover, the 1:1 mixture exhibited a reduced inflammatory effect compared to dithranol alone, as reflected by the upregulation of cyclooxygenase-2 by 45% and 136%, respectively. In spite of the 1:1 mixture showing a greater downregulation of Ki-67 and a 2-fold reduction of proliferating cell nuclear antigen (both cellular markers of proliferation) than dithranol, dithranol showed a much greater induction of cleaved caspase-3 protein expression (upregulated by 287%, compared to 85% for the 1:1 mixture). This suggests that when dithranol was administered with naproxen, inhibition of cell growth plays a more important role in the antiproliferation effects than the induction of apoptotic cell death. These results confirm that the codrug would lead to a better therapeutic profile and fewer adverse effects compared to its parent compounds.

Reforming the CDM for sustainable development: lessons learned and policy futures

The Clean Development Mechanism (CDM) has successfully demonstrated that market-based mechanisms can achieve some cost effective emissions reductions in developing countries. However the distribution of CDM projects has been extremely uneven across countries and regions, and a few technologies and sectors have dominated the early stages of CDM experience. This has caused some to question whether the CDM has fallen short of its potential in contributing to sustainable development. We review the broad patterns of CDM project approvals and evaluate 10 CDM projects according to their sustainability benefits. The difficulty of defining “sustainable development” and the process of defining criteria by individual non-Annex 1 governments has meant that sustainable development concerns have been marginalized in some countries. Given these observed limitations, we present possible CDM policy futures, focusing on the main proposals for a post-2012 climate regime. Five options for enhancing the sustainable development benefits in the CDM are discussed, including proactive approaches to favour eligibility of emission reduction projects which ensure such co-benefits.

Plant and invertebrate resources for farmland birds in pastoral landscapes

On 16 UK livestock holdings within pastoral landscapes, we investigated the provision of plant and invertebrate resources for farmland birds in spring barley and winter wheat cereal-based whole crop silages as alternatives to maize and grass silages. The benefits of low input barley systems were also investigated; barley fields were subjected to two separate herbicide sub-treatments on a split-field design (high input broad-spectrum or low input narrow spectrum herbicides). The abundance of plant resources and invertebrates was assessed for three growing seasons during summer and winter for each crop type. The study clearly demonstrated the value of spring barley for the provision of plant resources when compared to the other silage cropping systems, whilst invertebrate responses were variable. No differences in plant and invertebrate resources were found between the barley treatments. Throughout the year, forage maize afforded the lowest provision of resources for farmland birds, and because it is likely that maize will continue to be grown in pastoral areas, the value of this habitat needs to be improved if farmland birds are to benefit. To provide plant and invertebrate resources for farmland birds in pastoral landscapes we strongly advocate the growing of spring sown barley whole-crop silage followed by over-wintering stubbles. © 2011 Elsevier B.V. All rights reserved.

Are the NICE guidelines for Obsessive Compulsive Disorder being used in primary care?

This study aims to: 1) assess the proportion of General Practioners (GPs) who are aware of or who have read the National Institute for Health and Clinical Excellence (NICE; 2005a) guidelines for Obsessive Compulsive Disorder (OCD), 2) compare this with the proportion of other mental health disorders found by previous research and 3) establish the prevalence of OCD in primary care. Questionnaires were sent to all GPs (n = 795) and practice managers (n = 157) in Berkshire and Buckinghamshire, South East England. These contained 19 questions and took 5 min to complete. After the first set of responses, larger practices were visited and telephoned to encourage further responses. The response rates were 10.1% from GPs and 19.1% from practice managers. In all, 48.7% of the GPs were aware of the NICE guidelines for OCD and 30.3% reported that they had read them – higher than for Post-Traumatic Stress Disorder, but lower than for depression. Of registered patients, 0.2% were diagnosed with OCD, lower than the 1.1% found in epidemiological studies.

The first international workshop on the role and impact of mathematics in medicine: a collective account

The First International Workshop on The Role and Impact of Mathematics in Medicine (RIMM) convened in Paris in June 2010. A broad range of researchers discussed the difficulties, challenges and opportunities faced by those wishing to see mathematical methods contribute to improved medical outcomes. Finding mechanisms for inter- disciplinary meetings, developing a common language, staying focused on the medical problem at hand, deriving realistic mathematical solutions, obtaining

Flooding, resettlement and change in livelihoods: evidence from rural Mozambique

Post-disaster development policies, such as resettlement, can have major impacts on communities. This article concerns how and why people's livelihoods change as a result of resettlement, and what relocated people's views of such changes are, in the context of natural disasters. It presents two historically-grounded, comparative case studies of post-flood resettlement in rural Mozambique. The studies show a movement away from rain-fed subsistence agriculture towards commercial agriculture and non-agricultural activities. Ability to secure a viable livelihood was a major determinant of whether resettlers remained in their new locations or returned to the river valleys despite the risks that floods posed. The findings suggest that more research is required into 1) understanding why resettlers choose to stay in or abandon designated resettlement areas; 2) what is meant by 'voluntary' and 'involuntary' resettlement in the context of post-disaster reconstruction; and 3) what the policy drivers for resettlement are in developing countries.

Early detection of ovarian cancer in samples pre-diagnosis using CA125 and MALDI-MS peaks

Aim: A nested case-control discovery study was undertaken 10 test whether information within the serum peptidome can improve on the utility of CA125 for early ovarian cancer detection. Materials and Methods: High-throughput matrix-assisted laser desorption ionisation mass spectrometry (MALDI-MS) was used to profile 295 serum samples from women pre-dating their ovarian cancer diagnosis and from 585 matched control samples. Classification rules incorporating CA125 and MS peak intensities were tested for discriminating ability. Results: Two peaks were found which in combination with CA125 discriminated cases from controls up to 15 and 11 months before diagnosis, respectively, and earlier than using CA125 alone. One peak was identified as connective tissue-activating peptide III (CTAPIII), whilst the other was putatively identified as platelet factor 4 (PF4). ELISA data supported the down-regulation of PF4 in early cancer cases. Conclusion: Serum peptide information with CA125 improves lead time for early detection of ovarian cancer. The candidate markers are platelet-derived chemokines, suggesting a link between platelet function and tumour development.

A novel satellite mission concept for upper air water vapour, aerosol and cloud observations using integrated path differential absorption LiDAR limb sounding

We propose a new satellite mission to deliver high quality measurements of upper air water vapour. The concept centres around a LiDAR in limb sounding by occultation geometry, designed to operate as a very long path system for differential absorption measurements. We present a preliminary performance analysis with a system sized to send 75 mJ pulses at 25 Hz at four wavelengths close to 935 nm, to up to 5 microsatellites in a counter-rotating orbit, carrying retroreflectors characterized by a reflected beam divergence of roughly twice the emitted laser beam divergence of 15 µrad. This provides water vapour profiles with a vertical sampling of 110 m; preliminary calculations suggest that the system could detect concentrations of less than 5 ppm. A secondary payload of a fairly conventional medium resolution multispectral radiometer allows wide-swath cloud and aerosol imaging. The total weight and power of the system are estimated at 3 tons and 2,700 W respectively. This novel concept presents significant challenges, including the performance of the lasers in space, the tracking between the main spacecraft and the retroreflectors, the refractive effects of turbulence, and the design of the telescopes to achieve a high signal-to-noise ratio for the high precision measurements. The mission concept was conceived at the Alpbach Summer School 2010.

Promoting resilient livelihoods through adaptive social protection: lessons from 124 programmes in South Asia

Adaptive Social Protection refers to efforts to integrate social protection (SP), disaster risk reduction (DRR) and climate change adaptation (CCA). The need to integrate these three domains is now increasingly recognized by practitioners and academics. Relying on 124 agricultural programmes implemented in 5 countries in Asia, this paper considers how these elements are being brought together, and explores the potential gains of these linkages. The analysis shows that full integration of SP, DRR and CCA interventions is still relatively limited but that when it occurs, integration helps to shift the time horizon beyond short-term interventions aimed at supporting peoples’ coping strategies and/or graduation objectives, toward longer-term interventions that can assist in promoting transformation towards climate and disaster resilient livelihood options.

Effects of seed addition on beetle assemblages during the re-creation of species-rich lowland hay meadows

Species-rich lowland hay meadows are of conservation importance for both plants and invertebrates; however, they have declined in area across Europe as a result of conversion to other land uses and management intensification. The re-creation of these grasslands on ex-arable land provides a valuable approach to increasing the extent and conservation value of this threatened habitat. Over a 3-year period a replicated block design was used to test whether introducing seeds promoted the re-creation of both plant and phytophagous beetle assemblages typical of a target hay meadow. Seeds were harvested from local hay meadows, and applied to experimental plots in the form of either green hay or brush harvesting seeds. Green hay spreading achieved the greatest success in re-creating plant and phytophagous beetle assemblages. While re-creation success increased over time for both taxa, for the phytophagous beetles the greatest increase in re-creation success relative to the establishment year also occurred where green hay was applied. We also considered the phytophagous beetles in terms of functional traits that describe host plant specificity, larval feeding location and dispersal. Phytophagous beetle functional trait composition was most similar to the target hay meadow assemblage where some form of seed addition was used, i.e. hay spreading or brush harvested seeds. This study identified the importance of introducing target plant species as a mechanism to promote the re-creation of phytophagous beetle communities. Seed addition methods (e.g. green hay spreading) are crucial to successful hay meadow re-creation.