Cancer's sweet tooth for serine

Exemplified by the cancer cell's preference for glycolysis (the Warburg effect), altered metabolism has taken centerstage as an emerging hallmark of cancer. Charting the landscape of cancer metabolic addictions should reveal new avenues for therapeutic attack. Two recent studies found subsets of human melanoma and breast cancers to have high levels of phosphoglycerate dehydrogenase (PHGDH), a key enzyme for serine biosynthesis, and these cancer cells are dependent on PHGDH for their growth and survival. Tumors may thus harbor distinct metabolic alterations to support their malignancy, and targeting enzymes such as PHGDH might prove a viable therapeutic strategy in this scenario

Convexity-Increasing Morphs of Planar Graphs

We study the problem of convexifying drawings of planar graphs. Given any planar straight-line drawing of an internally 3-connected graph, we show how to morph the drawing to one with strictly convex faces while maintaining planarity at all times. Our morph is convexity-increasing, meaning that once an angle is convex, it remains convex. We give an efficient algorithm that constructs such a morph as a composition of a linear number of steps where each step either moves vertices along horizontal lines or moves vertices along vertical lines. Moreover, we show that a linear number of steps is worst-case optimal. To obtain our result, we use a well-known technique by Hong and Nagamochi for finding redrawings with convex faces while preserving y-coordinates. Using a variant of Tutte's graph drawing algorithm, we obtain a new proof of Hong and Nagamochi's result which comes with a better running time. This is of independent interest, as Hong and Nagamochi's technique serves as a building block in existing morphing algorithms.Comment: Preliminary version in Proc. WG 201

Understanding cost of care for patients on renal replacement therapy: looking beyond fixed tariffs.

BACKGROUND: In a number of countries, reimbursement to hospitals providing renal dialysis services is set according to a fixed tariff. While the cost of maintenance dialysis and transplant surgery are amenable to a system of fixed tariffs, patients with established renal failure commonly present with comorbid conditions that can lead to variations in the need for hospitalization beyond the provision of renal replacement therapy. METHODS: Patient-level cost data for incident renal replacement therapy patients in England were obtained as a result of linkage of the Hospital Episodes Statistics dataset to UK Renal Registry data. Regression models were developed to explore variations in hospital costs in relation to treatment modality, number of years on treatment and factors such as age and comorbidities. The final models were then used to predict annual costs for patients with different sets of characteristics. RESULTS: Excluding the cost of renal replacement therapy itself, inpatient costs generally decreased with number of years on treatment for haemodialysis and transplant patients, whereas costs for patients receiving peritoneal dialysis remained constant. Diabetes was associated with higher mean annual costs for all patients irrespective of treatment modality and hospital setting. Age did not have a consistent effect on costs. CONCLUSIONS: Combining predicted hospital costs with the fixed costs of renal replacement therapy showed that the total cost differential for a patient continuing on dialysis rather than receiving a transplant is considerable following the first year of renal replacement therapy, thus reinforcing the longer-term economic advantage of transplantation over dialysis for the health service.<br/

Sex-specific mortality forecasting for UK countries: a coherent approach

This paper introduces a gender specific model for the joint mortality projection of three countries (England and Wales combined, Scotland, and Northern Ireland) of the United Kingdom. The model, called 2-tier Augmented Common Factor model, extends the classical Lee and Carter [26] and Li and Lee [32] models, with a common time factor for the whole UK population, a sex specific period factor for males and females, and a specific time factor for each country within each gender. As death counts in each subpopulation are modelled directly, a Poisson framework is used. Our results show that the 2-tier ACF model improves the in-sample fitting compared to the use of independent LC models for each subpopulation or of independent Li and Lee models for each couple of genders within each country. Mortality projections also show that the 2-tier ACF model produces coherent forecasts for the two genders within each country and different countries within each gender, thus avoiding the divergence issues arising when independent projections are used. The 2-tier ACF is further extended to include a cohort term to take into account the faster improvements of the UK ‘golden generation’

Variation of health-related quality of life assessed by caregivers and patients affected by severe childhood infections.

BACKGROUND: The agreement between self-reported and proxy measures of health status in ill children is not well established. This study aimed to quantify the variation in health-related quality of life (HRQOL) derived from young patients and their carers using different instruments. METHODS: A hospital-based cross-sectional survey was conducted between August 2010 and March 2011. Children with meningitis, bacteremia, pneumonia, acute otitis media, hearing loss, chronic lung disease, epilepsy, mild mental retardation, severe mental retardation, and mental retardation combined with epilepsy, aged between five to 14 years in seven tertiary hospitals were selected for participation in this study. The Health Utilities Index Mark 2 (HUI2), and Mark 3 (HUI3), and the EuroQoL Descriptive System (EQ-5D) and Visual Analogue Scale (EQ-VAS) were applied to both paediatric patients (self-assessment) and caregivers (proxy-assessment). RESULTS: The EQ-5D scores were lowest for acute conditions such as meningitis, bacteremia, and pneumonia, whereas the HUI3 scores were lowest for most chronic conditions such as hearing loss and severe mental retardation. Comparing patient and proxy scores (n = 74), the EQ-5D exhibited high correlation (r = 0.77) while in the HUI2 and HUI3 patient and caregiver scores were moderately correlated (r = 0.58 and 0.67 respectively). The mean difference between self and proxy-assessment using the HUI2, HUI3, EQ-5D and EQ-VAS scores were 0.03, 0.05, -0.03 and -0.02, respectively. In hearing-impaired and chronic lung patients the self-rated HRQOL differed significantly from their caregivers. CONCLUSIONS: The use of caregivers as proxies for measuring HRQOL in young patients affected by pneumococcal infection and its sequelae should be employed with caution. Given the high correlation between instruments, each of the HRQOL instruments appears acceptable apart from the EQ-VAS which exhibited low correlation with the others

Comparing amyloid-β plaque burden with antemortem PiB PET in autosomal dominant and late-onset Alzheimer disease

Pittsburgh compound B (PiB) radiotracer for positron emission tomography (PET) imaging can bind to different types of amyloid-β plaques and blood vessels (cerebral amyloid angiopathy). However, the relative contributions of different plaque subtypes (diffuse versus cored/compact) to in vivo PiB PET signal on a region-by-region basis is incompletely understood. Of particular interest is whether the same staging schemes for summarizing amyloid-β burden are appropriate for both late-onset and autosomal dominant forms of Alzheimer disease (LOAD and ADAD). Here we compared antemortem PiB PET with follow-up postmortem estimation of amyloid-β burden using stereologic methods to estimate the relative area fraction of diffuse and cored/compact amyloid-β plaques across 16 brain regions in 15 individuals with ADAD and 14 individuals with LOAD. In ADAD, we found that PiB PET correlated with diffuse plaques in the frontal, parietal, temporal, and striatal regions commonly used to summarize amyloid-β burden in PiB PET, and correlated with both diffuse and cored/compact plaques in the occipital lobe and parahippocampal gyrus. In LOAD, we found that PiB PET correlated with both diffuse and cored/compact plaques in the anterior cingulate, frontal lobe (middle frontal gyrus), and parietal lobe, and showed additional correlations with diffuse plaque in the amygdala and occipital lobe, and with cored/compact plaque in the temporal lobe. Thus, commonly used PiB PET summary regions predominantly reflect diffuse plaque burden in ADAD and a mixture of diffuse and cored/compact plaque burden in LOAD. In direct comparisons of ADAD and LOAD, postmortem stereology identified much greater mean amyloid-β plaque burdens in ADAD versus LOAD across almost all brain regions studied. However, standard PiB PET did not recapitulate these stereologic findings, likely due to non-trivial amyloid-β plaque burdens in ADAD within the cerebellum and brainstem – commonly used reference regions in PiB PET. Our findings suggest that PiB PET summary regions correlate with amyloid-β plaque burden in both ADAD and LOAD; however, they might not be reliable in direct comparisons of regional amyloid-β plaque burden between the two forms of AD

Evidence for distinct coastal and offshore communities of bottlenose dolphins in the north east Atlantic.

Bottlenose dolphin stock structure in the northeast Atlantic remains poorly understood. However, fine scale photo-id data have shown that populations can comprise multiple overlapping social communities. These social communities form structural elements of bottlenose dolphin (Tursiops truncatus) [corrected] populations, reflecting specific ecological and behavioural adaptations to local habitats. We investigated the social structure of bottlenose dolphins in the waters of northwest Ireland and present evidence for distinct inshore and offshore social communities. Individuals of the inshore community had a coastal distribution restricted to waters within 3 km from shore. These animals exhibited a cohesive, fission-fusion social organisation, with repeated resightings within the research area, within a larger coastal home range. The offshore community comprised one or more distinct groups, found significantly further offshore (>4 km) than the inshore animals. In addition, dorsal fin scarring patterns differed significantly between inshore and offshore communities with individuals of the offshore community having more distinctly marked dorsal fins. Specifically, almost half of the individuals in the offshore community (48%) had characteristic stereotyped damage to the tip of the dorsal fin, rarely recorded in the inshore community (7%). We propose that this characteristic is likely due to interactions with pelagic fisheries. Social segregation and scarring differences found here indicate that the distinct communities are likely to be spatially and behaviourally segregated. Together with recent genetic evidence of distinct offshore and coastal population structures, this provides evidence for bottlenose dolphin inshore/offshore community differentiation in the northeast Atlantic. We recommend that social communities should be considered as fundamental units for the management and conservation of bottlenose dolphins and their habitat specialisations

Options for sampling and stratification for national forest inventories to implement REDD+ under the UNFCCC

<p>Abstract</p> <p>Background</p> <p>Developing countries that are willing to participate in the recently adopted (16^thSession of the Conference of Parties (COP) in Cancun) mitigation mechanism of Reducing emissions from Deforestation and Forest Degradation - and the role of conservation, sustainable management of forests and enhancement of forest carbon stocks (REDD+) - will have to establish a national forest monitoring system in order to assess anthropogenic forest-related greenhouse gas emissions by sources and removals by sinks. Such a system should support the Measurement, Reporting and Verification (MRV) requirement of the United Nations Framework Convention on Climate Change (UNFCCC) as the REDD+ mechanism is results-based. A national forest inventory (NFI) is one potential key component of such an MRV system. Following the Decision adopted during the 15^thSession of the COP in Copenhagen, the most recent Intergovernmental Panel on Climate Change (IPCC) Guidance and Guidelines should be used as a basis for estimating anthropogenic forest-related greenhouse gas emissions by sources and removals by sinks and changes in forest carbon stocks and area.</p> <p>Results</p> <p>First, we present the key indispensable elements of the IPCC Guidance and Guidelines that have been developed to fulfil the UNFCCC reporting requirements. This is done in order to set the framework to develop the MRV requirement in which a NFI for REDD+ implementation could be developed. Second, within this framework, we develop and propose a novel scheme for the stratification of forest land for REDD+. Finally, we present some non-exhaustive optional elements within this framework that a country could consider to successfully operationalise and implement its REDD+ NFI.</p> <p>Conclusion</p> <p>Evidently, both the methodological guidance and political decisions on REDD+ under the UNFCCC will continue to evolve. Even so, and considering that there exists decades of experience in setting up traditional NFIs, developing a NFI that a country may use to directly support REDD+ activities under the UNFCCC represents the development of a new challenge in this field. It is therefore important that both the scientific community and national implementing agencies acquaint themselves with both the context and content of this challenge so that REDD+ mitigation actions may be implemented successfully and with environmental integrity. This paper provides important contributions to the subject through our proposal of the stratification of forest land for REDD+.</p