Early soft rot colonization of Scots sapwood pine in above-ground exposure

The early colonization of Scots pine (Pinus sylvestris L.) sapwood exposed above ground (staple bed) was studied. Two different types of exposures were used, one in an open field and the other in a shaded field. Decay type and degree of degradation due to soft rot, and mass and strength loss of wood were correlated. Fungal species in Scots pine sapwood were identified by sequencing, using the fungal nuclear ribosomal DNA (nrDNA) after 24 months.The most abundant decay type found was soft rot, which also agreed with the mass loss (7–8%). Pine sapwood did not differ significantly between the two sites regarding the average mass loss during the time of exposure. The early colonization of wood by soft rot fungi together with mass loss indicates that this fungal type might be more common in above-ground conditions than recognized earlier.     

Recommendations for Integrating Restoration Ecology and Conservation Biology in Ponderosa Pine Forests of the Southwestern United States

Over the past century, ponderosa pine–dominated landscapes of the southwestern United States have been altered by human activities such as grazing, timber harvest, road building, and fire exclusion. Most forested areas within these landscapes now show increased susceptibility to stand‐replacing fires, insect outbreaks, and drought‐related mortality. Recent large wildfires in the region have spurred public interest in large‐scale fuel reduction and restoration programs, which create perceived and real conflicts with the conservation of biodiversity. Conservation concerns include the potential for larger road networks, soil and understory disturbance, exotic plant invasion, and the removal of large trees in treated areas. Pursuing prescribed burning, thinning, or other treatments on the broad scale that many scientists and managers envision requires the reconciliation of ecological restoration with biodiversity conservation. This study presents recommendations from a workshop for integrating the principles and practices of restoration ecology and conservation biology, toward the objective of restoring the composition, structure, and function of dry ponderosa pine forests. Planning on the scale of hundreds of thousands of hectares offers opportunities to achieve multiple objectives (e.g., rare species protection and restoration of ecological structures and processes) that cannot easily be addressed on a site‐by‐site basis. However, restoration must be coordinated with conservation planning to achieve mutual objectives and should include strict guidelines for protection of rare, declining, and sensitive habitats and species.     

Improved variance estimation of classification performance via reduction of bias caused by small sample size

Background  

Supervised learning for classification of cancer employs a set of design examples to learn how to discriminate between tumors. In practice it is crucial to confirm that the classifier is robust with good generalization performance to new examples, or at least that it performs better than random guessing. A suggested alternative is to obtain a confidence interval of the error rate using repeated design and test sets selected from available examples. However, it is known that even in the ideal situation of repeated designs and tests with completely novel samples in each cycle, a small test set size leads to a large bias in the estimate of the true variance between design sets. Therefore different methods for small sample performance estimation such as a recently proposed procedure called Repeated Random Sampling (RSS) is also expected to result in heavily biased estimates, which in turn translates into biased confidence intervals. Here we explore such biases and develop a refined algorithm called Repeated Independent Design and Test (RIDT).     

Description and genetic mapping of Polypodia: an X-linked dominant mouse mutant with ectopic caudal limbs and other malformations

In this report we present a spontaneous mouse mutant, named Polypodia (Ppd), that primarily exhibits ectopic, ventral/caudal limbs and associated pelvic girdle malformation or duplication. Less penetrant features include diphallia, microphthalmia, small kidney, curled or kinked tail, forelimb anomaly, and skin papillae. Ppd mice have a normal karyotype and no large-scale genomic deletions or insertions by BAC-based array comparative genomic hybridization (CGH). Ppd is X-linked dominant with approximately 20% penetrance on the C3H background and maps to X:61.6 Mb-X:71.24 Mb. The limb and a subset of the nonlimb anomalies are similar to those in offspring from retinoic acid-treated dams at E4.5-5.5 and feature overlap with the Disorganization mouse mutant and human patients with ectopic legs. We hypothesize that Ppd affects very early steps in the formation of caudal structures including limb and appendage number. The existence of noncaudal anomalies implies the involvement of Ppd in a broad array of cell fate decisions.     

Current approaches using genetic distances produce poor estimates of landscape resistance to interindividual dispersal

Landscape resistance reflects how difficult it is for genes to move across an area with particular attributes (e.g. land cover, slope). An increasingly popular approach to estimate resistance uses Mantel and partial Mantel tests or causal modelling to relate observed genetic distances to effective distances under alternative sets of resistance parameters. Relatively few alternative sets of resistance parameters are tested, leading to relatively poor coverage of the parameter space. Although this approach does not explicitly model key stochastic processes of gene flow, including mating, dispersal, drift and inheritance, bias and precision of the resulting resistance parameters have not been assessed. We formally describe the most commonly used model as a set of equations and provide a formal approach for estimating resistance parameters. Our optimization finds the maximum Mantel r when an optimum exists and identifies the same resistance values as current approaches when the alternatives evaluated are near the optimum. Unfortunately, even where an optimum existed, estimates from the most commonly used model were imprecise and were typically much smaller than the simulated true resistance to dispersal. Causal modelling using Mantel significance tests also typically failed to support the true resistance to dispersal values. For a large range of scenarios, current approaches using a simple correlational model between genetic and effective distances do not yield accurate estimates of resistance to dispersal. We suggest that analysts consider the processes important to gene flow for their study species, model those processes explicitly and evaluate the quality of estimates resulting from their model.     

Good Manufacturing Practices (GMP) manufacturing of advanced therapy medicinal products: a novel tailored model for optimizing performance and estimating costs

Background aimsAdvanced therapy medicinal products (ATMP) have gained considerable attention in academia due to their therapeutic potential. Good Manufacturing Practice (GMP) principles ensure the quality and sterility of manufacturing these products. We developed a model for estimating the manufacturing costs of cell therapy products and optimizing the performance of academic GMP-facilities.MethodsThe “Clean-Room Technology Assessment Technique” (CTAT) was tested prospectively in the GMP facility of BCRT, Berlin, Germany, then retrospectively in the GMP facility of the University of California-Davis, California, USA. CTAT is a two-level model: level one identifies operational (core) processes and measures their fixed costs; level two identifies production (supporting) processes and measures their variable costs. The model comprises several tools to measure and optimize performance of these processes. Manufacturing costs were itemized using adjusted micro-costing system.ResultsCTAT identified GMP activities with strong correlation to the manufacturing process of cell-based products. Building best practice standards allowed for performance improvement and elimination of human errors. The model also demonstrated the unidirectional dependencies that may exist among the core GMP activities. When compared to traditional business models, the CTAT assessment resulted in a more accurate allocation of annual expenses. The estimated expenses were used to set a fee structure for both GMP facilities. A mathematical equation was also developed to provide the final product cost.ConclusionsCTAT can be a useful tool in estimating accurate costs for the ATMPs manufactured in an optimized GMP process. These estimates are useful when analyzing the cost-effectiveness of these novel interventions.     

Shifts in malaria vector species composition and transmission dynamics along the Kenyan coast over the past 20 years

Background

Over the past 20 years, numerous studies have investigated the ecology and behaviour of malaria vectors and Plasmodium falciparum malaria transmission on the coast of Kenya. Substantial progress has been made to control vector populations and reduce high malaria prevalence and severe disease. The goal of this paper was to examine trends over the past 20 years in Anopheles species composition, density, blood-feeding behaviour, and P. falciparum sporozoite transmission along the coast of Kenya.

Methods

Using data collected from 1990 to 2010, vector density, species composition, blood-feeding patterns, and malaria transmission intensity was examined along the Kenyan coast. Mosquitoes were identified to species, based on morphological characteristics and DNA extracted from Anopheles gambiae for amplification. Using negative binomial generalized estimating equations, mosquito abundance over the period were modelled while adjusting for season. A multiple logistic regression model was used to analyse the sporozoite rates.

Results

Results show that in some areas along the Kenyan coast, Anopheles arabiensis and Anopheles merus have replaced An. gambiae sensu stricto (s.s.) and Anopheles funestus as the major mosquito species. Further, there has been a shift from human to animal feeding for both An. gambiae sensu lato (s.l.) (99% to 16%) and An. funestus (100% to 3%), and P. falciparum sporozoite rates have significantly declined over the last 20 years, with the lowest sporozoite rates being observed in 2007 (0.19%) and 2008 (0.34%). There has been, on average, a significant reduction in the abundance of An. gambiae s.l. over the years (IRR?=?0.94, 95% CI 0.90–0.98), with the density standing at low levels of an average 0.006 mosquitoes/house in the year 2010.

Conclusion

Reductions in the densities of the major malaria vectors and a shift from human to animal feeding have contributed to the decreased burden of malaria along the Kenyan coast. Vector species composition remains heterogeneous but in many areas An. arabiensis has replaced An. gambiae as the major malaria vector. This has important implications for malaria epidemiology and control given that this vector predominately rests and feeds on humans outdoors. Strategies for vector control need to continue focusing on tools for protecting residents inside houses but additionally employ outdoor control tools because these are essential for further reducing the levels of malaria transmission.     

Low C-Reactive Protein Levels in a Traditional West-African Population Living in a Malaria Endemic Area

Background

C-reactive protein (CRP) levels are reported to be elevated in populations of African descent living in affluent environments compared to populations of European ancestry. However, the natural history of CRP levels in populations of African descent living under adverse environments remains largely unknown.

Methods

CRP levels were measured with a high sensitivity assay in 624 apparently healthy individuals who contributed blood as part of a study on innate immune responsiveness in a traditional Ghanaian population living under adverse environmental conditions in a malaria endemic area. As a comparison, we included CRP measurements from 2931 apparently healthy individuals from the Dutch population that were included in the same batch of CRP analyses. Associations between CRP and body mass index (BMI), immune responsiveness, and P. falciparum parasitaemia were investigated.

Results

In an age- and sex-adjusted model, CRP levels were 0.54 mg/L lower in the Ghanaian compared to the Dutch cohort (1.52 vs. 0.98 mg/L, p<0.001). When accounting for the substantially higher average BMI in the Dutch compared to the Ghanaians (25.6 vs. 18.4 kg/m²) the difference in CRP levels disappeared. BMI associated positively with CRP in the Dutch but not in the Ghanaians. In individuals with an acute phase response, CRP levels were higher in the Ghanaian compared to the Dutch cohort (24.6 vs. 17.3 mg/L, p = 0.04). Levels of CRP were positively related to immune responsiveness and P. falciparum parasitaemia (all p<0.001) among Ghanaians.

Conclusions

Our study demonstrates that West-Africans do not exhibit an inherently high inflammatory state. The role of genes, environment and gene-environment interaction in explaining reports of elevated CRP levels in populations of African ancestry when compared to other ethnicities living in affluent environments thus merits further investigation.