Amphotericin B: How Much Is Enough?

The total curative dose of amphotericin B for any given fungal infection or specific patient is not precisely known. Prior to the availability of lipid formulations of amphotericin B (LFAB), dosing of amphotericin B was dictated by its associated toxicity. The unique pharmacokinetic features of each LFAB have led to differences in their recommended doses. Most published data have evaluated doses of 3–5 mg/kg/day, although niches exist for both higher and lower doses. Low-dose LFAB allows for intravenous broad-spectrum antifungal coverage without drug-drug interactions and with reduced toxicity. High-dose LFAB demonstrates increased fungal clearance in animal models, although this has not translated to improved clinical outcomes for most invasive fungal infections. Although available data do not demonstrate significant benefit associated with high-dose therapy, for liposomal amphotericin B, the data also demonstrate no significant harm. As such, the use of high-dose liposomal amphotericin B for salvage therapy may be a consideration.     

How Much Lox Is a Grizzly Bear Worth?

Using grizzly bears as surrogates for "salmon ecosystem" function, the authors develop a generalizable ecosystem-based management framework that enables decision makers to quantify ecosystem-harvest tradeoffs between wild and human recipients of natural resources like fish.     

Phylogenetic Profiling: How Much Input Data Is Enough?

Phylogenetic profiling is a well-established approach for predicting gene function based on patterns of gene presence and absence across species. Much of the recent developments have focused on methodological improvements, but relatively little is known about the effect of input data size on the quality of predictions. In this work, we ask: how many genomes and functional annotations need to be considered for phylogenetic profiling to be effective? Phylogenetic profiling generally benefits from an increased amount of input data. However, by decomposing this improvement in predictive accuracy in terms of the contribution of additional genomes and of additional annotations, we observed diminishing returns in adding more than ∼100 genomes, whereas increasing the number of annotations remained strongly beneficial throughout. We also observed that maximising phylogenetic diversity within a clade of interest improves predictive accuracy, but the effect is small compared to changes in the number of genomes under comparison. Finally, we show that these findings are supported in light of the Open World Assumption, which posits that functional annotation databases are inherently incomplete. All the tools and data used in this work are available for reuse from http://lab.dessimoz.org/14_phylprof. Scripts used to analyse the data are available on request from the authors.     

Much Improved Water Use Efficiency of Rice under Non-Flooded Mulching Cultivation

Water shortage is increasingly limiting the luxury use of water in rice cultivation. In this study, non-flooded mulching cultivation of rice only consumed a fraction of the water that was needed for traditional flooded cultivation and largely maintained the grain yield. We also investigated the growth and development of rice plants and examined grain yield formation when rice was subjected to non-flooded mulching cultivation. One indica hybrid rice combination was grown in a field experiment and three cultivation methods, traditional flooding （TF）, non-flooded straw mulching cultivation （SM） and non-flooded plastic mulching cultivation （PM）, were conducted during the whole season. Grain yield showed that there was no significant difference between SM and TF rice, but the grain yield of SM cultivation was significantly higher than that of PM. The tiller numbers were inhibited in the early stage under non-flooded mulching cultivation, but the situation was reversed at the later period. Both SM and PM rice reduced dry matter accumulation of shoot, but increased root dry weight, enhanced the remobilization of assimilates from stems to grains and increased the harvest index. During the middle and later grain filling period, mulched plants showed a faster decrease in chlorophyll concentrations, photosynthetic rates of flag leaves and root activity than TF rice, indicating that non-flooded mulching cultivation enhanced plant senescence. In comparison, SM treatment produced higher grain yield and, more dry matter accumulation and panicle numbers than the PM treatment. The overall results suggest that high yield of non-flooded mulching cultivation of rice can be achieved with much improved irrigaUonal water use efficiency.     

How Much Ecology Do We Need to Know to Restore Mediterranean Ecosystems?

Despite important advances in ecological knowledge of Mediterranean‐type ecosystems, advances in restoration ecology have not seen a parallel increase in these systems. Although some concepts such as positive plant–plant interaction (facilitation) have received attention in the restoration ecology community, others such as phenotypic plasticity have not. Some concepts (e.g., environmental heterogeneity) are mature enough for a wide use in restoration, whereas available knowledge on others (e.g., facilitation, plasticity) is less conclusive. However, the scientific knowledge is in general enough to significantly improve the guidelines for restoration of Mediterranean ecosystems. Our review suggests that (1) the extent of facilitation in dry ecosystems is partially understood, with supporting, but somewhat contradictory empirical evidence for its potential use in restoration; (2) the influence of habitat heterogeneity on plant performance and plasticity is only beginning to be understood, with a strong bias toward patterns of structural heterogeneity and negligible information on functional heterogeneity; and (3) sound evaluations of phenotypic plasticity might be useful to increase the success of restoration practices in patchy Mediterranean environments. Future global change scenarios involving temperature rise, reduced precipitation, increased frequency of extreme climatic events, and important land use changes and fragmentation must be particularly considered when restoring Mediterranean ecosystems. Further research on how to incorporate results on facilitation, environmental heterogeneity, and plasticity within a global change framework is clearly needed.     

Revisiting Gender Differences in Somatic Symptoms of Depression: Much Ado about Nothing?

Background

Women have a higher prevalence of Major Depressive Disorder (MDD) and report more severe depressive symptoms than men. Several studies have suggested that gender differences in depression may occur because women report higher levels of somatic symptoms than men. Those studies, however, have not controlled or matched for non-somatic symptoms. The objective of this study was to examine if women report relatively more somatic symptoms than men matched on cognitive/affective symptoms.

Methods

Male and female patients receiving treatment for MDD in outpatient psychiatric clinics in New Jersey and Pennsylvania, USA were matched on Beck Depression Inventory-II (BDI-II) cognitive/affective symptom scores. Male and female BDI-II somatic symptom scores were compared using independent samples 2-tailed t-tests.

Results

Of 472 male and 1,026 female patients, there were 470 male patients (mean age = 40.1 years, SD = 15.1) and 470 female patients (mean age = 43.1 years, SD = 17.2) successfully matched on BDI-II cognitive/affective symptom scores. Somatic symptoms accounted for 35% of total BDI-II scores for male patients versus 38% for matched female patients. Female patients had somatic symptom scores on average 1.3 points higher than males (p<.001), equivalent to 4% of the total BDI-II scores of female patients. Only 5% of male patients and 7% of female patients scored 2 or higher on all BDI-II somatic symptom items.

Conclusions

Gender differences in somatic scores were very small. Thus, differences in the experience and reporting of somatic symptoms would not likely explain gender differences in depression rates and symptom severity.     

Environmental Load from Dutch Private Consumption: How Much Damage Takes Place Abroad?

This article describes a method for determining the environmental load of Dutch private consumption. The method generates detailed information about consumption-related environmental impacts. The environmental load of households (direct) and production (indirect) was determined for 360 expenditure categories reported in the Dutch Expenditure Survey. The indirect environmental load was calculated with linked input-output tables covering worldwide production and trade. The environmental load per Euro turnover of industries was linked to consumer expenditures. With this method we can quantify several types of environmental load per expenditure category and per economic production region.
It was found that food production, room heating, and car use are the most important elements in the environmental load of Dutch private consumption. The impacts taking place abroad were—with the exception of emission of greenhouse gases and road traffic noise—found to be larger than domestic impacts. Most land use was found to take place in developing (non-OECD) countries, whereas most emissions occur in industrialized (OECD) countries.     

Rapamycin and Ageing: When,for How Long,and How Much?

正The mechanistic target of rapamycin(mTOR)is a nutrient and growth factor responsive kinase that modulates lifespan in species from yeast to mice(Johnson et al.,2013b).mTOR exists in two complexes within cells,mTOR complexⅠ(mTORC1)and mTOR complex 2(mTORC2)(Laplante and Sabatini,2012).Abundant evidence suggests that mTORC1is the primary mTOR complex involved in regulating longevity:mutations that reduce the     

Natural Image Coding in V1: How Much Use Is Orientation Selectivity?

Orientation selectivity is the most striking feature of simple cell coding in V1 that has been shown to emerge from the reduction of higher-order correlations in natural images in a large variety of statistical image models. The most parsimonious one among these models is linear Independent Component Analysis (ICA), whereas second-order decorrelation transformations such as Principal Component Analysis (PCA) do not yield oriented filters. Because of this finding, it has been suggested that the emergence of orientation selectivity may be explained by higher-order redundancy reduction. To assess the tenability of this hypothesis, it is an important empirical question how much more redundancy can be removed with ICA in comparison to PCA or other second-order decorrelation methods. Although some previous studies have concluded that the amount of higher-order correlation in natural images is generally insignificant, other studies reported an extra gain for ICA of more than 100%. A consistent conclusion about the role of higher-order correlations in natural images can be reached only by the development of reliable quantitative evaluation methods. Here, we present a very careful and comprehensive analysis using three evaluation criteria related to redundancy reduction: In addition to the multi-information and the average log-loss, we compute complete rate–distortion curves for ICA in comparison with PCA. Without exception, we find that the advantage of the ICA filters is small. At the same time, we show that a simple spherically symmetric distribution with only two parameters can fit the data significantly better than the probabilistic model underlying ICA. This finding suggests that, although the amount of higher-order correlation in natural images can in fact be significant, the feature of orientation selectivity does not yield a large contribution to redundancy reduction within the linear filter bank models of V1 simple cells.     

Protein Docking by the Interface Structure Similarity: How Much Structure Is Needed?

The increasing availability of co-crystallized protein-protein complexes provides an opportunity to use template-based modeling for protein-protein docking. Structure alignment techniques are useful in detection of remote target-template similarities. The size of the structure involved in the alignment is important for the success in modeling. This paper describes a systematic large-scale study to find the optimal definition/size of the interfaces for the structure alignment-based docking applications. The results showed that structural areas corresponding to the cutoff values <12 Å across the interface inadequately represent structural details of the interfaces. With the increase of the cutoff beyond 12 Å, the success rate for the benchmark set of 99 protein complexes, did not increase significantly for higher accuracy models, and decreased for lower-accuracy models. The 12 Å cutoff was optimal in our interface alignment-based docking, and a likely best choice for the large-scale (e.g., on the scale of the entire genome) applications to protein interaction networks. The results provide guidelines for the docking approaches, including high-throughput applications to modeled structures.     

Deep Imaging: How Much of the Proteome Does Current Top-Down Technology Already Resolve?

Effective proteome analyses are based on interplay between resolution and detection. It had been claimed that resolution was the main factor limiting the use of two-dimensional gel electrophoresis. Improved protein detection now indicates that this is unlikely to be the case. Using a highly refined protocol, the rat brain proteome was extracted, resolved, and detected. In order to overcome the stain saturation threshold, high abundance protein species were excised from the gel following standard imaging. Gels were then imaged again using longer exposure times, enabling detection of lower abundance, less intensely stained protein species. This resulted in a significant enhancement in the detection of resolved proteins, and a slightly modified digestion protocol enabled effective identification by standard mass spectrometric methods. The data indicate that the resolution required for comprehensive proteome analyses is already available, can assess multiple samples in parallel, and preserve critical information concerning post-translational modifications. Further optimization of staining and detection methods promises additional improvements to this economical, widely accessible and effective top-down approach to proteome analysis.     

How Much Do Metamemory Beliefs Contribute to the Font-Size Effect in Judgments of Learning?

Evidence shows that the font size of study items significantly influences judgments of learning (JOLs) and that people’s JOLs are generally higher for larger words than for smaller words. Previous studies have suggested that font size influences JOLs in a belief-based way. However, few studies have directly examined how much people’s beliefs contribute to the font-size effect in JOLs. This study investigated the degree to which font size influenced JOLs in a belief-based way. In Experiment 1, one group of participants (learners) studied words with different font sizes and made JOLs, whereas another group of participants (observers) viewed the learners'' study phase and made JOLs for the learners. In Experiment 2, participants made both JOLs and belief-based recall predictions for large and small words. Our results suggest that metamemory beliefs play an important role in the font-size effect in JOLs.     

How Much Remains Undetected? Probability of Molecular Detection of Human Plasmodia in the Field

Background

In malaria endemic areas, most people are simultaneously infected with different parasite clones. Detection of individual clones is hampered when their densities fluctuate around the detection limit and, in case of P. falciparum, by sequestration during part of their life cycle. This has important implications for measures of levels of infection or for the outcome of clinical trials. This study aimed at measuring the detectability of individual P. falciparum and P. vivax parasite clones in consecutive samples of the same patient and at investigating the impact of sampling strategies on basic epidemiological measures such as multiplicity of infection (MOI).

Methods

Samples were obtained in a repeated cross-sectional field survey in 1 to 4.5 years old children from Papua New Guinea, who were followed up in 2-monthly intervals over 16 months. At each follow-up visit, two consecutive blood samples were collected from each child at intervals of 24 hours. Samples were genotyped for the polymorphic markers msp2 for P. falciparum and msp1F3 and MS16 for P. vivax. Observed prevalence and mean MOI estimated from single samples per host were compared to combined data from sampling twice within 24 h.

Findings and Conclusion

Estimated detectability was high in our data set (0.79 [95% CI 0.76–0.82] for P. falciparum and, depending on the marker, 0.61 [0.58–0.63] or 0.73 [0.71–0.75] for P. vivax). When genotyping data from sequential samples, collected 24 hours apart, were combined, the increase in measured prevalence was moderate, 6 to 9% of all infections were missed on a single day. The effect on observed MOI was more pronounced, 18 to 31% of all individual clones were not detected in a single bleed. Repeated sampling revealed little difference between detectability of P. falciparum and P. vivax.     

How Much Do I Give? Reevaluation of Insulin Dosing Estimation Formulas Using Continuous Glucose Monitoring

ObjectiveTo reevaluate current formulas for determining the total basal insulin dosage (TBD), insulin to carbohydrate ratio (ICR), and correction factor (CF) from weight or total daily dosage (TDD) in pump-treated patients with type 1 diabetes mellitus.MethodsFrom a post hoc analysis of data from 4 previously published studies, subjects who met the inclusion criteria were selected. No subject was duplicated. For all studies, the basal glucose target was to have fewer than 20% of glucose readings greater than 170 mg/dL and to have 10% or fewer glucose readings less than 70 mg/dL. Bolus insulin was adjusted to achieve a 2to 4-hour postbolus glucose value within 20% of the premeal glucose (ICR) or 80 to 120 mg/dL from premeal hyperglycemia (CF). In the first 2 studies, dosing titration by CGM was performed from 72-hour CGM tracings every week to every 6 weeks. In the other 2 studies, 24to 72-hour CGM downloads and insulin adjustments were done each weekday.ResultsOf 101 participants, 61 (59% women) met the inclusion criteria. Estimation formulas could be rounded to the following: TBD = 0.2 × weight (kg) or 0.4 × TDD; ICR = 300 ÷ TDD; and CF = 1500 ÷ TDD. In particular the relationship between all 3 dosing factors could be represented as 100 ÷ TBD = ICR = CF ÷ 4.5.ConclusionsThese results suggest that current formulas give a higher estimate for TBD and a lower estimate for the bolus dose. (Endocr Pract. 2010;16:428-432)     

How Much is Enough? Estimating the Minimum Sampling Required for Effective Monitoring of African Reserves

Effective biological monitoring in developing countries requires a balance of rigour and practicality. Unfortunately, there exist few general guidelines to help practitioners design monitoring programs that reach this balance. Here, we analyse a 33-year monitoring program from Ghana, West Africa, to provide both specific and general suggestions for monitoring in developing countries. Since the late 1960s the Ghana Wildlife Division has monitored more than 40 wildlife species with monthly surveys at sites throughout Ghana's nature reserves. These data present unparalleled opportunities to illuminate the scale and pattern of changes in animal abundance over time and the forces that drive these changes. We used sub-sampling of the Ghana monitoring data for four species in two savanna reserves to identify the minimum level of monitoring necessary to reliably detect changes in wildlife populations over 5-year intervals. We used a similar approach to estimate the minimum sampling needed to infer changes in abundance of hunters in reserves. Our results highlight the relative importance of comprehensive spatial and temporal sampling and suggest a requirement of no less than one monitoring site per every 285 km² in large reserves and 65 km² in smaller reserves. We discuss briefly the cost of effective monitoring and the relevance of our results to other regions of Africa and the world.