Gene Expression Profiling of the Cephalothorax and Eyestalk in Penaeus Monodon during Ovarian Maturation.

In crustaceans, a range of physiological processes involved in ovarian maturation occurs in organs of the cephalothorax including the hepatopancrease, mandibular and Y-organ. Additionally, reproduction is regulated by neuropeptide hormones and other proteins released from secretory sites within the eyestalk. Reproductive dysfunction in captive-reared prawns, Penaeus monodon, is believed to be due to deficiencies in these factors. In this study, we investigated the expression of gene transcripts in the cephalothorax and eyestalk from wild-caught and captive-reared animals throughout ovarian maturation using custom oligonucleotide microarray screening. We have isolated numerous transcripts that appear to be differentially expressed throughout ovarian maturation and between wild-caught and captive-reared animals. In the cephalothorax, differentially expressed genes included the 1,3-beta-D-glucan-binding high-density lipoprotein, 2/3-oxoacyl-CoA thiolase and vitellogenin. In the eyestalk, these include gene transcripts that encode a protein that modulates G-protein coupled receptor activity and another that encodes an architectural transcription factor. Each may regulate the expression of reproductive neuropeptides, such as the crustacean hyperglycaemic hormone and molt-inhibiting hormone. We could not identify differentially expressed transcripts encoding known reproductive neuropeptides in the eyestalk of either wild-caught or captive-reared prawns at any ovarian maturation stage, however, this result may be attributed to low relative expression levels of these transcripts. In summary, this study provides a foundation for the study of target genes involved in regulating penaeid reproduction.

Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study

Objective To quantify and compare the treatment effect and risk of bias of trials reporting biomarkers or intermediate outcomes (surrogate outcomes) versus trials using final patient relevant primary outcomes. Design Meta-epidemiological study. Data sources All randomised clinical trials published in 2005 and 2006 in six high impact medical journals: Annals of Internal Medicine, BMJ, Journal of the American Medical Association, Lancet, New England Journal of Medicine, and PLoS Medicine. Study selection Two independent reviewers selected trials. Data extraction Trial characteristics, risk of bias, and outcomes were recorded according to a predefined form. Two reviewers independently checked data extraction. The ratio of odds ratios was used to quantify the degree of difference in treatment effects between the trials using surrogate outcomes and those using patient relevant outcomes, also adjusted for trial characteristics. A ratio of odds ratios >1.0 implies that trials with surrogate outcomes report larger intervention effects than trials with patient relevant outcomes. Results 84 trials using surrogate outcomes and 101 using patient relevant outcomes were considered for analyses. Study characteristics of trials using surrogate outcomes and those using patient relevant outcomes were well balanced, except for median sample size (371 v 741) and single centre status (23% v 9%). Their risk of bias did not differ. Primary analysis showed trials reporting surrogate endpoints to have larger treatment effects (odds ratio 0.51, 95% confidence interval 0.42 to 0.60) than trials reporting patient relevant outcomes (0.76, 0.70 to 0.82), with an unadjusted ratio of odds ratios of 1.47 (1.07 to 2.01) and adjusted ratio of odds ratios of 1.46 (1.05 to 2.04). This result was consistent across sensitivity and secondary analyses. Conclusions Trials reporting surrogate primary outcomes are more likely to report larger treatment effects than trials reporting final patient relevant primary outcomes. This finding was not explained by differences in the risk of bias or characteristics of the two groups of trials.

Reproductive interference between honey bee species in artificial sympatry

Reproductive isolation between closely related species is often incomplete. The Western honey bee, Apis mellifera, and the Eastern hive bee, A. cerana have been allopatric for millions of years, but are nonetheless similar in morphology and behaviour. During the last century the two species were brought into contact anthropogenically, providing potential opportunities for interspecific matings. Hybrids between A. mellifera and A. cerana are inviable, so natural interspecific matings are of concern because they may reduce the viability of A. cerana and A. mellifera populations – two of the world's most important pollinators. We examined the mating behaviour of A. mellifera and A. cerana queens and drones from Caoba Basin, China and Cairns, Australia. Drone mating flight times overlap in both areas. Analysis of the spermathecal contents of queens with species-specific genetic markers indicated that in Caoba Basin, 14% of A. mellifera queens mated with at least one A. cerana male, but we detected no A. cerana queens that had mated with A. mellifera males. Similarly, in Cairns, no A. cerana queens carried A. mellifera sperm, but one third of A. mellifera queens had mated with at least one A. cerana male. No hybrid embryos were detected in eggs laid by interspecifically-mated A. mellifera queens in either location. However A. mellifera queens artificially inseminated with A. cerana sperm produced inviable hybrid eggs, or unfertilised drones. This suggests that reproductive interference will impact the viability of honey bee populations wherever A. cerana and A. mellifera are in contact. This article is protected by copyright. All rights reserved.

Nonparametric traversability estimation in partially occluded and deformable terrain

Terrain traversability estimation is a fundamental requirement to ensure the safety of autonomous planetary rovers and their ability to conduct long-term missions. This paper addresses two fundamental challenges for terrain traversability estimation techniques. First, representations of terrain data, which are typically built by the rover’s onboard exteroceptive sensors, are often incomplete due to occlusions and sensor limitations. Second, during terrain traversal, the rover-terrain interaction can cause terrain deformation, which may significantly alter the difficulty of traversal. We propose a novel approach built on Gaussian process (GP) regression to learn, and consequently to predict, the rover’s attitude and chassis configuration on unstructured terrain using terrain geometry information only. First, given incomplete terrain data, we make an initial prediction under the assumption that the terrain is rigid, using a learnt kernel function. Then, we refine this initial estimate to account for the effects of potential terrain deformation, using a near-to-far learning approach based on multitask GP regression. We present an extensive experimental validation of the proposed approach on terrain that is mostly rocky and whose geometry changes as a result of loads from rover traversals. This demonstrates the ability of the proposed approach to accurately predict the rover’s attitude and configuration in partially occluded and deformable terrain.

Analysing the Impact of Learning Inputs - Application to Terrain Traversability Estimation

Data-driven approaches such as Gaussian Process (GP) regression have been used extensively in recent robotics literature to achieve estimation by learning from experience. To ensure satisfactory performance, in most cases, multiple learning inputs are required. Intuitively, adding new inputs can often contribute to better estimation accuracy, however, it may come at the cost of a new sensor, larger training dataset and/or more complex learning, some- times for limited benefits. Therefore, it is crucial to have a systematic procedure to determine the actual impact each input has on the estimation performance. To address this issue, in this paper we propose to analyse the impact of each input on the estimate using a variance-based sensitivity analysis method. We propose an approach built on Analysis of Variance (ANOVA) decomposition, which can characterise how the prediction changes as one or more of the input changes, and also quantify the prediction uncertainty as attributed from each of the inputs in the framework of dependent inputs. We apply the proposed approach to a terrain-traversability estimation method we proposed in prior work, which is based on multi-task GP regression, and we validate this implementation experimentally using a rover on a Mars-analogue terrain.

Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial

Background The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and gefitinib in this setting. Methods This multicentre, international, open-label, exploratory, randomised controlled phase 2B trial (LUX-Lung 7) was done at 64 centres in 13 countries. Treatment-naive patients with stage IIIB or IV NSCLC and a common EGFR mutation (exon 19 deletion or Leu858Arg) were randomly assigned (1:1) to receive afatinib (40 mg per day) or gefitinib (250 mg per day) until disease progression, or beyond if deemed beneficial by the investigator. Randomisation, stratified by EGFR mutation type and status of brain metastases, was done centrally using a validated number generating system implemented via an interactive voice or web-based response system with a block size of four. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. Coprimary endpoints were progression-free survival by independent central review, time-to-treatment failure, and overall survival. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01466660. Findings Between Dec 13, 2011, and Aug 8, 2013, 319 patients were randomly assigned (160 to afatinib and 159 to gefitinib). Median follow-up was 27·3 months (IQR 15·3–33·9). Progression-free survival (median 11·0 months [95% CI 10·6–12·9] with afatinib vs 10·9 months [9·1–11·5] with gefitinib; hazard ratio [HR] 0·73 [95% CI 0·57–0·95], p=0·017) and time-to-treatment failure (median 13·7 months [95% CI 11·9–15·0] with afatinib vs 11·5 months [10·1–13·1] with gefitinib; HR 0·73 [95% CI 0·58–0·92], p=0·0073) were significantly longer with afatinib than with gefitinib. Overall survival data are not mature. The most common treatment-related grade 3 or 4 adverse events were diarrhoea (20 [13%] of 160 patients given afatinib vs two [1%] of 159 given gefitinib) and rash or acne (15 [9%] patients given afatinib vs five [3%] of those given gefitinib) and liver enzyme elevations (no patients given afatinib vs 14 [9%] of those given gefitinib). Serious treatment-related adverse events occurred in 17 (11%) patients in the afatinib group and seven (4%) in the gefitinib group. Ten (6%) patients in each group discontinued treatment due to drug-related adverse events. 15 (9%) fatal adverse events occurred in the afatinib group and ten (6%) in the gefitinib group. All but one of these deaths were considered unrelated to treatment; one patient in the gefitinib group died from drug-related hepatic and renal failure. Interpretation Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC compared with gefitinib, with a manageable tolerability profile. These data are potentially important for clinical decision making in this patient population.

2nd ESMO Consensus Conference in Lung Cancer: Locally advanced stage III non-small-cell lung cancer

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11–12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.

Comparison of partial extraction reagents for assessing potential bioavailability of heavy metals in sediments

Assessment of heavy metal bioavailability in sediments is complex because of the number of partial extraction methods available for the assessment and the general lack of certified reference materials. This study evaluates five different extraction methodologies to ascertain the relative strengths and weaknesses of each method. The results are then compared to previously published work to ascertain the most effective partial extraction technique, which was established to be dilute (0.75 – 1 M) nitric acid solutions. These results imply that single reagent; weak acid extractions provide a better assessment of potentially bioavailable metals than the chelating agents used in sequential extraction methods.

Importance of carbon dioxide physiological forcing to future climate change

An increase in atmospheric carbon dioxide (CO2) concentration influences climate both directly through its radiative effect (i.e., trapping longwave radiation) and indirectly through its physiological effect (i.e., reducing transpiration of land plants). Here we compare the climate response to radiative and physiological effects of increased CO2 using the National Center for Atmospheric Research (NCAR) coupled Community Land and Community Atmosphere Model. In response to a doubling of CO2, the radiative effect of CO2 causes mean surface air temperature over land to increase by 2.86 ± 0.02 K (± 1 standard error), whereas the physiological effects of CO2 on land plants alone causes air temperature over land to increase by 0.42 ± 0.02 K. Combined, these two effects cause a land surface warming of 3.33 ± 0.03 K. The radiative effect of doubling CO2 increases global runoff by 5.2 ± 0.6%, primarily by increasing precipitation over the continents. The physiological effect increases runoff by 8.4 ± 0.6%, primarily by diminishing evapotranspiration from the continents. Combined, these two effects cause a 14.9 ± 0.7% increase in runoff. Relative humidity remains roughly constant in response to CO2-radiative forcing, whereas relative humidity over land decreases in response to CO2-physiological forcing as a result of reduced plant transpiration. Our study points to an emerging consensus that the physiological effects of increasing atmospheric CO2 on land plants will increase global warming beyond that caused by the radiative effects of CO2.

Why is there a short-term increase in global precipitation in response to diminished CO2 forcing?

Recently, it was found that a reduction in atmospheric CO2 concentration leads to a temporary increase in global precipitation. We use the Hadley Center coupled atmosphere-ocean model, HadCM3L, to demonstrate that this precipitation increase is a consequence of precipitation sensitivity to changes in atmospheric CO2 concentrations through fast tropospheric adjustment processes. Slow ocean cooling explains the longer-term decrease in precipitation. Increased CO2 tends to suppress evaporation/precipitation whereas increased temperatures tend to increase evaporation/precipitation. When the enhanced CO2 forcing is removed, global precipitation increases temporarily, but this increase is not observed when a similar negative radiative forcing is applied as a reduction of solar intensity. Therefore, transient precipitation increase following a reduction in CO2-radiative forcing is a consequence of the specific character of CO2 forcing and is not a general feature associated with decreases in radiative forcing. Citation: Cao, L., G. Bala, and K. Caldeira (2011), Why is there a short-term increase in global precipitation in response to diminished CO2 forcing?, Geophys. Res. Lett., 38, L06703, doi:10.1029/2011GL046713.

Albedo enhancement of marine clouds to counteract global warming: impacts on the hydrological cycle

Recent studies have shown that changes in solar radiation affect the hydrological cycle more strongly than equivalent CO(2) changes for the same change in global mean surface temperature. Thus, solar radiation management ``geoengineering'' proposals to completely offset global mean temperature increases by reducing the amount of absorbed sunlight might be expected to slow the global water cycle and reduce runoff over land. However, proposed countering of global warming by increasing the albedo of marine clouds would reduce surface solar radiation only over the oceans. Here, for an idealized scenario, we analyze the response of temperature and the hydrological cycle to increased reflection by clouds over the ocean using an atmospheric general circulation model coupled to a mixed layer ocean model. When cloud droplets are reduced in size over all oceans uniformly to offset the temperature increase from a doubling of atmospheric CO(2), the global-mean precipitation and evaporation decreases by about 1.3% but runoff over land increases by 7.5% primarily due to increases over tropical land. In the model, more reflective marine clouds cool the atmospheric column over ocean. The result is a sinking motion over oceans and upward motion over land. We attribute the increased runoff over land to this increased upward motion over land when marine clouds are made more reflective. Our results suggest that, in contrast to other proposals to increase planetary albedo, offsetting mean global warming by reducing marine cloud droplet size does not necessarily lead to a drying, on average, of the continents. However, we note that the changes in precipitation, evaporation and P-E are dominated by small but significant areas, and given the highly idealized nature of this study, a more thorough and broader assessment would be required for proposals of altering marine cloud properties on a large scale.

Climate forcing and response to idealized changes in surface latent and sensible heat

Land use and land cover changes affect the partitioning of latent and sensible heat, which impacts the broader climate system. Increased latent heat flux to the atmosphere has a local cooling influence known as `evaporative cooling', but this energy will be released back to the atmosphere wherever the water condenses. However, the extent to which local evaporative cooling provides a global cooling influence has not been well characterized. Here, we perform a highly idealized set of climate model simulations aimed at understanding the effects that changes in the balance between surface sensible and latent heating have on the global climate system. We find that globally adding a uniform 1 W m(-2) source of latent heat flux along with a uniform 1 W m(-2) sink of sensible heat leads to a decrease in global mean surface air temperature of 0.54 +/- 0.04 K. This occurs largely as a consequence of planetary albedo increases associated with an increase in low elevation cloudiness caused by increased evaporation. Thus, our model results indicate that, on average, when latent heating replaces sensible heating, global, and not merely local, surface temperatures decrease.

Dependence of climate forcing and response on the altitude of black carbon aerosols

Black carbon aerosols absorb solar radiation and decrease planetary albedo, and thus can contribute to climate warming. In this paper, the dependence of equilibrium climate response on the altitude of black carbon is explored using an atmospheric general circulation model coupled to a mixed layer ocean model. The simulations model aerosol direct and semi-direct effects, but not indirect effects. Aerosol concentrations are prescribed and not interactive. It is shown that climate response of black carbon is highly dependent on the altitude of the aerosol. As the altitude of black carbon increases, surface temperatures decrease; black carbon near the surface causes surface warming, whereas black carbon near the tropopause and in the stratosphere causes surface cooling. This cooling occurs despite increasing planetary absorption of sunlight (i.e. decreasing planetary albedo). We find that the trend in surface air temperature response versus the altitude of black carbon is consistent with our calculations of radiative forcing after the troposphere, stratosphere, and land surface have undergone rapid adjustment, calculated as ``regressed'' radiative forcing. The variation in climate response from black carbon at different altitudes occurs largely from different fast climate responses; temperature dependent feedbacks are not statistically distinguishable. Impacts of black carbon at various altitudes on the hydrological cycle are also discussed; black carbon in the lowest atmospheric layer increases precipitation despite reductions in solar radiation reaching the surface, whereas black carbon at higher altitudes decreases precipitation.