Current and projected gaps in the availability of radiotherapy in the Asia-Pacific region: a country income-group analysis

Background: Cancer incidence and mortality is increasing rapidly worldwide, with a higher cancer burden observed in the Asia-Pacific region than in other regions. To date, evidence-based modelling of radiotherapy demand has been based on stage data from high-income countries (HIC) that do not account for the later stage at presentation seen in many low-income and middle-income countries (LMICs). We aimed to estimate the current and projected demand and supply in megavoltage radiotherapy machines in the Asia-Pacific region, using a national income-group adjusted model. Methods: Novel LMIC radiotherapy demand and outcome models were created by adjusting previously developed models that used HIC cancer staging data. These models were applied to the cancer case mix (ie, the incidence of each different cancer) in each LMIC in the Asia-Pacific region to estimate the current and projected optimal radiotherapy utilisation rate (ie, the proportion of cancer cases that would require radiotherapy on the basis of guideline recommendations), and to estimate the number of megavoltage machines needed in each country to meet this demand. Information on the number of megavoltage machines available in each country was retrieved from the Directory of Radiotherapy Centres. Gaps were determined by comparing the projected number of megavoltage machines needed with the number of machines available in each region. Megavoltage machine numbers, local control, and overall survival benefits were compared with previous data from 2012 and projected data for 2040. Findings: 57 countries within the Asia-Pacific region were included in the analysis with 9·48 million new cases of cancer in 2020, an increase of 2·66 million from 2012. Local control was 7·42% and overall survival was 3·05%. Across the Asia-Pacific overall, the current optimal radiotherapy utilisation rate is 49·10%, which means that 4·66 million people will need radiotherapy in 2020, an increase of 1·38 million (42%) from 2012. The number of megavoltage machines increased by 1261 (31%) between 2012 and 2020, but the demand for these machines increased by 3584 (42%). The Asia-Pacific region only has 43·9% of the megavoltage machines needed to meet demand, ranging from 9·9–40·5% in LMICs compared with 67·9% in HICs. 12 000 additional megavoltage machines will be needed to meet the projected demand for 2040. Interpretation: The difference between supply and demand with regard to megavoltage machine availability has continued to widen in LMICs over the past decade and is projected to worsen by 2040. The data from this study can be used to provide evidence for the need to incorporate radiotherapy in national cancer control plans and to inform governments and policy makers within the Asia-Pacific region regarding the urgent need for investment in this sector. Funding: The Regional Cooperative Agreement for Research, Development and Training Related to Nuclear Science and Technology for Asia and the Pacific (RCA) Regional Office (RCARP03)

Dealing with locally-driven degradation: A quick start option under REDD+

The paper reviews a number of challenges associated with reducing degradation and its related emissions through national approaches to REDD+ under UNFCCC policy. It proposes that in many countries, it may in the short run be easier to deal with the kinds of degradation that result from locally driven community over-exploitation of forest for livelihoods, than from selective logging or fire control. Such degradation is low-level, but chronic, and is experienced over very large forest areas. Community forest management programmes tend to result not only in reduced degradation, but also in forest enhancement; moreover they are often popular, and do not require major political shifts. In principle these approaches therefore offer a quick start option for REDD+. Developing reference emissions levels for low-level locally driven degradation is difficult however given that stock losses and gains are too small to be identified and measured using remote sensing, and that in most countries there is little or no forest inventory data available. We therefore propose that forest management initiatives at the local level, such as those promoted by community forest management programmes, should monitor, and be credited for, only the net increase in carbon stock over the implementation period, as assessed by ground level surveys at the start and end of the period. This would also resolve the problem of nesting (ensuring that all credits are accounted for against the national reference emission level), since communities and others at the local level would be rewarded only for increased sequestration, while the national reference emission level would deal only with reductions in emissions from deforestation and degradation

Exploring compact binary merger host galaxies and environments with zELDA

Compact binaries such as double neutron stars or a neutron star paired with a black hole, are strong sources of gravitational waves during coalescence and also the likely progenitors of various electromagnetic phenomena, notably short-duration gamma-ray bursts (SGRBs), and kilonovae. In this work, we generate populations of synthetic binaries and place them in galaxies from the large-scale hydrodynamical galaxy evolution simulation, eagle. With our zELDA code, binaries are seeded in proportion to star formation rate, and we follow their evolution to merger using both the bpass and cosmic binary stellar evolution codes. We track their dynamical evolution within their host galaxy potential, to estimate the galactocentric distance at the time of the merger. Finally, we apply observational selection criteria to allow comparison of this model population with the legacy sample of SGRBs. We find a reasonable agreement with the redshift distribution (peaking at 0.5 26)

Transcriptome pathways unique to dehydration tolerant relatives of modern wheat

Among abiotic stressors, drought is a major factor responsible for dramatic yield loss in agriculture. In order to reveal differences in global expression profiles of drought tolerant and sensitive wild emmer wheat genotypes, a previously deployed shock-like dehydration process was utilized to compare transcriptomes at two time points in root and leaf tissues using the Affymetrix GeneChip(R) Wheat Genome Array hybridization. The comparison of transcriptomes reveal several unique genes or expression patterns such as differential usage of IP(3)-dependent signal transduction pathways, ethylene- and abscisic acid (ABA)-dependent signaling, and preferential or faster induction of ABA-dependent transcription factors by the tolerant genotype that distinguish contrasting genotypes indicative of distinctive stress response pathways. The data also show that wild emmer wheat is capable of engaging known drought stress responsive mechanisms. The global comparison of transcriptomes in the absence of and after dehydration underlined the gene networks especially in root tissues that may have been lost in the selection processes generating modern bread wheats

The translation, validity and reliability of the German version of the Fremantle Back Awareness Questionnaire

Background: The Fremantle Back Awareness Questionnaire (FreBAQ) claims to assess disrupted self-perception of the back. The aim of this study was to develop a German version of the Fre-BAQ (FreBAQ-G) and assess its test-retest reliability, its known-groups validity and its convergent validity with another purported measure of back perception. Methods: The FreBaQ-G was translated following international guidelines for the transcultural adaptation of questionnaires. Thirty-five patients with non-specific CLBP and 48 healthy participants were recruited. Assessor one administered the FreBAQ-G to each patient with CLBP on two separate days to quantify intra-observer reliability. Assessor two administered the FreBaQ-G to each patient on day 1. The scores were compared to those obtained by assessor one on day 1 to assess inter-observer reliability. Known-groups validity was quantified by comparing the FreBAQ-G score between patients and healthy controls. To assess convergent validity, patient\u27s FreBAQ-G scores were correlated to their two-point discrimination (TPD) scores. Results: Intra- and Inter-observer reliability were both moderate with ICC3.1 = 0.88 (95%CI: 0.77 to 0.94) and 0.89 (95%CI: 0.79 to 0.94), respectively. Intra- and inter-observer limits of agreement (LoA) were 6.2 (95%CI: 5.0±8.1) and 6.0 (4.8±7.8), respectively. The adjusted mean difference between patients and controls was 5.4 (95%CI: 3.0 to 7.8, p\u3c0.01). Patient\u27s FreBAQ-G scores were not associated with TPD thresholds (Pearson\u27s r = -0.05, p = 0.79). Conclusions: The FreBAQ-G demonstrated a degree of reliability and known-groups validity. Interpretation of patient level data should be performed with caution because the LoA were substantial. It did not demonstrate convergent validity against TPD. Floor effects of some items of the FreBAQ-G may have influenced the validity and reliability results. The clinimetric properties of the FreBAQ-G require further investigation as a simple measure of disrupted self-perception of the back before firm recommendations on its use can be made

Enhanced Protection against Ebola Virus Mediated by an Improved Adenovirus-Based Vaccine

Jason S. Richardson is with the Public Health Agency of Canada, Michel K. Yao is with the Public Health Agency of Canada, Kaylie N. Tran is with the Public Health Agency of Canada and University of Manitoba, Maria A. Croyle is with UT Austin, James E. Strong is with the Public Health Agency of Canada and University of Manitoba, Heinz Feldmann is with the Public Health Agency of Canada and University of Manitoba, Gary P. Kobinger is with the Public Health Agency of Canada and University of Manitoba.Background -- The Ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. Currently, replication defective adenovirus-based Ebola vaccine is being studied in a phase I clinical trial. Another Ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to Ebola infection. In this report, we modified the common recombinant adenovirus serotype 5-based Ebola vaccine expressing the wild-type ZEBOV glycoprotein sequence from a CMV promoter (Ad-CMVZGP). The immune response elicited by this improved expression cassette vector (Ad-CAGoptZGP) and its ability to afford protection against lethal ZEBOV challenge in mice was compared to the standard Ad-CMVZGP vector. Methodology/Principal Findings -- Ad-CMVZGP was previously shown to protect mice, guinea pigs and nonhuman primates from an otherwise lethal challenge of Zaire ebolavirus. The antigenic expression cassette of this vector was improved through codon optimization, inclusion of a consensus Kozak sequence and reconfiguration of a CAG promoter (Ad-CAGoptZGP). Expression of GP from Ad-CAGoptZGP was substantially higher than from Ad-CMVZGP. Ad-CAGoptZGP significantly improved T and B cell responses at doses 10 to 100-fold lower than that needed with Ad-CMVZGP. Additionally, Ad-CAGoptZGP afforded full protections in mice against lethal challenge at a dose 100 times lower than the dose required for Ad-CMVZGP. Finally, Ad-CAGoptZGP induced full protection to mice when given 30 minutes post-challenge. Conclusions/Significance -- We describe an improved adenovirus-based Ebola vaccine capable of affording post-exposure protection against lethal challenge in mice. The molecular modifications of the new improved vaccine also translated in the induction of significantly enhanced immune responses and complete protection at a dose 100 times lower than with the previous generation adenovirus-based Ebola vaccine. Understanding and improving the molecular components of adenovirus-based vaccines can produce potent, optimized product, useful for vaccination and post-exposure therapy.Financial support was received from the following sources: The Public Health Agency of Canada and the Chemical, Biological, Radiological or Nuclear Research and Technology Initiative (grant #CRTI-06-0218RD awarded to GPK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Pharmac

PAR1 is selectively over expressed in high grade breast cancer patients: a cohort study

<p>Abstract</p> <p>Background</p> <p>The protease-activated receptor (PAR1) expression is correlated with the degree of invasiveness in cell lines. Nevertheless it has never been directed involved in breast cancer patients progression. The aim of this study was to determine whether PAR1 expression could be used as predictor of metastases and mortality.</p> <p>Methods</p> <p>In a cohort of patients with infiltrating ductal carcinoma studied longitudinally since 1996 and until 2007, PAR1 over-expression was assessed by immunoblotting, immunohistochemistry, and flow citometry. Chi-square and log rank tests were used to determine whether there was a statistical association between PAR1 overexpression and metastases, mortality, and survival. Multivariate analysis was performed including HER1, stage, ER and nodes status to evaluate PAR1 as an independent prognostic factor.</p> <p>Results</p> <p>Follow up was 95 months (range: 2–130 months). We assayed PAR1 in a cohort of patients composed of 136 patients; we found PAR1 expression assayed by immunoblotting was selectively associated with high grade patients (50 cases of the study cohort; P = 0.001). Twenty-nine of 50 (58%) patients overexpressed PAR1, and 23 of these (46%) developed metastases. HER1, stage, ER and PAR1 overexpression were robustly correlated (Cox regression, P = 0.002, P = 0.024 and P = 0.002 respectively). Twenty-one of the 50 patients (42%) expressed both receptors (PAR1 and HER1 P = 0.0004). We also found a statistically significant correlation between PAR1 overexpression and increased mortality (P = 0.0001) and development of metastases (P = 0.0009).</p> <p>Conclusion</p> <p>Our data suggest PAR1 overexpression may be involved in the development of metastases in breast cancer patient and is associated with undifferentiated cellular progression of the tumor. Further studies are needed to understand PAR1 mechanism of action and in a near future assay its potential use as risk factor for metastasis development in high grade breast cancer patients.</p

Identification of female sex pheromone for monitoring the barred tooth striped moth, trichopteryx polycommata, a priority conservation species

Pheromone-baited traps can be excellent tools for sensitive detection of insects of conservation concern. Here, identification of the sex pheromone of Trichopteryx polycommata (Denis & Schiffermüller, 1775), an under-recorded UK priority species, is reported. In analyses of extracts of the pheromone glands of female T. polycommata by gas chromatography coupled to electroantennographic recording from the antenna of a male moth, a single active component was detected. This was identified as (Z,Z)-6,9-nonadecadiene (Z,Z6,9-19:H) by comparison of its mass spectrum and retention times with those of the synthetic standard. In a pilot field trial in Kent, UK, T. polycommata males were caught in pheromone traps baited with lures loaded with 1 mg and 2 mg (Z,Z)-6,9-19:H. Optimum lure loading was identified in a further five trials in Kent, Sussex and Lancashire where lures of 0, 0.001, 0.01, 0.1, 1, 2, 5 and 10 mg loadings were tested. Traps baited with 1 to 10 mg of ZZ6,9-19:H caught significantly more T. polycommata than traps baited with 0 mg and 0.001 mg. In a pilot survey of T. polycommata using pheromone lures around Morecambe Bay, UK, T. polycommata males were captured at 122 new sites within the three counties where trials took place, demonstrating the potential of pheromone monitoring to increase knowledge of abundance, distribution and ecology of this elusive species

Multiple order-up-to policy for mitigating bullwhip effect in supply chain network

This paper proposes a multiple order-up-to policy based inventory replenishment scheme to mitigate the bullwhip effect in a multi-stage supply chain scenario, where various transportation modes are available between the supply chain (SC) participants. The proposed policy is similar to the fixed order-up-to policy approach where replenishment decision “how much to order” is made periodically on the basis of the predecided order-up-to inventory level. In the proposed policy, optimal multiple order-up-to levels are assigned to each SC participants, which provides decision making reference point for deciding the transportation related order quantity. Subsequently, a mathematical model is established to define optimal multiple order-up-to levels for each SC participants that aims to maximize overall profit from the SC network. In parallel, the model ensures the control over supply chain pipeline inventory, high satisfaction of customer demand and enables timely utilization of available transportation modes. Findings from the various numerical datasets including stochastic customer demand and lead times validate that—the proposed optimal multiple order-up-to policy based inventory replenishment scheme can be a viable alternative for mitigating the bullwhip effect and well-coordinated SC. Moreover, determining the multiple order-up-to levels is a NP hard combinatorial optimization problem. It is found that the implementation of new emerging optimization algorithm named bacterial foraging algorithm (BFA) has presented superior optimization performances. The robustness and applicability of the BFA algorithm are further validated statistically by employing the percentage heuristic gap and two-way ANOVA analysis

Model parameterization to simulate and compare the PAR absorption potential of two competing plant species

Mountain pastures dominated by the pasture grass Setaria sphacelata in the Andes of southern Ecuador are heavily infested by southern bracken (Pteridium arachnoideum), a major problem for pasture management. Field observations suggest that bracken might outcompete the grass due to its competitive strength with regard to the absorption of photosynthetically active radiation (PAR). To understand the PAR absorption potential of both species, the aims of the current paper are to (1) parameterize a radiation scheme of a two-big-leaf model by deriving structural (LAI, leaf angle parameter) and optical (leaf albedo, transmittance) plant traits for average individuals from field surveys, (2) to initialize the properly parameterized radiation scheme with realistic global irradiation conditions of the Rio San Francisco Valley in the Andes of southern Ecuador, and (3) to compare the PAR absorption capabilities of both species under typical local weather conditions. Field data show that bracken reveals a slightly higher average leaf area index (LAI) and more horizontally oriented leaves in comparison to Setaria. Spectrometer measurements reveal that bracken and Setaria are characterized by a similar average leaf absorptance. Simulations with the average diurnal course of incoming solar radiation (1998–2005) and the mean leaf–sun geometry reveal that PAR absorption is fairly equal for both species. However, the comparison of typical clear and overcast days show that two parameters, (1) the relation of incoming diffuse and direct irradiance, and (2) the leaf–sun geometry play a major role for PAR absorption in the two-big-leaf approach: Under cloudy sky conditions (mainly diffuse irradiance), PAR absorption is slightly higher for Setaria while under clear sky conditions (mainly direct irradiance), the average bracken individual is characterized by a higher PAR absorption potential. (∼74 MJ m−2 year−1). The latter situation which occurs if the maximum daily irradiance exceeds 615 W m−2 is mainly due to the nearly orthogonal incidence of the direct solar beam onto the horizontally oriented frond area which implies a high amount of direct PAR absorption during the noon maximum of direct irradiance. Such situations of solar irradiance favoring a higher PAR absorptance of bracken occur in ∼36% of the observation period (1998–2005). By considering the annual course of PAR irradiance in the San Francisco Valley, the clear advantage of bracken on clear days (36% of all days) is completely compensated by the slight but more frequent advantage of Setaria under overcast conditions (64% of all days). This means that neither bracken nor Setaria show a distinct advantage in PAR absorption capability under the current climatic conditions of the study area