bluuebunny/crossref_metadata_2025 huggingface dataset:
PD53 Efficacy And Safety Of Nicotinamide In Hemodialysis Patients
Authors: Hussain Salman , Singh Ambrish , Habib Anwar , Najmi Abul Kalam
Published: January 2019

Introduction:

Hyperphosphatemia is a most common problem in dialysis patients. Phosphorus imbalance in dialysis patients increases the risk of developing the bone mineral disorder and cardiovascular mortality. Randomized controlled trials (RCTs) presented variable findings concerning the reduction of phosphorous level in nicotinamide user. So, this systematic review is aimed to explore the efficacy and safety of nicotinamide in hemodialysis patients.

Methods:

This systematic review was conducted by adhering to the PRISMA guidelines. Study for inclusion was identified by running the suitable keywords in databases including PubMed, Embase, and Cochrane central from inception to 31 October 2017. Cochrane risk of bias tool was used to judge the quality of included RCTs. The change in serum phosphorus level was the primary outcome, while the change in other biochemical parameters including serum calcium, calcium-phosphorus product level, iPTH, platelets, lipid profile parameters, and the safety profile was considered under secondary outcomes. Review Manager (RevMan v5.3) was used for statistical analysis.

Results:

Finally four articles were qualified for inclusion in this study with a total of 274 participants of which 136 were in the treatment (nicotinamide) group. All the included studies showed statistically significant reduction in mean serum phosphorous, calcium-phosphorus product level in the treatment arm at the end point of the study, while the reduction in the placebo group was not statistically significant in all the studies. Among other biochemical parameters analyzed, only high-density lipoprotein (HDL) was found to be significantly increased from baseline to the endpoint of the study in the nicotinamide group, while the placebo group showed no significant change in all the included studies except the study by Shahbazian et al. Thrombocytopenia was the most commonly reported adverse event in the treatment group followed by diarrhea.

Conclusions:

Nicotinamide was found to be effective in the management of hyperphosphatemia in hemodialysis patients. The safety profile was found to be satisfactory.
PD55 Diagnostic Accuracy Of Line Probe Assay Technique Compared To Sensitivity Test
Authors: Leite Betânia , Gomes Dalila , da Mata Fabiana
Published: January 2019

Introduction:

Antimicrobial resistance is a serious public health problem at the global level. The sensitivity test in liquid and solid media-based techniques is traditionally used in Brazil for the diagnosis of resistant tuberculosis (TB). However, the time required for the diagnosis of this test is, on average, 60 (sixty) days, a period considered to be very high, especially considering certain vulnerable populations (street dwellers), since the long time to the result of the test makes it difficult to establish a second contact between the health institution and the individual, resulting in people without access to diagnosis and appropriate treatment. The line probe assay (LPA) technique often replaces the use of the sensitivity test in many countries, being considered of low time for the diagnosis, ranging from 24 to 48 hours.

Methods:

We searched the Medline databases (via Pubmed), Embase, and The Cochrane Library, with the aim of finding systematic reviews with meta-analyses. The articles were screened by titles and abstracts and later the full text reading was carried out, according to the inclusion criteria.

Results:

Three systematic reviews with meta-analysis were selected. The interventions evaluated the LPA technique compared to the conventional drug sensitivity test. The evaluated tests showed good performance as rapid screening tests for resistance to rifampicin in high prevalence sites. However, although the test results for resistance to isoniazid showed good specificity, there was a high variability in sensitivity estimates.

Conclusions:

This study reinforces the idea that the LPA technique may contribute to the previous diagnosis, and this is a probable strategy to control the disease, especially in vulnerable populations that are more likely to be affected by tuberculosis. For a broader analysis of the benefit of the technique, further studies are suggested.
PD62 Off-Label Use Of Medicines For Public Health Needs
Authors: Mega Tacila , Rabelo Roberta , Vidal Juliana , de Brito Artur Felipe
Published: January 2019

Introduction:

The use of drugs for clinical conditions that differ from those approved in prescribing information (product labels) is known as off-label use. In Brazil, the Brazilian Health Regulatory Agency (ANVISA) is the official organization that regulates the use of health technologies. For technologies to be incorporated into the Brazilian public health system, registration with ANVISA is mandatory. However, occasionally, it is necessary to evaluate technologies for off-label use in the interests of public health. This study aimed to identify the health technologies recommended by the National Committee for Health Technology Incorporation (CONITEC) with an off-label indication between January 2012 and October 2017.

Methods:

A descriptive study was undertaken using data available on the CONITEC website.

Results:

The study identified seven drugs with a favorable recommendation for off-label use: everolimus, sirolimus, and tacrolimus as immunosuppressants in transplant recipients; clozapine for bipolar affective disorder; pentoxifylline for cutaneous leishmaniosis mucosa; risperidone for adults with autism spectrum disorder, and bevacizumab for age-related macular degeneration and diabetic macular edema. For these decisions the Committee considered the scientific evidence available for the indication proposed, the severity of the disease, and the existence or absence of alternative treatments. This was possible because Brazilian legislation allows ANVISA to authorize the off-label use of health technologies provided that the analysis is supported by scientific evidence regarding effectiveness, accuracy, and safety for the intended purpose.

Conclusions:

The off-label use of health technologies is a worldwide practice that can favor vulnerable populations and neglected diseases. This practice should be seen as positive when there is evidence supporting off-label use, and such decisions should not be influenced by political, economic, or marketing considerations.
PD64 Diagnostic Accuracy Of The Nitrate Reductase Assay Technique
Authors: Gomes Dalila , Leite Betânia , da Mata Fabiana Araujo Figueiredo
Published: January 2019

Introduction:

The conventional drug sensitivity test is traditionally used in Brazil to diagnose drug-resistant tuberculosis. However, the test can take up to 60 days to return a diagnosis, which is considered too long for certain vulnerable populations. Therefore, this study analyzed the available scientific evidence on the accuracy and time to diagnosis of the nitrate reductase assay for diagnosing resistant tuberculosis, compared with the conventional drug sensitivity test.

Methods:

We searched MEDLINE, Embase, and The Cochrane Library for systematic reviews with meta-analyses. The articles were screened by title and abstract. The full-texts of potentially relevant articles were then screened according to the inclusion criteria.

Results:

Three systematic reviews with meta-analyses were selected that compared the nitrate reductase assay with the conventional drug sensitivity test. The accuracy of the nitrate reductase assay was satisfactory in most of the results when compared with the sensitivity test, except for one study that showed low sensitivity for the detection of streptomycin resistance. In addition, the nitrate reductase assay had a shorter time to diagnosis than the drug sensitivity test.

Conclusions:

The results of this study reinforce the idea that the nitrate reductase assay may diagnose drug-resistant tuberculosis earlier than the conventional drug sensitivity test and be a helpful strategy for controlling the disease, especially in vulnerable populations that are more likely to be affected by tuberculosis. For a broader analysis of the benefit of the assay, it is suggested that studies investigate the impact of the shorter time to diagnosis on morbidity and mortality in patients with drug-resistant tuberculosis. In addition, economic analyses comparing the nitrate reductase assay with the sensitivity test are recommended to evaluate the cost-benefit ratio.
VP02 Real-World Evidence (RWE) And CADTH Pan-Canadian Oncology Drug Review
Authors: Han Dolly , Tiruneh Missale , Chambers Alexandra , Haynes Adam
Published: January 2019

Introduction:

The pan-Canadian Oncology Drug Review (pCODR) program was established by Canada's provincial and territorial Ministries of Health (except Quebec) to assess cancer drug therapies and make recommendations to guide drug reimbursement decisions. The pCODR Expert Review Committee (pERC) makes reimbursement recommendations, providing a rationale for the recommendation and next steps for stakeholders. The objective of this analysis was to identify reviews and reasons pERC has requested real-world evidence (RWE) data collection.

Methods:

A retrospective analysis of pERC Final Recommendations (January 2012 – May 2017) was conducted. pERC Final Recommendations include drug information, reimbursement recommendation, rationale for recommendation following pERC's Deliberative Framework (clinical benefit, patient-based values, economic evaluation, and adoption feasibility), next steps for jurisdictions to consider to support their funding decisions, summary of deliberations, and evidence in brief. Reviews were included if there was a next step advising the collection of RWE to reduce uncertainty in the drug under review.

Results:

Out of eighty-four reviews, forty-one (forty-eight percent) included a next step to collect RWE to address a gap in the available evidence. Reasons for RWE data collection, in descending order of frequency, were to inform: sequencing of available therapies; magnitude of clinical benefit and cost-effectiveness or the true cost-effectiveness; duration of treatment and cost-effectiveness; defining the population or disease progression; quality of life; and dosage.

Conclusions:

In almost half of pERC's recommendation there is an indication that there is a gap in the existing evidence that could potentially be addressed through the collection of RWE. This reflects the rising number of new cancer drugs, limited evidence supporting submissions (for example non-comparative studies), and newer drugs such as immunotherapies which may not have a fixed treatment duration. Further research includes development of mechanisms for RWE data collection to help inform pERC recommendations and assist stakeholders with adoption feasibility of reviewed drugs.
VP06 The Effectiveness And Ethics Of Prenatal Testing For Cystic Fibrosis
Authors: Kessels Sharon , Newton Skye , Carter Drew , Merlin Tracy
Published: January 2019

Introduction:

Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasians, occurring in one out of every 2,500–2,800 births worldwide, and is associated with a high burden of disease. In Australia, prenatal testing for CF is indicated for pregnant couples identified as carriers or when a fetus is found to have an ‘echogenic bowel’ (FEB). We aimed to determine the effectiveness of prenatal CF testing and to assess ethical dimensions. A key challenge in assessing a prenatal test is selecting appropriate endpoints to indicate clinical effectiveness.

Methods:

A systematic review was conducted and a linked evidence approach was used to answer the effectiveness question. The literature on ethical considerations relating to prenatal testing was also reviewed.

Results:

No studies were identified on the direct effectiveness of prenatal CF testing or downstream consequences. Linked evidence showed good diagnostic performance with a test failure rate of 4.5 percent. Termination of pregnancy occurred in the majority of cases where two mutations were identified in a fetus of carrier parents (155/163; 95 percent), indicating testing impacts clinical management. In FEB cases with CF, termination occurred in around sixty-five percent of pregnancies. Both terminating a pregnancy and having a child with CF were associated with poor short term parental psychological outcomes. Evidence indicates prenatal testing leads to a decreased number of CF-affected births. However, ethical analyses indicated that ‘informed decisions’ should have been the primary outcome of interest.

Conclusions:

Proper counselling prior to testing ensures that the aim of prenatal testing is informing reproductive choices in a non-directive way, rather than decreasing the number of CF-affected births (which is ethically problematic). These results suggest that for health technology assessments undertaken on contentious topics, ethical analysis should be undertaken first so appropriate endpoints are selected for the subsequent systematic review of clinical evidence and for the economic model.
VP17 Hepatitis C Virus Treatment: A Meta-Analysis Of Long-Term Efficacy
Authors: Inserra Chiara , Davies Sophia Campbell , Piacenza Mariagrazia , Bignamini Angelo , Minghetti Paola , Zerega Grazia
Published: January 2019

Introduction:

The efficacy of second generation direct-acting antiviral agents (DAAs-2), in terms of sustained viral response (SVR) 12 weeks after the end of treatment (EOT), has widely been proven; however, long-term efficacy is still controversial due to the low number of available studies with a small number of patients. The objective of this study is to conduct a systematic review and, if possible, a meta-analysis of existing clinical evidence of the long-term efficacy (SVR longer than 12 weeks after EOT) of DAAs-2 for hepatitis C virus (HCV) treatment.

Methods:

A systematic review was performed with the use of CENTRAL, MEDLINE, Embase, Pubmed and SBBL-CILEA/METACRAWLER databases. Trials were initially screened by the title; secondly, full papers and abstracts were analysed. The meta-analysis included randomised controlled trials (RCTs) with adult patients affected by HCV, treated with DAAs-2 and assessed for longer than 12 weeks after EOT. Study quality assessment was undertaken using the Jadad scale. Heterogeneity analysis of the studies was conducted with chi-square and I2. The statistical analysis of the efficacy rate was performed using the meta package with the R software. The effect estimate was expressed in risk ratio (RR) with 95% confidence interval (CI 95%) and pooled using a random effects model.

Results:

Of the 106 identified studies, 11 high quality RCTs were included for meta-analysis (25 were duplicate publications, 70 did not meet the inclusion criteria). Considered genotypes were 1 (n = 9), 2 (n = 1), 3 (n = 1). Meta-analysis included 3,720 patients (2,698 treated with DAAs-2; 1,022 treated with placebo or a first generation DAA±Ribavirin±Pegylated interferon). Heterogeneity between studies was high (p<0.001; I2 = 90.2%); however, it was absorbed by the model (τ2 = 0,08). Long-term efficacy was expressed as SVR 24 weeks after EOT, since longer timescales were not available. According to the pooled RR, the incidence of efficacy was 1.5 (CI 95%: 1.24−1.83, p < 0.001).

Conclusions:

The meta-analysis demonstrated that DAAs-2 for HCV treatment have long-term efficacy at SVR 24 weeks after the EOT; however, the number of studies is mostly based on genotype 1. More RCTs are required to confirm long-term efficacy at more than six months after EOT for all treated genotypes.
VP26 A Critical Appraisal Tool For Systematic Mixed Studies Reviews
Authors: Hong Quan Nha , Pluye Pierre , Fàbregues Sergi , Bartlett Gillian , Boardman Felicity , Cargo Margaret , Dagenais Pierre , Gagnon Marie-Pierre , Griffiths Frances , Nicolau Belinda , O'Cathain Alicia , Rousseau Marie-Claude , Vedel Isabelle
Published: January 2019

Introduction:

Systematic mixed studies reviews are a type of systematic review that combine qualitative, quantitative and mixed methods studies. They are gaining in popularity due to their potential for providing in-depth answers to complex clinical problems and practical concerns. However, several challenges are encountered in systematic mixed studies reviews because of the heterogeneity of included study designs. One of these challenges is related to the quality appraisal of included studies. To address this challenge, a critical appraisal tool for assessing the quality of quantitative, qualitative and mixed methods studies was developed in 2007: the Mixed Methods Appraisal Tool (MMAT). The aim of this project was to strengthen the content validity of the MMAT.

Methods:

A new version of the MMAT was developed using the results from a literature review on critical appraisal tools and a modified e-Delphi study with methodological experts (n = 73) to identify the core relevant criteria to include in the MMAT.

Results:

The results of this project and the new version of the MMAT will be presented. The MMAT has three main characteristics. First, it can be used for different study designs since it includes criteria for qualitative, quantitative and mixed methods studies. Second, the MMAT focuses on the core relevant methodological criteria and has five criteria per category of study. Third, it includes specific criteria for assessing mixed methods studies.

Conclusions:

Currently, there exists over 500 critical appraisal tools, making the task of selecting the proper tools for use in systematic mixed studies reviews more difficult. The MMAT offers an alternative solution by proposing a unique tool that can appraise the quality of different study designs. Also, by limiting to core criteria, the MMAT can provide a more time efficient assessment.
VP40 Robotic Surgery: From Health Technology Assessment To State Health Policy
Authors: Fennessy Paul , King Richard
Published: January 2019

Introduction:

The aging population means more men are diagnosed with prostate cancer, resulting in greater demand for treatment. Robot-assisted radical prostatectomy (RARP) claims to offer additional benefits to patients and providers. The independent Victorian Health Technology Program Advisory Committee assessed safety, clinical effectiveness and cost effectiveness evidence and financial impact to inform policy, access and reimbursement decision-making by state government policy makers and public hospital providers.

Methods:

Public and private hospital activity and costs for 2008–09 to 2012–13 from the Victorian Admitted Episodes Database (VAED) and the Victorian Cost Data Collection (VCDC) were identified. Data were extracted and reviewed based on (i) DRGs M01A and B, (ii) primary diagnostic code C61 (ICD-10-AM), and (iii) Australian Classification of Health Interventions procedure codes for open (ORP), laparoscopic (LRP) and RARP, supplemented by Victorian Prostate Cancer Clinical Registry data. English language Health Technology Assessments (HTAs)/systematic reviews published January 2009 to January 2015 were identified and analysed with comparative clinical outcomes data for RARP vs. ORP and RARP vs. LRP analysed. Not all reported the same data and most outcomes data presented were odds ratios and risk ratios.

Results:

RARP offers patients a shorter length of stay (LOS) compared with ORP or LRP, but the procedure takes longer to perform. While RARP has similar safety and clinical effectiveness profiles compared with ORP and LRP, published data do not unequivocally demonstrate that RARP is superior to ORP or LRP in terms of clinical outcomes. RARP is more expensive than ORP and LRP. The cost differential increases when capital costs are taken into account. Cost offsets from a reduced LOS are insufficient to justify the higher cost.

Conclusions:

Since RARP produces similar clinical outcomes to ORP and LRP but at a higher cost, the Victorian Health Technology Program Advisory Committee considered the case for public sector support of RARP is weak and provided two recommendations: (i) State Government resources are not used to procure RARP capital equipment; (ii) public hospitals can refer patients to a RARP provider, provided costs are negotiated prior to patient transfer and fully covered by the referring hospital.
The New York City–New Orleans connection: Evidence from constraint ranking comparison
Authors: Carmichael Katie , Becker Kara
Published: January 2019

New York City English (NYCE) and New Orleans English (NOE) demonstrate remarkable similarity for cities located 1300 miles apart. Though the question of whether these dialects feature a shared history has fueled papers on the subject (Berger, 1980; Labov, 2007), there remain a number of issues with the historical record that prevent researchers from arriving at a consensus (Eble, 2016). This article presents linguistic evidence from constraint ranking comparisons of variable nonrhoticity andbought-raising in comparable contemporary samples of NYCE and NOE speakers. Findings demonstrate strikingly similar systems for (r), but dissimilar systems forbought-raising. We examine the results of our analyses in the context of evidence from previous comparisons of NYCE and NOE, concluding that the resemblance between the two dialects is likely due to diffusion from New York City to New Orleans, occurring in the 19th century beforebought-raising emerged in either variety.
Incomplete neutralization in African American English: The case of final consonant voicing
Authors: Farrington Charlie
Published: January 2019

In many varieties of African American English (AAE), glottal stop replacement and deletion of word-final /t/ and /d/ results in consonant neutralization, while the underlying voicing distinction may be maintained by other cues, such as vowel duration. Here, I examine the relationship between vowel duration, final glottal stop replacement, and deletion of word-final /t, d/ to determine whether the phonological contrast of consonant voicing is maintained through duration of the preceding vowel. Data come from conversational interviews of AAE speakers in North Carolina, Tennessee, and Washington, DC. Results indicate that glottalization and deletion of word-final /t/ and /d/ are widespread across the speakers in the analysis. Additionally, the duration of vowels is significantly longer before underlying /d/ than /t/ for consonant neutralized contexts, thus showing that duration, normally a secondary cue to final voicing, may be becoming a primary cue in AAE.
Does Care Experience Affect Policy Interests? Male Legislators, Parental Leave, and Political Priorities in Sweden
Authors: Stensota Helena Olofsdotter
Published: January 2019

A central argument in theories on women's political interests has been that the sexual division of labor, inter alia, gives women greater experience of responsibility for the care of others, especially children, which in turn influences their political attitudes. However, the specifics of this claim have not been sufficiently examined in prior literature. By applying unique data on Swedish legislators’ subjective policy preferences and use of their parental leave over time, this article explores empirically whether the personal roles of members of parliament (MPs) in reproduction affect their political preferences, regardless of their sex. The analysis reveals that men's interest in social policy tends to increase after being on parental leave while in office, whereas women's interest in social and family policy remains strong, regardless. This finding might indicate a care experience mechanism at work, pertinent also to men, but with a possibly shallower content. The analysis raises the question: are care issues, previously seen as women's issues, now becoming human issues? It further contributes to the discussion on ways to measure gender other than using sex as proxy.
Using GRACE to Explain Variations in the Earth's Oblateness
Authors: Sun Yu , Riva Riccardo , Ditmar Pavel , Rietbroek Roelof
Published: January 2019

We present a new approach to estimate time variations in J2. Those variations are represented as the sum of contributions from individual sources. This approach uses solely Gravity Recovery And Climate Experiment (GRACE) data and the geoid fingerprints of mass redistributions that take place both at the surface and in the interior of the solid Earth. The results agree remarkably well with those based on satellite laser ranging, while estimates of the sources explain the observed variations in J2. Seasonal variations are dominated by terrestrial water storage and by mass redistribution in the atmosphere and ocean. Trends, however, are primarily controlled by the Greenland and Antarctic ice sheets and by glacial isostatic adjustment. The positive trend from surface mass variations is larger than the negative trend due to glacial isostatic adjustment and leads to an overall rising trend during the GRACE period (2002–2017).
Formation of Tropical Anvil Clouds by Slow Evaporation
Authors: Seeley Jacob T. , Jeevanjee Nadir , Langhans Wolfgang , Romps David M.
Published: January 2019

Tropical anvil clouds play a large role in the Earth's radiation balance, but their effect on global warming is uncertain. The conventional paradigm for these clouds attributes their existence to the rapidly declining convective mass flux below the tropopause, which implies a large source of detraining cloudy air there. Here we test this paradigm by manipulating the sources and sinks of cloudy air in cloud‐resolving simulations. We find that anvils form in our simulations because of the long lifetime of upper‐tropospheric cloud condensates, not because of an enhanced source of cloudy air below the tropopause. We further show that cloud lifetimes are long in the cold upper troposphere because the saturation specific humidity is much smaller there than the condensed water loading of cloudy updrafts, which causes evaporative cloud decay to act very slowly. Our results highlight the need for novel cloud‐fraction schemes that align with this decay‐centric framework for anvil clouds.
Warming Effects of Spring Rainfall Increase Methane Emissions From Thawing Permafrost
Authors: Neumann Rebecca B. , Moorberg Colby J. , Lundquist Jessica D. , Turner Jesse C. , Waldrop Mark P. , McFarland Jack W. , Euskirchen Eugenie S. , Edgar Colin W. , Turetsky Merritt R.
Published: January 2019

Methane emissions regulate the near‐term global warming potential of permafrost thaw, particularly where loss of ice‐rich permafrost converts forest and tundra into wetlands. Northern latitudes are expected to get warmer and wetter, and while there is consensus that warming will increase thaw and methane emissions, effects of increased precipitation are uncertain. At a thawing wetland complex in Interior Alaska, we found that interactions between rain and deep soil temperatures controlled methane emissions. In rainy years, recharge from the watershed rapidly altered wetland soil temperatures, warming the top ~80 cm of soil in spring and summer and cooling it in autumn. When soils were warmed by spring rainfall, methane emissions increased by ~30%. The warm, deep soils early in the growing season likely supported both microbial and plant processes that enhanced emissions. Our study identifies an important and unconsidered role of rain in governing the radiative forcing of thawing permafrost landscapes.
Remote Sensing of Radiation Belt Energetic Electrons Using Lightning Triggered Upper Band Chorus
Authors: Hosseini Poorya , Gołkowski Mark , Harid Vijay
Published: January 2019

Observations of magnetospheric chorus being triggered by lightning‐induced whistlers are rare but provide a unique opportunity to remotely diagnose wave‐particle interactions in the Earth's radiation belts. The observations presented herein are unique in that whistlers, originating from lightning, are seen to trigger upper band chorus repeatedly over the course of 2 hr. Each whistler exhibits a distinct upper frequency cutoff that is used to estimate the anisotropy of the hot plasma distribution. Resulting anisotropy estimates are in good agreement with previous in situ measurements. While the anisotropy determines wave growth in the linear regime, access to the nonlinear regime requires the in situ wave amplitude to exceed the threshold for phase trapping of energetic electrons. The results suggest that while upper band chorus is less favorable to be spontaneously generated, the conditions in this band are more conducive for triggering of the chorus instability by an external input wave.
Modeling Global Riverine DOC Flux Dynamics From 1951 to 2015
Authors: Li Mingxu , Peng Changhui , Zhou Xiaolu , Yang Yanzheng , Guo Yanrong , Shi Guohua , Zhu Qiuan
Published: January 2019

Climate change has a profound impact on the global carbon cycle, including effects on riverine carbon pools, which connect terrestrial, oceanic, and atmospheric carbon pools. Until now, terrestrial ecosystem models have rarely incorporated riverine carbon components into global carbon budgets. Here we developed a new process‐based model, TRIPLEX‐HYDRA (TRIPLEX‐hydrological routing algorithm), that considers the production, consumption, and transport processes of nonanthropogenic dissolved organic carbon (DOC) from soil to river ecosystems. After the parameter calibration, model results explained more than 50% of temporal variations in all but three rivers. Validation results suggested that DOC yield simulated by TRIPLEX‐HYDRA has a good fit (R2 = 0.61, n = 71, p < 0.001) with global river observations. And then, we applied this model for global rivers. We found that mean DOC yield of global river approximately 1.08 g C/m2 year, where most high DOC yield appeared in the rivers from high northern or tropic regions. Furthermore, our results suggested that global riverine DOC flux appeared a significant decrease trend (average rate: 0.38 Pg C/year) from 1951 to 2015, although the variation patterns of DOC fluxes in global rivers are diverse. A decreasing trend in riverine DOC flux appeared in the middle and high northern latitude regions (30–90°N), which could be attributable to an increased flow path and DOC degradation during the transport process. Furthermore, increasing trend of DOC fluxes is found in rivers from tropical regions (30°S–30°N), which might be related to an increase in terrestrial organic carbon input. Many other rivers (e.g., Mississippi, Yangtze, and Lena rivers) experienced no significant changes under a changing environment.
Radiocarbon Age Offsets Between Two Surface Dwelling Planktonic Foraminifera Species During Abrupt Climate Events in the SW Iberian Margin
Authors: Ausín Blanca , Haghipour Negar , Wacker Lukas , Voelker Antje H. L. , Hodell David , Magill Clayton , Looser Nathan , Bernasconi Stefano M. , Eglinton Timothy I.
Published: January 2019

This study identifies temporal biases in the radiocarbon ages of the planktonic foraminifera species Globigerina bulloides and Globigerinoides ruber (white) in a sediment core from the SW Iberian margin (so‐called Shackleton site). Leaching of the outer shell and measurement of the radiocarbon content of both the leachate and leached sample enabled us to identify surface contamination of the tests and its impact on their 14C ages. Incorporation of younger radiocarbon on the outer shell affected both species and had a larger impact downcore. Interspecies comparison of the 14C ages of the leached samples reveal systematic offsets with 14C ages for G. ruber being younger than G. bulloides ages during the last deglaciation and part of the Early and mid‐Holocene. The greatest offsets (up to 1,030 years) were found during Heinrich Stadial 1, the Younger Dryas, and part of the Holocene. The potential factors differentially affecting these two planktonic species were assessed by complementary 14C, oxygen and carbon isotopes, and species abundance determinations. The coupled effect of bioturbation with changes in the abundance of G. ruber is invoked to account for the large age offsets. Our results highlight that 14C ages of planktonic foraminifera might be largely compromised even in settings characterized by high sediment accumulation rates. Thus, a careful assessment of potential temporal biases must be performed prior to using 14C ages for paleoclimate investigations or radiocarbon calibrations (e.g., marine calibration curve Marine13, Reimer et al., 2013, https://doi.org/10.2458/azu_js_rc.55.16947).
Histone demethylase KDM6B has an anti-tumorigenic function in neuroblastoma by promoting differentiation
Authors: Yang Liqun , Zha Yunhong , Ding Jane , Ye Bingwei , Liu Mengling , Yan Chunhong , Dong Zheng , Cui Hongjuan , Ding Han-Fei
Published: January 2019

Induction of differentiation is a therapeutic strategy in high-risk neuroblastoma, a childhood cancer of the sympathetic nervous system. Neuroblastoma differentiation requires transcriptional upregulation of neuronal genes. How this process is regulated at epigenetic levels is not well understood. Here we report that the histone H3 lysine 27 demethylase KDM6B is an epigenetic activator of neuroblastoma cell differentiation. KDM6B mRNA expression is downregulated in poorly differentiated high-risk neuroblastomas and upregulated in differentiated tumors, and high KDM6B expression is prognostic for better survival in neuroblastoma patients. In neuroblastoma cell lines, KDM6B depletion promotes cell proliferation, whereas KDM6B overexpression induces neuronal differentiation and inhibits cell proliferation and tumorgenicity. Mechanistically, KDM6B epigenetically activates the transcription of neuronal genes by removing the repressive chromatin marker histone H3 lysine 27 trimethylation. In addition, we show that KDM6B functions downstream of the retinoic acid-HOXC9 axis in inducing neuroblastoma cell differentiation: KDM6B expression is upregulated by retinoic acid via HOXC9, and KDM6B is required for HOXC9-induced neuroblastoma cell differentiation. Finally, we present evidence that KDM6B interacts with HOXC9 to target neuronal genes for epigenetic activation. These findings identify a KDM6B-dependent epigenetic mechanism in the control of neuroblastoma cell differentiation, providing a rationale for reducing histone H3 lysine 27 trimethylation as a strategy for enhancing differentiation-based therapy in high-risk neuroblastoma.
BRCA2 deficiency instigates cGAS-mediated inflammatory signaling and confers sensitivity to tumor necrosis factor-alpha-mediated cytotoxicity
Authors: Heijink Anne Margriet , Talens Francien , Jae Lucas T. , van Gijn Stephanie E. , Fehrmann Rudolf S. N. , Brummelkamp Thijn R. , van Vugt Marcel A. T. M.
Published: January 2019

Loss of BRCA2 affects genome stability and is deleterious for cellular survival. Using a genome-wide genetic screen in near-haploid KBM-7 cells, we show that tumor necrosis factor-alpha (TNFα) signaling is a determinant of cell survival upon BRCA2 inactivation. Specifically, inactivation of the TNF receptor (TNFR1) or its downstream effector SAM68 rescues cell death induced by BRCA2 inactivation. BRCA2 inactivation leads to pro-inflammatory cytokine production, including TNFα, and increases sensitivity to TNFα. Enhanced TNFα sensitivity is not restricted to BRCA2 inactivation, as BRCA1 or FANCD2 inactivation, or hydroxyurea treatment also sensitizes cells to TNFα. Mechanistically, BRCA2 inactivation leads to cGAS-positive micronuclei and results in a cell-intrinsic interferon response, as assessed by quantitative mass-spectrometry and gene expression profiling, and requires ASK1 and JNK signaling. Combined, our data reveals that micronuclei induced by loss of BRCA2 instigate a cGAS/STING-mediated interferon response, which encompasses re-wired TNFα signaling and enhances TNFα sensitivity.
Costless metabolic secretions as drivers of interspecies interactions in microbial ecosystems
Authors: Pacheco Alan R. , Moel Mauricio , Segrè Daniel
Published: January 2019

Metabolic exchange mediates interactions among microbes, helping explain diversity in microbial communities. As these interactions often involve a fitness cost, it is unclear how stable cooperation can emerge. Here we use genome-scale metabolic models to investigate whether the release of “costless” metabolites (i.e. those that cause no fitness cost to the producer), can be a prominent driver of intermicrobial interactions. By performing over 2 million pairwise growth simulations of 24 species in a combinatorial assortment of environments, we identify a large space of metabolites that can be secreted without cost, thus generating ample cross-feeding opportunities. In addition to providing an atlas of putative interactions, we show that anoxic conditions can promote mutualisms by providing more opportunities for exchange of costless metabolites, resulting in an overrepresentation of stable ecological network motifs. These results may help identify interaction patterns in natural communities and inform the design of synthetic microbial consortia.
Current fossil fuel infrastructure does not yet commit us to 1.5 °C warming
Authors: Smith Christopher J. , Forster Piers M. , Allen Myles , Fuglestvedt Jan , Millar Richard J. , Rogelj Joeri , Zickfeld Kirsten
Published: January 2019

Committed warming describes how much future warming can be expected from historical emissions due to inertia in the climate system. It is usually defined in terms of the level of warming above the present for an abrupt halt of emissions. Owing to socioeconomic constraints, this situation is unlikely, so we focus on the committed warming from present-day fossil fuel assets. Here we show that if carbon-intensive infrastructure is phased out at the end of its design lifetime from the end of 2018, there is a 64% chance that peak global mean temperature rise remains below 1.5 °C. Delaying mitigation until 2030 considerably reduces the likelihood that 1.5 °C would be attainable even if the rate of fossil fuel retirement was accelerated. Although the challenges laid out by the Paris Agreement are daunting, we indicate 1.5 °C remains possible and is attainable with ambitious and immediate emission reduction across all sectors.
Whole rumen metagenome sequencing allows classifying and predicting feed efficiency and intake levels in cattle
Authors: Delgado Beatriz , Bach Alex , Guasch Isabel , González Carmen , Elcoso Guillermo , Pryce Jennie E. , Gonzalez-Recio Oscar
Published: January 2019

The current research was carried out to determine the associations between the rumen microbiota and traits related with feed efficiency in a Holstein cattle population (n = 30) using whole metagenome sequencing. Improving feed efficiency (FE) is important for a more sustainable livestock production. The variability for the efficiency of feed utilization in ruminants is partially controlled by the gastrointestinal microbiota. Modulating the microbiota composition can promote a more sustainable and efficient livestock. This study revealed that most efficient cows had larger relative abundance ofBacteroidetes(P = 0.041) andPrevotella(P = 0.003), while lower, but non-significant (P = 0.119), relative abundance ofFirmicutes.Methanobacteria(P = 0.004) andMethanobrevibacter(P = 0.003) were also less abundant in the high-efficiency cows. A de novo metagenome assembly was carried out using de Bruijn graphs in MEGAHIT resulting in 496,375 contigs. An agnostic pre-selection of microbial contigs allowed high classification accuracy for FE and intake levels using hierarchical classification. These microbial contigs were also able to predict FE and intake levels with accuracy of 0.19 and 0.39, respectively, in an independent population (n = 31). Nonetheless, a larger potential accuracy up to 0.69 was foreseen in this study for datasets that allowed a larger statistical power. Enrichment analyses showed that genes within these contigs were mainly involved in fatty acids and cellulose degradation pathways. The findings indicated that there are differences between the microbiota compositions of high and low-efficiency animals both at the taxonomical and gene levels. These differences are even more evident in terms of intake levels. Some of these differences remain even between populations under different diets and environments, and can provide information on the feed utilization performance without information on the individual intake level.
Fabrication of Miniaturized Paper-Based Microfluidic Devices (MicroPADs)
Authors: Strong E. Brandon , Schultz Spencer A. , Martinez Andres W. , Martinez Nathaniel W.
Published: January 2019

Microfluidic paper-based analytical devices (microPADs) are emerging as cost-effective and portable platforms for point-of-care assays. A fundamental limitation of microPAD fabrication is the imprecise nature of most methods for patterning paper. The present work demonstrates that paper patterned via wax printing can be miniaturized by treating it with periodate to produce higher-resolution, high-fidelity microPADs. The optimal miniaturization parameters were determined by immersing microPADs in various concentrations of aqueous sodium periodate (NaIO4) for varying lengths of time. This treatment miniaturized microPADs by up to 80% in surface area, depending on the concentration of periodate and length of the reaction time. By immersing microPADs in 0.5-M NaIO4 for 48 hours, devices were miniaturized by 78% in surface area, and this treatment allowed for the fabrication of functional channels with widths as small as 301 µm and hydrophobic barriers with widths as small as 387 µm. The miniaturized devices were shown to be compatible with redox-based colorimetric assays and enzymatic reactions. This miniaturization technique provides a new option for fabricating sub-millimeter-sized features in paper-based fluidic devices without requiring specialized equipment and could enable new capabilities and applications for microPADs.
Occurrence of the potent mutagens 2- nitrobenzanthrone and 3-nitrobenzanthrone in fine airborne particles
Authors: Santos Aldenor G. , da Rocha Gisele O. , de Andrade Jailson B.
Published: January 2019

Polycyclic aromatic compounds (PACs) are known due to their mutagenic activity. Among them, 2-nitrobenzanthrone (2-NBA) and 3-nitrobenzanthrone (3-NBA) are considered as two of the most potent mutagens found in atmospheric particles. In the present study 2-NBA, 3-NBA and selected PAHs and Nitro-PAHs were determined in fine particle samples (PM 2.5) collected in a bus station and an outdoor site. The fuel used by buses was a diesel-biodiesel (96:4) blend and light-duty vehicles run with any ethanol-to-gasoline proportion. The concentrations of 2-NBA and 3-NBA were, on average, under 14.8 µg g−1 and 4.39 µg g−1, respectively. In order to access the main sources and formation routes of these compounds, we performed ternary correlations and multivariate statistical analyses. The main sources for the studied compounds in the bus station were diesel/biodiesel exhaust followed by floor resuspension. In the coastal site, vehicular emission, photochemical formation and wood combustion were the main sources for 2-NBA and 3-NBA as well as the other PACs. Incremental lifetime cancer risk (ILCR) were calculated for both places, which presented low values, showing low cancer risk incidence although the ILCR values for the bus station were around 2.5 times higher than the ILCR from the coastal site.
Two new species of dictyostelid cellular slime molds in high-elevation habitats on the Qinghai-Tibet Plateau, China
Authors: Liu Pu , Zou Yue , Li Shu , Stephenson Steven L. , Wang Qi , Li Yu
Published: January 2019

Dictyostelid cellular slime molds (dictyostelids) are key components of soil microbes. The Qinghai-Tibet Plateau is characterized by unique and important forest types because of the considerable range in elevation which exists. During the period of 2012, 2013 and 2016, 12 species of dictyostelids were yielded from samples collected in this region, including two new species and three new records for China. Six other species were new records for this region. Ontogeny, morphology, ultrastructure and systematic molecular analyses (SSU & ITS) of D. minimum and D. multiforme confirm that they are Goup 4 new species. The ornamentation of the surface of dictyostelids’ spores is the first time to be observed until now. In the SSU phylogenetic tree generated in the present study, Synstelium, not assigned to order and family before, was assigned to the clade Acytosteliaceae in the Acytosteliales firstly. To our knowledge, the study reported herein is the first investigation of dictyostelid biodiversity carried out at elevations above 2000 m. Sorocarp size, sorus size, spore length, ratio of sorus and sorophore, and ratio of sorus and spore size were positively correlated with increasing elevation and no linear correlated with forest type, according to the results of linear regression analysis.
Quantum dot activated indium gallium nitride on silicon as photoanode for solar hydrogen generation
Authors: Kumar Praveen , Devi Pooja , Jain Rishabh , Shivaprasad S. M. , Sinha R. K. , Zhou Guofu , Nötzel Richard
Published: January 2019

Nitride alloys are considered potential candidates as photoelectrodes for photoelectrochemical water splitting. Here we show an In0.25Ga0.75N layer activated by indium nitride quantum dots as efficient photoanode for photoelectrochemical hydrogen generation by water splitting when directly grown on cheap silicon (111) substrates. Photocurrent measurements show more than five times enhancement by the indium nitride quantum dots compared to a bare In0.25Ga0.75N-on-silicon photoanode. The maximum incident photon-to-current conversion efficiency is 44% at 550 nm at 0.4 V, the applied-bias photon-to-current efficiency is 4.1% and the hydrogen and oxygen generation rates are 75 µmol h−1 cm−2 and 33 µmol h−1 cm−2 at 0.2 V under 100 mW cm−2 white light illumination.
Electron Beam Curing of Monomer/Liquid Crystal Blends
Authors: Bouchakour Mohammed , Derouiche Yazid , Bouberka Zohra , Beyens Christophe , Supiot Philippe , Dubois Frédéric , Riahi Farid , Maschke Ulrich
Published: January 2019

This chapter focuses on a comparison of two polymerization/crosslinking methods to produce polymer/liquid crystal (LC) systems: rapid UV-visible irradiation and high voltage accelerated electron beams (EB), with comparable exposure times. The comparison was performed in terms of some physical properties such as phase diagrams, polymerization and phase separation kinetics, morphologies, and electro-optical responses. During polymerization and crosslinking, the longer the spacing between the two acrylic double bonds or the higher the molecular weight, the more rapid was the monomer conversion under UV-light; however, the reverse was found for EB-curing. The PDLC films produced by EB curing had more homogenous and regular morphologies. The electro-optical responses of various PDLC systems showed significant differences between the UV-cured samples and those cured by EB. It was found that the driving voltages considerably increased in the case of the UV-cured systems. For the contrast ratios, which are important for applications, EB-cured systems confirm their higher quality. Moreover, EB curing leads to considerable monomer conversions without a photoinitiator which may act as an impurity that might have negative impact on the electro-optical performance of the obtained PDLC films.
Electrical Color Tuning in Polymer-stabilized Cholesteric Liquid Crystals
Authors: Yang Deng-Ke
Published: January 2019

Cholesteric liquid crystals consist of chiral rod-like molecules which self-assemble into a helical structure. The molecules twist periodically along an axis which is orthogonal to the long molecular axis. For cholesteric liquid crystals with a helical pitch comparable to the wavelength of visible light, they Bragg reflect light. In this chapter we discuss polymer-stabilized cholesteric liquid crystals where polymer networks are dispersed in the liquid crystals to control the electro-optical properties of the liquid crystals. The reflection of the polymer-stabilized cholesteric liquid crystals can be tuned by applying electric voltages. The materials are of great practical importance and can be used in many applications such as reflective displays, writing tablets, tuneable color filters and tuneable mirror-less lasers.