Using eggshell membranes as a DNA source for population genetic research

In the context of population genetic research, a faster and less invasive method of DNA sampling would allow large-scale assessments of genetic diversity and genetic differentiation with the help of volunteer observers. The aim of this study was to investigate the usefulness of eggshell membranes as a DNA source for population genetic research, by addressing eggshell membrane DNA quality, degeneration and cross-contamination. To this end, a comparison was made with blood-derived DNA samples. We have demonstrated 100% successful DNA extraction from post-hatched Black-tailed Godwit (Limosa limosa) eggshell membranes as well as from blood samples. Using 11 microsatellite loci, DNA amplification success was 99.1% for eggshell membranes and 97.7% for blood samples. Genetic information within eggshell membrane DNA in comparison to blood DNA was not affected (F-ST = -0.01735, P = 0.999) by degeneration or possible cross-contamination. Furthermore, neither degeneration nor cross-contamination was apparent in total genotypic comparison of eggshell membrane DNA and blood sample DNA. Our research clearly illustrates that eggshell membranes can be used for population genetic research

Guiding cities under increased droughts: The limits to sustainable urban futures

Climate change is likely to increase droughts. The vulnerability of cities to droughts is increasing worldwide. Policy responses from cities to droughts lack consideration of long-term climatic and socio-economic scenarios, and focus on short-term emergency actions that disregard sustainability in the connected regional and river basin systems. We aim to explore the dynamics of the water-energy-land nexus in urban systems suffering increased climate change-related droughts, and their implications for sustainability. We complement a case study with a literature review providing cross-regional insights, and detail pervasive knowledge, policy and ambition gaps in the interaction between cities and droughts. We show that water availability with low emissions, without compromising ecosystems and with low costs to society, poses a local-scale limit to sustainable urban growth, a new concept delineating the limits to growth in cities. We conclude that urban and river basin planners need to institutionalize transparency and cross-sectoral integration in multi-sector partnerships, to consider long-term land use planning together with water and energy, and to apply integrated climate services to cities. Our study reveals the importance of including land, water and energy in long-term urban planning, and to connect them with the county, region, river basin and global scales. © 2021 The Author(s)The authors would like to express their gratitude for limited contributions, comments and discussions that helped to improve the manuscript to Muhamad Bahri, Jörg Cortekar, Mirabela Marin, Serban Octavian Davidescu, Iñaki Torres Cobián, and to two anonymous reviewers that helped to substantially improve the manuscript. Valuable feedback obtained in two conference sessions co‑lead by some of the authors (at Adaptation Futures 2018 in Cape Town, and at the 4th European Climate Change Adaptation conference, in Lisbon in 2019) is acknowledged. The authors acknowledge financial support from the project CLISWELN funded by ERA4CS. ERA4CS is an ERA-NET initiated by JPI Climate, and CLISWELN is funded by BMBF (DE), UEFISCDI (RO), BMBWF and FFG (AT), and MINECO (ES), with co-funding from the European Union (Grant 690462 ). This paper and the content included in it do not represent the opinion of the European Union, and the European Union is not responsible for any use that might be made of its content. Marta OlazabalThe authors would like to express their gratitude for limited contributions, comments and discussions that helped to improve the manuscript to Muhamad Bahri, Jörg Cortekar, Mirabela Marin, Serban Octavian Davidescu, Iñaki Torres Cobián, and to two anonymous reviewers that helped to substantially improve the manuscript. Valuable feedback obtained in two conference sessions co‑lead by some of the authors (at Adaptation Futures 2018 in Cape Town, and at the 4th European Climate Change Adaptation conference, in Lisbon in 2019) is acknowledged. The authors acknowledge financial support from the project CLISWELN funded by ERA4CS. ERA4CS is an ERA-NET initiated by JPI Climate, and CLISWELN is funded by BMBF (DE), UEFISCDI (RO), BMBWF and FFG (AT), and MINECO (ES), with co-funding from the European Union (Grant 690462 ). This paper and the content included in it do not represent the opinion of the European Union, and the European Union is not responsible for any use that might be made of its content. Marta Olazaba

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

Background: Fluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In this paper, we systematically review all clinically tested fluorescent agents for application in FGS for glioma and all preclinically tested agents with the potential for FGS for glioma. Methods: We searched the PubMed and Embase databases for all potentially relevant studies through March 2016. We assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression-free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events. Results: The search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5-aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified. Conclusions: 5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives

CD39 activity correlates with stage and inhibits platelet reactivity in chronic lymphocytic leukemia

<p>Abstract</p> <p>Background</p> <p>Chronic lymphocytic leukemia (CLL) is characterized by accumulation of mature appearing lymphocytes and is rarely complicated by thrombosis. One possible explanation for the paucity of thrombotic events in these patients may be the presence of the ecto-nucleotidase CD39/NTDPase-1 on the surface of the malignant cells in CLL. CD39 is the major promoter of platelet inhibition <it>in vivo </it>via its metabolism of ADP to AMP. We hypothesize that if CD39 is observed on CLL cells, then patients with CLL may be relatively protected against platelet aggregation and recruitment and that CD39 may have other effects on CLL, including modulation of the disease, via its metabolism of ATP.</p> <p>Methods</p> <p>Normal and malignant lymphocytes were isolated from whole blood from patients with CLL and healthy volunteers. Enzyme activity was measured via radio-TLC assay and expression via FACS. Semi-quantititative RT-PCR for CD39 splice variants and platelet function tests were performed on several samples.</p> <p>Results</p> <p>Functional assays demonstrated that ADPase and ATPase activities were much higher in CLL cells than in total lymphocytes from the normal population on a per cell basis (p-value < 0.00001). CD39 activity was elevated in stage 0–2 CLL compared to stage 3–4 (p < 0.01). FACS of lymphocytes demonstrated CD39 expression on > 90% of normal and malignant B-lymphocytes and ~8% of normal T-lymphocytes. RT-PCR showed increased full length CD39 and splice variant 1.5, but decreased variant 1.3 in CLL cells. Platelet function tests showed inhibition of platelet activation and recruitment to ADP by CLL cells.</p> <p>Conclusion</p> <p>CD39 is expressed and active on CLL cells. Enzyme activity is higher in earlier stages of CLL and decreased enzyme activity may be associated with worsening disease. These results suggest that CD39 may play a role in the pathogenesis of malignancy and protect CLL patients from thrombotic events.</p

Validation of the Dutch version of the Multidimensional Adolescent Functioning Scale (MAFS)

Background: The Multidimensional Adolescent Functioning Scale (MAFS) is a 23-item, self-report questionnaire assessing psychosocial functioning in adolescents aged 12-17 years. It captures three domains of functioning: \u27general functioning\u27, \u27family-related functioning\u27, and \u27peer-related functioning\u27. The original English version has good psychometric properties. The aim of the current paper was to translate the MAFS to Dutch and to investigate the psychometric properties of this translation. Methods: After translation, the Dutch MAFS was assessed in 397 adolescents aged 12-17 years, assessed at schools. Internal consistency, factor structure and correlations with other questionnaires assessing functioning, psychopathology and well-being were investigated. Results: A hierarchical/bifactor model with a general factor that loads on all items (MAFS-general) and three group factors, loading respectively on the GF, FF and PF items, was found to describe the data best. Internal consistency of the MAFS total score (&alpha; = 0.87) was good and of the subscales (&alpha; = 0.74-0.80) acceptable. Comparable alphas were found in males and females. Correlations between MAFS subscales ranged from 0.33 to 0.43, indicating sufficient differentiation. The MAFS general factor score and group factor scores showed positive correlations with other measures of good functioning and well-being, and negative correlations with measures of psychopathology, supporting convergent and divergent validity. Conclusions: The Dutch translation of the MAFS has adequate psychometric properties to assess three domains of functioning in adolescents from the general population aged 12-17 years. The MAFS is freely accessible in the Appendix and easy to administe

Generating a checking sequence with a minimum number of reset transitions

Given a finite state machine M, a checking sequence is an input sequence that is guaranteed to lead to a failure if the implementation under test is faulty and has no more states than M. There has been much interest in the automated generation of a short checking sequence from a finite state machine. However, such sequences can contain reset transitions whose use can adversely affect both the cost of applying the checking sequence and the effectiveness of the checking sequence. Thus, we sometimes want a checking sequence with a minimum number of reset transitions rather than a shortest checking sequence. This paper describes a new algorithm for generating a checking sequence, based on a distinguishing sequence, that minimises the number of reset transitions used.This work was supported in part by Leverhulme Trust grant number F/00275/D, Testing State Based Systems, Natural Sciences and Engineering Research Council (NSERC) of Canada grant number RGPIN 976, and Engineering and Physical Sciences Research Council grant number GR/R43150, Formal Methods and Testing (FORTEST)

Effectiveness and toxicity of lenvatinib in refractory thyroid cancer:Dutch real-life data

Objective: The SELECT trial showed progression-free survival (PFS) benefit for lenvatinib for advanced radioiodine-refractory differentiated thyroid cancer (RAI-refractory or RR-DTC) patients, on which current clinical practice is based. We assessed whether the effectiveness and toxicity of lenvatinib in real-life clinical practice in the Netherlands were comparable to the pivotal SELECT trial. Methods: From three Dutch centres Electronic Health Records (EHRs) of patients treated in the lenvatinib compassionate use program or as standard of care were reviewed and checked for SELECT eligibility criteria. Baseline characteristics, safety, and efficacy measures were compared and PFS and overall survival (OS) were calculated. Furthermore, PFS was compared to estimates of PFS reported in other studies. Results: A total of 39 DTC patients with a median age of 62 years were analysed. Of these, 27 patients (69%) did not fulfil the SELECT eligibility criteria. The most common grade >= 3 toxicities were hypertension (n = 11, 28%), diarrhoea (n = 7, 18%), vomiting (n = 4, 10%), and gallbladder disease (n = 3, 8%). Median PFS and median OS were 9.7 (95% confidence interval (CI): 4.0-15.5) and 18.3 (95% CI: 4.9-31.7) months, respectively, response rate was 38% (95% CI: 23-54%). PFS in the Dutch real-life situation was comparable to previous real-life studies, but inferior to PFS as shown in the SELECT trial (P = 0.04). Conclusions: PFS in our non-trial population was significantly shorter than in the SELECT trial population. In the interpretation of results, differences in the real-life population and the SELECT study population regarding patient characteristics should be taken into account

Iron Tetrasulfonatophthalocyanine-Catalyzed Starch Oxidation Using H2O2:Interplay between Catalyst Activity, Selectivity, and Stability

Oxidized starch can be efficiently prepared using H2O2 as an oxidant and iron(III) tetrasulfophthalocyanine (FePcS) as a catalyst, with properties in the same range as those for commercial oxidized starches prepared using NaOCl. Herein, we performed an in-depth study on the oxidation of potato starch focusing on the mode of operation of this green catalytic system and its fate as the reaction progresses. At optimum batch reaction conditions (H2O2/FePcS molar ratio of 6000, 50 °C, and pH 10), a high product yield (91 wt %) was obtained with substantial degrees of substitution (DSCOOH of 1.4 and DSCO of 4.1 per 100 AGU) and significantly reduced viscosity (197 mPa·s) by dosing H2O2. Model compound studies showed limited activity of the catalyst for C6 oxidation, indicating that carboxylic acid incorporation likely results from C-C bond cleavage events. The influence of the process conditions on the stability of the FePcS catalyst was studied using UV-vis and Raman spectroscopic techniques, revealing that both increased H2O2 concentration and temperature promote the irreversible degradation of the FePcS catalyst at high pH. The rate and extent of FePcS degradation were found to strongly depend on the initial H2O2 concentration where also the rapid decomposition of H2O2 by FePcS occurs. These results explain why the slow addition of H2O2 in combination with low FePcS catalyst concentration is beneficial for the efficient application in starch oxidation

Ego-Splitting and the Transcendental Subject. Kant’s Original Insight and Husserl’s Reappraisal

In this paper, I contend that there are at least two essential traits that commonly define being an I: self-identity and self-consciousness. I argue that they bear quite an odd relation to each other in the sense that self-consciousness seems to jeopardize self-identity. My main concern is to elucidate this issue within the range of the transcendental philosophies of Immanuel Kant and Edmund Husserl. In the first section, I shall briefly consider Kant’s own rendition of the problem of the Egosplitting. My reading of the Kantian texts reveals that Kant himself was aware of this phenomenon but eventually deems it an unexplainable fact. The second part of the paper tackles the same problematic from the standpoint of Husserlian phenomenology. What Husserl’s extensive analyses on this topic bring to light is that the phenomenon of the Ego-splitting constitutes the bedrock not only of his thought but also of every philosophy that works within the framework of transcendental thinking