Association of childhood acute lymphoblastic leukaemia with cancers in family members

Children whose twins have had leukaemia have a higher risk of contracting acute lymphoblastic leukaemia (ALL), confirming a prenatal origin of the disease. This association was not true when considering other types of affected first-degree relatives. Children whose fathers were diagnosed with testicular cancer have a higher risk of ALL

The emerging structure of the Extended Evolutionary Synthesis: where does Evo-Devo fit in?

The Extended Evolutionary Synthesis (EES) debate is gaining ground in contemporary evolutionary biology. In parallel, a number of philosophical standpoints have emerged in an attempt to clarify what exactly is represented by the EES. For Massimo Pigliucci, we are in the wake of the newest instantiation of a persisting Kuhnian paradigm; in contrast, Telmo Pievani has contended that the transition to an EES could be best represented as a progressive reformation of a prior Lakatosian scientific research program, with the extension of its Neo-Darwinian core and the addition of a brand-new protective belt of assumptions and auxiliary hypotheses. Here, we argue that those philosophical vantage points are not the only ways to interpret what current proposals to ‘extend’ the Modern Synthesis-derived ‘standard evolutionary theory’ (SET) entail in terms of theoretical change in evolutionary biology. We specifically propose the image of the emergent EES as a vast network of models and interweaved representations that, instantiated in diverse practices, are connected and related in multiple ways. Under that assumption, the EES could be articulated around a paraconsistent network of evolutionary theories (including some elements of the SET), as well as models, practices and representation systems of contemporary evolutionary biology, with edges and nodes that change their position and centrality as a consequence of the co-construction and stabilization of facts and historical discussions revolving around the epistemic goals of this area of the life sciences. We then critically examine the purported structure of the EES—published by Laland and collaborators in 2015—in light of our own network-based proposal. Finally, we consider which epistemic units of Evo-Devo are present or still missing from the EES, in preparation for further analyses of the topic of explanatory integration in this conceptual framework

Systematic Evaluation of Serotypes Causing Invasive Pneumococcal Disease among Children Under Five: The Pneumococcal Global Serotype Project

Hope Johnson and colleagues calculate the global and regional burden of serotype-specific pneumococcal disease in children under the age of five

Strengthening global-change science by integrating aeDNA with paleoecoinformatics

Ancient environmental DNA (aeDNA) data are close to enabling insights into past global-scale biodiversity dynamics at unprecedented taxonomic extent and resolution. However, achieving this potential requires solutions that bridge bioinformatics and paleoecoinformatics. Essential needs include support for dynamic taxonomic inferences, dynamic age inferences, and precise stratigraphic depth. Moreover, aeDNA data are complex and heterogeneous, generated by dispersed researcher networks, with methods advancing rapidly. Hence, expert community governance and curation are essential to building high-value data resources. Immediate recommendations include uploading metabarcoding-based taxonomic inventories into paleoecoinformatic resources, building linkages among open bioinformatic and paleoecoinformatic data resources, harmonizing aeDNA processing workflows, and expanding community data governance. These advances will enable transformative insights into global-scale biodiversity dynamics during large environmental and anthropogenic changes

Company for the Ultra-high Density, Ultra-short Period Sub-Earth GJ 367 b: Discovery of Two Additional Low-mass Planets at 11.5 and 34 Days

GJ 367 is a bright (V ≈ 10.2) M1 V star that has been recently found to host a transiting ultra-short period sub-Earth on a 7.7 hr orbit. With the aim of improving the planetary mass and radius and unveiling the inner architecture of the system, we performed an intensive radial velocity follow-up campaign with the HARPS spectrograph—collecting 371 high-precision measurements over a baseline of nearly 3 yr—and combined our Doppler measurements with new TESS observations from sectors 35 and 36. We found that GJ 367 b has a mass of M b = 0.633 ± 0.050 M ⊕ and a radius of R b = 0.699 ± 0.024 R ⊕, corresponding to precisions of 8% and 3.4%, respectively. This implies a planetary bulk density of ρ b = 10.2 ± 1.3 g cm−3, i.e., 85% higher than Earth’s density. We revealed the presence of two additional non-transiting low-mass companions with orbital periods of ∼11.5 and 34 days and minimum masses of M c sin i c = 4.13 ± 0.36 M ⊕ and M d sin i d = 6.03 ± 0.49 M ⊕, respectively, which lie close to the 3:1 mean motion commensurability. GJ 367 b joins the small class of high-density planets, namely the class of super-Mercuries, being the densest ultra-short period small planet known to date. Thanks to our precise mass and radius estimates, we explored the potential internal composition and structure of GJ 367 b, and found that it is expected to have an iron core with a mass fraction of 0.91 − 0.23 + 0.07 . How this iron core is formed and how such a high density is reached is still not clear, and we discuss the possible pathways of formation of such a small ultra-dense planet

Risks of myeloid malignancies in patients with autoimmune conditions

Autoimmune conditions are associated with an elevated risk of lymphoproliferative malignancies, but few studies have investigated the risk of myeloid malignancies. From the US Surveillance Epidemiology and End Results (SEER)-Medicare database, 13 486 myeloid malignancy patients (aged 67+ years) and 160 086 population-based controls were selected. Logistic regression models adjusted for gender, age, race, calendar year and number of physician claims were used to estimate odds ratios (ORs) for myeloid malignancies in relation to autoimmune conditions. Multiple comparisons were controlled for using the Bonferroni correction (P<0.0005). Autoimmune conditions, overall, were associated with an increased risk of acute myeloid leukaemia (AML) (OR 1.29) and myelodysplastic syndrome (MDS, OR 1.50). Specifically, AML was associated with rheumatoid arthritis (OR 1.28), systemic lupus erythematosus (OR 1.92), polymyalgia rheumatica (OR 1.73), autoimmune haemolytic anaemia (OR 3.74), systemic vasculitis (OR 6.23), ulcerative colitis (OR 1.72) and pernicious anaemia (OR 1.57). Myelodysplastic syndrome was associated with rheumatoid arthritis (OR1.52) and pernicious anaemia (OR 2.38). Overall, autoimmune conditions were not associated with chronic myeloid leukaemia (OR 1.09) or chronic myeloproliferative disorders (OR 1.15). Medications used to treat autoimmune conditions, shared genetic predisposition and/or direct infiltration of bone marrow by autoimmune conditions, could explain these excess risks of myeloid malignancies

Spatio-structural granularity of biological material entities

<p>Abstract</p> <p>Background</p> <p>With the continuously increasing demands on knowledge- and data-management that databases have to meet, ontologies and the theories of granularity they use become more and more important. Unfortunately, currently used theories and schemes of granularity unnecessarily limit the performance of ontologies due to two shortcomings: (i) they do not allow the integration of multiple granularity perspectives into one granularity framework; (ii) they are not applicable to cumulative-constitutively organized material entities, which cover most of the biomedical material entities.</p> <p>Results</p> <p>The above mentioned shortcomings are responsible for the major inconsistencies in currently used spatio-structural granularity schemes. By using the Basic Formal Ontology (BFO) as a top-level ontology and Keet's general theory of granularity, a granularity framework is presented that is applicable to cumulative-constitutively organized material entities. It provides a scheme for granulating complex material entities into their constitutive and regional parts by integrating various compositional and spatial granularity perspectives. Within a scale dependent resolution perspective, it even allows distinguishing different types of representations of the same material entity. Within other scale dependent perspectives, which are based on specific types of measurements (e.g. weight, volume, etc.), the possibility of organizing instances of material entities independent of their parthood relations and only according to increasing measures is provided as well. All granularity perspectives are connected to one another through overcrossing granularity levels, together forming an integrated whole that uses the <it>compositional object perspective </it>as an integrating backbone. This granularity framework allows to consistently assign structural granularity values to all different types of material entities.</p> <p>Conclusions</p> <p>The here presented framework provides a spatio-structural granularity framework for all domain reference ontologies that model cumulative-constitutively organized material entities. With its multi-perspectives approach it allows querying an ontology stored in a database at one's own desired different levels of detail: The contents of a database can be organized according to diverse granularity perspectives, which in their turn provide different <it>views </it>on its content (i.e. data, knowledge), each organized into different levels of detail.</p

The Hemorrhagic Coli Pilus (HCP) of Escherichia coli O157:H7 Is an Inducer of Proinflammatory Cytokine Secretion in Intestinal Epithelial Cells

Enterohemorrhagic Escherichia coli (EHEC) O157:H7, the causative agent of hemorrhagic colitis and the hemolytic uremic syndrome (HUS), produces long bundles of type IV pili (TFP) called hemorrhagic coli pili (HCP). HCP are capable of mediating several phenomena associated with pathogenicity: i) adherence to human and bovine epithelial cells; ii) invasion of epithelial cells; iii) hemagglutination of rabbit erythrocytes; iv) biofilm formation; v) twitching motility; and vi) specific binding to laminin and fibronectin. HCP are composed of a 19 kDa pilin subunit (HcpA) encoded by the hcpA chromosomal gene (called prepilin peptidase-dependent gene [ppdD] in E. coli K-12).In this study we investigated the potential role of HCP of E. coli O157:H7 strain EDL933 in activating the release of pro- and anti-inflammatory cytokines from a variety of host epithelial cells. We found that purified HCP and a recombinant HcpA protein induced significant release of IL-8 and TNF-alpha, from cultured polarized intestinal cells (T84 and HT-29 cells) and non-intestinal HeLa cells. Levels of proinflammatory IL-8 and TNF-alpha, but not IL-2, IL6, or IL-10 cytokines, were increased in the presence of HCP and recombinant HcpA after 6 h of incubation with >or=50 ng/ml of protein, suggesting that stimulation of IL-8 and TNF-alpha are dose and time-dependent. In addition, we also demonstrated that flagella are potent inducers of cytokine production. Furthermore, MAPK activation kinetics studies showed that EHEC induces p38 phosphorylation under HCP-producing conditions, and ERK1/2 and JNK activation was detectable after 3 h of EHEC infection. HT-29 cells were stimulated with epidermal growth factor stimulation of HT-29 cells for 30 min leading to activation of three MAPKs.The HcpA pilin monomer of the HCP produced by EHEC O157:H7 is a potent inducer of IL-8 and TNF-alpha release, an event which could play a significant role in the pathogenesis of hemorrhagic colitis caused by this pathogen

Chronic kidney disease and valvular heart disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Chronic kidney disease (CKD) is a major risk factor for valvular heart disease (VHD). Mitral annular and aortic valve calcifications are highly prevalent in CKD patients and commonly lead to valvular stenosis and regurgitation, as well as complications including conduction system abnormalities and endocarditis. VHD, especially mitral regurgitation and aortic stenosis, is associated with significantly reduced survival among CKD patients. Knowledge related to VHD in the general population is not always applicable to CKD patients because the pathophysiology may be different, and CKD patients have a high prevalence of comorbid conditions and elevated risk for periprocedural complications and mortality. This Kidney Disease: Improving Global Outcomes (KDIGO) review of CKD and VHD seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of VHD in CKD by summarizing knowledge gaps, areas of controversy, and priorities for research

A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer: design and methodological challenges

<p>Abstract</p> <p>Background</p> <p>Advances in childhood cancer treatment over the past decades have significantly improved survival, resulting in a rapidly growing group of survivors. However, both chemo- and radiotherapy may adversely affect reproductive function. This paper describes the design and encountered methodological challenges of a nationwide study in the Netherlands investigating the effects of treatment on reproductive function, ovarian reserve, premature menopause and pregnancy outcomes in female childhood cancer survivors (CCS), the DCOG LATER-VEVO study.</p> <p>Methods</p> <p>The study is a retrospective cohort study consisting of two parts: a questionnaire assessing medical, menstrual, and obstetric history, and a clinical assessment evaluating ovarian and uterine function by hormonal analyses and transvaginal ultrasound measurements. The eligible study population consists of adult female 5-year survivors of childhood cancer treated in the Netherlands, whereas the control group consists of age-matched sisters of the participating CCS. To date, study invitations have been sent to 1611 CCS and 429 sister controls, of which 1215 (75%) and 333 (78%) have responded so far. Of these responders, the majority consented to participate in both parts of the study (53% vs. 65% for CCS and sister controls respectively). Several challenges were encountered involving the study population: dealing with bias due to the differences in characteristics of several types of (non-) participants and finding an adequately sized and well-matched control group. Moreover, the challenges related to the data collection process included: differences in response rates between web-based and paper-based questionnaires, validity of self-reported outcomes, interpretation of clinical measurements of women using hormonal contraceptives, and inter- and intra-observer variation of the ultrasound measurements.</p> <p>Discussion</p> <p>The DCOG LATER-VEVO study will provide valuable information about the reproductive potential of paediatric cancer patients as well as long-term survivors of childhood cancer. Other investigators planning to conduct large cohort studies on late effects may encounter similar challenges as those encountered during this study. The solutions to these challenges described in this paper may be useful to these investigators.</p> <p>Trial registration</p> <p>NTR2922; <url>http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922</url></p