Childhood cancer incidence in South Africa, 1987 - 2007

Background. Childhood cancer is an emerging problem in Africa. Its extent is hazy because data are scarce, but it should be addressed. This is the first report from the South African Children’s Tumour Registry (SACTR), which covers the whole of South Africa (SA). It provides minimal estimates of cancer incidence and discusses the challenges of cancer surveillance and control in a child population in a middleincome country. Only about 2% of the African population is covered by cancer registries producing comparable incidence data.Objective. To present and interpret incidence patterns and trends of childhood cancer over a 21-year period. The results should raise awareness of the problem of childhood cancer in an African population and provide sensible data for taking this problem in hand.Methods. All eligible and validated cancer cases registered in the SACTR over the period 1987 - 2007 and classified according to the International Classification of Childhood Cancer were included. Population data were retrieved from official sources and estimated for the population subcategories. Incidence rates were standardised to the world standard and time trends were evaluated using joinpoint models, adjusting for sex and age.Results. Based on the 11 699 cases, the overall age-standardised average annual incidence rate was 45 per million. Threefold differences in the overall incidence rates were observed between the ethnic groups, ranging from 116 for whites to 37 for black Africans, and they differed by diagnostic group. Differences between the nine provinces of SA relate to the ethnic composition and prevailing socioeconomic status. The overall incidence rate declined by 1.2% per year for the whole country (p<0.01). However, the decline was mainly observed during the first few years of the study period, after which rates stabilised or increased.Conclusions. Diagnosis and notification of childhood cancer should improve. The differences in incidence between ethnic groups suggest the priorities for cancer control

Non-universal minimal Z' models: present bounds and early LHC reach

We consider non-universal 'minimal' Z' models, whose additional U(1) charge is a non-anomalous linear combination of the weak hypercharge Y, the baryon number B and the partial lepton numbers (L_e, L_mu, L_tau), with no exotic fermions beyond three standard families with right-handed neutrinos. We show that the observed pattern of neutrino masses and mixing can be fully reproduced by a gauge-invariant renormalizable Lagrangian, and flavor-changing neutral currents in the charged lepton sector are suppressed by a GIM mechanism. We then discuss the phenomenology of some benchmark models. The electrophilic B-3L_e model is significantly constrained by electroweak precision tests, but still allows to fit the hint of an excess observed by CDF in dielectrons but not in dimuons. The muonphilic B-3L_mu model is very mildly constrained by electroweak precision tests, so that even the very early phase of the LHC can explore significant areas of parameter space. We also discuss the hadrophobic L_mu-L_tau model, which has recently attracted interest in connection with some puzzling features of cosmic ray spectra.Comment: 29 pages, 13 figure

Partial complementation of Sinorhizobium meliloti bacA mutant phenotypes by the Mycobacterium tuberculosis BacA protein

The Sinorhizobium meliloti BacA ABC transporter protein plays an important role in its nodulating symbiosis with the legume alfalfa (Medicago sativa). The Mycobacterium tuberculosis BacA homolog was found to be important for the maintenance of chronic murine infections, yet its in vivo function is unknown. In the legume plant as well as in the mammalian host, bacteria encounter host antimicrobial peptides (AMPs). We found that the M. tuberculosis BacA protein was able to partially complement the symbiotic defect of an S. meliloti BacA-deficient mutant on alfalfa plants and to protect this mutant in vitro from the antimicrobial activity of a synthetic legume peptide, NCR247, and a recombinant human \u3b2-defensin 2 (HBD2). This finding was also confirmed using an M. tuberculosis insertion mutant. Furthermore, M. tuberculosis BacA-mediated protection of the legume symbiont S. meliloti against legume defensins as well as HBD2 is dependent on its attached ATPase domain. In addition, we show that M. tuberculosis BacA mediates peptide uptake of the truncated bovine AMP, Bac71-16. This process required a functional ATPase domain. We therefore suggest that M. tuberculosis BacA is important for the transport of peptides across the cytoplasmic membrane and is part of a complete ABC transporter. Hence, BacA-mediated protection against host AMPs might be important for the maintenance of latent infections

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

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

Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the Coronavirus Disease 2019 (COVID-19) Pandemic: An ACC /SCAI Consensus Statement

The COVID-19 pandemic has strained health care resources around the world causing many institutions to curtail or stop elective procedures. This has resulted in the inability to care for patients valvular and structural heart disease (SHD) in a timely fashion potentially placing these patients at increased risk for adverse cardiovascular complications including congestive heart failure and death. The effective triage of these patients has become challenging in the current environment as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic versus the risk of delaying a needed procedure. In this document, we suggest guidelines as to how to triage patients in need of SHD interventions and provide a framework of how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, we address the triage of patients in need of trans-catheter aortic valve replacement and percutaneous mitral valve repair. We also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic

Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the COVID-19 Pandemic: An ACC/SCAI Position Statement

The coronavirus disease-2019 (COVID-19) pandemic has strained health care resources around the world, causing many institutions to curtail or stop elective procedures. This has resulted in an inability to care for patients with valvular and structural heart disease in a timely fashion, potentially placing these patients at increased risk for adverse cardiovascular complications, including CHF and death. The effective triage of these patients has become challenging in the current environment as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic against the risk of delaying a needed procedure. In this document, the authors suggest guidelines for how to triage patients in need of structural heart disease interventions and provide a framework for how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, the authors address the triage of patients in need of transcatheter aortic valve replacement and percutaneous mitral valve repair. The authors also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic

A flexible mathematical model platform for studying branching networks : experimentally validated using the model actinomycete, Streptomyces coelicolor

Branching networks are ubiquitous in nature and their growth often responds to environmental cues dynamically. Using the antibiotic-producing soil bacterium Streptomyces as a model we have developed a flexible mathematical model platform for the study of branched biological networks. Streptomyces form large aggregates in liquid culture that can impair industrial antibiotic fermentations. Understanding the features of these could aid improvement of such processes. The model requires relatively few experimental values for parameterisation, yet delivers realistic simulations of Streptomyces pellet and is able to predict features, such as the density of hyphae, the number of growing tips and the location of antibiotic production within a pellet in response to pellet size and external nutrient supply. The model is scalable and will find utility in a range of branched biological networks such as angiogenesis, plant root growth and fungal hyphal networks

A gastrointestinal rotavirus infection mouse model for immune modulation studies

<p>Abstract</p> <p>Background</p> <p>Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The current study was conducted to assess whether colostrum containing rotavirus-specific antibodies (Gastrogard-R^®) could protect against rotavirus infection. In addition, this illness model was used to study modulatory effects of intervention on several immune parameters after re-infection.</p> <p>Methods</p> <p>BALB/c mice were treated by gavage once daily with Gastrogard-R^®from the age of 4 to 10 days, and were inoculated with rhesus rotavirus (RRV) at 7 days of age. A secondary inoculation with epizootic-diarrhea infant-mouse (EDIM) virus was administered at 17 days of age. Disease symptoms were scored daily and viral shedding was measured in fecal samples during the post-inoculation periods. Rotavirus-specific IgM, IgG and IgG subclasses in serum, T cell proliferation and rotavirus-specific delayed-type hypersensitivity (DTH) responses were also measured.</p> <p>Results</p> <p>Primary inoculation with RRV induced a mild but consistent level of diarrhea during 3-4 days post-inoculation. All mice receiving Gastrogard-R^®were 100% protected against rotavirus-induced diarrhea. Mice receiving both RRV and EDIM inoculation had a lower faecal-viral load following EDIM inoculation then mice receiving EDIM alone or Gastrogard-R^®. Mice receiving Gastrogard-R^®however displayed an enhanced rotavirus-specific T-cell proliferation whereas rotavirus-specific antibody subtypes were not affected.</p> <p>Conclusions</p> <p>Preventing RRV-induced diarrhea by Gastrogard-R^®early in life showed a diminished protection against EDIM re-infection, but a rotavirus-specific immune response was developed including both B cell and T cell responses. In general, this intervention model can be used for studying clinical symptoms as well as the immune responses required for protection against viral re-infection.</p

How large should whales be?

The evolution and distribution of species body sizes for terrestrial mammals is well-explained by a macroevolutionary tradeoff between short-term selective advantages and long-term extinction risks from increased species body size, unfolding above the 2g minimum size induced by thermoregulation in air. Here, we consider whether this same tradeoff, formalized as a constrained convection-reaction-diffusion system, can also explain the sizes of fully aquatic mammals, which have not previously been considered. By replacing the terrestrial minimum with a pelagic one, at roughly 7000g, the terrestrial mammal tradeoff model accurately predicts, with no tunable parameters, the observed body masses of all extant cetacean species, including the 175,000,000g Blue Whale. This strong agreement between theory and data suggests that a universal macroevolutionary tradeoff governs body size evolution for all mammals, regardless of their habitat. The dramatic sizes of cetaceans can thus be attributed mainly to the increased convective heat loss is water, which shifts the species size distribution upward and pushes its right tail into ranges inaccessible to terrestrial mammals. Under this macroevolutionary tradeoff, the largest expected species occurs where the rate at which smaller-bodied species move up into large-bodied niches approximately equals the rate at which extinction removes them.Comment: 7 pages, 3 figures, 2 data table