Can Peto's paradox be used as the null hypothesis to identify the role of evolution in natural resistance to cancer? A critical review

BACKGROUND: Carcinogenesis affects not only humans but almost all metazoan species. Understanding the rules driving the occurrence of cancers in the wild is currently expected to provide crucial insights into identifying how some species may have evolved efficient cancer resistance mechanisms. Recently the absence of correlation across species between cancer prevalence and body size (coined as Peto's paradox) has attracted a lot of attention. Indeed, the disparity between this null hypothesis, where every cell is assumed to have an identical probability to undergo malignant transformation, and empirical observations is particularly important to understand, due to the fact that it could facilitate the identification of animal species that are more resistant to carcinogenesis than expected. Moreover it would open up ways to identify the selective pressures that may be involved in cancer resistance. However, Peto's paradox relies on several questionable assumptions, complicating the interpretation of the divergence between expected and observed cancer incidences. DISCUSSIONS: Here we review and challenge the different hypotheses on which this paradox relies on with the aim of identifying how this null hypothesis could be better estimated in order to provide a standard protocol to study the deviation between theoretical/theoretically predicted and observed cancer incidence. We show that due to the disproportion and restricted nature of available data on animal cancers, applying Peto's hypotheses at species level could result in erroneous conclusions, and actually assume the existence of a paradox. Instead of using species level comparisons, we propose an organ level approach to be a more accurate test of Peto's assumptions. SUMMARY: The accuracy of Peto's paradox assumptions are rarely valid and/or quantifiable, suggesting the need to reconsider the use of Peto's paradox as a null hypothesis in identifying the influence of natural selection on cancer resistance mechanisms.

Molecular organization of small plasmids bearing blaTEM-1 and conferring resistance to β-lactams in Haemophilus influenzae

TEM-1 is the dominant β-lactamase of Haemophilus influenzae and can be located on small plasmids. Three distinct plasmids with sizes from 4,304 to 5,646 nucleotides (nt) were characterized: pA1606, pA1209, and pPN223. In addition to TEM-1 and a replication enzyme of the Rep 3 superfamily, pA1606 carries a Tn3 resolvase gene and pA1606 and pA1209 carry an open reading frame (ORF) similar to a plasmid recombination enzyme gene described in Gram-positive bacteria. The plasmids transformed strain Rd to the ampicillin-resistant phenotype.

Novel blaROB-1-bearing plasmid conferring resistance to β-lactams in Haemophilus parasuis isolates from healthy weaning pigs

Haemophilus parasuis, the causative agent of Glässer's disease, is one of the early colonizers of the nasal mucosa of piglets. It is prevalent in swine herds, and lesions associated with disease are fibrinous polyserositis and bronchopneumonia. Antibiotics are commonly used in disease control, and resistance to several antibiotics has been described in H. parasuis. Prediction of H. parasuis virulence is currently limited by our scarce understanding of its pathogenicity. Some genes have been associated with H. parasuis virulence, such as lsgB and group 1 vtaA, while biofilm growth has been associated with nonvirulent strains. In this study, 86 H. parasuis nasal isolates from farms that had not had a case of disease for more than 10 years were obtained by sampling piglets at weaning. Isolates were studied by enterobacterial repetitive intergenic consensus PCR and determination of the presence of lsgB and group 1 vtaA, biofilm formation, inflammatory cell response, and resistance to antibiotics. As part of the diversity encountered, a novel 2,661-bp plasmid, named pJMA-1, bearing the blaROB-1 β-lactamase was detected in eight colonizing strains. pJMA-1 was shown to share a backbone with other small plasmids described in the Pasteurellaceae, to be 100% stable, and to have a lower biological cost than the previously described plasmid pB1000. pJMA-1 was also found in nine H. parasuis nasal strains from a separate collection, but it was not detected in isolates from the lesions of animals with Glässer's disease or in nontypeable Haemophilus influenzae isolates. Altogether, we show that commensal H. parasuis isolates represent a reservoir of β-lactam resistance genes which can be transferred to pathogens or other bacteria.

Randomized controlled trial of an intervention to change cardiac misconceptions in myocardial infarction patients

There is converging evidence that changing beliefs about an illness leads to positive recovery outcomes. However, cardiac misconceptions interventions have been investigated mainly in Angina or Coronary Heart Disease patients, and less in patients following Myocardial Infarction (MI). In these patients, cardiac misconceptions may play a role in the adjustment or lifestyle changes. This article reports a randomized controlled trial of an intervention designed to reduce the strength of misconceptions in patients after a first MI. The primary outcome was the degree of change in misconceptions and the secondary outcomes were: exercise, smoking status, return to work and mood (anxiety and depression). Patients in the intervention condition (n = 60) were compared with a control group (n = 67) receiving usual care. Both groups were evaluated at baseline and 4, 8 and 12 months after hospital discharge. There was a significant time-by-group interaction for the total score of cardiac misconceptions. Patients in the intervention group significantly decreased their total score of cardiac misconceptions at 4 months compared with the control group and this difference was sustained over time. Patients in the intervention group were also more likely to exercise at the follow-up period after MI than the control group. This intervention was effective in reducing the strength of cardiac misconceptions in MI patients and had a positive impact on health behaviour outcomes. These results support the importance of misconceptions in health behaviours and the utility of belief change interventions in promoting health in patients with Myocardial Infarction.

Conservative management in very elderly patients with severe aortic stenosis: Time to change?

Despite current recommendations, a high percentage of patients with severe symptomatic aortic stenosis are managed conservatively. The aim of this study was to study symptomatic patients undergoing conservative management from the IDEAS registry, describing their baseline clinical characteristics, mortality, and the causes according to the reason for conservative management. Consecutive patients with severe aortic stenosis diagnosed at 48 centers during January 2014 were included. Baseline clinical characteristics, echocardiographic data, Charlson index, and EuroSCORE-II were registered, including vital status and performance of valve intervention during one-year follow-up. For the purpose of this substudy we assessed symptomatic patients undergoing conservative management, including them in 5 groups according to the reason for performing conservative management [I: comorbidity/frailty (128, 43.8%); II: dementia 18 (6.2%); III: advanced age 34 (11.6%); IV: patients’ refusal 62 (21.2%); and V: other reasons 50 (17.1%)]. We included 292 patients aged 81.5 ± 9 years. Patients from group I had higher Charlson index (4 ± 2.3), higher EuroSCORE-II (7.5 ± 6), and a higher overall (42.2%) and non-cardiac mortality (16.4%) than the other groups. In contrast, patients from group III had fewer comorbidities, lower EuroSCORE-II (4 ± 2.5), and low overall (20.6%) and non-cardiac mortality (5.9%). Patients with severe symptomatic aortic stenosis managed conservatively have different baseline characteristics and clinical course according to the reason for performing conservative management. A prospective assessment of comorbidity and other geriatric syndromes might contribute to improve therapeutic strategy in this clinical setting.

The perils of change leadership

Professor Karen Starr, Foundation Chair, School Development and Leadership at Deakin University, presents findings of research on how Principals experience resistance to change in their schools.

A public health intervention to change knowledge, attitudes and behaviour regarding alcohol consumption in pregnancy

Aim. To evaluate the effectiveness of a public health intervention aimed at changing knowledge, attitudes and behaviour. Methods. A non-blinded parallel group randomised controlled trial of pregnant women over 18 years of age. Women were recruited in the second trimester and assigned to one of two treatment groups. Both groups completed an initial questionnaire assessing knowledge, attitudes, and practices relating to alcohol consumption during pregnancy. The intervention group then received a mocktail recipe booklet and participants were asked to share the information with their partner. The control group received standard antenatal care. A follow-up questionnaire was conducted four weeks post birth. Primary outcome measures were a knowledge score of the health risks associated with alcohol consumption during pregnancy and an attitude score toward drinking during pregnancy. Secondary outcome measures included whether or not the woman and her partner abstained from drinking. Ethical approval was granted by the Women’s and Children’s Health Network and the University of South Australia. Results. A total of 161 participants were recruited at baseline (intervention = 82, control = 79) and 96 participants completed the trial (intervention = 49, control = 47). The findings suggest that the mocktail booklet was effective at improving knowledge (p<0.001; effect size 0.80) and improving attitudes towards drinking during pregnancy (p=0.017; effect size 0.43) in the intervention group compared to the control group. Although women in the intervention group were 30% more likely to abstain from drinking than in the control group (RR=1.3, 95% CI 0.97 – 1.75), this result was not statistically significant (p=0.077). Conclusions. Knowledge regarding the effects of alcohol consumption as well as attitudes towards drinking significantly improved as a result of a mocktail recipe booklet. Improving knowledge and changing attitudes has the potential to change health behaviour. Therefore, this intervention may reduce the percentage of women who continue to drink alcohol while they are pregnant and improve outcomes for infants and children.

Impact and significance of the 2016 ‘Campaign to change the male face of Parliament’ in Iran

Iranian women have never represented more than 5.9% of sittingparliamentarians in the Islamic Republic of Iran. This compares poorlywith relevant regional and global averages. In the lead up to the 2016parliamentary elections, the women’s movement took action to address thelow representation of women in the legislature by launching the ‘Campaignto Change the Male Face of Parliament’. The Campaign did not reach its goalof achieving 50 seats for women in the 2016–2020 Parliament. It was alsosubject to some criticism for effectively (or apparently) legitimising whatmany women view as a broken form of government unable to promote andprotect women’s rights in any meaningful sense. However, the Campaignwas an important exercise in democracy and had significant higher-orderimpacts on voter behaviour and women’s capacities. Through personalcommunication with three Campaign activists, this profile provides anauthoritative account of the Campaign experience and its impact andsignificance for the future of women’s empowerment in Iran.

Characterisation of Brazilian wheat cultivars in relation to the presence of the gene Fhb1 for resistance to Fusarium head blight.

2016

Use of doubled haploid lines via isolated microspore culture for the introgression of resistance to Fusarium head blight into wheat elite cultivars.

2016

Tobacco budworm resistance to pyrethroids: resistance spectra, synergists, and substitute insecticides.

1988

Genotypic profile of Pantanal creole sheep regarding susceptibility or resistance to scrapie.

The objective of this work was to determine the genotypic profile specific to scrapie in codons 136, 154, and 171 of the PRNP gene of the Pantanal creole sheep. Genomic DNA was extracted from blood samples collected from 66 sheep, and the regions of interest on the DNA strand were amplified by PCR. Five haplotypes were identified: ARR, alanine, arginine, arginine; ARQ, alanine, arginine, glutamine; AHQ, alanine, histidine, glutamine; ARH, alanine, arginine, histidine; and VRQ, valine, arginine, glutamine. The most common genotypes were ARQ/ARQ (27%) and ARR/ARQ (24%). The genotypic profile of the Pantanal creole sheep shows low to moderate susceptibility.

Sensitization and Disposition to Change Facing the Challenges of the New Educational Circumstances

This article is about the necessity of an up to date vision in teachers’ training. It starts with the latest studies and advances surrounding learning-along-life term. It presents a set of topics inspired in the contributions of new fields of study connected to learning. Such contributions, as neuroscience, should be considered in the decisions related to future teachers’ training, thus favoring the transformation of the pedagogical practice. Awareness and disposition to change are essential requirements for teacher trainers who will drive investigative processes and pedagogical proposals generation; all of this according to the new and dynamic knowledge society.

Investigation of the mechanism of resistance to glyphosate herbicide in hairy fleaban.

The resistance of weeds to herbicides is a consequence of one or more mechanisms in the plant, responsible for not allowing the herbicide to act properly at the active site.