Study of tRNA modifying enzymes and codon usage bias in cancer

Recent evidences indicate that tRNA modifications and tRNA modifying enzymes may play important roles in complex human diseases such as cancer, neurological disorders and mitochondrial-linked diseases. We postulate that expression deregulation of tRNA modifying enzymes affects the level of tRNA modifications and, consequently, their function and the translation efficiency of their tRNA corresponding codons. Due to the degeneracy of the genetic code, most amino acids are encoded by two to six synonymous codons. This degeneracy and the biased usage of synonymous codons cause alterations that can span from protein folding to enhanced translation efficiency of a select gene group. In this work, we focused on cancer and performed a meta-analysis study to compare microarray gene expression profiles, reported by previous studies and evaluate the codon usage of different types of cancer where tRNA modifying enzymes were found de-regulated. A total of 36 different tRNA modifying enzymes were found de-regulated in most cancer datasets analyzed. The codon usage analysis revealed a preference for codons ending in AU for the up-regulated genes, while the down-regulated genes show a preference for GC ending codons. Furthermore, a PCA biplot analysis showed this same tendency. We also analyzed the codon usage of the datasets where the CTU2 tRNA modifying enzyme was found deregulated as this enzyme affects the wobble position (position 34) of specific tRNAs. Our data points to a distinct codon usage pattern between up and downregulated genes in cancer, which might be caused by the deregulation of specific tRNA modifying enzymes. This codon usage bias may augment the transcription and translation efficiency of some genes that otherwise, in a normal situation, would be translated less efficiently.

Investigating bias in recreational fishing surveys: Fishers listed in public telephone directories fish similarly to their unlisted counterparts

Several recent offsite recreational fishing surveys have used public landline telephone directories as a sampling frame. Sampling biases inherent in this method are recognised, but are assumed to be corrected through demographic data expansion. However, the rising prevalence of mobile-only households has potentially increased these biases by skewing raw samples towards households that maintain relatively high levels of coverage in telephone directories. For biases to be corrected through demographic expansion, both the fishing participation rate and fishing activity must be similar among listed and unlisted fishers within each demographic group. In this study, we tested for a difference in the fishing activity of listed and unlisted fishers within demographic groups by comparing their avidity (number of fishing trips per year), as well as the platform used (boat or shore) and species targeted on their most recent fishing trip. 3062 recreational fishers were interviewed at 34 tackle stores across 12 residential regions of Queensland, Australia. For each fisher, data collected included their fishing avidity, the platform used and species targeted on their most recent trip, their gender, age, residential region, and whether their household had a listed telephone number. Although the most avid fishers were younger and less likely to have a listed phone number, cumulative link models revealed that avidity was not affected by an interaction of phone listing status, age group and residential region (p > 0.05). Likewise, binomial generalized linear models revealed that there was no interaction between phone listing, age group and avidity acting on platform (p > 0.05), and platform was not affected by an interaction of phone listing status, age group, and residential region (p > 0.05). Ordination of target species using Bray-Curtis dissimilarity indices found a significant but irrelevant difference (i.e. small effect size) between listed and unlisted fishers (ANOSIM R < 0.05, p < 0.05). These results suggest that, at this time, the fishing activity of listed and unlisted fishers in Queensland is similar within demographic groups. Future research seeking to validate the assumptions of recreational fishing telephone surveys should investigate fishing participation rates of listed and unlisted fishers within demographic groups.

Information and the evolution of codon bias

The informational properties of biological systems are the subject of much debate and research. I present a general argument in favor of the existence and central importance of information in organisms, followed by a case study of the genetic code (specifically, codon bias) and the translation system from the perspective of information. The codon biases of 831 Bacteria and Archeae are analyzed and modeled as points in a 64-dimensional statistical space. The major results are that (1) codon bias evolution does not follow canonical patterns, and (2) the use of coding space in organsims is a subset of the total possible coding space. These findings imply that codon bias is a unique adaptive mechanism that owes its existence to organisms' use of information in representing genes, and that there is a particularly biological character to the resulting biased coding and information use.

Red Imported Fire Ants: a threat to eastern Australian wildlife?

The discovery of the Red Imported Fire ants (Solenopsis invicta) in Brisbane on 22 February 2001 sent shock waves through urban and rural communities alike. This article is an attempt to address the often repeated question ‘What will become of Australia's unique fauna if they spread along Australia's eastern seaboard?

Aniseikonia tests: The role of viewing mode, response bias, and size-color illusions.

PURPOSE To identify the factors responsible for the poor validity of the most common aniseikonia tests, which involve size comparisons of red-green stimuli presented haploscopically. METHODS Aniseikonia was induced by afocal size lenses placed before one eye. Observers compared the sizes of semicircles presented haploscopically via color filters. The main factor under study was viewing mode (free viewing versus short presentations under central fixation). To eliminate response bias, a three-response format allowed observers to respond if the left, the right, or neither semicircle appeared larger than the other. To control decisional (criterion) bias, measurements were taken with the lens-magnified stimulus placed on the left and on the right. To control for size-color illusions, measurements were made with color filters in both arrangements before the eyes and under binocular vision (without color filters). RESULTS Free viewing resulted in a systematic underestimation of lens-induced aniseikonia that was absent with short presentations. Significant size-color illusions and decisional biases were found that would be mistaken for aniseikonia unless appropriate action is taken. CONCLUSIONS To improve their validity, aniseikonia tests should use short presentations and include control conditions to prevent contamination from decisional/response biases. If anaglyphs are used, presence of size-color illusions must be checked for. TRANSLATIONAL RELEVANCE We identified optimal conditions for administration of aniseikonia tests and appropriate action for differential diagnosis of aniseikonia in the presence of response biases or size-color illusions. Our study has clinical implications for aniseikonia management.

Doctors' thinking about the system as a threat to patient safety

‘Systems thinking’ is an important feature of the emerging ‘patient safety’ agenda. As a key component of a ‘safety culture’, it encourages clinicians to look past individual error to recognise the latent factors that threaten safety. This paper investigates whether current medical thinking is commensurate with the idea of ‘systems thinking’ together with its implications for policy. The findings are based on qualitative semistructured interviews with specialist physicians working within one NHS District General Hospital in the English Midlands. It is shown that, rather then favouring a 'person-centred’ perspective, doctors readily identify ‘the system’ as a threat to patient safety. This is not necessarily a reflection of the prevailing safety discourse or knowledge of policy, but reflects a tacit understanding of how services are (dis)organised. This line of thinking serves to mitigate individual wrong-doing and protect professional credibility by encouraging doctors to accept and accommodate the shortcomings of the system, rather than participate in new forms of organisational learning.

Der Anti-Bias-Ansatz als Methode politischer Erwachsenenbildung

Vorurteile, Macht und Diskriminierung sind die zentralen Themen des Anti-Bias-Ansatzes, der Diskriminierung auf zwischenmenschlicher, struktureller und gesellschaftlich-kultureller Ebene berücksichtigt. Die eigene Verwobenheit in Machtverhältnisse und damit verbundene Erfahrungen von Diskriminierung und Privilegierung sind dabei der Ausgangspunkt des Lernens. Vision ist eine vorurteilsbewusste, diskriminierungskritische und machtsensible Gesellschaft. Der vorliegende Beitrag stellt den Anti-Bias-Ansatz als Methode politischer Erwachsenenbildung vor. Hierfür werden die (Macht-)Mechanismen der Entstehung, Verinnerlichung und Reproduktion von Vorurteilen und Diskriminierung beleuchtet und wird die Intersektionalität (Überkreuzung) verschiedener Differenzlinien ausgemacht und aufgedeckt. Den Abschluss bildet ein Beispiel konkreter Umsetzung. (DIPF/Orig.)

Empirical evidence of bias in the design of experimental stroke studies: a metaepidemiologic approach

Background and Purpose: At least part of the failure in the transition from experimental to clinical studies in stroke has been attributed to the imprecision introduced by problems in the design of experimental stroke studies. Using a metaepidemiologic approach, we addressed the effect of randomization, blinding, and use of comorbid animals on the estimate of how effectively therapeutic interventions reduce infarct size. Methods: Electronic and manual searches were performed to identify meta-analyses that described interventions in experimental stroke. For each meta-analysis thus identified, a reanalysis was conducted to estimate the impact of various quality items on the estimate of efficacy, and these estimates were combined in a meta meta-analysis to obtain a summary measure of the impact of the various design characteristics. Results: Thirteen meta-analyses that described outcomes in 15 635 animals were included. Studies that included unblinded induction of ischemia reported effect sizes 13.1% (95% CI, 26.4% to 0.2%) greater than studies that included blinding, and studies that included healthy animals instead of animals with comorbidities overstated the effect size by 11.5% (95% CI, 21.2% to 1.8%). No significant effect was found for randomization, blinded outcome assessment, or high aggregate CAMARADES quality score. Conclusions: We provide empirical evidence of bias in the design of studies, with studies that included unblinded induction of ischemia or healthy animals overestimating the effectiveness of the intervention. This bias could account for the failure in the transition from bench to bedside of stroke therapies.

Polio eradication efforts in regions of geopolitical strife: the Boko Haram threat to efforts in sub-Saharan Africa.

The World Health Organization aims to eradicate wild poliovirus worldwide by the end of 2018. Cameroon and Nigeria, neighboring countries, have been affected by the terrorist and militant activities of the Islamist sect Boko Haram. Impacted regions are mainly the far North of Cameroon and Northern Nigeria. Targets of Boko Haram aggression in these zones include violence against polio workers, disruption of polio immunization campaigns, with consequent reduced access to health care and immunization. In addition to this significant problem, Northern Nigeria has historically seen rejection of polio virus vaccine initiatives. It remains to know how health systems can continue operations against polio in areas where Boko Haram operates. If appropriate measures are not urgently taken, it will be not possible to meet the 2018 goal of polio virus eradication. The response should include specialized immunization activities in conflict zones, will engagement of leaders. Countries should also explore immunization activities by soldiers and military personnel.

Good laboratory practice: preventing introduction of bias at the bench

Background and Purpose—As a research community, we have failed to demonstrate that drugs which show substantial efficacy in animal models of cerebral ischemia can also improve outcome in human stroke. Summary of Review—Accumulating evidence suggests this may be due, at least in part, to problems in the design, conduct and reporting of animal experiments which create a systematic bias resulting in the overstatement of neuroprotective efficacy. Conclusions—Here, we set out a series of measures to reduce bias in the design, conduct and reporting of animal experiments modeling human stroke.

Zika is not a reason for missing the Olympic Games in Rio de Janeiro: response to the open letter of Dr Attaran and colleagues to Dr Margaret Chan, Director - General, WHO, on the Zika threat to the Olympic and Paralympic Games

Attaran and colleagues in an open letter to WHO expressed their concern about the upcoming Olympic and Paralympic Games in Rio de Janeiro and the threat posed by the Zika epidemic (Attaran 2016). We agree that Zika virus is of great public health concern and much remains to be known about this disease. Care should be taken to reduce the risk of infection, especially to pregnant women. However, we argue that this is not sufficient reason for changing the original plans for the Games, in particular because of the time of the year when they will take place. The present article outlines several scientific results related to Zika and mosquito-borne infectious diseases dynamics that we believe ratify the current position of WHO in not endorsing the postponing or relocation of the 2016 Olympic and Paralympic Games (WHO 2016).

Tribes under threat : the collective behavior of firms during the stock market crisis

Due to their unpredictable behavior, stock markets are examples of complex systems. Yet, the dominant analysis of these markets as- sumes simple stochastic variations, eventually tainted by short-lived memory. This paper proposes an alternative strategy, based on a stochastic geometry defining a robust index of the structural dynamics of the markets and based on notions of topology defining a new coef- ficient that identifies the structural changes occurring on the S&P500 set of stocks. The results demonstrate the consistency of the random hypothesis as applied to normal periods but they also show its in- adequacy as to the analysis of periods of turbulence, for which the emergence of collective behavior of sectoral clusters of firms is mea- sured. This behavior is identified as a meta-routine.

Bia’s smile: an health education instrument on cleft lip and palate

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.

Do hatchery-reared sea urchins pose a threat to genetic diversity in wild populations?

In salmonids, the release of hatchery-reared fish has been shown to cause irreversible genetic impacts on wild populations. However, although responsible practices for producing and releasing genetically diverse, hatchery-reared juveniles have been published widely, they are rarely implemented. Here, we investigated genetic differences between wild and early-generation hatchery-reared populations of the purple sea urchin Paracentrotus lividus (a commercially important species in Europe) to assess whether hatcheries were able to maintain natural levels of genetic diversity. To test the hypothesis that hatchery rearing would cause bottleneck effects (that is, a substantial reduction in genetic diversity and differentiation from wild populations), we compared the levels and patterns of genetic variation between two hatcheries and four nearby wild populations, using samples from both Spain and Ireland. We found that hatchery-reared populations were less diverse and had diverged significantly from the wild populations, with a very small effective population size and a high degree of relatedness between individuals. These results raise a number of concerns about the genetic impacts of their release into wild populations, particularly when such a degree of differentiation can occur in a single generation of hatchery rearing. Consequently, we suggest that caution should be taken when using hatchery-reared individuals to augment fisheries, even for marine species with high dispersal capacity, and we provide some recommendations to improve hatchery rearing and release practices. Our results further highlight the need to consider the genetic risks of releasing hatchery-reared juveniles into the wild during the establishment of restocking, stock enhancement and sea ranching programs.

Prevalence of chronic diseases in private healthcare sector of South Africa: A threat to public health

Purpose: To evaluate the prevalence of patients suffering from registered chronic disease list (CDL) conditions in a section of the South African private health sector from 2008 - 2012. Methods: This study was a retrospective analysis of the medicine claims database of a nationally (South African) representative Pharmacy Benefit Management (PBM) company data between 2008 and 2012. Statistical analysis was used to analyse the data. Descriptive analysis was performed to calculate the prevalence of CDL conditions for the entire population, and stratified by age and gender. However, MIXED linear modelling was used to determine changes in the average number of CDL conditions per patient, adjusted for age and gender from 2008 - 2012. Results: An increase of 0.20 in chronic diseases was observed from 2008 - 2012 in patients having any CDL condition, with an average of 1.57 (1.57 - 1.58, 95 % CI) co-morbid CDL conditions in 2008 and 1.77 (1.77 - 1.78, 95 % CI) in 2012. This increase in average number of CDL conditions per patient between 2008 and 2012 was statistically significant (p < 0.05), but with no large practical significance (d < 0.8). Conclusion: Prevalence of patients with CDL conditions along with risk of co-morbidity has been increasing with time in the private health sector of South Africa. Risk of increased co-morbidity with age and among different genders was prevalent.