Concurrent and Concordant Anal and Oral Human PapillomaVirus Infections Are Not Associated with Sexual Behavior in At-Risk Males

Men who have sex with men (MSM) harbor the highest prevalence of anal and oral Human Papillomavirus (HPV) infection, particularly if HIV-infected. We investigated anal and oral HPV infections in HIV-infected and HIV-uninfected MSM, to assess concurrent (HPV detected at both sites, irrespective of the genotypes), and concordant infections (same genotype[s] detected at both sites). Matched anal and oral samples from 161 MSM (85 HIV-infected, and 76 HIV-uninfected) were tested with the Linear Array. Determinants of concurrent and concordant infections were evaluated using logistic regression. Anal infections were 4 to 7 times more frequent than oral infections in both study groups (p < 0.0001). Concurrent infections were not significantly different in HIV-infected (25.9%) and HIV-uninfected MSM (17.1%), p = 0.18. A concordant infection was found in 15 MSM (9.3%). Concordance was for one genotype in 14 individuals and for four genotypes in the remaining subject. In the overall population, only age was independently associated with a concurrent infection (AOR = 3.10, 95% CI: 1.34–7.19 for >39 vs. ≤39 years). None of the parameters of sexual behavior showed independent association with concordant infections. Among MSM, concordant anal and oral HPV infections do not seem to be explained by sexual behavior, but might derive from sequential acquisition by autoinoculation.

The Mutational Landscape of Myeloid Leukaemia in Down Syndrome

Children with Down syndrome (DS) are particularly prone to haematopoietic disorders. Paediatric myeloid malignancies in DS occur at an unusually high frequency and generally follow a well-defined stepwise clinical evolution. First, the acquisition of mutations in the GATA1 transcription factor gives rise to a transient myeloproliferative disorder (TMD) in DS newborns. While this condition spontaneously resolves in most cases, some clones can acquire additional mutations, which trigger myeloid leukaemia of Down syndrome (ML-DS). These secondary mutations are predominantly found in chromatin and epigenetic regulators—such as cohesin, CTCF or EZH2—and in signalling mediators of the JAK/STAT and RAS pathways. Most of them are also found in non-DS myeloid malignancies, albeit at extremely different frequencies. Intriguingly, mutations in proteins involved in the three-dimensional organization of the genome are found in nearly 50% of cases. How the resulting mutant proteins cooperate with trisomy 21 and mutant GATA1 to promote ML-DS is not fully understood. In this review, we summarize and discuss current knowledge about the sequential acquisition of genomic alterations in ML-DS.

Flipping Interferometric Module for Simultaneous Dual-Wavelength Unwrapping of Quantitative Phase Maps of Biological Cells

We present an imaging platform for stain-free quantitative imaging of biological cells using a simultaneous dual-wavelength holographic module. We use this module to experimentally solve the problem of 2π phase ambiguities that occurs in spatial locations where the optical thickness of the sample is larger than the wavelength. Thus, the process does not require using digital phase unwrapping that is computational heavy and impairs real-time processing. The proposed method is not limited to sequential acquisition of two quantitative phase maps in different times, but rather allows optical multiplexing of two off-axis holograms on the camera at once, enabling acquisition of fast dynamic processes. The module is simple and portable, making it attractive for clinical use. We demonstrate using the module for quantitative phase imaging of cancer and sperm cells.

Cross-linguistic influence in simultaneous and early sequential acquisition: Null subjects and null objects in Polish-German bilingualism

Aims and objectives/purpose/research questions: The topic of cross-linguistic influence regarding the overt or null expression of arguments has been frequently considered regarding bilinguals acquiring language pairs in which the null option is licensed by one and not both of the two languages. The goal of this study is to investigate whether simultaneous and sequential bilinguals differ from monolinguals in the case of the acquisition of Polish and German; that is, languages which both license null subjects and null objects, but in which the nature of the null arguments clearly differs. We focus on the acquisition of null arguments as silent but syntactically active bundles of features. Design/methodology/approach: We compare the use of null subjects and null objects by 72 bilingual and 45 monolingual children in experimental setting: acceptability judgement and sentence repetition. Data and analysis: The distribution of null arguments in production and judgement data of simultaneous and early sequential bilinguals was compared to the data of monolinguals. Findings/conclusions: The study has revealed that early sequential Polish-German bilinguals avoid null subjects in L2 German at an advanced stage of acquisition, even though null subjects are quite frequent in their L1. The slower acquisition of null subjects in early L2 German in comparison to null objects in the case of Polish-German bilinguals demonstrates that the dissimilarity between the null subjects in both languages may lead to the delay effect in the acquisition. The findings suggest that the cross-linguistic influence is due to the increased complexity inherent to the integration of syntactic and pragmatic information in case of null arguments. Originality: Unlike previous studies, we focus on the acquisition of null arguments in a language pair, Polish and German, in which the null option is licensed by both grammars, and in which the nature of the null arguments clearly differ.

Iodine quantification and detectability thresholds among major dual-energy CT platforms

Objectives: To estimate the minimum detectable iodine concentration on multiple dual-energy CT (DECT) platforms. Methods and materials: A phantom containing iodine concentrations ranging from 0 to 10 mg ml−1 was scanned with five dual-energy platforms (two rapid kilo volt switching (r-kVs), one dual source (DS), one sequential acquisition and one split-filter). Serial dilutions of 300 mg ml−1 iodinated contrast material were used to generate concentrations below 2 mg ml−1. Iodine density and virtual monoenergetic images were reviewed by three radiologists to determine the minimum visually detectable iodine concentration. Contrast-to-noise ratios (CNRs) were calculated. Results: 1 mg mL−1 (~0.8 mg mL−1 corrected) was the minimum visually detectable concentration among the platforms and could be seen by all readers on the third-generation r-kVs and DS platforms. Conclusions: At low concentrations, CNR for monoenergetic images was highest on the DS platform and lowest in the sequential acquisition and split-filter platforms. Advances in knowledge: The results of this study corroborate previous in vivo estimates of iodine detection limits at DECT and provide a comparison for the performance of different DECT platforms at low iodine concentrations in vitro.

Mutators drive evolution of multi-resistance to antibiotics

Combination therapy aims to prevent growth of organisms not resistant to all component drugs, making it an obvious strategy for countering the global rise of multi-drug resistance. However, success relies on preventing resistance from arising to all component drugs before full inhibition is reached during treatment. Here, we investigated whether bacterial populations can overcome combination therapy by evolving ‘multi-resistance’, i.e. independent resistance mutations to multiple drugs, during single-drug and combination antibiotic treatment. Using both experimental evolution and in silico stochastic simulations, we studied resistance evolution in a common laboratory strain of bacteria (Escherichia coli K-12 BW25113). Populations were exposed to either single-drug or combination treatments involving rifampicin and nalidixic acid, with concentrations increasing through time. For wild-type populations, multi-resistance was not detected in any of the experimental populations, and simulations predict its evolution should be rare. However, populations comprising mixtures of wild-type and ‘mutator’ strains were readily capable of evolving multi-resistance. Increasing the initial frequency of mutators resulted in a higher proportion of populations evolving multi-resistance. Experiments and simulations produced the same qualitative-and in many cases, quantitative-insights about the association between resistance, mutators and antibiotic treatment. In particular, both approaches demonstrated that multi-resistance can arise through sequential acquisition of independent resistance mutations, without a need to invoke multi-drug resistance mechanisms. Crucially, we found multi-resistance evolved even when not directly favoured by natural selection, i.e. under single-drug treatments. Simulations revealed this resulted from elevated mutation supply caused by genetic hitch-hiking of the mutator allele on single-drug resistant backgrounds. Our results suggest that combination therapy does not necessarily prevent sequential acquisition of multiple drug resistances via spontaneous mutation when mutators are present. Indeed both combination and single-drug treatments actively promoted multi-resistance, meaning that combination therapy will not be a panacea for the antibiotic resistance crisis.