Unleashing the full power of LHCb to probe stealth new physics.

In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.

Mycobacterium abscessus subspecies abscessus infection associated with cosmetic surgical procedures: Cases series.

BACKGROUND: Mycobacterium abscessus is one of the most pathogenic and drug-resistant opportunistic microorganisms among the nontuberculous mycobacteria (NTM) involved in skin and soft tissue infections (SSTI) associated with cosmetic surgical procedures. However, NTM infection is often wrongly diagnosed initially causing prolonged suffering. Here is described the author's experience working with patients who developed M. abscessus SSTI after cosmetic procedures. METHODS: Patients who developed NTM infection after undergoing cosmetic procedures, and who presented at the Hospital Metropolitano and Hospital Vozandes (Quito, Ecuador) between 2013-2016. A review of patient medical records was performed. RESULTS: Five patients with culture proven M. abscessus subspecies abscessus SSTI after cosmetic surgeries were identified. All patients were treated with aggressive surgical debridement and antibiotics. CONCLUSIONS: A rapidly spreading wound infection presenting two or more weeks after a cosmetic procedure that fails to respond to standard antimicrobial therapy should raise suspicion for NTM infection. Samples for acid-fast bacilli smear, cultures, and PCR from infected tissue should be taken. Surgical drainage and debridement are recommended along with a long course of antibiotics. In the absence of clinical trials, a combination of amikacin, imipenem, and clarithromycin may be an adequate initial treatment for M. abscessus subspecies abscessus SSTI in immunocompetent patients.

Segniliparus rugosus from the sputum of a child with cystic fibrosis in Ecuador: challenges in bacterial identification.

Using sequencing analyses of the 16S rRNA gene, we identified Segniliparus rugosus in an 8-year-old child with cystic fibrosis. We describe the difficulties we encountered in identifying this bacterium. To the best of our knowledge, this is the first reported case of S. rugosus in Ecuador.

Ready-to-eat street food: a potential source for dissemination of multidrug-resistant Escherichia coli epidemic clones in Quito, Ecuador.

Ready-to-eat food contamination with ESBL-producing Escherichia coli is a growing health concern. Some of these strains also are epidemic clones and can cause community-associated infections that are difficult to treat. In this study, the occurrence of ESBL-producing E. coli contaminated ready-to-eat street food in Quito, Ecuador was evaluated. In total, 150 samples were collected randomly in the most crowded sites of the city. In all, 34 samples (34/150; 22·6%) were positive for total thermotolerant (44·5°C) coliforms resistant to cefotaxime. MALDI-TOF analysis identified that the E. coli was found in 20 food samples (20/34; 59%). ESBL gene blaCTX-M-55 was identified in nine isolates, blaCTX-M-15 in six isolates, blaCTX-M-14 in two isolates, and one isolate each harboured blaCTX-M-24 , blaCTX-M-65 , blaCTX-M-55 and blaCTX-M-8 . Phylogenetic groups like A and B1 were the most common, followed by groups D and B2. MLST analysis identified 12 different sequence types (STs), the most common was ST162. Recognized epidemic clonal groups ST410, ST131 and ST744 were encountered. Ready-to-eat street food is a potential way of spreading ESBL-producing E. coli epidemic clones in Quito, Ecuador. SIGNIFICANCE AND IMPACT OF THE STUDY: This study identified ESBL-producing Escherichia coli epidemic clones: ST131, ST410 and ST744 in ready-to-eat street food samples. Street food is a possible way to spread harm multidrug-resistant (MDR) E. coli strains in the community. Studies to identify the contamination sources of this kind of food are needed to tackle MDR E. coli dissemination.

Effects of multiphase transitions and reactive extrusion on in situ thermoplasticization/succination of cassava starch.

In this work, the effects of the multiphase transitions of starch, the screw configuration, and the conditions of reactive extrusion (REX) on the in situ thermoplasticization/succination of cassava starch were studied. Spectroscopic analyses indicated successful esterification during the REX with the appearance of characteristic bands of carbonyl ester groups. After the REX, the starch developed B- and V-type structures, with the OSA starches showing an additional peak at 7.1°. As the degree of substitution increased, a greater number of partially gelatinized granules were embedded in the starch matrix; an additional degradation temperature of 364.5 °C and a lower weight loss at the degradation temperature of the starch were observed. The incorporation of OS groups via REX imparts better thermal stability. The processing conditions helped prepare a thermoplastic-succinate starch in a single step through an environmentally friendly process.

Genetic diversity and drug resistance of Mycobacterium tuberculosis in Ecuador.

BACKGROUND: The genetic diversity of Mycobacterium tuberculosis in Quito, Ecuador is not well known. OBJECTIVE: To investigate mutations related to drug resistance and bacterial genotypes in M. tuberculosis strains in Ecuador. DESIGN: This was a retrospective study of M. tuberculosis isolates from 104 patients. Isolates were phenotypically resistant to rifampicin (RMP) and/or isoniazid (INH). The genotype was determined using 24-locus mycobacterial interspersed repetitive units-variable-number tandem repeats (MIRU-VNTR). RESULTS: Isolates showed mutations in the rpoB and katG genes, and the inhA promoter. In rpoB, we found 13 genetic alterations at codons 511, 513, 514, 515, 516, 526 and 531. Forty-six (44.2%) RMP-resistant isolates belonged to codon 531. In katG, there were nine genetic alterations at codons 296, 312, 314, 315, 322, 324 and 351. Fifty-three (51%) INH-resistant isolates belonged to codon 315. Five mutations not previously described were identified in katG: Thr324Ser, Thr314Ala, Ala312Pro, Trp351Stop and deleted G at 296 codon. The Latin American Mediterranean (LAM) (33.7%) and Ghana (30.8%) lineages presented most of the main mutations observed. CONCLUSION: This is the first report from Ecuador; it describes five new mutations in katG and indicates that LAM is the most prevalent lineage.

Serious fungal infections in Ecuador.

There is a dearth of data from Ecuador on the burden of life-threatening fungal disease entities; therefore, we estimated the burden of serious fungal infections in Ecuador based on the populations at risk and available epidemiological databases and publications. A full literature search was done to identify all epidemiology papers reporting fungal infection rates. WHO, ONU-AIDS, Index Mundi, Global Asthma Report, Globocan, and national data [Instituto Nacional de Estadística y Censos (INEC), Ministerio de Salud Pública (MSP), Sociedad de Lucha Contra el Cáncer (SOLCA), Instituto Nacional de Donación y Trasplante de Órganos, Tejidos y Células (INDOT)] were reviewed. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE. Ecuador has a variety of climates from the cold of the Andes through temperate to humid hot weather at the coast and in the Amazon basin. Ecuador has a population of 15,223,680 people and an average life expectancy of 76 years. The median estimate of the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) population at risk for fungal disease (<200 CD4 cell counts) is ∼10,000, with a rate of 11.1% (1100) of histoplasma, 7% (700) of cryptococcal meningitis, and 11% (1070) of Pneumocystis pneumonia. The burden of candidemia is 1037. Recurrent Candida vaginitis (≥4 episodes per year) affects 307,593 women aged 15-50 years. Chronic pulmonary aspergillosis probably affects ∼476 patients following tuberculosis (TB). Invasive aspergillosis is estimated to affect 748 patients (∼5.5/100,000). In addition, allergic bronchopulmonary aspergillosis (ABPA) in asthma and severe asthma with fungal sensitization (SAFS) were estimated to affect 26,642 and 45,013 people, respectively. Our estimates indicate that 433,856 (3%) of the population in Ecuador is affected by serious fungal infection.

EARLY-ESLI study: Long-term experience with eslicarbazepine acetate after first monotherapy failure.

PURPOSE: Evaluate real-life experience with eslicarbazepine acetate (ESL) after first monotherapy failure in a large series of patients with focal epilepsy. METHOD: Multicentre, retrospective, 1-year, observational study in patients older than 18 years, with focal epilepsy, who had failed first antiepileptic drug monotherapy and who received ESL. Data from clinical records were analysed at baseline, 3, 6 and 12 months to assess effectiveness and tolerability. RESULTS: Eslicarbazepine acetate was initiated in 253 patients. The 1-year retention rate was 92.9%, and the final median dose of ESL was 800 mg. At 12 months, 62.3% of patients had been seizure free for 6 months; 37.3% had been seizure free for 1 year. During follow-up, 31.6% of the patients reported ESL-related adverse events (AEs), most commonly somnolence (8.7%) and dizziness (5.1%), and 3.6% discontinued due to AEs. Hyponatraemia was observed in seven patients (2.8%). After starting ESL, 137 patients (54.2%) withdrew the prior monotherapy and converted to ESL monotherapy; 75.9% were seizure free, 87.6% were responders, 4.4% worsened, and 23.4% reported ESL-related AEs. CONCLUSION: Use of ESL after first monotherapy failure was associated with an optimal seizure control and tolerability profile. Over half of patients were converted to ESL monotherapy during follow-up.

Colistin-resistant Escherichia coli clinical isolate harbouring the mcr-1 gene in Ecuador.

Colistin resistance mediated by the mcr-1 gene has been reported worldwide, but to date not from the Andean region, South America. We report the first clinical isolate of Escherichia coli harbouring the mcr-1 gene in Ecuador. The strain was isolated from peritoneal fluid from a 14-year-old male with acute appendicitis, and subjected to molecular analysis. The minimum inhibitory concentration of colistin for the strain was 8 mg/ml and it was susceptible to carbapenems but resistant to tigecycline. The strain harboured mcr-1 and bla CTX-M-55 genes and was of sequence type 609. The recognition of an apparently commensal strain of E. coli harbouring mcr-1 serves as an alert to the presence in the region of this recently described resistance mechanism to one of the last line of drugs available for the treatment of multi-resistant Gram-negative infections.

Otolith shape lends support to the sensory drive hypothesis in rockfishes.

The sensory drive hypothesis proposes that environmental factors affect both signalling dynamics and the evolution of signals and receivers. Sound detection and equilibrium in marine fishes are senses dependent on the sagittae otoliths, whose morphological variability appears intrinsically linked to the environment. The aim of this study was to understand if and which environmental factors could be conditioning the evolution of this sensory structure, therefore lending support to the sensory drive hypothesis. Thus, we analysed the otolith shape of 42 rockfish species (Sebastes spp.) to test the potential associations with the phylogeny, biological (age), ecological (feeding habit and depth distribution) and biogeographical factors. The results showed strong differences in the otolith shapes of some species, noticeably influenced by ecological and biogeographical factors. Moreover, otolith shape was clearly conditioned by phylogeny, but with a strong environmental effect, cautioning about the use of this structure for the systematics of rockfishes or other marine fishes. However, our most relevant finding is that the data supported the sensory drive hypothesis as a force promoting the radiation of the genus Sebastes. This hypothesis holds that adaptive divergence in communication has significant influence relative to other life history traits. It has already been established in Sebastes for visual characters and organs; our results showed that it applies to otolith transformations as well (despite the clear influence of feeding and depth), expanding the scope of the hypothesis to other sensory structures.

Panniculitis caused by Mycobacterium monacense mimicking erythema induratum: a case in Ecuador.

We report the first case of recently characterized species M. monacense associated with chronic nodular vasculitis, infecting a young woman. This case represents the first isolation of M. monacense from Ecuador. The isolate was identified by conventional and molecular techniques.

Automatized Patient-Specific Methodology for Numerical Determination of Biomechanical Corneal Response.

This work presents a novel methodology for building a three-dimensional patient-specific eyeball model suitable for performing a fully automatic finite element (FE) analysis of the corneal biomechanics. The reconstruction algorithm fits and smooths the patient's corneal surfaces obtained in clinic with corneal topographers and creates an FE mesh for the simulation. The patient's corneal elevation and pachymetry data is kept where available, to account for all corneal geometric features (central corneal thickness-CCT and curvature). Subsequently, an iterative free-stress algorithm including a fiber's pull-back is applied to incorporate the pre-stress field to the model. A convergence analysis of the mesh and a sensitivity analysis of the parameters involved in the numerical response is also addressed to determine the most influential features of the FE model. As a final step, the methodology is applied on the simulation of a general non-commercial non-contact tonometry diagnostic test over a large set of 130 patients-53 healthy, 63 keratoconic (KTC) and 14 post-LASIK surgery eyes. Results show the influence of the CCT, intraocular pressure (IOP) and fibers (87%) on the numerical corneal displacement (U(Num)) the good agreement of the U(Num) with clinical results, and the importance of considering the corneal pre-stress in the FE analysis. The potential and flexibility of the methodology can help improve understanding of the eye biomechanics, to help to plan surgeries, or to interpret the results of new diagnosis tools (i.e., non-contact tonometers).

Characterization of the first report of Mycobacterium timonense infecting an HIV patient in an Ecuadorian hospital.

Mycobacterium timonense is a non-tuberculous mycobacteria (NTM) described in southern France in 2009, and to our knowledge, not reported again as a human pathogen in indexed literature. The aim of this work was to characterize the first clinical isolate of M. timonense in Ecuador. Time of growth, biochemical tests, thin layer growth test, PCR-RFLP analysis of the hsp65 gene and MALDI-TOF spectra analysis were not able to identify the species. The species identification was achieved through sequencing of rrs, hsp65 and rpoB genes. The results highlight the necessity to set up a sequencing method to identify emerging NTM in Ecuadorian clinical facilities.

Integration of conflict into integrative taxonomy: fitting hybridization in species delimitation of Mesocarabus (Coleoptera: Carabidae).

In species differentiation, characters may not diverge synchronously, and there are also processes that shuffle character states in lineages descendant from a common ancestor. Species are thus expected to show some degree of incongruence among characters; therefore, taxonomic delimitation can benefit from integrative approaches and objective strategies that account for character conflict. We illustrate the potential of exploiting conflict for species delimitation in a study case of ground beetles of the subgenus Carabus (Mesocarabus), where traditional taxonomy does not accurately delimit species. The molecular phylogenies of four mitochondrial and three nuclear genes, cladistic analysis of the aedeagus, ecological niche divergence and morphometry of pronotal shape in more than 500 specimens of Mesocarabus show that these characters are not fully congruent. For these data, a three-step operational strategy is proposed for species delimitation by (i) delineating candidate species based on the integration of incongruence among conclusive lines of evidence, (ii) corroborating candidate species with inconclusive lines of evidence and (iii) refining a final species proposal based on an integrated characterization of candidate species based on the evolutionary analysis of incongruence. This procedure provided a general understanding of the reticulate process of hybridization and introgression acting on Mesocarabus and generated the hypothesis of seven Mesocarabus species, including two putative hybrid lineages. Our work emphasizes the importance of incorporating critical analyses of character and phylogenetic conflict to infer both the evolutionary history and species boundaries through an integrative taxonomic approach.

Resistant gram-negative infections in the outpatient setting in Latin America.

Latin America has a high rate of community-associated infections caused by multidrug-resistant Enterobacteriaceae relative to other world regions. A review of the literature over the last 10 years indicates that urinary tract infections (UTIs) by Escherichia coli, and intra-abdominal infections (IAIs) by E. coli and Klebsiella pneumoniae, were characterized by high rates of resistance to trimethoprim/sulfamethoxazole, quinolones, and second-generation cephalosporins, and by low levels of resistance to aminoglycosides, nitrofurantoin, and fosfomycin. In addition, preliminary data indicate an increase in IAIs by Enterobacteriaceae producing extended-spectrum ß-lactamases, with reduced susceptibilities to third- and fourth-generation cephalosporins. Primary-care physicians in Latin America should recognize the public health threat associated with UTIs and IAIs by resistant Gram-negative bacteria. As the number of therapeutic options become limited, we recommend that antimicrobial prescribing be guided by infection severity, established patient risk factors for multidrug-resistant infections, acquaintance with local antimicrobial susceptibility data, and culture collection.

Integration of molecular, ecological, morphological and endosymbiont data for species delimitation within the Pnigalio soemius complex (Hymenoptera: Eulophidae).

Integrative taxonomy is a recently developed approach that uses multiple lines of evidence such as molecular, morphological, ecological and geographical data to test species limits, and it stands as one of the most promising approaches to species delimitation in taxonomically difficult groups. The Pnigalio soemius complex (Hymenoptera: Eulophidae) represents an interesting taxonomical and ecological study case, as it is characterized by a lack of informative morphological characters, deep mitochondrial divergence, and is susceptible to infection by parthenogenesis-inducing Rickettsia. We tested the effectiveness of an integrative taxonomy approach in delimiting species within the P. soemius complex. We analysed two molecular markers (COI and ITS2) using different methods, performed multivariate analysis on morphometric data and exploited ecological data such as host-plant system associations, geographical separation, and the prevalence, type and effects of endosymbiont infection. The challenge of resolving different levels of resolution in the data was met by setting up a formal procedure of data integration within and between conflicting independent lines of evidence. An iterative corroboration process of multiple sources of data eventually indicated the existence of several cryptic species that can be treated as stable taxonomic hypotheses. Furthermore, the integrative approach confirmed a trend towards host specificity within the presumed polyphagous P. soemius and suggested that Rickettsia could have played a major role in the reproductive isolation and genetic diversification of at least two species.

Acute and subacute toxic effects produced by microcystin-YR on the fish cell lines RTG-2 and PLHC-1.

Approximately 80 microcystins (MCs) variants have been isolated in surface water worldwide. The toxicity of the most frequently MCs are encountered, MC-LR and MC-RR, has been extensively studied in humans and animals. However, studies dealing with MC-YR toxicity are still scarce. In this work, the toxic effects of MC-YR were investigated in the fish cell line PLHC-1, derived from a hepatocellular carcinoma of the topminnow Poeciliopsis lucida, and RTG-2 fibroblast-like cells derived from the gonads of rainbow trout Oncorhynchus mykiss. After 48 h, morphological and biochemical changes (total protein content, neutral red uptake and methylthiazol tetrazolium salt metabolization) were determined. The most sensitive endpoint for both cell lines was the reduction of total protein content, with EC(50) values of 35 microM for PLHC-1 cells and 67 microM for the RTG-2 cell line. Lysosomal function and methylthiazol tetrazolium salt metabolization were stimulated at low concentrations, while they decreased at high doses. Increase of piknotic cells, rounding effects, reduction in cell number and cell size, hydropic degeneration, and death mainly by necrosis but also by apoptosis were observed in the morphological study. Furthermore, PLHC-1 cells are more sensitive than RTG-2 cells to MC-YR exposure. These results were similar to those obtained when both cell lines were exposed for 24h to a Microcystis aeruginosa isolated strain extract containing MC-LR.

Evaluation of a rapid culture method for tuberculosis diagnosis: a Latin American multi-center study.

SETTINGS: Tuberculosis (TB) diagnostic laboratories in Latin America. OBJECTIVES: Evaluation of thin-layer agar (TLA) compared to Löwenstein-Jensen (LJ) culture for the diagnosis of TB. DESIGN: Phase II prospective study in six laboratories. Samples included sputum and extra-pulmonary specimens from patients with a clinical diagnosis of TB. Respiratory samples were decontaminated using NaOH/ NALC; all samples were centrifuged, stained with Ziehl-Neelsen for acid-fast bacilli (AFB), cultured on LJ and TLA and identified according to recommended procedures. Sensitivity and likelihood ratios (LR), growth detection time and contamination rate were calculated for both media. RESULTS: A total of 1118 clinical specimens were studied. Cultures detected Mycobacterium tuberculosis in all AFB-positive samples, whereas for AFB-negative specimens LJ detected 3.2% and TLA 4.4%. Sensitivity was 92.6% (95%CI 87.9-95.9) and 84.7% (95%CI 78.8-89.0) for TLA and LJ, respectively. Positive and negative LRs were similar. Contamination was 5.1% for TLA and 3.0% for LJ. Median time to detection of a positive culture was 11.5 days (95%CI 9.3-15.0) for TLA and 30.5 days (95%CI 26.9-39.0) for LJ (P < 0.0001). CONCLUSION: Difference in the characteristics of the participating laboratories, the disease prevalence and the number and type of specimens processed did not affect the overall performance of TLA as compared to LJ, supporting the robustness of the method and its feasibility in different laboratory settings.

Testing introgressive hybridization hypotheses using statistical network analysis of nuclear and cytoplasmic haplotypes in the leaf beetle Timarcha goettingensis species complex.

Previous studies of leaf beetles (Chrysomelidae) in the Timarcha goettingensis species complex using mitochondrial (cox2) and nuclear (ITS-2 rRNA) markers revealed two main clades confined to the Iberian Peninsula and the rest of Europe but showing incongruent distributions indicative of gene exchange between both groups. Because of the anastomosing nature of hybridization, which disrupts the cladistic structure of character variation, phylogenetic trees might be inappropriate to represent and study this process. Here we test for evidence of hybridization in the T. goettingensis complex by analyzing the extra homoplasy arising in hybrid genomes from the simultaneous analysis of genetically independent markers. Haplotype networks obtained by Templeton's statistical parsimony analysis were generated for combined (concatenated) cox2 and ITS-2 sequences from 167 individuals of the T. goettingensis complex. Networks were used to detect runs of homoplasious characters physically clustered along a nucleotide sequence, as evidence for recombination between both gene partitions. A hypergeometric tail probability for the chance occurrence of physically clustered character changes on the connections linking networks of genotypes was applied. The test recognized two instances of statistically significant clustering, indicating the presence of cox2-ITS-2 mosaic genotypes and reticulation of both main T. goettingensis clades, supporting the reticulate origin of samples of T. maritima in southwestern France and T. sinuatocollis/T. monserratensis in the eastern Pyrenees. Although the assessment of reticulation in DNA sequences does not provide direct proof for hybridization, the geographical distribution of mosaic genotypes in the vicinity of "pure" genotypes supports the effect of gene flow between the two divergent lineages. The study demonstrates the utility of statistical parsimony networks for the detection of hybrids in the growing number of phylogeographic studies based on multiple gene markers.