Simultaneous Whole Mitochondrial Genome Sequencing with Short Overlapping Amplicons Suitable for Degraded DNA Using the Ion Torrent Personal Genome Machine

Whole mitochondrial (mt) genome analysis enables a considerable increase in analysis throughput, and improves the discriminatory power to the maximum possible phylo

On Passion and Sports Fans:A Look at Football

The purpose of the present research was to test the applicability of the Dualistic Model of Passion (Vallerand et al., 2003) to being a sport (football) fan. The model posits that passion is a strong inclination toward an activity that individuals like (or even love), that they value, and in which they invest time and energy. Furthermore, two types of passion are proposed: harmonious and obsessive passion. While obsessive passion entails an uncontrollable urge to engage in the passionate activity, harmonious passion entails a sense of volition while engaging in the activity. Finally, the model posits that harmonious passion leads to more adaptive outcomes than obsessive passion. Three studies provided support for this dualistic conceptualization of passion. Study 1 showed that harmonious passion was positively associated with adaptive behaviours (e.g., celebrate the team’s victory), while obsessive passion was rather positively associated with maladaptive behaviours (e.g., to risk losing one’s employment to go to the team’s game). Study 2 used a short Passion Scale and showed that harmonious passion was positively related to the positive affective life of fans during the 2006 FIFA World Cup, psychological health (self-esteem and life satisfaction), and public displays of adaptive behaviours (e.g., celebrating one’s team victory in the streets), while obsessive passion was predictive of maladaptive affective life (e.g., hating opposing team’s fans) and behaviours (e.g., mocking the opposing team’s fans). Finally, Study 3 examined the role of obsessive passion as a predictor of partner’s conflict that in turn undermined partner’s relationship satisfaction. Overall, the present results provided support for the Dualistic Model of Passion. The conceptual and applied implications of the findings are discussed

MAPlex: A massively parallel sequencing ancestry analysis multiplex for Asia-Pacific populations

© 2019 The Authors Current forensic ancestry-informative panels are limited in their ability to differentiate populations in the Asia-Pacific region. MAPlex (Multiplex for the Asia-Pacific), a massively parallel sequencing (MPS) assay, was developed to improve differentiation of East Asian, South Asian and Near Oceanian populations found in the extensive cross-continental Asian region that shows complex patterns of admixture at its margins. This study reports the development of MAPlex; the selection of SNPs in combination with microhaplotype markers; assay design considerations for reducing the lengths of microhaplotypes while preserving their ancestry-informativeness; adoption of new population-informative multiple-allele SNPs; compilation of South Asian-informative SNPs suitable for forensic AIMs panels; and the compilation of extensive reference and test population genotypes from online whole-genome-sequence data for MAPlex markers. STRUCTURE genetic clustering software was used to gauge the ability of MAPlex to differentiate a broad set of populations from South and East Asia, the West Pacific regions of Near Oceania, as well as the other globally distributed population groups. Preliminary assessment of MAPlex indicates enhanced South Asian differentiation with increased divergence between West Eurasian, South Asian and East Asian populations, compared to previous forensic SNP panels of comparable scale. In addition, MAPlex shows efficient differentiation of Middle Eastern individuals from Europeans. MAPlex is the first forensic AIM assay to combine binary and multiple-allele SNPs with microhaplotypes, adding the potential to detect and analyze mixed source forensic DNA

Towards simultaneous individual and tissue identification: A proof-of-principle study on parallel sequencing of STRs, amelogenin, and mRNAs with the Ion Torrent PGM

Abstract DNA-based individual identification and RNA-based tissue identification represent two commonly-used tools in forensic investigation, aiming to identify crime scene sample donors and helping to provide links between DNA-identified sample donors and criminal acts. Currently however, both analyses are typically performed separately. In this proof-of-principle study, we developed an approach for the simultaneous analysis of forensic STRs, amelogenin, and forensic mRNAs based on parallel targeted DNA/RNA sequencing using the Ion Torrent Personal Genome Machine® (PGM™) System coupled with the AmpliSeq™ targeted amplification. We demonstrated that 9 autosomal STRs commonly used for individual identification (CSF1PO, D16S539, D3S1358, D5S818, D7S820, D8S1179, TH01, TPOX, and vWA), the AMELX/AMELY system widely applied for sex identification, and 12 mRNA markers previously established for forensic tissue identification (ALAS2 and SPTB for peripheral blood, MMP10 and MMP11 for menstrual blood, HTN3 and STATH for saliva, PRM1 and TGM4 for semen, CYP2B7P1 and MUC4 for vaginal secretion, CCL27 and LCE1C for skin) together with two candidate reference mRNA markers (HPRT1 and SDHA) can all be successfully combined. Unambiguous mRNA-based tissue identification was achieved in all samples from all forensically relevant tissues tested, and STR sequencing analysis of the tissue sample donors was 100% concordant with conventional STR profiling using a commercial kit. Successful STR analysis was obtained from 1 ng of genomic DNA and mRNA analysis from 10 ng total RNA; however, sensitivity limits were not investigated in this proof-of-principle study and are expected to be much lower. Since dried materials with noticeable RNA degradation and small DNA/RNA amplicons with high-coverage sequencing were used, the achieved correct individual and tissue identification demonstrates the suitability of this approach for analyzing degraded materials in future forensic applications. Overall, our study demonstrates the feasibility of simultaneously obtaining multilocus STR, amelogenin, and multilocus mRNA information for combined individual and tissue identification from a small sample of degraded biological material. Moreover, our study marks the first step towards combining many DNA/RNA markers for various forensic purposes to increase the effectiveness of molecular forensic analysis and to allow more forensically relevant information to be obtained from limited forensic material

The complexities of breast cancer desmoplasia

The stromal, or 'desmoplastic', responses seen histologically in primary breast carcinomas can vary from being predominantly cellular (fibroblasts/myofibroblasts) with little collagen to being a dense acellular tissue. The mechanisms underlying the stromal response are complex; paracrine activation of myofibroblasts by growth factors is important but the contribution of cytokines/chemokines should not be ignored. A recent xenograft study has proposed that platelet-derived growth factor (PDGF) is the initiator of the desmoplastic response, but this has not been confirmed by (limited) analyses in vivo. Further studies are required to elaborate the mechanisms of the desmoplastic response, to determine its role in breast cancer progression and whether it is the same for all carcinomas

Analysis of 1560 inpatient and outpatient Escherichia coli isolates from across Canada - Results from the CANWARD 2007 study CANWARD 2007

OBJeCtIveS: Escherichia coli was the most common pathogen isolated in the Canadian Ward Surveillance Study (CANWARD 2007) and remains one of the most common pathogens isolated in all health care settings. An in-depth analysis of all E coli isolates was performed to determine the distribution and demographics associated with resistance to antimicrobials, presence of extended-spectrum beta-lactamases (ESBLs) and multidrug resistance (MDR; concurrent resistance to agents from three or more different antimicrobial classes). MethODS: The CANWARD 2007 study characterized pathogens isolated from inpatient (surgical and medical wards, and intensive care units) and outpatient (emergency departments and clinics) areas of 12 Canadian hospitals between January and December 2007. E coli susceptibility to 12 antimicrobials was determined, ESBL production was determined, and a multivariate nominal logistic regression model was designed to determine if sex, isolation from a sterile site, inpatient versus outpatient status, and age were significantly associated with susceptibility to the tested antimicrobials, MDR or ESBL production. ReSuLtS: In total, 1702 E coli isolates, representing 21.6% of all isolates collected in the CANWARD 2007 study, were investigated. Of these, 1560 isolates fell within the primary objective of the study and were included in the present analysis. Susceptibilities were greater than 90% for meropenem (100%), ertapenem (100%), tigecycline (99.9%), piperacillin-tazobactam (97.9%), cefepime (97.9%), ceftriaxone (95.4%), nitrofurantoin (95.2%), cefoxitin (94.8%), amoxicillinclavulanate (92.9%) and gentamicin (91.4%). Cefazolin (89.4%), the fluoroquinolones (ciprofloxacin, 79.4%; levofloxacin, 79.9%) and trimethoprim-sulfamethoxazole (75.7%) were less active agents. In the multivariate model, invasive isolates were significantly associated with lower susceptibility rates for trimethoprim-sulfamethoxazole. Increasing age was associated with lower susceptibility to fluoroquinolones, ceftriaxone, cefepime, gentamicin and nitrofurantoin, as well as ESBL production. Sex was not associated with resistance to any antimicrobial or to ESBL production. Inpatient status was associated with higher resistance rates to amoxicillin-clavulanate, cefazolin, fluoroquinolones and trimethoprim-sulfamethoxazole. Isolation of an ESBL producer was only found to be independently associated with age, being more common in older patients. MDR was not found to be associated with any variable measured when ESBL producers were excluded from analysis. CONCLuSIONS: E coli antimicrobial susceptibility varies according to patient factors. Age and inpatient status were the most important determinants in the present analysis and should be considered when prescribing empirical antimicrobial therapy. Fluoroquinolones and sulfonamides should be used cautiously and in consideration of local resistance patterns for infections caused by E coli, due to lower susceptibility rates. Independent factors associated with antimicrobial resistance were age, inpatient status and isolation from a sterile site. These factors should be considered when empirically treating infections likely caused by E coli. Local antimicrobial prescribing practices, in particular the liberal use of fluoroquinolones, and inadequate infection control practices may be reducing susceptibility rates. OBJeCtIFS : L'Escherichia coli était le pathogène le plus isolé dans l'étude CANWARD 2007 sur la surveillance des services aux hospitalisés canadiens et demeure l'un des pathogènes les plus isolés en milieu de santé. On a effectué une analyse approfondie de tous les isolats d'E coli pour déterminer la répartition et la démographie associées à la résistance aux antimicrobiens ainsi qu'à la présence de bêta-lactamases à large spectre (ESBL) et de multirésistance (résistance conjointe à au moins trois classes d'antimicrobiens). MÉthODOLOGIe : L'étude CANWARD 2007 caractérisait les pathogènes isolés de patients hospitalisés (service de chirurgie, service médical et unité de soins intensifs) et ambulatoires (urgence et cliniques) de 12 hôpitaux canadiens entre janvier et décembre 2007. On a déterminé la susceptibilité de l'E coli à 12 antimicrobiens ainsi que la production d'ESBL et conçu un modèle de régression logistique nominale multivariée pour déterminer si le sexe, l'isolement d'un foyer stérile, le statut de patient hospitalisé ou ambulatoire et l'âge s'associaient de manière significative à la susceptibilité aux antimicrobiens vérifiés, à la multirésistance ou à la production d'ESBL. RÉSuLtAtS : Au total, on a évalué 1 072 isolats d'E coli, représentant 21,6 % de tous les isolats prélevés dans le cadre de l'étude CANWARD 2007. De ce nombre, 1 560 isolats respectaient l'objectif primaire de l'étude et ont été inclus dans la présente analyse. Les susceptibilités étaient supérieures à 90 % pour le méropénem (100 %), l'ertapénem (100 %), la tigécycline (99,9 %), la pipéracilline-tazobactam (97,9 %), la céfépime (97.9 %), la ceftriaxone (95,4 %), la nitrofurantoïne (95,2 %), la céfoxitine (94,8 %), l'amoxicilline-clavulanate (92,9 %) et la gentamicine (91,4 %). La céfazoline (89,4 %), les fluoroquinolones (ciprofloxacine, 79,4 %, lévofloxacine, 79,9 %) et le triméthoprim-sulfaméthoxazole (75,7 %) étaient moins actifs. Dans le modèle multivarié, les isolats envahissants étaient associés de manière marquée à des taux de susceptibilité plus faibles pour le triméthoprim-sulfaméthoxazole. Le vieillissement s'associait à une susceptibilité plus faible aux fluoroquinolones, à la ceftriaxone, à la suite page suivante Lagacé-Wiens et al Can J Infect Dis Med Microbiol Vol 20 Suppl A Spring 2009 50A E scherichia coli is the most commonly isolated clinically relevant Gram-negative organism in most health care settings (1-3). Although most commonly associated with urinary tract infections, all body sites can be involved. Furthermore, resistance to multiple antimicrobials is increasing and multidrug resistant (MDR; concurrent resistance to agents from three or more different antimicrobial classes) isolates are common (1,4,5). Appropriate empirical antimicrobial choice must take into account local resistance patterns and other demographic variables such as patient age, site and severity of infection, sex, inpatient status as well as previous antimicrobial use, stay in hospitals or personal care homes, and colonization with antimicrobial resistant organisms (1,6). The purpose of the present study was to provide an in-depth analysis of patient factors associated with drug resistance in the most commonly isolated organism overall in Canadian hospitals. MethODS E coli isolates were obtained as part of the Canadian Ward Surveillance Study (CANWARD 2007), which collected isolates submitted to 12 clinical microbiology laboratories from tertiary care hospitals in seven provinces across Canada. Submitting sites and collection strategy are described elsewhere in the present supplement (2). Isolates had to be deemed clinically significant by the referring laboratory's current specimen work-up protocol. Demographic information collected with each isolate included patient age, sex, site of infection and the location of patient contact (surgical or medical ward, emergency room, intensive care unit [ICU] or hospital clinic). A minimum number of isolates from each hospital location and anatomical site was requested to provide more power to the study. The implication of this collection strategy is that the anatomical distribution of pathogen isolation and inpatient versus outpatient distribution does not reflect the true distribution in the population studied. Isolates were collected within both primary and secondary study objectives and only isolates collected within the primary objective were considered in this analysis. For statistical analysis, age was divided into four categories: 20 years and younger, 21 to 60 years, 61 to 80 years, and 81 years and older, and location of patient contact was divided into either inpatient (wards and ICUs) or outpatient (emergency room and clinics). Information on previous antimicrobial exposure, hospitalization duration and underlying medical conditions was not available. Antimicrobial susceptibility to amoxicillin-clavulanate, cefazolin, cefepime, ceftriaxone, ciprofloxacin, gentamicin, nitrofurantoin, levofloxacin, meropenem, ertapenem, piperacillin-tazobactam, tigecycline and trimethoprim-sulfamethoxazole was determined using broth dilution as described elsewhere in the present supplement (2). Screening for ESBL production was achieved using a 1 µg/mL or greater ceftriaxone breakpoint and confirmation was with the Clinical and Laboratory Standards Institute-recommended disk diffusion method (7). Univariate analysis using the c 2 (or Fisher's exact test where required) was undertaken to identify relationships between susceptibility to each of the antimicrobials and ESBL production; and the following variables: sex, age group, inpatient/outpatient status and isolation from a sterile site (blood, cerebrospinal fluid, synovial fluid). Relationships where the P<0.20 in the univariate analysis were included in a multivariate nominal logistic regression model to determine independent explanatory variables. Initially, a full factorial multiple logistic regression analysis was performed using the potential explanatory variables identified in the univariate analysis for each antimicrobial, and then a backward selection so that all factors remaining in the model were statistically significant at a 5% level (P<0.05). Statistical analysis was undertaken using JMP software version 7.0 (SAS Institute Inc, USA). ReSuLtS Of 7881 total organisms, 1702 E coli (21.6%) were collected from the CANWARD 2007 study, making it the most common organism isolated from patients in Canadian hospitals overall. Of these, 1560 fell within the primary objective and the remaining 142 were submitted as putative ESBL producers for separate analysis and excluded from the present analysis. The mean age of patients infected with E coli was 56.9 years; 12.3% of E coli isolates were from patients younger than 21 years, 34.7% were 21 to 60 years of age, 33.9% were 61 to 80 years of age and 19.1% were older than 80 years of age. There were more samples from women (59.3%); with both sexes combined, 50.5% were invasive isolates (all bloodstream), and 40.7% were from urine, 6.4% from respiratory sources and 2.4% from wounds. Note that the sampling strategy was biased to include a surplus of bloodstream isolates to have greater numbers of these for analysis and this does not represent the true source distribution of E coli infections. The distribution among provinces was British Columbia, 9.7%; Alberta, 7.6%; Saskatchewan, 9.1%; Manitoba, 9.2%; Ontario, 28.3%; Quebec, 29.2% and Nova Scotia, 6.9%. Isolates were not obtained from Newfoundland, Nunavut, the Northwest Territories, Yukon, New Brunswick or Prince Edward Island. Minimum inhibitory concentrations (MICs) required to inhibit 50% and 90% of organisms (MIC 50 , MIC 90 ) and percentage of isolates susceptible to the antimicrobials are provided in Resistance in E coli from Canadian inpatients and outpatients Can J Infect Dis Med Microbiol DISCuSSION Low susceptibility of ICU E coli isolates to fluoroquinolones and trimethoprim-sulfamethoxazole was not unexpected given the wide use of these antimicrobials in both inpatients and outpatients. In particular, the dramatic increase in fluoroquinolone resistance has been observed in many settings (8-10). Our observations suggest that first-generation cephalosporins and amoxicillin-clavulanate are still useful agents for infections caused by E coli in that susceptibility rates remain near 90% overall. This is particularly true of outpatient isolates where susceptibility is greater than 90% for both these agents. On the contrary, low susceptibility to fluoroquinolones even in the outpatient setting (84%) begins to bring into question the use of these agents as first line for infections commonly caused by E coli, such as urinary tract infections. Trimethoprimsulfamethoxazole susceptibility rates are below 80% in both inpatient and outpatient settings and should only be used for infections empirically in the context of supportive data from local antibiograms or definitive susceptibility data. In our multivariate model, increasing age was independently associated with reduced susceptibility to fluoroquinolones, nitrofurantoin, ceftriaxone, cefepime, gentamicin and ESBL production. The association between age and fluoroquinolone susceptibility has been demonstrated previously and is likely due to increasing exposure to fluoroquinolones over time and avoidance of fluoroquinolone use in children Predictably, inpatient isolates had lower susceptibility to several antibiotics, including amoxicillin-clavulanate, fluoroquinolones, cefazolin and trimethoprim-sulfamethoxazole. Interestingly, susceptibility to antimicrobials commonly used in the inpatient setting (ceftriaxone, cefepime, gentamicin, carbapenems and piperacillin-tazobactam) did not appear to be significantly affected by inpatient status. This is reassuring in that these antimicrobials maintain good activity overall in the hospital setting. The reason that antimicrobials commonly used in the community are most affected by inpatient status is not known, but may be due to general practitioners using these antimicrobials to treat outpatients and selection bias occurring because poor response due to antimicrobial resistance requires admission for parenteral antimicrobials. Interestingly, sex was not a predictor of susceptibility to any of the antimicrobials tested after adjusting for other factors in the multivariate model. Although large differences were seen between susceptibility to fluoroquinolones, both inpatient status and age appeared to be confounding factors in the effect of sex on fluoroquinolone resistance. The absence of a sex effect contradicts the findings of others Meropenem, ertapenem, piperacillin-tazobactam, tigecycline and cefoxitin were not significantly associated with any demographic variable in the multivariate model. Low overall resistance rates accounts for these observations. Our study had some limitations. We could not collect patient information such as length of stay, previous antimicrobial exposure and underlying disease. Although of great interest for the prediction of antimicrobial resistance, the effect of these variables cannot be determined with our data. Also, our isolates reflect only information from the 12 centres studied and our data may not reflect the antimicrobial susceptibility patterns of all hospitals in Canada. However, this study does provide valuable information about the factors predicting antimicrobial susceptibility of E coli in one of the largest of inpatient and outpatient populations in Canada studied to date

Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000–300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10−10). The risk allele, while ancestral, has a frequency of ∼1.4%, suggesting strong negative selection and increases risk for SCD by 1.92–fold per allele (95% CI 1.57–2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006)

School Effects on the Wellbeing of Children and Adolescents

Well-being is a multidimensional construct, with psychological, physical and social components. As theoretical basis to help understand this concept and how it relates to school, we propose the Self-Determination Theory, which contends that self-determined motivation and personality integration, growth and well-being are dependent on a healthy balance of three innate psychological needs of autonomy, relatedness and competence. Thus, current indicators involve school effects on children’s well-being, in many diverse modalities which have been explored. Some are described in this chapter, mainly: the importance of peer relationships; the benefits of friendship; the effects of schools in conjunction with some forms of family influence; the school climate in terms of safety and physical ecology; the relevance of the teacher input; the school goal structure and the implementation of cooperative learning. All these parameters have an influence in promoting optimal functioning among children and increasing their well-being by meeting the above mentioned needs. The empirical support for the importance of schools indicates significant small effects, which often translate into important real-life effects as it is admitted at present. The conclusion is that schools do make a difference in children’s peer relationships and well-being

Getting a grip on sensorimotor effects in lexical-semantic processing

One of the strategies that researchers have used to investigate the role of sensorimotor information in lexical-semantic processing is to examine effects of words’ rated body-object interaction (BOI; the ease with which the human body can interact with a word’s referent). Processing tends to be facilitated for words with high BOI compared to words with low BOI, across a wide variety of tasks. Such effects have been referenced in debates over the nature of semantic representations, but their theoretical import has been limited by the fact that BOI is a fairly coarse measure of sensorimotor experience with words’ referents. In the present study we collected ratings for 621 words on seven semantic dimensions (graspability, ease of pantomime, number of actions, animacy, size, danger, and usefulness) in order to investigate which attributes are most strongly related to BOI ratings, and to lexical-semantic processing. BOI ratings were obtained from previous norming studies (Bennett, Burnett, Siakaluk, & Pexman, 2011; Tillotson, Siakaluk, & Pexman, 2008) and measures of lexical-semantic processing were obtained from previous behavioural megastudies involving the semantic categorization task (concrete/abstract decision; Pexman, Heard, Lloyd, & Yap, 2017) and the lexical decision task (Balota et al., 2007). Results showed that the motor dimension of graspability, ease of pantomime, and number of actions were all related to BOI and that these dimensions together explained more variance in semantic processing than did BOI ratings alone. These ratings will be useful for researchers who wish to study how different kinds of bodily interactions influence lexical-semantic processing and cognition