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Objectives/Goals: Digital recruitment can improve participant engagement in medical research, but its potential to introduce demographic and socioeconomic biases is unclear. This study investigates pathways participants took during a digital recruitment workflow in neurology, examining potential associations with socioeconomic and demographic factors. Methods/Study Population: As part of an ongoing study aiming to remotely capture speech from patients with neurologic disease, most participants seen in neurology on our campus are invited to complete a self-administered speech examination. We exported participant data from Epic (semi-automated identification and invitation), Qualtrics (eligibility screening), the participant tracking database (consent), and the recording platform (completion) for March to July 2024. Data visualization was performed using a Sankey diagram. Socioeconomic status was assessed using the housing-based socioeconomic status (HOUSES) index and area deprivation index (ADI) national rank. Kruskal–Wallis and Wilcoxon rank-sum tests were used to compare the median age, socioeconomic indices, and time taken to reach different steps of the study. Results/Anticipated Results: Of the 5846 invited participants, 57% were from urban areas, 23% from rural areas, and 20% from urban clusters. Most did not read/respond (2739) or declined (1749) the initial invitation via Epic. Of the 1358 interested participants, 415 completed the study. Participants from urban areas completed enrollment steps faster than those from rural areas and urban clusters, though the variance was large (42.6 ± 41.4 days vs. 50.6 ± 42.2 days and 50 ± 43.9 days, respectively; p = 0.030). Female participants took longer to complete enrollment than males (48.7 ± 44 days vs. 40.5 ± 38.8 days; p = 0.026). Participants who successfully finished the study had significantly lower ADI national ranks compared to other common pathways (40.6 ± 19; p = 0.0021). No associations were found with the HOUSES indices. Discussion/Significance of Impact: Our findings support differences in participant engagement, with urban participants and males more likely to complete enrollment steps. Those who finished the study were less disadvantaged suggesting potential bias in digital recruitment. These findings can inform strategies to improve digital recruitment in neurology research.
As part of the Research Domain Criteria (RDoC) initiative, the NIMH seeks to improve experimental measures of cognitive and positive valence systems for use in intervention research. However, many RDoC tasks have not been psychometrically evaluated as a battery of measures. Our aim was to examine the factor structure of 7 such tasks chosen for their relevance to schizophrenia and other forms of serious mental illness. These include the n-back, Sternberg, and self-ordered pointing tasks (measures of the RDoC cognitive systems working memory construct); flanker and continuous performance tasks (measures of the RDoC cognitive systems cognitive control construct); and probabilistic learning and effort expenditure for reward tasks (measures of reward learning and reward valuation constructs).
Participants and Methods:
The sample comprised 286 cognitively healthy participants who completed novel versions of all 7 tasks via an online recruitment platform, Prolific, in the summer of 2022. The mean age of participants was 38.6 years (SD = 14.5, range 18-74), 52% identified as female, and stratified recruitment ensured an ethnoracially diverse sample. Excluding time for instructions and practice, each task lasted approximately 6 minutes. Task order was randomized. We estimated optimal scores from each task including signal detection d-prime measures for the n-back, Sternberg, and continuous performance task, mean accuracy for the flanker task, win-stay to win-shift ratio for the probabilistic learning task, and trials completed for the effort expenditure for reward task. We used parallel analysis and a scree plot to determine the number of latent factors measured by the 7 task scores. Exploratory factor analysis with oblimin (oblique) rotation was used to examine the factor loading matrix.
Results:
The scree plot and parallel analyses of the 7 task scores suggested three primary factors. The flanker and continuous performance task both strongly loaded onto the first factor, suggesting that these measures are strong indicators of cognitive control. The n-back, Sternberg, and self-ordered pointing tasks strongly loaded onto the second factor, suggesting that these measures are strong indicators of working memory. The probabilistic learning task solely loaded onto the third factor, suggesting that it is an independent indicator of reinforcement learning. Finally, the effort expenditure for reward task modestly loaded onto the second but not the first and third factors, suggesting that effort is most strongly related to working memory.
Conclusions:
Our aim was to examine the factor structure of 7 RDoC tasks. Results support the RDoC suggestion of independent cognitive control, working memory, and reinforcement learning. However, effort is a factorially complex construct that is not uniquely or even most strongly related to positive valance. Thus, there is reason to believe that the use of at least 6 of these tasks are appropriate measures of constructs such as working memory, reinforcement learning and cognitive control.
Agricultural workers are immersed in environments associated with increased risk for adverse psychiatric and neurological outcomes. Agricultural work-related risks to brain health include exposure to pesticides, heavy metals, and organic dust. Despite this, there is a gap in our understanding of the underlying brain systems impacted by these risks. This study explores clinical and cognitive domains, and functional brain activity in agricultural workers. We hypothesized that a history of agricultural work-related risks would be associated with poorer clinical and cognitive outcomes as well as changes in functional brain activity within cortico-striatal regions.
Participants and Methods:
The sample comprised 17 agricultural workers and a comparison group of 45 non-agricultural workers recruited in the Northern Colorado area. All participants identified as White and non-Hispanic. The mean age of participants was 51.7 years (SD = 21.4, range 18-77), 60% identified as female, and 37% identified as male. Participants completed the National Institute of Health Toolbox (NIH Toolbox) and Montreal Cognitive Assessment (MoCA) on their first visit. During the second visit, they completed NIH Patient-Reported Outcomes Measurement Information System (PROMIS) measures and underwent functional magnetic resonance imaging (fMRI; N = 15 agriculture and N = 35 non-agriculture) while completing a working memory task (Sternberg). Blood oxygen-level dependent (BOLD) response was compared between participants. Given the small sample size, the whole brain voxel-wise group comparison threshold was set at alpha = .05, but not otherwise corrected for multiple comparisons. Cohen’s d effect sizes were estimated for all voxels.
Results:
Analyses of cognitive scores showed significant deficits in episodic memory for the agricultural work group. Additionally, the agricultural work group scored higher on measures of self-reported anger, cognitive concerns, and social participation. Analyses of fMRI data showed increased BOLD activity around the orbitofrontal cortex (medium to large effects) and bilaterally in the entorhinal cortex (large effects) for the agricultural work group. The agricultural work group also showed decreased BOLD activity in the cerebellum and basal ganglia (medium to large effects).
Conclusions:
To our knowledge, this study provides the first-ever evidence showing differences in brain activity associated with a history of working in agriculture. These findings of poorer memory, concerns about cognitive functioning, and increased anger suggest clinical relevance. Social participation associated with agricultural work should be explored as a potential protective factor for cognition and brain health. Brain imaging data analyses showed increased activation in areas associated with motor functioning, cognitive control, and emotion. These findings are limited by small sample size, lack of diversity in our sample, and coarsely defined risk. Despite these limitations, the results are consistent with an overall concern that risks associated with agricultural work can lead to cognitive and psychiatric harm via changes in brain health. Replications and future studies with larger sample sizes, more diverse participants, and more accurately defined risks (e.g., pesticide exposure) are needed.
Deficits in cognitive ability are common among patients with schizophrenia. The MATRICS Consensus Cognitive Battery (MCCB) was designed to assess cognitive ability in studies of patients diagnosed with schizophrenia and has demonstrated high test-retest reliability with minimal practice effects, even in multi-site trials. However, given the motivational challenges associated with schizophrenia, it is unknown whether performance on MCCB tasks affects performance at later stages of testing. The goal of this study was to determine whether there are differences between people with and without schizophrenia in how their performance on individual MCCB tasks influences their performance throughout the battery.
Participants and Methods:
The sample comprised 92 total participants including 49 cognitively healthy comparison participants and 43 outpatients diagnosed with schizophrenia. The mean age of participants was 44.2 years (SD = 12.0, range 21–69) and 61% identified as male. The Trail Making Test, Brief Assessment of Cognition in Schizophrenia, Hopkins Verbal Learning Test – Revised, Letter-Number Span, and Category Fluency from the MCCB were administered in the same order at 2 different sites and studies from 2016–2022. The autocorrelation between t-scores for task scores within each participant was computed and then compared between control and outpatient participants to determine if there are differences between groups. Group mean t-scores for each task were also compared between groups.
Results:
We found no significant difference in autocorrelations across MCCB tasks between healthy comparison participants and outpatients. However, mean performance in all tasks was lower for the outpatient group than for the healthy comparison group. None of the tasks used stood out as having significantly lower mean scores than other tasks for either group.
Conclusions:
Our findings suggest that performance on individual MCCB tasks do not affect performance throughout the battery differently between the healthy comparison group and outpatients. This suggests that participants with schizophrenia are not particularly reactive to past performance on MCCB tasks. Additionally, this finding further supports use of the MCCB in this population. Further research is needed to determine whether subgroups of patients and/or different batteries of measures show different patterns of reactivity.
Post study questionnaires are used in design studies to uncover data about design reasoning and intent. A study was conducted where activities the study participants performed were compared to the participants’ statements about those activities, collected immediately after the study via a questionnaire. The goal was to explore the reliability of post study evaluations. Disagreements between performed and reported activities were identified, and recommendations made to, where possible, include more objective measures of design activity.
The incidence of infections from extended-spectrum β-lactamase (ESBL)–producing Enterobacterales (ESBL-E) is increasing in the United States. We describe the epidemiology of ESBL-E at 5 Emerging Infections Program (EIP) sites.
Methods
During October–December 2017, we piloted active laboratory- and population-based (New York, New Mexico, Tennessee) or sentinel (Colorado, Georgia) ESBL-E surveillance. An incident case was the first isolation from normally sterile body sites or urine of Escherichia coli or Klebsiella pneumoniae/oxytoca resistant to ≥1 extended-spectrum cephalosporin and nonresistant to all carbapenems tested at a clinical laboratory from a surveillance area resident in a 30-day period. Demographic and clinical data were obtained from medical records. The Centers for Disease Control and Prevention (CDC) performed reference antimicrobial susceptibility testing and whole-genome sequencing on a convenience sample of case isolates.
Results
We identified 884 incident cases. The estimated annual incidence in sites conducting population-based surveillance was 199.7 per 100,000 population. Overall, 800 isolates (96%) were from urine, and 790 (89%) were E. coli. Also, 393 cases (47%) were community-associated. Among 136 isolates (15%) tested at the CDC, 122 (90%) met the surveillance definition phenotype; 114 (93%) of 122 were shown to be ESBL producers by clavulanate testing. In total, 111 (97%) of confirmed ESBL producers harbored a blaCTX-M gene. Among ESBL-producing E. coli isolates, 52 (54%) were ST131; 44% of these cases were community associated.
Conclusions
The burden of ESBL-E was high across surveillance sites, with nearly half of cases acquired in the community. EIP has implemented ongoing ESBL-E surveillance to inform prevention efforts, particularly in the community and to watch for the emergence of new ESBL-E strains.
We have adapted the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) Science Pipelines to process data from the Gravitational-wave Optical Transient Observer (GOTO) prototype. In this paper, we describe how we used the LSST Science Pipelines to conduct forced photometry measurements on nightly GOTO data. By comparing the photometry measurements of sources taken on multiple nights, we find that the precision of our photometry is typically better than 20 mmag for sources brighter than 16 mag. We also compare our photometry measurements against colour-corrected Panoramic Survey Telescope and Rapid Response System photometry and find that the two agree to within 10 mmag (1$\sigma$) for bright (i.e., $\sim 14{\rm th} \mathrm{mag}$) sources to 200 mmag for faint (i.e., $\sim 18{\rm th} \mathrm{mag}$) sources. Additionally, we compare our results to those obtained by GOTO’s own in-house pipeline, gotophoto, and obtain similar results. Based on repeatability measurements, we measure a $5\sigma$L-band survey depth of between 19 and 20 magnitudes, depending on observing conditions. We assess, using repeated observations of non-varying standard Sloan Digital Sky Survey stars, the accuracy of our uncertainties, which we find are typically overestimated by roughly a factor of two for bright sources (i.e., $< 15{\rm th} \mathrm{mag}$), but slightly underestimated (by roughly a factor of 1.25) for fainter sources ($> 17{\rm th} \mathrm{mag}$). Finally, we present lightcurves for a selection of variable sources and compare them to those obtained with the Zwicky Transient Factory and GAIA. Despite the LSST Software Pipelines still undergoing active development, our results show that they are already delivering robust forced photometry measurements from GOTO data.
Concerns have been raised about the utility of self-report assessments in predicting future suicide attempts. Clinicians in pediatric emergency departments (EDs) often are required to assess suicidal risk. The Death Implicit Association Test (IAT) is an alternative to self-report assessment of suicidal risk that may have utility in ED settings.
Methods
A total of 1679 adolescents recruited from 13 pediatric emergency rooms in the Pediatric Emergency Care Applied Research Network were assessed using a self-report survey of risk and protective factors for a suicide attempt, and the IAT, and then followed up 3 months later to determine if an attempt had occurred. The accuracy of prediction was compared between self-reports and the IAT using the area under the curve (AUC) with respect to receiver operator characteristics.
Results
A few self-report variables, namely, current and past suicide ideation, past suicidal behavior, total negative life events, and school or social connectedness, predicted an attempt at 3 months with an AUC of 0.87 [95% confidence interval (CI), 0.84–0.90] in the entire sample, and AUC = 0.91, (95% CI 0.85–0.95) for those who presented without reported suicidal ideation. The IAT did not add significantly to the predictive power of selected self-report variables. The IAT alone was modestly predictive of 3-month attempts in the overall sample ((AUC = 0.59, 95% CI 0.52–0.65) and was a better predictor in patients who were non-suicidal at baseline (AUC = 0.67, 95% CI 0.55–0.79).
Conclusions
In pediatric EDs, a small set of self-reported items predicted suicide attempts within 3 months more accurately than did the IAT.
The past few decades have seen the burgeoning of wide-field, high-cadence surveys, the most formidable of which will be the Legacy Survey of Space and Time (LSST) to be conducted by the Vera C. Rubin Observatory. So new is the field of systematic time-domain survey astronomy; however, that major scientific insights will continue to be obtained using smaller, more flexible systems than the LSST. One such example is the Gravitational-wave Optical Transient Observer (GOTO) whose primary science objective is the optical follow-up of gravitational wave events. The amount and rate of data production by GOTO and other wide-area, high-cadence surveys presents a significant challenge to data processing pipelines which need to operate in near-real time to fully exploit the time domain. In this study, we adapt the Rubin Observatory LSST Science Pipelines to process GOTO data, thereby exploring the feasibility of using this ‘off-the-shelf’ pipeline to process data from other wide-area, high-cadence surveys. In this paper, we describe how we use the LSST Science Pipelines to process raw GOTO frames to ultimately produce calibrated coadded images and photometric source catalogues. After comparing the measured astrometry and photometry to those of matched sources from PanSTARRS DR1, we find that measured source positions are typically accurate to subpixel levels, and that measured L-band photometries are accurate to $\sim50$ mmag at $m_L\sim16$ and $\sim200$ mmag at $m_L\sim18$. These values compare favourably to those obtained using GOTO’s primary, in-house pipeline, gotophoto, in spite of both pipelines having undergone further development and improvement beyond the implementations used in this study. Finally, we release a generic ‘obs package’ that others can build upon, should they wish to use the LSST Science Pipelines to process data from other facilities.
Sugar-sweetened beverage (SSB) consumption in early childhood is a public health concern. Adequate hydration in early childhood is also important. We developed a national research agenda to improve beverage consumption patterns among 0–5-year-olds. This article focuses on the process used to develop this research agenda.
Design:
A mixed methods, multi-step process was used to develop the research agenda, including: (i) a scientific advisory committee; (ii) systematic reviews on strategies to reduce SSB consumption and increase water access and consumption; (iii) two stakeholder surveys to first identify and then rank strategies to reduce SSB consumption and increase water access and consumption; (iv) key informant interviews to better understand determinants of beverage consumption and strategies to improve beverage consumption patterns among high-risk groups; (v) an in-person convening with experts; and (vi) developing the final research agenda.
Setting:
This process included research and stakeholders from across the United States.
Participants:
A total of 276 participants completed survey 1 and 182 participants completed survey 2. Key informant interviews were conducted with 12 stakeholders. Thirty experts attended the convening, representing academia, government, and non-profit sectors.
Results:
Thirteen key issue areas and 59 research questions were developed. Priority topics were beverage consumption recommendations, fruit-flavoured drink consumption, interventions tailored to high-risk groups, and family engagement in childcare.
Conclusions:
This research agenda lays the groundwork for research efforts to improve beverage patterns of young children. The methods used can be a template to develop research agendas for other public health issues.
The aim of this research was to look at the emergence of wearable technology and the internet of things (IoT) and their current and potential use in the health and care area. There is a wide and ever-expanding range of wearables, devices, apps, data aggregators and platforms allowing the measurement, tracking and aggregation of a multitude of health and lifestyle measures, information and behaviours. The use and application of such technology and the corresponding richness of data that it can provide bring the health and care insurance market both potential opportunities and challenges. Insurers across a range of fields are already engaging with this type of technology in their proposition designs in areas such as customer engagement, marketing and underwriting. However, it seems like we are just at the start of the journey, on a learning curve to find the optimal practical applications of such technology with many aspects as yet untried, tested or indeed backed up with quantifiable evidence. It is clear though that technology is only part of the solution, on its own it will not engage or change behaviours and insurers will need to consider this in terms of implementation and goals. In the first weeks of forming this working party, it became evident that the potential scope of this technology, the information already out there and the pace of development of it, is almost overwhelming. With many yet-unanswered questions the paper focuses on pulling together in one place relevant information for the consideration of the health and care actuary, and also to open the reader’s eyes to potential future innovations by drawing on use of the technology in other markets and spheres, and the “science fiction–like” new technology that is just around the corner. The paper explores:
an overview of wearables and IoT and available measures,
examples of how this technology is currently being used,
data considerations,
risks and challenges,
future technology developments and
what this may mean for the future of insurance.
Insurers who engage now are likely to be on an evolving business case model and product development journey, over which they can build up their understanding and interpretation of the data that this technology can provide. An exciting area full of potential – when and how will you get involved?
Innovation Concept: The outcome of emergency medicine training is to produce physicians who can competently run an emergency department (ED) shift. While many workplace-based ED assessments focus on discrete tasks of the discipline, others emphasize assessment of performance across the entire shift. However, the quality of assessments is generally poor and these tools often lack validity evidence. The use of entrustment scale anchors may help to address these psychometric issues. The aim of this study was to develop and gather validity evidence for a novel tool to assess a resident's ability to independently run an ED shift. Methods: Through a nominal group technique, local and national stakeholders identified dimensions of performance reflective of a competent ED physician. These dimensions were included in a new tool that was piloted in the Department of Emergency Medicine at the University of Ottawa during a 4-month period. Psychometric characteristics of the items were calculated, and a generalizability analysis used to determine the reliability of scores. An ANOVA was conducted to determine whether scores increased as a function of training level (junior = PGY1-2, intermediate = PGY3, senior = PGY4-5), and varied by ED treatment area. Safety for independent practice was analyzed with a dichotomous score. Curriculum, Tool or Material: The developed Ottawa Emergency Department Shift Observation Tool (O-EDShOT) includes 12-items rated on a 5-point entrustment scale with a global assessment item and 2 short-answer questions. Eight hundred and thirty-three assessment were completed by 78 physicians for 45 residents. Mean scores differed significantly by training level (p < .001) with junior residents receiving lower ratings (3.48 ± 0.69) than intermediate residents who received lower ratings (3.98 ± 0.48) than senior residents (4.54 ± 0.42). Scores did not vary by ED treatment area (p > .05). Residents judged to be safe to independently run the shift had significantly higher mean scores than those judged not to be safe (4.74 ± 0.31 vs 3.75 ± 0.66; p < .001). Fourteen observations per resident, the typical number recorded during a 1-month rotation, were required to achieve a reliability of 0.80. Conclusion: The O-EDShOT successfully discriminated between junior, intermediate and senior-level residents regardless of ED treatment area. Multiple sources of evidence support the O-EDShOT producing valid scores for assessing a resident's ability to independently run an ED shift.
Type 2 diabetes (T2D) is a chronic disease that disproportionately affects Indigenous Australians. We have previously reported the localization of a novel T2D locus by linkage analysis to chromosome 2q24 in a large admixed Indigenous Australian pedigree (Busfield et al. (2002). American Journal of Human Genetics, 70, 349–357). Here we describe fine mapping of this region in this pedigree, with the identification of SNPs showing strong association with T2D: rs3845724 (diabetes p = 7 × 10−4), rs4668106 (diabetes p = 9 × 10−4) and rs529002 (plasma glucose p = 3 × 10−4). These associations were successfully replicated in an independent collection of Indigenous Australian T2D cases and controls. These SNPs all lie within the gene encoding ceramide synthase 6 (CERS6) and thus may regulate ceramide synthesis.
Radio galaxies of intermediate power dominate the radio-power injection in the Universe as a whole, due to the break in the radio luminosity function, and so are of special interest. The population spans FR I, FR II, and hybrid morphologies, resides in a full range of environmental richness, and sources of all ages are amenable to study. We describe structures and interactions, with emphasis on sources with deep high-resolution Chandra X-ray data. As compared with low-power sources there is evidence that the physics changes, and the work done in driving shocks can exceed that in evacuating cavities. A range of morphologies and phenomena is identified.
Mental disorder is common among individuals with neurological illness. We aimed to characterise the patient population referred for psychiatry assessment at a tertiary neurology service in terms of neurological and psychiatric diagnoses and interventions provided.
Methods
We studied all individuals referred for psychiatry assessment at a tertiary neurology service over a 2-year period (n= 82).
Results
The most common neurological diagnoses among those referred were epilepsy (16%), Parkinson’s disease (15%) and multiple sclerosis (8%). The most common reasons for psychiatric assessment were low mood or anxiety (48%) and medically unexplained symptoms or apparent functional or psychogenic disease (21%). The most common diagnoses among those with mental disorder were mood disorders (62%), and neurotic, stress-related and somatoform disorders, including dissociative (conversion) disorders (28%). Psychiatric diagnosis was not related to gender, neurological diagnosis or psychiatric history.
Conclusion
Individuals with neurological illness demonstrate significant symptoms of a range of mental disorders. There is a need for further research into the characteristics and distribution of mental disorder in individuals with neurological illness, and for the enhancement of integrated psychiatric and neurological services to address the comorbidities demonstrated in this population.
Genes involved in pathways regulating body weight may operate differently in men and women. To determine whether sex-limited genes influence the obesity-related phenotype body mass index (BMI), we have conducted a general non- scalar sex-limited genome-wide linkage scan using variance components analysis in Mx (Neale, 2002). BMI measurements and genotypic data were available for 2053 Australian female and male adult twins and their siblings from 933 families. Clinical measures of BMI were available for 64.4% of these individuals, while only self-reported measures were available for the remaining participants. The mean age of participants was 39.0 years of age (SD 12.1 years). The use of a sex-limited linkage model identified areas on the genome where quantitative trait loci (QTL) effects differ between the sexes, particularly on chromosome 8 and 20, providing us with evidence that some of the genes responsible for BMI may have different effects in men and women. Our highest linkage peak was observed at 12q24 (–log10p = 3.02), which was near the recommended threshold for suggestive linkage (–log10p = 3.13). Previous studies have found evidence for a quantitative trait locus on 12q24 affecting BMI in a wide range of populations, and candidate genes for non- insulin-dependent diabetes mellitus, a consequence of obesity, have also been mapped to this region. We also identified many peaks near a –log10p of 2 (threshold for replicating an existing finding) in many areas across the genome that are within regions previously identified by other studies, as well as in locations that harbor genes known to influence weight regulation.
Genes in the TGF9 signaling pathway play important roles in the regulation of ovarian follicle growth and ovulation rate. Mutations in three genes in this pathway, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and the bone morphogenetic protein receptor B 1 (BMPRB1), influence dizygotic (DZ) twinning rates in sheep. To date, only variants in GDF9 and BMP15, but not their receptors transforming growth factor ß receptor 1 (TGFBR1), bone morphogenetic protein receptor 2 (BMPR2) and BMPR1B, have been investigated with respect to their roles in human DZ twinning. We screened for rare and novel variants in TGFBR1, BMPR2 and BMPR1B in mothers of dizygotic twins (MODZT) from twin-dense families, and assessed association between genotyped and imputed variants and DZ twinning in another large sample of MODZT. Three novel variants were found: a deep intronic variant in BMPR2, and one intronic and one non-synonymous exonic variant in BMPRB1 which would result in the replacement of glutamine by glutamic acid at amino acid position 294 (p.Gln294Glu). None of these variants were predicted to have major impacts on gene function. However, the p.Gln294Glu variant changes the same amino acid as a sheep BMPR1B functional variant and may have functional consequences. Six BMPR1B variants were marginally associated with DZ twinning in the larger case-control sample, but these were no longer significant once multiple testing was taken into account. Our results suggest that variation in the TGF9 signaling pathway type II receptors has limited effects on DZ twinning rates in humans.
Genetic diversity of Trypanosoma cruzi may play a role in pathogenesis of Chagas disease forms. Natural populations are classified into 6 Discrete Typing Units (DTUs) Tc I-VI with taxonomical status. This study aimed to identify T. cruzi DTUs in bloodstream and tissue samples of Argentinean patients with Chagas disease. PCR-based strategies allowed DTU identification in 256 clinical samples from 239 Argentinean patients. Tc V prevailed in blood from both asymptomatic and symptomatic cases and Tc I was more frequent in bloodstream, cardiac tissues and chagoma samples from immunosuppressed patients. Tc II and VI were identified in a minority of cases, while Tc III and Tc IV were not detected in the studied population. Interestingly, Tc I and Tc II/VI sequences were amplified from the same skin biopsy slice from a kidney transplant patient suffering Chagas disease reactivation. Further data also revealed the occurrence of mixed DTU populations in the human chronic infection. In conclusion, our findings provide evidence of the complexity of the dynamics of T. cruzi diversity in the natural history of human Chagas disease and allege the pathogenic role of DTUs I, II, V and VI in the studied population.