bluuebunny/crossref_metadata_2025 huggingface dataset:
DEVELOPMENT OF A SCORING SYSTEM FOR THE NURSING WORKLOAD IN A PEDIATRIC INTENSIVE CARE UNIT
Authors: Eberle Alexa , Jouvet Philippe , Charette Sylvie , Provost Bryan
Published: May 2018

BACKGROUND

Nursing workload evaluation tools are designed to determine adequate staffing for a given shift. Only retrospective tools that do not predict the number of nurses needed to start a shift exist. A prospective nursing workload evaluation tool (SJ score), developed by a group of nurses with items based on previously published retrospective scores and clinical experience, includes 16 weighted sections (scored from 0 to >100 with 1 point ≈ 5 min nurse workload).

OBJECTIVES

This study’s aim is to assess the reliability and validity of the SJ score in the Paediatric Intensive Care Unit (PICU).

DESIGN/METHODS

Inclusion criteria: children admitted in a PICU, age < 18 yo. Exclusion criteria: already included 3 times in this study (phase 1 only) or children discharged 2 hr after the beginning of the nurse shift studied. Children were scored for 8 hr nursing shifts. Phase 1 (pilot validation) required simultaneous prospective SJ scoring by the nurse in charge (NIC) and chief nurse (SC), then a retrospective SJ score by an independent trained investigator (AE). Phase 2 (validation in the real context of the PICU), which used an improved SJ score, required that each child had an SJ score prospectively by the NIC of the previous shift, then retrospectively by the NIC of the dedicated shift. Statistical analysis included the intraclass correlation (ICC) and a Bland Altman plot. Bland Altman was considered acceptable if mean difference was closed to 0. For ICC: 0.40<ICC<0.59_Fair, 0.60<ICC<0.74_Good, 0.75<ICC<1_Excellent.

RESULTS

165 patients’ shifts observations were performed in phase 1. In the comparison between the prospective score performed by the NIC and SC, the Bland Altman mean difference was -0.03 with limits of agreement between -3.63 and 3.58, and the ICC was good: 0.63 with 95%confidence interval (95ICC) from 0.40 to 0.93. In the comparison between the prospective score of the NIC and AE retrospective score, the ICC was fair: 0.52 with 95ICC from 0.32 to 0.78. In phase 2, 2599 patients’ shifts were studied. The Bland Altman mean difference was 0.21 with limits of agreement between -10.5 and 10.9, and the ICC was excellent: 0.86 with 95ICC from 0.85 to 0.87.

CONCLUSION

The SJ score prospectively predicted well nursing workload in a single PICU. Additional studies are needed to determine the validity in other PICUs.
EVALUATION OF EXECUTIVE FUNCTIONING AND BEHAVIOUR IN YOUNG ADOLESCENTS WITH ADHD: A FOLLOW-UP STUDY
Authors: Lemay Jean-Francois , Hai Tasmia , Kubas Hanna , MacMaster Frank
Published: May 2018

BACKGROUND

Executive functioning (EF) impairment is frequent in the ADHD population. Psychostimulant medications (e.g. Methylphenidate [MPH]) are considered effective in reducing EF symptomatology. Limited studies have investigated the long-term effects of MPH on EF in young adolescents with ADHD (A-ADHD).

OBJECTIVES

To evaluate EF and behaviour challenges across three time points in A-ADHD who were involved in a MPH treatment trial. EF and behavioural functioning were evaluated using two separate parent questionnaires.

DESIGN/METHODS

A total of 21 A-ADHD (males=62%; n=13), ages 9–14 (M=12.33 years, SD=1.55 years) were evaluated at three separate time points: 1) Baseline (BL: no medication); 2) Best Dose (BD: following a 4-week trial of MPH treatment); and 3) long term Follow-Up (FU: defined as up to 2 years following best dose). Parents completed two behaviour rating scales: Behaviour Rating Inventory of Executive Functioning (BRIEF) and Behaviour Assessment System for Children (BASC-2). Repeated measures analyses of variance (RmANOVA) were conducted measuring changes in EF and behavioural challenges over the three time points (BL, BD, and FU).

RESULTS

Significant differences were obtained in EF ratings over time on the BRIEF Behavioural Regulation Index (BRIEF-BRI; F (2,36) = 20.71, p < 0.001) and Metacognition Index (BRIEF-MI; F (2,36) = 26.83, p < 0.001). Pairwise comparison indicated a) significant decrease in symptom ratings for both indexes between time points BL and BD, and b) significant increase in symptom ratings for indexes between time points BD and FU. Similarly, behavioural ratings obtained on all BASC-2 indexes (Externalizing Problems, Internalizing Problems, Behavioral Symptoms, and Adaptive Skills) revealed a significant effect of time (F (2,36) range = 4.55 to 26.28, p range = <.001 to <.05). Pairwise comparison indicated a) significant decrease in symptom ratings across all BASC-2 indexes between BL and BD, and b) increase in symptom ratings across all BASC-2 indexes between BD and FU time points. Therefore, parent ratings indicated clinically significant difficulties with EF and behaviour during BL and FU and average EF and behaviour scores during BD.

CONCLUSION

During follow-up, parents of A-ADHD continue to report challenges in EF and in all aspects of behaviours and adaptive skills. Although parents reported positive changes during the MPH trial (BD), these behavioural improvements were not seen at follow-up. The combined use of screening tools for EF (BRIEF) and behaviour (BASC-2) might be of interest to paediatricians when monitoring medication responses in young adolescents with ADHD.
PERSPECTIVES OF NON-URBAN GENERAL PEDIATRICIANS ON DIAGNOSING AUTISM SPECTRUM DISORDER
Authors: Das Jennifer , Hartman Laura , King Gillian , Jones-Stokreef Nicola , Hepburn Charlotte Moore , Penner Melanie
Published: May 2018

BACKGROUND

Wait times for autism spectrum disorder (ASD) diagnosis contribute to delayed access to ASD interventions, which are most effective at young ages. General paediatricians (GPs) represent a potential resource for increasing diagnostic capacity and decreasing wait times for ASD diagnostic assessments. No current research has yet to solicit perspectives of non-urban GPs on ASD diagnosis.

OBJECTIVES

The objective of this project was to explore the perspectives of GPs practicing in smaller Ontario communities regarding their diagnostic processes and their role in ASD diagnostic assessment.

DESIGN/METHODS

We performed a qualitative study using thematic analysis of GPs’ experiences with cases of suspected ASD. GPs from three small/medium-sized Ontario communities (population range: 14,000–64,000) were recruited to provide variation in perspectives. Semi-structured interviews were conducted, transcribed, and coded. A preliminary theoretical framework was developed and sent to participants with a request for feedback (member checking). Feedback did not necessitate any significant changes to the framework.

RESULTS

14 GPs participated in interviews (7 from Community A, 4 from Community B, 3 from Community C). All participants considered ASD diagnosis to be in the GP’s scope of practice and part of their service to their community. Many sought out and self-funded additional ASD training as necessitated by their practices. Our framework identified three stages in the diagnosis of ASD: pre-assessment (gathering information prior to the first clinic visit), diagnosis, and service access. All of these stages are influenced by ecological factors including the individual patient/family, individual physician factors, factors reflecting the GP’s community group practice (i.e., how the group has decided its members will approach developmental referrals), and factors concerning the broader system of ASD care.

CONCLUSION

GPs practicing in non-urban Ontario communities routinely diagnose ASD and see this as part of their scope of practice. Compared to their urban counterparts, they emphasized a stronger sense of responsibility to provide this service to their communities. Strategies aimed at increasing diagnostic capacity should target group practices, increase availability of ASD specific training programs, and improve efficiency of clinic visits through pre-clinic information gathering. Further research regarding accuracy of GP assessments is required.
SUBNORMAL BIRTHWEIGHT AND INDUSTRIAL AIR POLLUTANTS – A COMPARISON OF SPATIAL-TEMPORAL HOT SPOT PATTERNS
Authors: Nielsen Charlene , Amrhein Carl , Serrano Lomelin Jesus , Zaiane Osmar , Vargas Alvaro Osornio
Published: May 2018

BACKGROUND

Disorders related to short gestation and low birth weight are the 2nd cause of infant death in Canada and have been increasing, especially in Alberta. Individual maternal risks are important but environmental exposures during pregnancy may restrict fetal growth. This contributes to small for gestational age (SGA: < tenth percentile weight for pregnancy duration) and low birth weight at term (LBWT: <2500 grams at ≥37 weeks-gestation).

OBJECTIVES

We examined the spatial-temporal patterns of SGA and LBWT with patterns of pollutants around conception, middle trimester, and birth.

DESIGN/METHODS

We aggregated postal code locations of mothers’ residences from the 2006–2012 birth registry in to space-time bins to analyze emerging hot spots. We applied the space-time pattern analysis on 70 industrial chemical emissions from the National Pollutant Release Inventory (NPRI) in estimated three month intervals. Then we statistically associated the classified patterns of SGA/LBWT with the pollutant patterns using the kappa statistic to determine how much the hot spot categories agree. The difference between kappa values indicated which trimester would be more important for which chemical.

RESULTS

​There was an increasing trend for SGA (consecutive hot spots) and for LBWT (sporadic hot spots) in major urban centers. There was an increasing trend for 15 chemicals (varying hot spots). 28 chemical patterns had a kappa index greater than 0.2 with SGA or LBWT patterns. Although there is poor agreement between the space-time patterns, the maximum kappa values occurred mostly with LBWT and around birth.

CONCLUSION

Spatial-temporal patterns of chemicals identified in published literature (e.g. particulate matter and gases) agreed more with timing around conception; however, there were additional pollutants identified during the birth trimester. Our research is moving us toward a better understanding of the spatial-temporal link between environment and early health.
EXERCISE AS AN EDUCATIONAL TOOL: A PILOT PROJECT
Authors: Bhardwaj Sumeet , McDougall Alexandre , Dhillon Navpreet , Grewal Jasleen , Burey Sharon
Published: May 2018

BACKGROUND

Exercise has been shown to have long term effects in improving social skills, scholastic performance and quality of life in all children. Unfortunately, physical education courses continue to have their dedicated curricular times reduced. Students may have as little as one period of curricular physical activity per week. Conversely, there is middle school in Windsor, Ontario that has implemented a daily curricular period dedicated to physical activity. This study aimed to assess the effects of this schools’ exercise programme on their students’ social skills, scholastic performance and quality of life.

OBJECTIVES

Our objective is to study the effects of a daily physical activity period as part of an educational curriculum on student physical fitness, academic performance and self reported quality of life.

DESIGN/METHODS

We undertook a naturalistic observational study that examined the results of a daily exercise program for Grade 7 students attending École Secondaire E.J. Lajeunesse in Windsor. At this school, all students in Grade 7 and Grade 8 participate in a daily one-and-a-half-hour exercise programme consisting of two different streams: hockey or dance. All Grade 7 students and their families attending the school were asked to participate in our research trial. To study the effects of the exercise programme, student physical fitness, academic performance, and self-rated quality of life were assessed. Specific outcome measures used include: 20 metre sprint test, beep test, squat strength, bench press strength, the Pediatric Quality of Life Inventory, academic grades in mathematics, English and French, and academic learning skills.

RESULTS

Due to difficulties in participant recruitment and retention, only the following results could be analyzed. After one year of the structured hockey exercise program, the participants demonstrated significant increases in sprint speed (p < 0.0001), beep test (p < 0.005), squat strength (p < 0.0001) and bench press strength (p < 0.0001). There was also an increase in scores assessing organization, independence, collaboration, initiative and self regulation. An increase was noted in the participant’s grades in English and French. Little change was seen in mathematics and science grades.

CONCLUSION

After one year of consistent exercise, study participants demonstrated significant improvements in physical fitness, learning skills and language studies performance. Our results outline multiple benefits of implementing an organized daily physical period as part of the educational curriculum. A follow up to this preliminary study is currently underway to evaluate the effectiveness of school exercise programs on ADHD symptoms.
CHARACTERISTICS OF ANEMIA AND IRON STATUS AND THEIR ASSOCIATIONS WITH BLOOD MANGANESE AND LEAD AMONG CHILDREN AGED FROM 3 TO 19 YEARS OLD FROM FOUR NORTHERN FIRST NATION COMMUNITIES IN QUEBEC
Authors: Tahir Emad
Published: May 2018

BACKGROUND

Prevalence of anemia and iron deficiency (ID) are higher among indigenous children in Canada, although few data are available in Quebec. Iron is metal that interact with the absorption of manganese (Mn) and Lead (Pb) cobalt (Co). ID is known to upregulate these metals, thereby increasing their absorption, concentration inside the body and their toxicity.

OBJECTIVES

The objectives of the present study are to: (i) Characterize ID and anemia prevalence and their protective/risk factors; and (ii) Study associations between blood Mn, Pb and iron status biomarkers.

DESIGN/METHODS

Data from The 2015 First Nation Youth Health and Environment Pilot Study was conducted among children (3 to 19 y, n = 198) from four First Nations communities in Quebec will be used in these study where, blood samples and anthropometric measures were collected, hemoglobin was measured on site using an Hemocue analyser. Protective/risk factors including education, food security, housing conditions and lifestyle and dietary habits were documented using interview-administered questionnaire to children’ parents. Serum ferritin and blood Pb, Mn, Co, Zn and Ca were measured by Modular P analyser and ICPMS. Descriptive and multiple regression statistical analyses adjusting for relevant co-variables were used.

RESULTS

Results showed ID and anemia prevalence of 20.7% and 17.6% respectively, among which 8.8% presented iron deficiency anemia. Moreover, up to 11.9% had elevated blood Mn (median = 15.9 µg/L, range 7.1 to 31.9 µg/L) of which 27.5% presented ID. However, blood Pb was low (median = 5.4 µg/L, range 1.8 to 50.8 µg/L). Multiple logistic regression analysis showed that crystal juice intake was associated with lower ID and anemia (OR (95%): 0.50 (0.30 - 0.82) and 0.47 (0.26 - 0.87) respectively) in girls. Likewise, the presence of hunter in the household was associated with lower anemia in girls (0.09 (0.02 - 0.53)). No factors were associated with ID in boys, and for anemia, lower serum ferritin and older age was associated with higher prevalence of anemia (1.08 (1.01 - 1.14) and 1.23 (1.02 - 1.48) respectively). In adjusted models, blood Mn was negatively associated with serum ferritin concentrations (ß = -0.05; p < 0.02) in girls and positively associated with blood Co (ß = 8.50; p < 0.01) in boys.

CONCLUSION

Findings on high prevalence of ID, anemia and elevated blood Mn among children form these First Nation communities support that, community and family activities increasing traditional foods consumption improve nutritional status and suggest that foods and beverages naturally rich in vitamin C - but lower in added sugar than crystal juice - would improve iron intake in girls, which would contribute to improve their iron status, decrease anemia and restore normal Mn blood levels.
THE PAEDIATRICIAN AS A LEADER: AN EDUCATIONAL INTERVENTION FOR HIGH-VALUE CARE
Authors: Foulds Jessica , Rajani Hasu , Forbes Karen
Published: May 2018

BACKGROUND

The CanMEDS framework for physician competency defines necessary competencies of medical practice, laying the foundation for medical education and subsequent practice in Canada to meet patient needs. The role of Leader highlights the importance of quality improvement, stewardship, health care resource allocation and ability to apply evidence and management processes to facilitate cost-appropriate care. Educational innovations in this domain have not previously been described.

OBJECTIVES

To evaluate the impact of an educational intervention developed to foster stewardship of health care resources for paediatricians in training.

DESIGN/METHODS

An educational workshop on high-value care was created for general paediatric residents. Prior to workshop development, the study team procured local costing information from microbiology, general chemistry/laboratory, pharmacy, and radiology. During the workshop, individual, small group and interactive activities were used to explore clinical decision making and associated costs, radiation dosing, and non-monetary implications of care. A pocket-card reference was developed for use during the exercises. To assess the impact of the workshop, participants completed a post-workshop reflection asking them to identify lessons learned and an action plan for providing high-value care. Qualitative exploration of statements was conducted using thematic analysis; individual responses were coded and grouped into three overarching themes for both lessons learned and action plan.

RESULTS

Forty-three learners participated in the workshop. Post-workshop reflections yielded 93 lessons learned statements, and 67 action plan statements. Lessons learned were grouped into three themes: Scope, Content and Judgement Statements. Within Scope, most statements were general (80%) versus specific. Content areas most frequently cited included cost (61%), diagnostic imaging (28%) including radiation exposure (14%), and non-monetary costs of care (17%). Inferences about aspects of learnings, such as those referring to expense, value or waste, were labelled as Judgement Statements, and were present in 50% of the responses. Action plan statements were grouped into themes of Scope, Content and Action Words. Responses were again generally focused (87%). Most frequent Content subtheme responses were: tests (37%), non-monetary costs of care (21%), and diagnostic imaging (12%). Action words were grouped into seven categories as depicted in Figure 1, with Consider as most frequent (46%).

CONCLUSION

Reflections on non-monetary costs and action plans that consider how investigations might change management seemed to resonate with our single centre paediatric trainees. Longitudinal follow-up may help identify most impactful components of this educational workshop.
CARING FOR THE CAREGIVER: EXPLORING THE EXPERIENCE OF CAREGIVING FOR A CHID WITH MEDICAL COMPLEXITY
Authors: Teicher Jessica , Weiser Natalie , Arje Danielle , Orkin Julia
Published: May 2018

BACKGROUND

Children with medical complexity (CMC) represent a growing population in the paediatric healthcare system. CMCs’ multiple health needs, illness severity, and fragility lead to a high degree of caregiver burnout, parental employment loss, and other social and financial consequences. Healthcare providers must consider a holistic view of the family, including consideration of social determinants of health [SDOH]: socio-economic status, employment, quality of housing, availability of social support, and access to healthcare services. This study addresses a gap in current research by exploring how caring for a CMC exacerbates social inequalities, and how these challenges may be mitigated.

OBJECTIVES

1. What are the SDOH impacting CMC and their families?

2. How do families report the impact of their child’s medical complexity on their social circumstances?

DESIGN/METHODS

A qualitative description approach was used to enable rich data collection through semi-structured interviews until thematic saturation was reached. Nine interviews were conducted with CMC caregivers who were chosen by purposeful sampling. The interview guide was developed by expert consultation and iteratively refined. Ethics approval and written consent were obtained. Interviews were recorded and transcribed verbatim. Three team members independently coded the interviews for recurrent themes to inform qualitative content analysis.

RESULTS

Caregiving for a CMC is all-consuming, requiring parents to take on roles including planner, medical professional, medical educator, and advocate. Parents of CMC report three major areas negatively impacted by caregiving: 1) physical and mental health; 2) personal relationships; and 3) finances. Additionally, three themes emerged describing enablers for resiliency: 1) the CMC’s health status when well or stable in hospital; 2) acceptance of one’s limitations as a caregiver and of the family’s ‘new normal’; and 3) broad supports including medical, personal, financial, and educational.

CONCLUSION

The wellbeing of CMC families is impacted by medical and social factors. An interdisciplinary model of care may offset some of the caregiver’s advocacy and medical educator responsibilities. Paediatricians can support families of CMC by providing comprehensive care for all components of the child’s health status, and by including routine assessment of the family’s SDOH. Finally, explicit discussion about parental expectations and caregiver burnout helps foster a positive therapeutic relationship with the family.
A Tale of Two States: How State Immigration Climate Affects Belonging to State and Country among Latinos
Authors: Schildkraut Deborah J , Jiménez Tomás R , Dovidio John F , Huo Yuen J
Published: May 2018

This study assesses the impact of different immigrant policy climates on how Latinos feel about themselves, their place in their state and country, and how they think they are viewed by others. Using survey data from Arizona and New Mexico, we find that Latinos in Arizona exhibit lower levels of belonging than Latinos in New Mexico, but their alienation is confined to the state level. We also find that the U.S. born are most sensitive to the state climate. We conclude that policies that delineate outsiders from insiders by immigration status have wide ranging effects that fall prominently on the U.S. born.
Race to the Bottom (of the Well): Groundwater in an Agricultural Production Treadmill
Authors: Sanderson Matthew R , Hughes Vivian
Published: May 2018

Groundwater from the Ogallala-High Plains Aquifer supports one of the most productive agriculture regions in the world. Yet, despite nearly 40 years of policies designed to conserve and sustain this vital resource, the Aquifer continues to be depleted at an unsustainable rate. We integrate propositions from treadmill of production theory and ecological modernization theory to develop a structural model, focusing especially on the role of technological modernization as a key mechanism motivating depletion. A time-sequenced path analysis of all counties in the Ogallala Aquifer region reveals that groundwater depletion has a strong internal momentum characteristic of an agricultural production treadmill. Technological modernization promotes depletion through Jevon’s Paradox. Increases in water efficiency—more crop per drop—are associated with less groundwater consumption, but more extensive deployments of irrigation infrastructures overwhelm the beneficial effects of increased water efficiency. An income-subsidy mechanism supports the treadmill dynamic. Agricultural production and increased water efficiency do not influence incomes. Instead, incomes are influenced mainly by expansions of irrigation technologies, which generates subsidies, and this dynamic puts further “spin” on the treadmill. The implications of the findings for theory and policy are discussed.
The Paradox of Legibility: Domestic Violence and Institutional Survivorhood
Authors: Sweet Paige L
Published: May 2018

Existing literature has demonstrated that victims of domestic violence and rape undergo processes of discipline when they interact with legal structures, transforming themselves into “worthy victims.” Intervening in this literature, I show how the medicalization of institutions surrounding domestic violence creates conditions under which women must prove their survivorhood, performing psychological recovery to achieve institutional legibility. Legal and therapeutic institutions create a matrix of demands on women’s lives, shaping their practices of survival and performances of self. Through interviews with domestic violence survivors, I show that women engage three strategies of transformation to make themselves credible survivors: (1) extracting domestic violence from their life stories; (2) explaining abuse through “self-esteem;” (3) performing survivorhood through “respectable” motherhood and sexuality. Through these processes, women craft a domestic violence narrative and an institutional performance of survivorhood, both of which allow them to navigate institutional pressures. These therapeutic narratives and performances, however, also rewrite the structural elements of violence into (feminized) accounts of psychological failure and overcoming. Thus, women navigate a paradox when they become survivors: they must tell stories of psychological recovery, even as those stories obfuscate the very infrastructure of violence. It is this disjuncture between individualized narratives of harm and the structural work of survival that I examine in this work. I develop the concept of the “paradox of legibility” to generalize this disjuncture, and to highlight women’s labor of making themselves credible amidst structural and institutional constraints.
Intravenous Immunoglobulin Therapy in Refractory Autoimmune Dysautonomias: A Retrospective Analysis of 38 Patients
Authors: Schofield Jill R. , Chemali Kamal R.
Published: May 2018

Background:

Intravenous immunoglobulin (IVIG) has recognized efficacy in autoimmune peripheral nerve disorders, but there has been limited study of the use of IVIG in autoimmune dysautonomias.

Study Question:

To determine the efficacy and safety of IVIG in patients with disabling, refractory autoimmune dysautonomias, including patients with postural tachycardia syndrome and gastrointestinal dysmotility.

Study Design:

Patients with one or more autonomic disorder(s) and persistent serological evidence for autoimmunity who were unable to work or attend school despite usual treatments for dysautonomia were treated with IVIG for at least 3 months at a dose of at least 1 gm/kg monthly.

Measures and Outcomes:

Outcome measures included the composite autonomic symptom scale 31 survey and a functional ability score.

Results:

There were 38 patients, 84% female and mean age of 28.4 years. Of patients, 83.5% improved on IVIG as defined by at least 20% improvement in the composite autonomic symptom scale 31 and/or functional ability score. The mean pretreatment functional ability score was 21% (mostly bedridden), which improved to a mean of 74% (nearing able to return to work/school) for responsive patients after at least 1 year of IVIG. The mean time to the first sign of response was 5.3 weeks. There were no serious adverse events. The Mayo autoimmune dysautonomia panel antibodies and traditional Sjögren antibodies were present in only 13% and 8% of patients, respectively, but antiphospholipid antibodies and novel Sjögren antibodies were present in 76% and 42% of patients, respectively.

Conclusions:

There is increasing evidence that IVIG is safe and effective in a subset of patients with autonomic disorders and evidence for autoimmunity. A 4-month IVIG trial should be considered in severely affected patients who are refractory to lifestyle and pharmacological therapies. Antiphospholipid antibodies and novel Sjögren antibodies are often present in these patients and correlate with a high response rate to IVIG.
Genetic risk for schizophrenia and developmental delay is associated with shape and microstructure of midline white matter structures
Authors: Drakesmith Mark , Parker Greg D , Smith Jacqueline , Linden Stefanie C , Rees Elliott , Williams Nigel , Owen Micheal J , Van Den Bree Marianne , Hall Jeremy , Jones Derek K , Linden David E J
Published: May 2018

Genomic copy number variants (CNVs) are amongst the most highly penetrant genetic risk factors for neuropsychiatric disorders. The scarcity of carriers of individual CNVs and their phenotypical heterogeneity limits investigations of the associated neural mechanisms and endophenotypes. We applied a novel design based on CNV penetrance for schizophrenia and developmental delay that allows us to identify structural sequelae that are most relevant to neuropsychiatric disorders. Our focus on brain structural abnormalities was based on the hypothesis that convergent mechanisms contributing to neurodevelopmental disorders would likely manifest in the macro- and microstructure of white matter and cortical and subcortical grey matter. 21 adult participants carrying neuropsychiatric risk CNVs (including those located at 22q11.2, 15q11.2, 1q21.1, 16p11.2, and 17q12) and 15 age- and gender matched controls underwent T1-weighted structural, diffusion and quantitative T1 relaxometry MRI.

The macro- and microstructural properties of the cingulum bundles were associated with penetrance for both developmental delay and schizophrenia, in particular curvature along the anterior-posterior axis (Sz: pcorr=0.026; DD: pcorr=0.035) and intracellular volume fraction (Sz: pcorr=0.019; DD: pcorr=0.064) Further principal component analysis showed alterations in the interrelationships between the volumes of several mid-line white matter structures (Sz: pcorr=0.055; DD, pcorr=0.027). In particular, the ratio of volumes in the splenium and body of the corpus callosum was significantly associated with both penetrance scores (Sz: p=0.037; DD; p=0.006). Our results are consistent with the notion that a significant alteration in developmental trajectories of mid-line white-matter structures constitutes a common neurodevelopmental aberration contributing to risk for schizophrenia and intellectual disability.
Longitudinal increases in structural connectome segregation and functional connectome integration are associated with better recovery after mild TBI
Authors: Kuceyeski Amy F. , Jamison Keith W. , Owen Julia P. , Raj Ashish , Mukherjee Pratik
Published: May 2018

Traumatic brain injury damages white matter pathways that connect brain regions, disrupting transmission of electrochemical signals and causing cognitive and emotional dysfunction. Connectome-level mechanisms for how the brain compensates for injury have not been fully characterized. Here, we collected serial MRI-based structural and functional connectome metrics and neuropsychological scores in 26 mild traumatic brain injury subjects (29.4±8.0 years, 20 male) at 1 and 6 months post-injury. We quantified the relationship between functional and structural connectomes using network diffusion model propagation time, a measure that can be interpreted as how much of the structural connectome is being utilized for the spread of functional activation, as captured via the functional connectome. Overall cognition showed significant improvement from 1 to 6 months (t25=−2.15, p=0.04). None of the structural or functional global connectome metrics were significantly different between 1 and 6 months, or when compared to 34 age- and gender-matched controls (28.6±8.8 years, 25 male). We predicted longitudinal changes in overall cognition from changes in global connectome measures using a partial least squares regression model (cross-validated R2= 0.27). We observe that increased network diffusion model propagation time, increased structural connectome segregation and increased functional connectome integration were related to better cognitive recovery. We interpret these findings as suggesting two connectome-based post-injury recovery mechanisms: one of neuroplasticity that increases functional connectome integration and one of remote white matter degeneration that increases structural connectome segregation. We hypothesize that our inherently multi-modal measure of network diffusion model propagation time captures the interplay between these two mechanisms.

Abbreviations

mild traumatic brain injury (mTBI), structural connectome (SC), functional connectome (FC), network diffusion (ND), functional MRI (fMRI), diffusion MRI (dMRI), principal component analysis (PCA), partial least squares regression (PLSR), confidence interval (CI), Attention Network Test (ANT), California Verbal Learning Test II (CVLT-II), Coma Recovery Scale – Revised (CRS-R)
Hybridization and postzygotic isolation promote reinforcement of male mating preferences in a diverse group of fishes with traditional sex roles
Authors: Moran Rachel L. , Zhou Muchu , Catchen Julian M. , Fuller Rebecca C.
Published: May 2018

Behavioral isolation is thought to arise early in speciation due to differential sexual and/or natural selection favoring different preferences and traits in different lineages. Alternatively, behavioral isolation can arise due to reinforcement favoring traits and preferences that prevent maladaptive hybridization. In darters, female preference for male coloration has been hypothesized to drive speciation, because behavioral isolation evolves before F1 inviability. However, as with many long-lived organisms, the fitness of second generation hybrids has not been assessed because raising animals to adulthood in the lab is challenging. Recently, reinforcement of male preferences has been implicated in darters because male preference for conspecific females is high in sympatry but absent in allopatry in multiple species pairs. The hypothesis that reinforcement accounts for behavioral isolation in sympatry assumes that hybridization and postzygotic isolation are present. Here, we used genomic and morphological data to demonstrate that hybridization is ongoing between orangethroat and rainbow darters and used hybrids collected from nature to measure postzygotic barriers across two hybrid generations. We observed sex ratio distortion in adult F1s and a dramatic reduction in backcross survival. Our findings indicate that selection to avoid hybridization promotes the evolution of male-driven behavioral isolation via reinforcement in this system.
TreeSwift: a massively scalable Python tree package
Authors: Moshiri N.
Published: May 2018

Phylogenetic trees are essential to evolutionary biology, and numerous methods exist that attempt to extract phylogenetic information applicable to a wide range of disciplines, such as epidemiology and metagenomics. Currently, the three main Python packages for trees are Bio.Phylo, DendroPy, and the ETE Toolkit, but as dataset sizes grow, parsing and manipulating ultra-large trees becomes impractical for these tools. To address this issue, we present TreeSwift, a user-friendly and massively scalable Python package for traversing and manipulating trees that is ideal for algorithms performed on ultra-large trees.
Reproduction costs can drive the evolution of groups
Authors: Pichugin Yuriy , Traulsen Arne
Published: May 2018

A fascinating wealth of life cycles is observed in biology, from unicellularity to the concerted fragmentation of multi-cellular units. However, the understanding of factors driving the evolution of life cycles is still limited. We investigate how reproduction costs influence this process. We consider a basic model of a group structured population of undifferentiated cells, where groups reproduce by fragmentation. Fragmentation events are associated with a cost expressed by either a fragmentation delay, a fragmentation risk, or a fragmentation loss. The introduction of such fragmentation costs vastly increases the set of potentially optimal life cycles. Based on these findings, we suggest that the evolution of life cycles and the splitting into multiple offspring can be directly associated with the fragmentation cost. Moreover, the impact of this cost alone is strong enough to drive the emergence of multicellular groups, even under scenarios that strongly disfavour groups compared to solitary individuals.
Renoprotective effects Of Dexmedetomidine against ischemia-reperfusion injury in streptozotocin-induced diabetic rats
Authors: Kim Seung Hyun , Jun Ji Hae , Oh Ju Eun , Shin Eun-Jung , Oh Young Jun , Choi Yong Seon
Published: May 2018

Background

Diabetic patients are susceptible to renal ischemia-reperfusion injury, which leads to perioperative complications. Nucleotide binding and oligomerization domain (NOD)-like receptor 3 inflammasome participates in the development of diabetes, and contributes to renal ischemia-reperfusion injury. Dexmedetomidine, a highly selective α2-adrenoreceptor agonist, shows renoprotective effects against ischemia-reperfusion injury. We aimed to elucidate the effects, underlying mechanisms, and optimal timing of dexmedetomidine treatment in diabetic rats.

Methods

Male Sprague-Dawley rats (60 animals, weighing 250-300 g) were randomly divided into normal-sham, diabetes-sham, diabetes-ischemia-reperfusion-control, diabetes-ischemia-reperfusion-dexmedetomidine-pre-treatment, and diabetes-ischemia-reperfusion-dexmedetomidine-post-treatment groups. Renal ischemia-reperfusion injury was induced in diabetic rats by occlusion of both renal arteries for 45 minutes followed by reperfusion for 24 hours. Dexmedetomidine (10 μg/kg) was administered intraperitoneally 1 hour before ischemia (pre-treatment) or upon reperfusion (post-treatment). After reperfusion, renal tissue was biochemically and histopathologically evaluated.

Results

Dexmedetomidine treatment attenuated IR-induced increase in NLRP3, caspase-1, IL-1β, phospho-AKT, and phospho-ERK signaling. Moreover, oxidative stress injury, inflammatory reactions, apoptosis, and renal tubular damage were favorably modulated by dexmedetomidine treatment. Furthermore, post-reperfusion treatment with dexmedetomidine was significantly more effective than pre-treatment in modulating inflammasome, AKT and ERK signaling, and oxidative stress.

Conclusions

This study shows that protective effects of dexmedetomidine in renal ischemia-reperfusion injury are preserved in diabetic conditions and may potentially provide a basis for the use of dexmedetomidine in clinical treatment of renal ischemia-reperfusion injury.
Novel immune cell subtypes linked to survival among African American women with triple-negative breast cancer
Authors: Purrington Kristen S. , Holowatyj Andreana N. , Cote Michele L. , Schwartz Ann G. , Chaudhry Rahman , Ali-Fehmi Rouba , Dyson Gregory , Colacino Justin , Boerner Julie , Bandyopadhyay Sudeshna
Published: May 2018

Triple negative breast cancer (TNBC) is an aggressive disease that is twice as likely to be diagnosed in African American (AA) women compared to white women, with poor clinical outcomes. Tumor infiltrating lymphocytes (TILs) are associated with improved survival for TNBC, but the relevance of TILs and immune cell subtypes to survival in AA women with TNBC is unknown. We evaluated histopathologic TIL counts and molecular characteristics among 60 AA women diagnosed with TNBC with linkage to clinical outcomes using data from the Metropolitan Detroit Cancer Surveillance System. We utilized whole genome expression profiling of TN tumors and cell type deconvolution analysis to evaluate the underlying mechanisms and immune cell subtypes associated with survival patterns in the context of TILs. TILs were significantly associated with improved survival [1-10% Hazard Ratio (HR)=0.32, 95% Confidence Interval (CI) 0.12-0.90, p=0.031; >10% HR=0.18, 95% CI 0.05-0.67, 9.9×10−3]. 524 transcripts (326 coding, 198 non-coding) were associated with TIL levels, 34 of which were associated with both TILs and survival (p<0.05). While only naïve B cells were associated with survival when considering individual cell types [Median HR=2.43, 95% CI 1.07-5.55, p=0.035], increased naïve B cells, plasma cells, and activated NK cells, and decreased resting mast cells, M1 macrophages, and monocytes were associated with transcripts that predicted worse survival. These data provide evidence for novel roles for these immune cells types in TNBC, and further studies are needed to validate these findings and identify determinants of patterns of immune response in TNBC relevant to the AA population.

We found that increased naïve B cells, plasma cells, and activated natural killer cells, and decreased resting mast cells, M1 macrophages, and monocytes were associated with expression biomarkers of worse survival among African American women with triple negative breast cancer.
Wild Steps in a Semi-wild Setting? Habitat Selection and Behavior of European Bison reintroduced to an Anthropogenic Landscape
Authors: Pedersen Pil Birkefeldt Møller , Olsen Joanna B. , Sandel Brody , Svenning Jens-Christian
Published: May 2018

Recently, several wild or semi-wild herds of European bison have been reintroduced across Europe. It is essential for future successful bison reintroductions to know how the European bison use different habitats, which environmental parameters drive their habitat selection, and whether their habitat use and behavioural patterns in new reintroduction sites differ from habitats where European bison have been roaming freely for a long time.

Here, we address these questions for a 40-ha enclosed site that has been inhabited by semi-free ranging European bison since 2012. The site, Vorup Meadows, is adjacent to the Gudenå river in Denmark and consists of human-modified riparian meadows. During 2013 we monitored the behavioural pattern and spatial use of the 11 bison present and in parallel carried out floristic analyses to assess habitat structure and food quality in the enclosure. We tested habitat use and selection against environmental parameters such as habitat characteristics, plant community traits, topography, and management area (release area vs. meadow area) using linear regression and spatial models.

The bison herd had comparable diurnal activity patterns as observed in previous studies on free-roaming bison herds. Topography emerged as the main predictor of the frequency of occurrence in our spatial models, with high-lying drier areas being used more. Bison did not prefer open areas over areas with tree cover when accounting for habitat availability. However, they spent significantly more time in the release area, a former agricultural field with supplementary fodder, than expected from availability compared to the rest of the enclosure, a meadow with tree patches. We wish to increase awareness of possible long-term ethological effects of the release site and the management protocols accomplished here that might reduce the ecological impact by the bison in the target habitat, and thereby compromise or even oppose the conservation goals of the conservation efforts.
Genome-wide discovery of epistatic loci affecting antibiotic resistance using evolutionary couplings
Authors: Schubert Benjamin , Maddamsetti Rohan , Nyman Jackson , Farhat Maha R. , Marks Debora S.
Published: May 2018

The analysis of whole genome sequencing data should, in theory, allow the discovery of interdependent loci that cause antibiotic resistance. In practice, however, identifying this epistasis remains a challenge as the vast number of possible interactions erodes statistical power. To solve this problem, we extend a method that has been successfully used to identify epistatic residues in proteins to infer genomic loci that are strongly coupled and associated with antibiotic resistance. Our method reduces the number of tests required for an epistatic genome-wide association study and increases the likelihood of identifying causal epistasis. We discovered 38 loci and 250 epistatic pairs that influence the dose needed to inhibit growth for five different antibiotics in 1,102 isolates ofNeisseria gonorrhoeaethat were confirmed in an independent dataset of 495 isolates. Many known resistance-affecting loci were recovered; however, the majority of loci occurred in unreported genes, includingmurEwhich was associated with cefixime. About half of the novel epistasis we report involved at least one locus previously associated with antibiotic resistance, including interactions betweengyrAandparCassociated with ciprofloxacin. Still, many combinations involved unreported loci and genes. Our work provides a systematic identification of epistasis pairs affecting antibiotic resistance inN. gonorrhoeaeand a generalizable method for epistatic genome-wide association studies.
Evolutionary Highways to Persistent Bacterial Infection
Authors: Bartell Jennifer A , Sommer Lea M , Haagensen Janus A J , Loch Anne , Espinosa Rocio , Molin Søren , Johansen Helle Krogh
Published: May 2018

Persistent infections require bacteria to evolve from their naïve colonization state by optimizing fitness in the host. This optimization involves coordinated adaptation of multiple traits, obscuring evolutionary trends and complicating infection management. Accordingly, we screen 8 infection-relevant phenotypes of 443 longitudinalPseudomonas aeruginosaisolates from 39 young cystic fibrosis patients over 10 years. Using statistical modeling, we map evolutionary trajectories and identify trait correlations accounting for patient-specific influences. By integrating previous genetic analyses of 474 isolates, we provide a window into early adaptation to the host, finding: 1) a 2-3 year timeline of rapid adaptation after colonization, 2) variant “naïve” and “adapted” states reflecting discordance between phenotypic and genetic adaptation, 3) adaptive trajectories leading to persistent infection via 3 distinct evolutionary modes, and 4) new associations between phenotypes and pathoadaptive mutations. Ultimately, we effectively deconvolute complex trait adaptation, offering a framework for evolutionary studies and precision medicine in clinical microbiology.