GENLIB: new function to simulate haplotype transmission in large complex genealogies.

SUMMARY: Founder populations with deep genealogical data are well suited for investigating genetic variants contributing to diseases. Here, we present a major update of the genealogical analysis R package GENLIB, centered around a new function which can simulate the transmission of haplotypes from founders to probands along very large and complex user-specified genealogies. AVAILABILITY AND IMPLEMENTATION: The latest update of the GENLIB package (v1.1.9) contains the new gen.simuHaplo() function and is available on the CRAN repository and from https://github.com/R-GENLIB/GENLIB. Examples can be accessed at https://github.com/R-GENLIB/simuhaplo_functions.

Unusual imaging findings associated with abdominal pediatric germ cell tumors.

Germ cell tumors of childhood are tumors arising from germline cells in gonadal or extragonadal locations. Extragonadal germ cell tumors are characteristically located in the midline, arising intracranially or in the mediastinum, retroperitoneum, or pelvis. These tumors are generally easily diagnosed due to typical sites of origin, characteristic imaging findings, and laboratory markers. However, germ cell tumors can be associated with unusual clinical syndromes or imaging features that can perplex the radiologist. This review will illustrate atypical imaging/clinical manifestations and complications of abdominal germ cell tumors in childhood. These features include unusual primary tumors such as multifocal primaries; local complications such as ovarian torsion or ruptured dermoid; atypical presentations of metastatic disease associated with burned-out primary tumor, growing teratoma syndrome, and gliomatosis peritonei; endocrine manifestations such as precocious puberty and hyperthyroidism; and antibody mediated paraneoplastic syndrome such as anti-N-methyl-D-aspartate-receptor antibody-mediated encephalitis. This review aims to illustrate unusual imaging features associated with the primary tumor, metastatic disease, or distant complications of abdominal germ cell tumors of childhood.

Genome-wide association study of age at menarche in the Taiwan Biobank suggests NOL4 as a novel associated gene.

Sexual maturation is a complex physiological process that involves multiple variables, such as genetic and environmental factors. Among females, age at menarche (AM) is a critical milestone for sexual maturation. This study aimed to identify genetic markers of AM using nationwide population cohort data in Taiwan. Females with self-reported AM between 10 and 16 years (N = 39,827) were eligible for the final analysis. To identify genetic signals related to AM, we conducted a genome-wide association study using a linear regression model and split-half meta-analysis method to verify our findings. The Functional Mapping and Annotation web-based platform was used for positional mapping and gene-based and gene-set analyses. The meta-analysis identified four significant loci, i.e., LIN28B (pooled P = 1.39 × 10-21), NOL4 (pooled P = 8.94 × 10-9), GPR45 (pooled P = 4.19 × 10-11), and LOC105373831 (pooled P = 4.37 × 10-8), that were associated with AM. MAGMA gene-based analysis revealed that LIN28B (P = 1.13 × 10-8), NOL4 (P = 2.27 × 10-7), RXRG (P = 4.34 × 10-7), ETV5 (P = 1.75 × 10-6), and HACE1 (P = 1.82 × 10-6) were significantly associated with AM, while the gene-set analysis identified a significantly enriched pathway involving mTOR signaling complex (FDR corrected P = 1.28 × 10-2). The results replicated evidence for several genetic markers associated with AM in the Taiwanese female population. Our analysis identified a novel locus (rs7239368) in NOL4 associated with AM (ß = 0.051 ± 0.009 years, pooled P = 8.94 × 10-9), whereas additional research is needed to validate its molecular role in sexual maturation.

The impact of fast food marketing on brand preferences and fast food intake of youth aged 10-17 across six countries.

BACKGROUND: Consumption of fast food, which is associated with poor diet, weight gain and the development of noncommunicable diseases, is high amongst youth. Fast food marketing, a modifiable determinant of excess weight and obesity, affects youth's food-related behaviours. This study aimed to examine the relationship between exposure to fast food marketing and the fast food brand preferences and intake amongst youth aged 10-17 across six countries. METHODS: Data from 9,695 youth respondents living in Australia, Canada, Chile, Mexico, the United Kingdom (UK) and the United States (US) were analyzed from the 2019 International Food Policy Study (IFPS) Youth Survey. Survey measures assessed exposure to fast food marketing and brand-specific marketing, and preference for these brands and fast food intake. Regression models adjusted for age, sex, income adequacy and ethnicity were used to examine the associations. RESULTS: Exposure to fast food marketing was positively associated with brand preferences and intake consistently across most countries. Overall, preference for McDonald's (OR:1.97; 95% CI:1.52, 2.56), KFC (OR:1.61; 95% CI:1.24, 2.09) and Subway (OR:1.73; 95% CI:1.34, 2.24) were highest when exposed to general fast food marketing ≥ 2x/week compared to never. Preference for McDonald's (OR:2.32; 95% CI:1.92, 2.79), KFC (OR:2.28; 95% CI:1.95, 2.68) and Subway (OR:2.75; 95% CI:2.32, 3.27) were also higher when exposed to marketing for each brand compared to not. Fast food intake was highest in Chile (IRR:1.90; 95% CI:1.45, 2.48), the UK (IRR:1.40; 95% CI:1.20, 1.63), Canada (IRR:1.32; 95% CI:1.19, 1.48), Mexico (IRR:1.26; 95% CI:1.05, 1.53) and the US (IRR:1.21; 95% CI:1.05, 1.41) when exposed to general fast food marketing ≥ 2x/week compared to never and was higher across most countries when exposed to brand-specific marketing compared to not. Respondents classified as ethnic minorities were more likely to report consuming fast food than ethnic majorities, and females were less likely to report consuming fast food than males. CONCLUSIONS: Exposure to fast food marketing is consistently and positively associated with brand preferences and fast food intake in all six countries. Our results highlight the need for strict government regulation to reduce exposure of unhealthy food marketing to youth in all six countries.

Comparison of mixed model based approaches for correcting for population substructure with application to extreme phenotype sampling.

BACKGROUND: Mixed models are used to correct for confounding due to population stratification and hidden relatedness in genome-wide association studies. This class of models includes linear mixed models and generalized linear mixed models. Existing mixed model approaches to correct for population substructure have been previously investigated with both continuous and case-control response variables. However, they have not been investigated in the context of extreme phenotype sampling (EPS), where genetic covariates are only collected on samples having extreme response variable values. In this work, we compare the performance of existing binary trait mixed model approaches (GMMAT, LEAP and CARAT) on EPS data. Since linear mixed models are commonly used even with binary traits, we also evaluate the performance of a popular linear mixed model implementation (GEMMA). RESULTS: We used simulation studies to estimate the type I error rate and power of all approaches assuming a population with substructure. Our simulation results show that for a common candidate variant, both LEAP and GMMAT control the type I error rate while CARAT's rate remains inflated. We applied all methods to a real dataset from a Québec, Canada, case-control study that is known to have population substructure. We observe similar type I error control with the analysis on the Québec dataset. For rare variants, the false positive rate remains inflated even after correction with mixed model approaches. For methods that control the type I error rate, the estimated power is comparable. CONCLUSIONS: The methods compared in this study differ in their type I error control. Therefore, when data are from an EPS study, care should be taken to ensure that the models underlying the methodology are suitable to the sampling strategy and to the minor allele frequency of the candidate SNPs.

Pediatric Hepatic Cystic Lesions: Differential Diagnosis and Multimodality Imaging Approach.

When a pediatric hepatic cystic lesion is identified at imaging, the differential diagnosis may be broad, including developmental, infectious, neoplastic, and posttraumatic or iatrogenic causes. The location of a cystic lesion and its number, size, composition, and relationship to the biliary system are features that help in narrowing the differential diagnosis. An incidentally detected simple hepatic cyst is the most commonly encountered. Ciliated foregut cysts are typically located in hepatic segment IVa. The presence of multiple cysts should raise suspicion for fibropolycystic liver disease, a group of related lesions-including biliary hamartoma and choledochal cyst-caused by abnormal embryologic development of the ductal plate. Communication of the cystic lesion with the biliary tree can confirm the diagnosis of choledochal cyst. In a neonate with jaundice, a cystic lesion at the porta hepatis should raise suspicion for choledochal cyst versus cystic biliary atresia. Hepatic abscess can appear cystlike, though typically with internal contents. In an immunocompromised child, multiple cystlike lesions should raise concern for fungal microabscesses. A complex cystic mass in a young child should raise suspicion for mesenchymal hamartoma, which can evolve into undifferentiated embryonal sarcoma if untreated. Hepatic hematoma and biloma can appear cystlike in children with a history of trauma or recent intervention. In neonates with an umbilical vein catheter (UVC), an intrahepatic cyst along the course of the UVC should raise concern for infusate extravasation. Familiarity with imaging findings and clinical features is essential for achieving accurate diagnosis of pediatric hepatic cystic lesions, which in turn can guide appropriate clinical management. Online supplemental material is available for this article. ©RSNA, 2022.

General and abdominal obesity trajectories across adulthood, and risk of prostate cancer: results from the PROtEuS study, Montreal, Canada.

PURPOSE: Greater body fatness is a probable cause of advanced prostate cancer (PCa). Body fat distribution and timing of exposure may be relevant. We investigated associations between body size trajectories and PCa incidence in a population-based case-control study in Montreal, Canada. METHODS: Cases (n = 1,931), aged ≤ 75 years, were diagnosed with PCa in 2005-2009; 1,994 controls were selected from the electoral list. Interviews were conducted to assess body mass index (BMI) and Stunkard's silhouette at ages 20, 40, 50, 60 years, and before interview. Current waist and hip circumferences were measured, and a predictive model estimated waist circumference in the past. BMI and waist circumference trajectories were determined to identify subgroups. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between anthropometric indicators and PCa. RESULTS: Subjects with a current BMI ≥ 30 kg/m2 had a lower risk of overall PCa (OR 0.71, 95% CI 0.59-0.85). Associations with adult BMI followed similar trends for less and more aggressive tumors, with stronger inverse relationships in early adulthood. Contrastingly, current waist circumference ≥ 102 cm was associated with elevated risk of high-grade PCa (OR 1.33, 95% CI 1.03-1.71). Men with increasing BMI or waist circumference adult trajectories had a lower risk of PCa, especially low-grade, than those in the normal-stable range. This was especially evident among men in the obese-increase group for BMI and waist circumference. CONCLUSION: Abdominal obesity increased the risk of aggressive PCa. The inverse relationship between body size trajectories and PCa may reflect PSA hemodilution, lower detection, and/or a true etiological effect.

Imaging Features of Neurofibromatosis Type 1 in the Abdomen and Pelvis.

OBJECTIVE. Loss of the neurofibromatosis type 1 (NF1) tumor suppressor protein causes uninhibited activation of the RAS oncogene, which leads to tumorigenesis in patients with NF1. This case-based review discusses imaging manifestations of NF1 in the abdomen and pelvis, highlighting key genetic associations and management to elucidate features different from the general population. CONCLUSION. The spectrum of pathologic findings includes gastrointestinal tumors such as gastrointestinal stromal tumors, genitourinary lesions including urogenital neurofibromas, vascular entities such as renal artery stenosis, and less common associations like lymphoma.

Osteoarthritis of the hip: are degenerative tears of the acetabular labrum predictable from features on hip radiographs?

BACKGROUND: A common feature of hip arthritis is the presence of labra tears. Recent literature suggests against the use of magnetic resonance imaging (MRI) in patients aged >45 years for the assessment of hip pain related to arthritis. PURPOSE: To determine if radiographic features of osteoarthritis detectable on routine hip radiographs are accurate and reliable surrogate markers of degenerative acetabular labral tears identified on MR arthrography (MRA) and corroborated during arthroscopy. MATERIAL AND METHODS: A retrospective study involving 86 symptomatic patients (hip pain) with radiologic work-up included MRA and pelvic or hip radiographs that underwent hip arthroscopy within three months. Imaging characteristics assessed on hip radiographs include measurements of superior acetabular, femoral head osteophyte, cortical thickness of the femoral shaft, and minimum joint space as well as presence of subchondral sclerosis of the femoral head and acetabulum, femoral shaft buttressing, and grade of arthritis. Presence of a labral tear was determined by consensus between three readers as well as by surgical correlation. The Pearson's chi-squared and Fisher's exact tests were used to compare presence of labral tears with each radiographic feature. RESULTS: Seventy-one patients (82.6%) had labral tears: 49 (69%) women and 22 (31%) men. Receiver operating characteristic analysis showed statistical significance (P<0.05) between presence of a labral tear and acetabular and femoral head osteophyte sizes but failed to demonstrate any significance regarding acetabular subchondral sclerosis, cortical thickness, buttressing, or minimum joint space. CONCLUSIONS: Radiographic markers such as the acetabular and femoral head osteophyte sizes demonstrated statistical significance with the presence of labral tears.

Atypical pulmonary metastases in children: pictorial review of imaging patterns.

Pulmonary metastases typically present as well-circumscribed solid nodules, often with a basilar and peripheral distribution due to hematogenous spread. When an atypical pattern of metastasis occurs, a lack of recognition may result in understaging or a delay in diagnosis. The purpose of this article is to review the imaging findings of atypical pulmonary metastatic disease in children. Atypical pulmonary metastatic patterns that can be seen in children include cavitary lesions, calcified pulmonary nodules, nodules with peritumoral halos, tree-in-bud or strial pattern secondary to tumor in peripheral pulmonary arterial branches, lymphangitic carcinomatosis, and miliary disease. An awareness of the spectrum of imaging findings of atypical pulmonary metastases along with an understanding of histopathological underpinnings will allow the radiologist to make an accurate diagnosis.

Age-Related Eye Disease and Cognitive Function: The Search for Mediators.

PURPOSE: Age-related eye disease may be associated with cognitive decline, but the scientific literature has not been consistent. Furthermore, no studies have been able to explain the relationship. Our objective was to assess whether older adults with age-related macular degeneration (AMD) or glaucoma performed worse on 6 cognitive tests compared with older adults with normal vision and, if so, to understand why. DESIGN: Cross-sectional analysis of hospital-based study (Maisonneuve-Rosemont Hospital Ophthalmology Clinics, Montréal, Canada). PARTICIPANTS: Three hundred thirty-six adults 65 years of age or older with either AMD, glaucoma, or normal vision. METHODS: Cognition was measured with 6 cognitive tests administered orally. Activity levels were measured using the Victoria Longitudinal Study Activity Lifestyle Questionnaire. Visual acuity and visual field were measured. Multiple linear regression was used. Mediation was assessed using structural equation modeling. MAIN OUTCOME MEASURES: Results of the verbal fluency test (animal and letter versions), the digit span test (forward and backward versions), and the logical memory test (immediate and delayed recall). RESULTS: People with glaucoma showed lower scores on 3 cognitive tests than the group with normal vision: the digit span forward and backward tests (ß = -0.8 [95% confidence interval (CI), -1.5 to -0.2] and ß = -0.7 [95% CI, -1.3 to -0.1], respectively) and the logical memory test with immediate recall (ß = -1.3 [95% CI, -2.4 to -0.2]). Activity levels statistically significantly mediated the relationship between glaucoma and the digit span forward test (P = 0.043; percentage of the total effect mediated, 17%). CONCLUSIONS: People with glaucoma showed lower scores on cognitive tests that may depend on verbal working memory and encoding. If confirmed in longitudinal studies, interventions should be developed that are appropriate for a visually impaired population to slow this cognitive decline.

Diagnostic Approach to Benign and Malignant Calcifications in the Abdomen and Pelvis.

Intra-abdominal calcifications are common. Multiple pathologic processes manifest within the abdomen and pelvis in association with calcifications, which can be benign, premalignant, or malignant. Although calcium deposition in the abdomen can occur secondary to various mechanisms, the most common cau se is cellular injury that leads to dystrophic calcifications. The authors provide a summary of various common and uncommon calcifications in the abdomen and pelvis, primarily using location to illuminate diagnostic significance. Six broad categories of calcifications in the abdomen and pelvis are recognized: mesenteric, peritoneal, retroperitoneal, organ-based, vascular, and musculoskeletal. In addition to site, the various patterns and morphology of calcifications encountered in various conditions can be helpful for diagnosis, especially those depicted on radiographs. For example, some patterns diagnostic for various conditions include round or oval stones in the biliary or urothelial tracts, curvilinear calcifications associated with cysts or neoplasms, and sheetlike calcifications along peritoneal surfaces in the setting of chronic peritoneal dialysis or metastatic disease. Organ encrustation with calcium may be a premalignant finding (eg, porcelain gallbladder). In addition, the development of calcium after initiation of treatment can be used as an indicator of response in conditions such as tuberculosis, lymphoma, and hydatid disease. As calcifications are almost invariably detected at imaging, it is imperative for radiologists to be aware of their diagnostic implications and use the presence of calcification in an organ, mass, or other anatomic location for problem solving. ©RSNA, 2020.

Sensitivity of a Next-Generation NIRS Device to Detect Low Mixed Venous Oxyhemoglobin Saturations in the Single Ventricle Population.

Regional cerebral oxygenation index (rSO2) based on near-infrared spectroscopy (NIRS) is frequently used to detect low venous oxyhemoglobin saturation (ScvO2). We compared the performance of 2 generations of NIRS devices. Clinically obtained, time-matched cerebral rSO2 and ScvO2 values were compared in infants monitored with the FORE-SIGHT (n = 73) or FORE-SIGHT ELITE (n = 47) by linear regression and Bland-Altman analyses. In both devices, cerebral rSO2 correlated poorly with measured ScvO2 (FORE-SIGHT partial correlation 0.50 [95% confidence interval {CI}, 0.40-0.58]; FORE-SIGHT ELITE partial correlation 0.47 [0.39-0.55]) and mean bias was +8 (standard deviation [SD] 13.2) for FORE-SIGHT and +14 (SD 12.5) for FORE-SIGHT ELITE. When ScvO2 was <30%, rSO2 was <40 in 8% of FORE-SIGHT ELITE readings. Future NIRS should be validated in more hypoxic cohorts.

A Color Flow Tract in Ultrasound-Guided Random Renal Core Biopsy Predicts Complications.

OBJECTIVES: To determine patient and procedural risk factors for major complications in ultrasound (US)-guided random renal core biopsy. METHODS: Random renal biopsies performed by radiologists in the US department at a single institution between 2014 and 2018 were retrospectively reviewed. The patient's age, sex, race, and estimated glomerular filtration rate (eGFR) were recorded. The biopsy approach, needle gauge, length of cores, number of throws, and presence of a color flow tract were recorded. Outcome data included minor and major complications. Associations between variables were tested with χ2 analyses and univariable/multivariable logistic regression models. RESULTS: A total of 231 biopsies (167 native and 64 allografts) were reviewed. There was no significant difference in the sex, age, race, or eGFR between native and allograft groups. The overall rate for any complication was 18.2%, with a 4.3% rate of major complications, which was significantly greater in native compared to allograft biopsies (6% versus 0%; P = .045). A risk analysis in native biopsies only showed that major complications were significantly associated with a low eGFR such that patients with stage 4 or 5 kidney disease had higher odds of complications (odds ratio [95% confidence interval]: stage 4, 9.405 [1.995-44.338]; P = .0393; stage 5, 10.749 [2.218-52.080]; P = .0203) than patients with normal function (eGFR >60 mL/min). The presence of a color flow tract portended a 10.7 times greater risk of having any complication (95% confidence interval, 4.595-24.994; P < .001). Other procedural factors were not significantly associated with complications. CONCLUSIONS: There is an increased risk of major complications in US-guided random native kidney biopsy in patients with a low eGFR (<30 mL/min) and a patent color flow tract in the immediate postbiopsy setting.

Modeling gene-environment interactions in longitudinal family studies: a comparison of methods and their application to the association between the IGF pathway and childhood obesity.

BACKGROUND: The interactive effect of the IGF pathway genes with the environment may contribute to childhood obesity. Such gene-environment interactions can take on complex forms. Detecting those relationships using longitudinal family studies requires simultaneously accounting for correlations within individuals and families. METHODS: We studied three methods for detecting interaction effects in longitudinal family studies. The twin model and the nonparametric partition-based score test utilized individual outcome averages, whereas the linear mixed model used all available longitudinal data points. Simulation experiments were performed to evaluate the methods' power to detect different gene-environment interaction relationships. These methods were applied to the Quebec Newborn Twin Study data to test for interaction effects between the IGF pathway genes (IGF-1, IGFALS) and environmental factors (physical activity, daycare attendance and sleep duration) on body mass index outcomes. RESULTS: For the simulated data, the twin model with the mean time summary statistic yielded good performance overall. Modelling an interaction as linear when the true model had a different relationship influenced power; for certain non-linear interactions, none of the three methods were effective. Our analysis of the IGF pathway genes showed suggestive association for the joint effect of IGF-1 variant at position 102,791,894 of chromosome 12 and physical activity. However, this association was not statistically significant after multiple testing correction. CONCLUSIONS: The analytical approaches considered in this study were not robust to different gene-environment interactions. Methodological innovations are needed to improve the current methods' performances for detecting non-linear interactions. More studies are needed in order to better understand the IGF pathway's role in childhood obesity development.

Characteristics and outcomes of antiretroviral-treated HIV-HBV co-infected patients in Canada?

BACKGROUND: Hepatitis B (HBV) and Human Immunodeficiency Virus (HIV) share common risk factors for exposure. Co-infected patients have an increased liver-related mortality risk and may have accelerated HIV progression. The epidemiology and demographic characteristics of HIV-HBV co-infection in Canada remain poorly defined. We compared the demographic and clinical characteristics and factors associated with advanced hepatic fibrosis between HIV and HIV-HBV co-infected patients. METHODS: A retrospective cohort analysis was conducted using data from the Canadian Observational Cohort (CANOC) Collaboration, including eight sites from British Columbia, Quebec, and Ontario. Eligible participants were HIV-infected patients who initiated combination ARV between January 1, 2000 and December 14, 2014. Demographic and clinical characteristics were compared between HIV-HBV co-infected and HIV-infected groups using chi-square or Fisher exact tests for categorical variables, and Wilcoxon's Rank Sum test for continuous variables. Liver fibrosis was estimated by the AST to Platelet Ratio Index (APRI). RESULTS: HBV status and APRI values were available for 2419 cohort participants. 199 (8%) were HBV co-infected. Compared to HIV-infected participants, HIV-HBV co-infected participants were more likely to use injection drugs (28% vs. 21%, p = 0.03) and be HCV-positive (31%, vs. 23%, p = 0.02). HIV-HBV co-infected participants had lower baseline CD4 T cell counts (188 cells/mm3, IQR: 120-360) compared to 235 cells/mm3 in HIV-infected participants (IQR: 85-294) (p = 0.0002) and higher baseline median APRI scores (0.50 vs. 0.37, p < 0.0001). This difference in APRI was no longer clinically significant at follow-up (0.32 vs. 0.30, p = 0.03). HIV-HBV co-infected participants had a higher mortality rate compared to HIV-infected participants (11% vs. 7%, p = 0.02). CONCLUSION: The prevalence, demographic and clinical characteristics of the HIV-HBV co-infected population in Canada is described. HIV-HBV co-infected patients have higher mortality, more advanced CD4 T cell depletion, and liver fibrosis that improves in conjunction with ARV therapy. The high prevalence of unknown HBV status demonstrates a need for increased screening among HIV-infected patients in Canada.

Utilization of key preventive measures for pregnancy complications and malaria among women in Jimma Zone, Ethiopia.

BACKGROUND: In Ethiopia, malaria infections and other complications during pregnancy contribute to the high burden of maternal morbidity and mortality. Preventive measures are available, however little is known about the factors influencing the uptake of maternal health services and interventions by pregnant women in Ethiopia. METHODS: We analyzed data from a community-based cross-sectional survey conducted in 2016 in three rural districts of Jimma Zone, Ethiopia, with 3784 women who had a pregnancy outcome in the year preceding the survey. We used multivariable logistic regression models accounting for clustering to identify the determinants of antenatal care (ANC) attendance and insecticide-treated net (ITN) ownership and use, and the prevalence and predictors of malaria infection among pregnant women. RESULTS: Eighty-four percent of interviewed women reported receiving at least one ANC visit during their last pregnancy, while 47% reported attending four or more ANC visits. Common reasons for not attending ANC included women's lack of awareness of its importance (48%), distance to health facility (23%) and unavailability of transportation (14%). Important determinants of ANC attendance included higher education level and wealth status, woman's ability to make healthcare decisions, and pregnancy intendedness. An estimated 48% of women reported owning an ITN during their last pregnancy. Of these, 55% reported to have always slept under it during their last pregnancy. Analysis revealed that the odds of owning and using ITNs were respectively 2.07 (95% CI: 1.62-2.63) and 1.73 (95% CI: 1.32-2.27) times higher among women who attended at least one ANC visit. The self-reported prevalence of malaria infection during pregnancy was low (1.4%) across the three districts. We found that young, uneducated, and unemployed women presented higher odds of malaria infection during their last pregnancy. CONCLUSION: ANC and ITN uptake during pregnancy in Jimma Zone fall below the respective targets of 95 and 90% set in the Ethiopian Health Sector Transformation Plan for 2020, suggesting that more intensive programmatic efforts still need to be directed towards improving access to these health services. Reaching ANC non-users and ITN ownership and use as part of ANC services could be emphasized to address these gaps.

Rationale and Design of the FREQUENCY Study: The Fetal Cardiac Registry of Québec to Improve Resource Utilization in Fetal Cardiology.

OBJECTIVE: Prenatal detection of congenital heart diseases (CHD) decreases morbidity and cost. To improve detections rates, most physicians refer pregnant women with high-risk pregnancies to fetal cardiologists even when there is no suspicion of CHD at the second trimester screening. This paper presents the rationale and detailed method of the Fetal Cardiac Registry of Québec to Improve Resource Utilization in Fetal Cardiology (FREQUENCY) study. The overall objective is to assess the impact of second trimester ultrasound screening (U/S) and referral pattern in fetal cardiology on detection rates, health care costs, and resource utilization, as well as perinatal morbidity and mortality. METHODS: This multicentre retrospective population-based cohort study will link fetal echocardiography data from all centres performing fetal echocardiography in Québec with administrative health care data. This data linking will allow the determination of a true denominator (all women in Québec who underwent second trimester U/S) with complete follow-up of up to 2 years for offspring. This protocol meets Canadian Task Force Classification II-2. RESULTS: The study investigators have collected and cleaned fetal echocardiography data for 24 259 eligible pregnancies referred to fetal cardiology. These data will be matched to approximately 860 000 pregnancies between 2007 and 2015. CONCLUSION: The results of the FREQUENCY study will shed light on the impact of the current prenatal CHD screening strategy in Canada.

Factors associated with human West Nile virus infection in Ontario: a generalized linear mixed modelling approach.

BACKGROUND: West Nile Virus (WNV) is a mosquito-borne pathogen that has become established in North America. Risk for human infection varies geographically in accordance with climate and population factors. Though often asymptomatic, human WNV infection can cause febrile illness or, rarely, neurologic disease. WNV has become a public health concern in Canada since its introduction in 2001. METHODS: To identify predictors of human WNV incidence at the public health unit (PHU) level in Ontario, Canada, we combined data on environmental and population characteristics of PHUs with historical mosquito and human surveillance records from 2002 to 2013. We examined the associations between annual WNV incidence and monthly climate indices (e.g. minimum and maximum temperature, average precipitation), land cover (e.g. deciduous forest, water), population structure (e.g. age and sex composition) and the annual percentage of WNV-positive mosquito pools from 2002 to 2013. We then developed a generalized linear mixed model with a Poisson distribution adjusting for spatial autocorrelation and repeat measures. Further to this, to examine potential 'early season' predictors of WNV incidence in a given year, we developed a model based on winter and spring monthly climate indices. RESULTS: Several climate indices, including mean minimum temperature (o C) in February (RR = 1.58, CI: [1.42, 1.75]), and the annual percentage of WNV-positive mosquito pools (RR = 1.07, CI: [1.04, 1.11]) were significantly associated with human WNV incidence at the PHU level. Higher winter minimum temperatures were also strongly associated with annual WNV incidence in the 'early season' model (e.g. February minimum temperature (RR = 1.91, CI: [1.73, 2.12]). CONCLUSIONS: Our study demonstrates that early season temperature and precipitation indices, in addition to the percentage of WNV-positive mosquito pools in a given area, may assist in predicting the likelihood of a more severe human WNV season in southern regions of Ontario, where WNV epidemics occur sporadically.

Survey highlights the need for specific interventions to reduce frequent conflicts between healthcare professionals providing paediatric end-of-life care.

AIMS: This study explored how paediatric healthcare professionals experienced and coped with end-of-life conflicts and identified how to improve coping strategies. METHODS: A questionnaire was distributed to all 2300 professionals at a paediatric university hospital, covering the frequency of end-of-life conflicts, participants, contributing factors, resolution strategies, outcomes and the usefulness of specific institutional coping strategies. RESULTS: Of the 946 professionals (41%) who responded, 466 had witnessed or participated in paediatric end-of-life discussions: 73% said these had led to conflict, more frequently between professionals (58%) than between professionals and parents (33%). Frequent factors included professionals' rotations, unprepared parents, emotional load, unrealistic parental expectations, differences in values and beliefs, parents' fear of hastening death, precipitated situations and uncertain prognosis. Discussions with patients and parents and between professionals were the most frequently used coping strategies. Conflicts were frequently resolved by the time of death. Professionals mainly supported designating one principal physician and nurse for each patient, two-step interdisciplinary meetings - between professionals then with parents - postdeath ethics meetings, bereavement follow-up protocols and early consultations with paediatric palliative care and clinical ethics services. CONCLUSION: End-of-life conflicts were frequent and predominantly occurred between healthcare professionals. Specific interventions could target most of the contributing factors.