The Mental Health of First Nations Children in Manitoba: A Population-Based Retrospective Cohort Study Using Linked Administrative Data: La santé mentale des enfants des Premières Nations au Manitoba : une étude de cohorte rétrospective dans la population, à l'aide de données administratives liées.

OBJECTIVE: First Nations children face a greater risk of experiencing mental disorders than other children from the general population because of family and societal factors, yet there is little research examining their mental health. This study compares diagnosed mental disorders and suicidal behaviours of First Nations children living on-reserve and off-reserve to all other children living in Manitoba. METHOD: The research team, which included First Nations and non-First Nations researchers, utilized population-based administrative data that linked de-identified individual-level records from the 2016 First Nations Research File to health and social information for children living in Manitoba. Adjusted rates and rate ratios of mental disorders and suicide behaviours were calculated using a generalized linear modelling approach to compare First Nations children (n = 40,574) and all other children (n = 197,109) and comparing First Nations children living on- and off-reserve. RESULTS: Compared with all other children, First Nations children had a higher prevalence of schizophrenia (adjusted rate ratio (aRR): 4.42, 95% confidence interval (CI), 3.36 to 5.82), attention-deficit hyperactivity disorder (ADHD; aRR: 1.21, 95% CI, 1.09 to 1.33), substance use disorders (aRR: 5.19; 95% CI, 4.25 to 6.33), hospitalizations for suicide attempts (aRR: 6.96; 95% CI, 4.36 to 11.13) and suicide deaths (aRR: 10.63; 95% CI, 7.08 to 15.95). The prevalence of ADHD and mood/anxiety disorders was significantly higher for First Nations children living off-reserve compared with on-reserve; in contrast, hospitalization rates for suicide attempts were twice as high on-reserve than off-reserve. When the comparison cohort was restricted to only other children in low-income areas, a higher prevalence of almost all disorders remained for First Nations children. CONCLUSION: Large disparities were found in mental health indicators between First Nations children and other children in Manitoba, demonstrating that considerable work is required to improve the mental well-being of First Nations children. Equitable access to culturally safe services is urgently needed and these services should be self-determined, planned, and implemented by First Nations people.

Intentional injury and violent death after intimate partner violence. A retrospective matched-cohort study.

The incidence of intimate partner violence (IPV) varies according to IPV definitions and data collection approaches. The criminal Justice system assesses IPV through a review of the evidence gathered by the police and the court hearings. We aimed to determine the association between IPV, as identified in criminal Justice disposition records, and subsequent healthcare-identified intentional injury inflicted by others, including violent death. We conducted a retrospective population-based matched-cohort study using linked multisectoral databases. Female adult Manitoba residents identified as victims of IPV in provincial prosecution and disposition records 2004 to 2016 (n = 20,469) were matched to three non-victims (n = 61,407) of similar age, relationship status and place of residence at the date of the IPV incident. Outcomes were first healthcare use for intentional injury and violent death, assessed in Emergency Department visits, hospitalizations and Vital Statistics deaths records. Conditional Cox Regression was used to obtain Hazard Ratios (HR) with 95% confidence intervals (CI). The risk of intentional injury was 8.5 per 1000 women among non-victims of IPV and 55.8 per 1000 women among IPV victims. The Hazard Ratios associated with IPV were 3.8 (95% CI: 3.4, 4.3) for intentional injury and 4.6 (95% CI: 2.3, 9.2) for violent death, after adjustment. IPV victims experienced half the risk of subsequent intentional injury if the accused received a probation sentence. Our findings suggest that Justice involvement represents an opportunity for intersectoral collaborative prevention of subsequent intentional injury among IPV victims.

A mutation in the viral sensor 2'-5'-oligoadenylate synthetase 2 causes failure of lactation.

We identified a non-synonymous mutation in Oas2 (I405N), a sensor of viral double-stranded RNA, from an ENU-mutagenesis screen designed to discover new genes involved in mammary development. The mutation caused post-partum failure of lactation in healthy mice with otherwise normally developed mammary glands, characterized by greatly reduced milk protein synthesis coupled with epithelial cell death, inhibition of proliferation and a robust interferon response. Expression of mutant but not wild type Oas2 in cultured HC-11 or T47D mammary cells recapitulated the phenotypic and transcriptional effects observed in the mouse. The mutation activates the OAS2 pathway, demonstrated by a 34-fold increase in RNase L activity, and its effects were dependent on expression of RNase L and IRF7, proximal and distal pathway members. This is the first report of a viral recognition pathway regulating lactation.

Interpregnancy Intervals in a Contemporary Manitoba Cohort: Prevalence of So-Called Suboptimal Intervals and Associated Maternal Characteristics.

OBJECTIVE: Short and long interpregnancy intervals (IPIs) have been associated with various adverse outcomes, and a 2016 American College of Obstetricians and Gynecologists' Committee Opinion recommends an optimal IPI of 18 months to 5 years. Descriptive data on the IPI in Canada are lacking. The objective of this study was to examine IPIs in a Manitoba cohort. METHODS: The study analyzed a subset of records from a larger dataset used to examine the IPI and adverse perinatal outcomes. For that study, Manitoba's Hospital Abstracts data were searched to identify births from 1985 to 2014. Each two consecutive live births to the same mother formed a sibling pair. The IPI was calculated as the interval between the two siblings' births, minus the younger sibling's GA. Information on maternal characteristics was extracted from various datasets housed in the Manitoba Population Research Data Repository. The current analysis examined second and higher-order births between 2010 and 2014. The proportion of suboptimal IPIs was determined and IPIs were cross-tabulated with birth year and maternal subgroups. RESULTS: More than half of pregnancies were conceived following a suboptimal interval. IPIs of less than 6 months - which have been associated with the highest risk of adverse outcomes - were more prevalent among certain subgroups. These included younger women as well as women who received inadequate prenatal care, smoked or drank alcohol during pregnancy, were low income, or did not graduate from high school. CONCLUSION: Suboptimal IPIs were common in this Manitoba cohort. Stakeholders should consider whether greater efforts to promote appropriate birth spacing are warranted.

Interpregnancy Interval and Congenital Anomalies: A Record-Linkage Study Using the Manitoba Population Research Data Repository.

OBJECTIVE: Congenital anomalies are a serious public health issue, and relatively few modifiable risk factors have been identified. Our objective was to investigate one such potential risk factor, the interpregnancy interval (IPI). METHODS: We conducted a secondary analysis of data housed at the Manitoba Centre for Health Policy. In-hospital live births and stillbirths of at least 20 weeks' gestation were identified, and consecutive births to the same mother were grouped into sibling pairs to calculate the IPI for the younger siblings of each pair. Logistic regression models were fit to examine the association between the IPI and any congenital anomaly, as well as CNS and chromosomal anomalies, while controlling for potentially confounding sociodemographic and clinical factors. RESULTS: Among 172 909 live births and stillbirths, the IPI was not significantly associated with congenital anomalies overall or with chromosomal anomalies. Short IPIs were associated with significantly increased odds of CNS anomalies relative to IPIs of 18-23 months (adjusted OR [aOR] for IPIs <6 months 2.15; 95% CI 1.48-3.12), whereas the aOR for IPIs ≥60 months was elevated but not statistically significant (aOR 1.50; 95% CI 0.96-2.34). In a sensitivity analysis in which the cohort was restricted to births from 2003 onwards (which yielded more complete data on health-related behaviours), the observed effect for IPIs shorter than 6 months and CNS anomalies was attenuated and no longer significant, but it remained elevated (aOR 1.65; 95% CI 0.85-3.24). CONCLUSION: The findings for CNS anomalies warrant further investigation.

Interpregnancy Interval and Adverse Perinatal Outcomes: A Record-Linkage Study Using the Manitoba Population Research Data Repository.

OBJECTIVE: To examine the association between the interpregnancy interval (IPI) and preterm birth, low birth weight, and SGA birth in a developed country with universal health coverage. METHODS: We conducted a secondary analysis of data housed at the Manitoba Centre for Health Policy. All live births in Manitoba hospitals over a 29-year period were identified and consecutive births to the same mother were grouped into sibling pairs to calculate the IPI for the younger siblings. Logistic regression models were fit to examine the association between the IPI and adverse perinatal outcomes, adjusted for potentially confounding sociodemographic and clinical factors. RESULTS: In a cohort of more than 171 000 births and relative to IPIs of 18 to 23 months, IPIs shorter than 12 and longer than 23 months were associated with significantly increased odds of preterm birth overall and both medically indicated and spontaneous preterm births, low birth weight, and SGA birth. The strongest association observed was for intervals shorter than 6 months and spontaneous preterm birth (adjusted OR 1.83, 95% CI 1.65-2.03). When the outcome was modelled as GA categories, the strongest association observed was for intervals shorter than 6 months and early preterm birth (<34 weeks' GA; adjusted OR 2.47, 95% CI 2.07-2.94). CONCLUSION: If the associations observed between the IPI and adverse perinatal outcomes in this large, population-based cohort are causal, birth spacing could form an important target of public health messaging in Canada.

Maternal diabetes mellitus and congenital anomalies of the kidney and urinary tract (CAKUT) in the child.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the primary cause of chronic kidney disease in children. The relevance of timing of diabetes mellitus (DM) exposure on risk of CAKUT in exposed children is unknown. STUDY DESIGN: Population-based nested case-control study. SETTING & PARTICIPANTS: Infants born between fiscal years 1996/1997 and 2009/2010 in Manitoba, Canada, identified using administrative data housed at the Manitoba Centre for Health Policy. PREDICTORS: Pregestational (including first 20 weeks' gestation) and gestational (>20 weeks) DM and relevant confounders (maternal age; renin-angiotensin-aldosterone system inhibitor use; low socioeconomic status; alcohol, illicit drug, and smoking use during pregnancy; region of residence; and size for gestational age [surrogate of glycemic control]). OUTCOME: CAKUT identified by International Classification of Diseases codes. RESULTS: 945 case patients with CAKUT and 4,725 controls (matched for gestational age, sex, and birth year) were identified. Maternal pregestational DM occurred in 39 (4.1%) of the CAKUT group and 111 (2.3%) controls (P = 0.002), whereas gestational DM occurred in 40 (4.2%) of the CAKUT group and 157 (3.3%) controls (P = 0.2). In the conditional multivariable logistic regression model, pregestational DM was associated with CAKUT (OR, 1.67; 95% CI, 1.14-2.46), whereas gestational DM was not (OR, 1.29; 95% CI, 0.90-1.85). Both large (LGA) and small for gestational age (SGA) also were associated significantly with CAKUT (LGA: OR, 1.34 [95% CI, 1.11-1.63]; SGA: OR, 1.59 [95% CI, 1.26-2.01]). LIMITATIONS: Lack of data for maternal glycemic control and body mass index. CONCLUSIONS: This study suggests that DM in the first 20 weeks of pregnancy is associated with CAKUT in exposed infants. The association between CAKUT and LGA suggests that poor glycemic control increases risk. Screening and intervention studies in women of childbearing age with DM are warranted to determine whether the risk of chronic kidney disease in children can be modified.

ELF5 suppresses estrogen sensitivity and underpins the acquisition of antiestrogen resistance in luminal breast cancer.

We have previously shown that during pregnancy the E-twenty-six (ETS) transcription factor ELF5 directs the differentiation of mammary progenitor cells toward the estrogen receptor (ER)-negative and milk producing cell lineage, raising the possibility that ELF5 may suppress the estrogen sensitivity of breast cancers. To test this we constructed inducible models of ELF5 expression in ER positive luminal breast cancer cells and interrogated them using transcript profiling and chromatin immunoprecipitation of DNA followed by DNA sequencing (ChIP-Seq). ELF5 suppressed ER and FOXA1 expression and broadly suppressed ER-driven patterns of gene expression including sets of genes distinguishing the luminal molecular subtype. Direct transcriptional targets of ELF5, which included FOXA1, EGFR, and MYC, accurately classified a large cohort of breast cancers into their intrinsic molecular subtypes, predicted ER status with high precision, and defined groups with differential prognosis. Knockdown of ELF5 in basal breast cancer cell lines suppressed basal patterns of gene expression and produced a shift in molecular subtype toward the claudin-low and normal-like groups. Luminal breast cancer cells that acquired resistance to the antiestrogen Tamoxifen showed greatly elevated levels of ELF5 and its transcriptional signature, and became dependent on ELF5 for proliferation, compared to the parental cells. Thus ELF5 provides a key transcriptional determinant of breast cancer molecular subtype by suppression of estrogen sensitivity in luminal breast cancer cells and promotion of basal characteristics in basal breast cancer cells, an action that may be utilised to acquire antiestrogen resistance.

Parental bereavement after the death of an offspring in a motor vehicle collision: a population-based study.

Motor vehicle collisions (MVCs) are the leading cause of death in young people in North America. The effects of such deaths on parents have not been systematically studied. Administrative data sets were used to identify all parents (n = 1,458) who had an offspring die in a MVC between 1996 and 2008 in the province of Manitoba, Canada. They were matched to general population control parents who had not had offspring die from any sudden cause during the study period. Generalized estimating equations were used to compare the rates of physician-diagnosed mental and physical disorders, social factors, and treatment utilization in the 2 parent groups in the 2 years before and after offspring death, with adjustment for confounding factors. The risk of depression among bereaved parents almost tripled (adjusted prevalence ratio = 2.85, 95% confidence interval: 2.44, 3.33; P < 0.001) during the 2 years after death of an offspring. Significant increases in the risk of anxiety disorders (adjusted prevalence ratio = 1.45, 95% confidence interval: 1.26, 1.67; P < 0.001) were also observed. When compared with nonbereaved parents, bereaved parents had significant increases in the risks of depression (P < 0.001), anxiety disorders (P < 0.001), marital break-up (P = 0.015), and physician visits for mental illness (P < 0.001) in the post-death period. In conclusion, parents who lose an offspring in a MVC experience considerable mental illness and marital disruption.

Intimate Partner Violence Among International and Interprovincial Migrants: A Population-Based Analysis of Canadian Linked Immigration and Justice Data.

Factors associated with IPV among immigrant women are not well understood. Using linked immigration and justice data, we compared the incidence of justice-identified IPV (JIIPV) among 58,564 international immigrant women born outside of Canada, 30,098 women born in other Canadian provinces (i.e., interprovincial migrants), and 88,662 long-term Manitoban resident women. International immigrant women had the lowest incidence of JIIPV compared to matched long-term Manitobans (adjusted hazard ratio (aHR) 0.49, 95% CI: 0.43-0.56) and interprovincial migrants (aHR 0.56, 95% CI: 0.43-0.73). Among immigrants, JIIPV varied substantially according to birthplace, increased with length of residence, and was less frequent among secondary immigrants.

Suicide and suicide attempts in children and adolescents in the child welfare system.

BACKGROUND: Few population studies have examined the psychiatric outcomes of children and adolescents in the child welfare system, and no studies have compared outcomes before and after entry into care. Our objective was to assess the relative rate (RR) of suicide, attempted suicide, admission to hospital and visits to physicians' offices among children and adolescents in care compared with those not in care. We also examined these outcomes within the child welfare population before and after entry into care. METHODS: We used population-level data to identify children and adolescents 5 to 17 years of age who were in care in Manitoba for the first time between Apr. 1, 1997, and Mar. 31, 2006, and a comparison cohort not in care. We compared the two cohorts to obtain RRs for the specified outcomes. We also determined RRs within the child welfare population relative to the same population two years before entry into care. RESULTS: We identified 8279 children and adolescents in care for the first time and a comparison cohort of 353 050 children and adolescents not in care. Outcome rates were higher among those in care than in the comparison cohort for suicide (adjusted RR 3.54, 95% confidence interval [CI] 2.11-5.95), attempted suicide (adjusted RR 2.11, 95% CI 1.84-2.43) and all other outcomes. However, adjusted RRs for attempted suicide (RR 0.27, 95% CI 0.21-0.34), admissions to hospital and physician visits decreased after entry into care. INTERPRETATION: Children and adolescents in care were at greater risk of suicide and attempting suicide than those who were not in care. Rates of suicide attempts and hospital admissions within this population were highest before entry into care and decreased thereafter.

Program for expectant and new mothers: a population-based study of participation.

BACKGROUND: The Manitoba Healthy Baby Program is aimed at promoting pre- and perinatal health and includes two components: 1) prenatal income supplement; 2) community support programs. The goal of this research was to determine the uptake of these components by target groups. METHODS: Data on participation in each of the two program components were linked to data on all hospital births in Manitoba between 2004/05 through 2007/08. Descriptive analyses of participation by maternal characteristics were produced. Logistic regression analyses were conducted to identify factors associated with participation in the two programs. Separate regressions were run for two groups of women giving birth during the study period: 1) total population; 2) those receiving provincial income assistance during the prenatal period. RESULTS: Almost 30% of women giving birth in Manitoba received the Healthy Baby prenatal income supplement, whereas only 12.6% participated in any community support programs. Over one quarter (26.4%) of pregnant women on income assistance did not apply for and receive the prenatal income supplement, despite all being eligible for it. Furthermore, 77.8% of women on income assistance did not participate in community support programs. Factors associated with both receipt of the prenatal benefit and participation in community support programs included lower SES, receipt of income assistance, obtaining adequate prenatal care, having completed high school and having depressive symptoms. Having more previous births was associated with higher odds of receiving the prenatal benefit, but lower odds of attending community support programs. Being married was associated with lower odds of receiving the prenatal benefit but higher odds of participating in community support programs. CONCLUSIONS: Although uptake of the Healthy Baby program in Manitoba is greater for women in groups at risk for poorer perinatal outcomes, a substantial number of women eligible for this program are not receiving it; efforts to reach these women should be enhanced.

Predictors of serious complications associated with lower gastrointestinal endoscopy in a major city-wide health region.

BACKGROUND: There are limited data regarding complications associated with colonoscopy and flexible sigmoidoscopy in usual clinical practice in Canada. OBJECTIVE: To determine the risk factors for lower gastrointestinal (GI) endoscopy-associated complications in usual clinical practice. METHODS: All outpatient lower GI endoscopies performed in Winnipeg (Manitoba) between April 1, 2004 and March 31, 2006, were identified from the provincial physicians' claims database. All subsequent hospital admissions within 30 days that documented potential complications associated with lower GI endoscopies were identified from the electronic hospital discharges database and reviewed. Multivariate generalized estimating equation regression analysis was performed to determine independent factors (patient, endoscopist and procedure) associated with the risk of developing complications. RESULTS: There were 29,990 outpatient lower GI endoscopies performed in Winnipeg during the years studied. Seventy-seven (0.26%) procedures were associated with complications requiring hospitalization within 30 days of the index procedure. Stricture dilation (rate ratio [RR] 23.14; 95% CI 6.70 to 76.51), polypectomy (RR 5.93; 95% CI 3.66 to 9.62), increasing patient age (for each year increase in age, RR 1.03; 95% CI 1.01 to 1.05) and performance of endoscopy by low-volume endoscopists (fewer than 200 procedures per year, RR 2.28; 95% CI 1.18 to 4.42) and family physicians (RR 2.23; 95% CI 1.39 to 3.58) were independently associated with complications. CONCLUSIONS: The results of the present study suggest that increasing patient age, complex procedures and performance of the index procedure by low-volume endoscopists are independent risk factors for lower GI endoscopy-associated complications in usual clinical practice. This suggests that it may be time to consider implementing minimum volume requirements for endoscopists performing non-screening lower GI endoscopies.

Overlap between child protection services and the youth justice system: protocol for a retrospective population-based cohort study using linked administrative data in Manitoba, Canada.

INTRODUCTION: Children who have a history of involvement in child protection services (CPS) are over-represented in the youth and adult criminal justice systems. There are significant health and socioeconomic implications for individuals involved in either or both CPS and the justice system. Understanding the 'overlap' between these two systems would provide insight into the health and social needs of this population. This protocol describes a research programme on the relationship between the child welfare and the youth justice systems, looking specifically at the population involved in both CPS and the youth justice system. We will examine the characteristics associated with involvement in these systems, justice system trajectories of individuals with a history of CPS involvement and early adult outcomes of children involved in both systems. METHODS AND ANALYSIS: Administrative data sets will be linked at the individual level for three cohorts born 1991, 1994 and 1998 in Manitoba, Canada. Involvement in CPS will be categorised as 'placed in out-of-home care', 'received in-home services, but was not placed in care' or 'no involvement'. Involvement in the youth justice system will be examined through contacts with police between ages 12 and 17 that either led to charges or did not proceed. Individual, maternal and neighbourhood characteristics will be examined to identify individuals at greatest risk of involvement in one or both systems. ETHICS AND DISSEMINATION: The study was approved by the University of Manitoba Health Research Ethics Board and permission to access data sets has been granted by all data providers. We also received approval for the study from the First Nations Health and Social Secretariat of Manitoba's Health Information Research Governance Committee and the Manitoba Metis Federation. Strategies to disseminate study results will include engagement of stakeholders and policymakers through meetings and workshops, scientific publications and presentations, and social media.

Prenatal, Maternal, and Early Childhood Factors Associated with Dental General Anesthesia to Treat Severe Early Childhood Caries.

Purpose: The purpose of this study was to identify prenatal, maternal, and early childhood factors associated with surgery to treat severe-early-childhood-caries (S-ECC) using general anesthesia (GA). Methods: A case-control study using administrative health care and social services data examined factors associated with surgery under GA. Subjects included children <72 months old undergoing GA for caries between fiscal years 2005/06 and 2010/11. Controls were children of the same age randomly chosen from the general population. Prenatal, birth, child, and maternal and family characteristics and use of health services were considered. Adjusted odds ratios (OR) and 95 percent confidence intervals (95% CI) were calculated using logistic regressions. Results: There were 16,015 cases reviewed. Variables with a higher likelihood of surgery included: child's age (1.02 (OR), 1.02 to 1.02 (95% CI)); large-for-gestational-age (1.24, 1.19 to 1.30); young maternal age at birth (1.47, 1.04 to 2.07); lower income quintiles (3.24, 3.04 to 3.45); receiving income assistance (1.61, 1.54 to 1.69); more hospital visits (1.17, 1.15 to 1.18); and a history of being "in care/foster care" (1.11, 1.04 to 1.19). Variables with less likelihood of surgery included: initiating breastfeeding before discharge (0.69, 0.67 to 0.72); low five-minute Apgar score (0.88, 0.79 to 0.97); being female (0.96, 0.93 to 0.99); mothers ≥ 30 years old at birth (0.86, 0.82 to 0.89); urban dwellers (0.47, 0.45 to 0.49); and higher physician visits (0.995, 0.99 to 1.00). Conclusion: Understanding risk factors associated with surgery for S-ECC may provide clues about promising prenatal and early childhood oral health interventions.

Identification of sequences that target BRCA1 to nuclear foci following alkylative DNA damage.

BRCA1 is a tumor suppressor involved in the maintenance of genome integrity. BRCA1 co-localizes with DNA repair proteins at nuclear foci in response to DNA double-strand breaks caused by ionizing radiation (IR). The response of BRCA1 to agents that elicit DNA single-strand breaks (SSB) is poorly defined. In this study, we compared chemicals that induce SSB repair and observed the most striking nuclear redistribution of BRCA1 following treatment with the alkylating agent methyl methanethiosulfonate (MMTS). In MCF-7 breast cancer cells, MMTS induced movement of endogenous BRCA1 into distinctive nuclear foci that co-stained with the SSB repair protein XRCC1, but not the DSB repair protein gamma-H2AX. XRCC1 did not accumulate in foci after ionizing radiation. Moreover, we showed by deletion mapping that different sequences target BRCA1 to nuclear foci induced by MMTS or by ionizing radiation. We identified two core MMTS-responsive sequences in BRCA1: the N-terminal BARD1-binding domain (aa1-304) and the C-terminal sequence aa1078-1312. These sequences individually are ineffective, but together they facilitated BRCA1 localization at MMTS-induced foci. Site-directed mutagenesis of two SQ/TQ motif serines (S1143A and S1280A) in the BRCA1 fusion protein reduced, but did not abolish, targeting to MMTS-inducible foci. This is the first report to describe co-localization of BRCA1 with XRCC1 at SSB repair foci. Our results indicate that BRCA1 requires BARD1 for targeting to different types of DNA lesion, and that distinct C-terminal sequences mediate selective recruitment to sites of double- or single-strand DNA damage.

The Manitoba Healthy Baby Prenatal Benefit Program: who is participating?

BACKGROUND: Programs offering income supplements for lower-income pregnant women have been introduced in order to reduce the incidence of poor perinatal outcomes. This study used a population-based approach to examine the characteristics of mothers who received the Healthy Baby Prenatal Benefit in Manitoba. METHODS: All women giving birth between August 2001 and April 2003 (n = 22,643) were studied using de-identified linked administrative data. Multivariate logistic regression was used to determine factors that predicted receipt of the benefit, adjusting for potential confounding effects. Separate regressions were run for all mothers, and for a group of mothers eligible to receive the benefit (N = 1962). RESULTS: Almost 29% of mothers giving birth during the study period received the prenatal benefit. Mothers were more likely to receive the benefit if they: lived outside of Winnipeg; received income assistance during pregnancy; were younger at their first birth; were unmarried; made prenatal physician visits; experienced maternal depression; were having a first birth; and lived in the lowest income areas. Despite all being eligible, only 67% of non-Winnipeg and 80% of Winnipeg women receiving income assistance received the benefit. Factors related to benefit receipt for those eligible were: living in Winnipeg; making prenatal visits; not being a young teen at current birth; and experiencing a first birth. CONCLUSION: It is important to look not only at the characteristics of benefit recipients but also at those not receiving the benefit, in order to develop strategies to reach those who may most need and benefit from the program.

Ornithine decarboxylase (ODC) expression pattern in human prostate tissues and ODC transgenic mice.

Ornithine decarboxylase (ODC) is the key enzyme in the polyamine synthesis pathway and is overexpressed in a variety of cancers. We have performed a detailed immunostaining analysis of the expression of ODC in normal, benign prostatic hyperplasia (BPH), and cancerous prostate tissues. We conclude that ODC is overexpressed in both BPH and neoplastic tissues and that ODC overexpression appears to be an early event in prostate carcinogenesis. The extent of overexpression decreases as cancer progresses. Interestingly, ODC overexpression was also detected in patients who underwent androgen ablation therapy, suggesting ODC overexpression may contribute to the androgen-independent survival of prostate cancer cells. ODC is perinuclear localized in BPH samples but is diffusely cytoplasmic in cancer samples. Having shown ODC overexpression in human prostate cancer, we developed prostate-specific ODC transgenic mice to further investigate whether ODC overexpression alone is a causal factor in prostate carcinogenesis. RT-PCR and immunostaining confirmed that ODC was overexpressed in a subset of prostate epithelial cells. Although minor nucleoli enlargements in some tissues were detected, gross morphological changes were not observed in transgenic prostates. Therefore, overexpression of ODC alone in this subset of prostate epithelial cells is not sufficient to induce prostate carcinogenesis.

Bereavement after sibling death: a population-based longitudinal case-control study.

The objective of this study was to examine mental disorders and treatment use among bereaved siblings in the general population. Siblings (N=7243) of all deceased children in the population of Manitoba, Canada who died between 1984 and 2009 were matched 1:3 to control siblings (N=21,729) who did not have a sibling die in the study period. Generalized estimating equations were used to compare the two sibling groups in the two years before and after the index child's death on physician-diagnosed mental disorders and treatment utilization, with adjustment for confounding factors including pre-existing mental illness. Analyses were stratified by age of the bereaved (<13 vs. 13+). Results revealed that, in the two years after the death of the child, bereaved siblings had significantly higher rates of mental disorders than control siblings, even after adjusting for pre-existing mental illness. When comparing the effect of a child's death on younger versus older siblings, the rise in depression rates from pre-death to post-death was significantly higher for siblings aged under 13 (p<0.0001), increasing more than 7-fold (adjusted relative rate, ARR=7.25, 95% CI: 3.65-14.43). Bereaved siblings aged 13+ had substantial morbidity in the two years after the death: 25% were diagnosed with a mental disorder (vs. 17% of controls), and they had higher rates of almost all mental disorder outcomes compared to controls, including twice the rate of suicide attempts (ARR=2.01, 95% CI: 1.29-3.12). Siblings in the bereaved cohort had higher rates of alcohol and drug use disorders already before the death of their sibling. In conclusion, the death of a child is associated with considerable mental disorder burden among surviving siblings. Pre-existing health problems and social disadvantage do not fully account for the increase in mental disorder rates.

Nuclear-cytoplasmic shuttling of BARD1 contributes to its proapoptotic activity and is regulated by dimerization with BRCA1.

The breast cancer-associated protein, BARD1, colocalizes with BRCA1 in nuclear foci in the S phase and after DNA damage, and the two proteins form a stable heterodimer implicated in DNA repair, protein ubiquitination, and control of mRNA processing. BARD1 has a BRCA1-independent proapoptotic activity; however, little is known about its regulation. Here, we show that BARD1 localization and apoptotic activity are regulated by nuclear-cytoplasmic shuttling. We identified a functional CRM1-dependent nuclear export sequence (NES) near the N-terminal RING domain of BARD1. The NES forms part of the BRCA1 dimerization domain, and coexpression of BRCA1 resulted in masking of the NES and nuclear retention of BARD1. In transient expression assays, BARD1 apoptotic activity was stimulated by nuclear export, and both apoptotic function and nuclear export were markedly reduced by BRCA1. Similar findings were obtained for endogenous BARD1. Silencing BRCA1 expression by siRNA, or disrupting the endogenous BARD1/BRCA1 interaction by peptide competition caused a reduction in BARD1 nuclear localization and foci formation, and increased the level of cytoplasmic BARD1 correlating with increased apoptosis. Our findings suggest that BRCA1/BARD1 heterodimer formation is important for optimal nuclear targeting of BARD1 and its role in DNA repair and cell survival.