Order Of Statistical Significance Research Articles

Understanding Factors Leading to Primary Cesarean Section and Vaginal Birth After Cesarean Delivery in the Friuli-Venezia Giulia Region (North-Eastern Italy), 2005\u20132015

Although there is no evidence that elevated rates of cesarean sections (CS) translate into reduced maternal/child perinatal morbidity or mortality, CS have been increasingly overused almost everywhere, both in high and low-income countries. The primary cesarean section (PCS) has become a major driver of the overall CS (OCS) rate, since it carries intrinsic risk of repeat CS (RCS) in future pregnancies. In our study we examined patterns of PCS, planned PCS (PPCS), vaginal birth after 1 previous CS (VBAC-1) and associated factors in Friuli Venezia Giulia (FVG), a region of North-Eastern Italy, collecting data from its 11 maternity centres (coded from A to K) during 2005–2015. By fitting three multiple logistic regression models (one for each delivery mode), we calculated the adjusted rates of PCS and PPCS among women without history of CS, whilst the calculation of the VBAC rate was restricted to women with just one previous CS (VBAC-1). Results, expressed as odds ratio (OR) with 95% confidence interval (95%CI), were controlled for the effect of hospital, calendar year as well as several factors related to the clinical and obstetric conditions of the mothers and the newborn, the obstetric history and socio-demographic background. In FVG during 2005–2015 there were 24,467 OCS (rate of 24.2%), 19,565 PCS (19.6%), 7,736 PPCS (7.7%) and 2,303 VBAC-1 (28.4%). We found high variability of delivery mode (DM) at hospital level, especially for PCS and PPCS. Breech presentation was the strongest determinant for PCS as well as PPCS. Leaving aside placenta previa/abuptio placenta/ante-partum hemorrhage, further significant factors, more importantly associated with PCS than PPCS were non-reassuring fetal status and obstructed labour, followed by (in order of statistical significance): multiple birth; eclampsia/pre-eclampsia; maternal age 40–44 years; placental weight 600-99 g; oligohydramios; pre-delivery LoS 3–5 days; maternal age 35–39 years; placenta weight 1,000–1,500 g; birthweight < 2,000 g; maternal age ≥ 45 years; pre-delivery LoS ≥ 6 days; mother’s age 30–34 years; low birthweight (2,000–2,500 g); polyhydramnions; cord prolaspe; ≥6 US scas performed during pregnancy and pre-term gestations (33–36 weeks). Significant factors for PPCS were (in order of statistical significance): breech presentation; placenta previa/abruptio placenta/ante-partum haemorrhage; multiple birth; pre-delivery LoS ≥ 3 days; placental weight ≥ 600 g; maternal age 40–44 years; ≥6 US scans performed in pregnancy; maternal age ≥ 45 and 35–39 years; oligohydramnios; eclampsia/pre-eclampsia; mother’s age 30–34 years; birthweight <2,000 g; polyhydramnios and pre-term gestation (33–36 weeks). VBAC-1 were more likely with gestation ≥ 41 weeks, placental weight <500 g and especially labour analgesia. During 2005–2015 the overall rate of PCS in FVG (19.6%) was substantially lower than the corresponding figure reported in 2010 for the entire Italy (29%) and still slightly under the most recent national PCS rate for 2017 (22.2%). The VBAC-1 rate on women with history of one previous CS in FVG was 28.4% (25.3% considering VBAC on all women with at least 1 previous CS), roughly three times the Italian national rate of 9% reported for 2017. The discrepancy between the OCS rate at country level (38.1%) and FVG’s (24.2%) is therefore mainly attributable to RCS. Although there was a marginal decrease of PCS and PPCS crudes rates over time in the whole region, accompained by a progressive enhancement of the crude VBAC rate, we found remarkable variability of DM across hospitals. To further contain the number of unnecessary PCS and promote VBAC where appropriate, standardized obstetric protocols should be introduced and enforced at hospital level. Decision-making on PCS should be carefully scrutinized, introducing a diagnostic second opinion for all PCS, particularly for term singleton pregancies with cephalic presentation and in case of obstructed labour as well as non-reassuring fetal status, grey areas potentially affected by subjective clinical assessment. This process of change could be facilitated with education of staff/patients by opinion leaders and prenatal counseling for women and partners, although clinical audits, financial penalties and rewards to efficient maternity centres could also be considered.

Abstract P4-11-05: Opioid prescriptions in the military health system breast cancer population, FY2007 – FY2014

Abstract Purpose: Opioid use among individuals with breast cancer is a safety concern because of adverse events including misuse, overdose, and death. To date, there are two published U.S. population-based studies of opioid use among breast cancer patients, both which address persistent opioid use after surgery. Here, we examine rates, amount, and cost of opioids prescribed to breast cancer patients over an 8-year period. Methods: We used Military Health System (MHS) outpatient, inpatient, and pharmacy claims data to select beneficiaries with a primary diagnoses of breast cancer, fiscal years (FY) 2007- 2014. Logistic regression models were used to identify predictors of having received &amp;gt; 1 opioid prescription within a year, and having received &amp;gt; 4 filled opioid prescriptions within a year. Simple linear regression and multiple regression were used to examine trends and predictors of reimbursed opioid cost. Results: Among 25,500 non-elderly breast cancer patients treated in the MHS each year, most were age 55-64, located in the southern U.S., and treated in civilian facilities only. On average per year, 75% had surgery, 90% radiation therapy, 19% chemotherapy, and 8% hospice care. Annual rates of receiving &amp;gt; 1 opiate prescription were stable across 8 years, 48.1% (FY2007) to 50.5% (FY2012 and FY2013). The annual number of opioid prescriptions per patient was also stable, 4.26 (FY2014) to 4.39 (FY2007). Average reimbursed cost of opioids steadily increased over time, $135 (FY2007) to $260 (FY2014) (p &amp;lt; 0.001). Based on regression models, the strongest predictors (p &amp;lt; 0.001) of having received &amp;gt; 1 opioid prescription were (in order of statistical significance): surgery, chemotherapy, civilian care only or mixed use civilian and military care, number of physical comorbid conditions, hospice use, and depression. The strongest predictors (p &amp;lt; 0.001) of &amp;gt; 4 opioid prescriptions per year were: depression, hospice use, number of physical comorbidities, and chemotherapy, followed by anxiety disorder, alcohol use disorder, and drug use disorder. The strongest predictors (p &amp;lt; 0.001) of high reimbursed opioid cost were: drug use disorder, hospice use, depression, civilian care only or mixed use civilian and military care, alcohol use disorder, number of physical comorbid conditions, receipt of chemotherapy, fiscal year, and anxiety disorder. Discussion: Half of individuals with a primary breast cancer diagnosis receive &amp;gt; 1 opioid prescription per year. Four overlapping constructs predict opioid prescriptions and cost: treatment modalities, physical and mental health comorbidities, severity of illness, and system of care. Increased cost over time coincides with current U.S. population reports suggesting rising daily opioid dosage. Despite limitations with claims data, the results suggest that opioid use among breast cancer patients need to be monitored and accompanied by documented clinical management plans. We recommend that oncology providers implement risk reduction strategies including screening for history of substance use and mental health comorbidities, and implementing guidelines specific for cancer patients such as those found in the Veterans Administration/Department of Defense Clinical Practice Guidelines for Opioid Therapy for Chronic Pain, v. 3.0. Citation Format: Jeffery DD, Hopkins L, Spevak CJ, Burke HB. Opioid prescriptions in the military health system breast cancer population, FY2007 – FY2014 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-11-05.

Prognostic Significance of Mitotic Rate in Localized Primary Cutaneous Melanoma: An Analysis of Patients in the Multi-Institutional American Joint Committee on Cancer Melanoma Staging Database

The aim of this study was to assess the independent prognostic value of primary tumor mitotic rate compared with other clinical and pathologic features of stages I and II melanoma. From the American Joint Committee on Cancer (AJCC) melanoma staging database, information was extracted for 13,296 patients with stages I and II disease who had mitotic rate data available. Survival times declined as mitotic rate increased. Ten-year survival ranged from 93% for patients whose tumors had 0 mitosis/mm(2) to 48% for those with ≥ 20/mm(2) (P < .001). Mean number of mitoses/mm(2) increased as the primary melanomas became thicker (1.0 for melanomas ≤ 1 mm, 3.5 for 1.01 to 2.0 mm, 7.3 for 3.01 to 4.0 mm, and 9.6 for > 8 mm). Ulceration was also associated with a higher mitotic rate; 59% of ulcerated melanomas had ≥ 5 mitoses/mm(2) compared with 16% of nonulcerated melanomas (P < .001). In a multivariate analysis of 10,233 patients, the independent predictive factors for survival in order of statistical significance were as follows: tumor thickness (χ(2) = 104.9; P < .001), mitotic rate (χ(2) = 67.0; P < .001), patient age (χ(2) = 48.2; P < .001), ulceration (χ(2) = 46.4; P < .001), anatomic site (χ(2) = 34.6; P < .001), and patient sex (χ(2) = 33.9; P < .001). Clark level of invasion was not an independent predictor of survival (χ(2) = 3.2; P = .37). A high mitotic rate in a primary melanoma is associated with a lower survival probability. Among the independent predictors of melanoma-specific survival, mitotic rate was the strongest prognostic factor after tumor thickness.

Newborn hearing screening on infants at risk

Objectives This article presents the results of newborn hearing screenings on infants at risk of hearing impairment at the French University Hospital of Besançon from 2001 to 2007. Materials and methods All newborns at risk of hearing impairment were tested according to the method recommended by the Joint Committee on Infant Hearing (JCIH): a two-step automated oto-acoustic emissions (AOAE) program, completed by an auditory brainstem response (ABR) for the positive diagnosis of hearing impairment. The screening started with AOAE on the third day of life, at the earliest. If one or both ears did not have AOAE, the infant was re-tested at which time, should the AOAE again be positive, ABR was performed. When the ABR threshold was 40 dB or more, the infant was referred to an audiologist specialized in infant deafness for diagnosis confirmation and management. Results Over the period, 1461 infants were screened, among whom 4.55% were diagnosed as deaf or hard of hearing. Nearly 10% of the infants were lost to follow up. Forty-six children had a sensorineural hearing impairment, of which 34 were bilateral and were managed before the age of 6 months. The risk factors for sensorineural hearing loss were (in order of statistical significance): severe birth asphyxia; neurological disorder; syndromes known to be associated with hearing loss; TORCH (toxoplasmosis, rubella, cytomegalovirus, herpes) infections; family history of deafness; age at the time of screening; and the association of 2 or more risk factors. However, birth weight inferior to 1500 g and premature birth before the 34th week of pregnancy did not show a statistically significant influence on sensorineural hearing loss. Craniofacial anomalies (mostly cleft palate and ear aplasia) were a significant factor for conductive hearing loss. Conclusion Our selected hearing screening on infants at risk allowed 60 deaf children access to early management. However, too many children were lost to follow up; which revealed that better information regarding risk of hearing loss must be provided to parents and paramedics and universal newborn screening needs to be performed. The most important result of this study is that in a population of hearing impaired children, with an impairment incidence close to what is commonly reported, the association of several risk factors proves to be a significant additional risk factor for hearing impairment.

Molecular differences in triple negative breast cancer between race/ethnicities.

Abstract Abstract #2089 Background: A disparity in prognosis of triple negative (TN) breast cancer (BC) has been observed between African American (AA) and Caucasian (CAU) race/ethnicities afflicted with this aggressive and invasive BC subtype. Etiological understanding of these differences involves accounting for several factors associated with phenotype and genotype. Here, we address the latter using the Illumina DASL (cDNA mediated, Annealing, Selection, Extension, and Ligation) assay to quantify mRNA expression of 512 breast cancer related genes in a cohort of 24 CAU and 56 AA TN BC tissues sourced from formalin-fixed, paraffin-embedded (FFPE) blocks.&amp;#x2028; Material and Methods: The DASL assay was used to measure mRNA expression levels from FFPE sourced tissues in both cohorts of self-identified patients. CAU BC patients were obtained from St. Mary's Hospital, Montreal, Quebec and AA BC patients were obtained from Grady Hospital, Atlanta, Georgia. RNA extraction used the RNA High Pure Kit (Roche) and was taken from archival FFPE tissues either 5µm tissue sections or cores. Differential mRNA regulation was identified by Significance Analysis of Microarrays (SAM) software using a false discover rate (FDR) less than 1% and a two fold-change criteria to determine differential regulation.&amp;#x2028; Results: In all, 33 genes were found differentially expressed between AA and CAU TN BC tumor samples, 32 of which were upregulated in the AA cohort, only 1 of which was upregulated in the CAU group. The upregulated gene in CAU TN BC was TFF1. Upregulated genes in the AA cohort (order of statistical significance according to SAM software) were KIF20A, EP300, AURKB, FGF4, C14orf155, USP22, EPOR, ZNF668, SCNN1G, MAPT, FLNB, EP400, LTA, ACOT11, RBP3, CSF3, E2F2, TGFB1, CCNE1, L1CAM, NDP, VWF, RHOB, FEN1, BIN1, KRT17, CDC42EP4, SERPINF1, CHI3L2, NES, BCL2, and RERG.&amp;#x2028; Discussion: TFF1 upregulated in the CAU population, has been indicated as biomarker of favorable prognosis in endocrine therapy in clinical studies which is consistent with race/ethnicity disparities. The remaining genes upregulated in the AA cohort include transcription factors E2F2 and RBP3/E2F1 both with cyclin binding domains which may interact with CCNE1, extracellular and adhesion related genes KRT17, L1CAM and FGF4, genes associated with cell cycle AURKB, EP400, and EP300 (activator of HIF-1A). Several RAS related genes were also found differentially expressed in the AA cohort including RHOB, RERG, BIN1, and EPOR. Moreover, it is worth mentioning that BCL2 which is expressed in the aggressive mammary cancer cell line MCF-7 was also found upregulated in the AA cohort. These initial findings suggest that several differentially regulated genes between AA and CAU race/ethnicities may account for the disparity in outcomes resultant in these populations. These initial data warrant further investigation which is currently ongoing. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2089.

Periodicities in the high-mass X-ray binary system RX J0146.9+6121/LS I+61°235

The high-mass X-ray binary RX J0146.9+6121, with optical counterpart LS I+61 ◦ 235 (V831 Cas), is an intriguing system on the outskirts of the open cluster NGC 663. It contains the slowest Be type X-ray pulsar known with a pulse period of around 1400 s and, primarily from the study of variation in the emission line profile of Hα, it is known to have a Be decretion disc with a one-armed density wave period of approximately 1240 d. Here we present the results of an extensive photometric campaign, supplemented with optical spectroscopy, aimed at measuring short time-scale periodicities. We find three significant periodicities in the photometric data at, in order of statistical significance, 0.34, 0.67 and 0.10 d. We give arguments to support the interpretation that the 0.34 and 0.10 d periods could be due to stellar oscillations of the B-type primary star and that the 0.67 d period is the spin period of the Be star with a spin axis inclination of 23 +10 −8 degrees. We measured a systemic velocity of −37.0 ± 4.3 km s −1 confirming that LS I+61 ◦ 235 has a high probability of membership in the young cluster NGC 663 from which the system’s age can be estimated as 20–25 Myr. From archival RXTE All Sky Monitor (ASM) data we further find ‘super’ X-ray outbursts roughly every 450 d. If these super outbursts are caused by the alignment of the compact star with the one-armed decretion disc enhancement, then the orbital period is approximately 330 d.

Nomograms to predict serious adverse events (SAEs) in patients (pts) enrolled in phase II clinical trials of molecularly targeted agents (MTAs)

6601 Background: The likelihood of experiencing a SAE in clinical trials with a MTA is of interest for clinicians discussing treatment options. Adverse event data from clinical trials in the Princess Margaret Hospital Phase II Consortium [PMH2C] database were analyzed to address this question. Methods: All pts in the PMH2C database treated at the phase II dose level with either a MTA alone or in combination regimens since 2001 were included. Generalised estimating equations were used to construct optimal regression models predicting the increased/decreased odds of a SAE of all causalities (defined as a grade 3+ non-hematologic adverse event, or a grade 4+ hematologic adverse event) during the first cycle of treatment relative to a ‘reference’ pt. Nomograms were constructed to ease interpretation and internal validation explored using bootstrapping on trials larger than 35 pts. Results: 576 pts (median age=60, 55% male, ECOG PS 0:1:2=259:284:35) were accrued to 42 studies. In order of statistical significance, higher ECOG PS, increased LDH, decreased albumin, increased Charlson score, increased number of target lesions, not having prior radiotherapy and decreased age were predictive of increased odds of cycle 1 SAE. As an example, a 56-year old patient with ECOG 2, Charlson score=0, 5 target lesions, LDH=1.70x upper limit of normal [ULN], albumin=0.84xULN and no prior radiation would have ∼3 times increased odds of a SAE in cycle 1, compared to a 63-year old with ECOG 1, Charlson score=0, 1 target lesion, LDH=0.76xULN, albumin=0.68xULN and no prior radiation. Internal validation of the 4 largest studies indicated moderate-good accuracy (estimated area under the receiver operating characteristic curve = 0.57–0.86). Conclusions: A nomogram was produced allowing estimation of the increased odds of a SAE during cycle 1 of therapy in a phase II trial setting. Actual risk can then be further estimated by incorporating clinical judgment of risks for an average pt when given a particular MTA. This nomogram can potentially improve patient knowledge, risk estimates and the decision-making process. External validation of the model is still necessary to adequately assess model reliability. No significant financial relationships to disclose.

Molecular typing of adult acute myeloid leukaemia: significance of translocations, tandem duplications, methylation, and selective gene expression profiling

Although a number of molecular aberrations have been described in acute myeloid leukaemia (AML), no study has yet determined their relative prognostic importance. We have analysed blast cells from 250 adult patients treated at the same institution during a 15-year period. Balanced translocations were detected by multiplex polymerase chain reaction in 13% of the cases. Internal tandem duplication (ITD) of the FLT3 gene and partial tandem duplication of the MLL gene were found in 24% and 4%, respectively. Promoter hypermethylation of the P15, CDH1, ER and MDR1 genes was observed in 71%, 64%, 40% and 4%, respectively. Compared with normal bone marrow, the chemotherapy resistance protein MRP1 and apoptosis related genes BAX and CASPASE3 were found to be overexpressed in AML blasts. Univariate analysis revealed that the most important determinants of prognosis were presence of balanced translocations, age, white blood cell count and extramedullary disease, in order of statistical significance. In a multivariate analysis, balanced translocations retained their prognostic significance and FLT3 ITD as well as high gene expression of MDR1 were negative prognostic factors. From these data, which are the first to compare these molecular aberrations directly, we conclude that, when a battery of molecular changes is evaluated for upfront significance in AML, recurrent translocations are of prime importance for treatment outcome.

Longitudinal study of men with mild symptoms of bladder outlet obstruction treated with watchful waiting for four years

Objectives To determine the risk of clinical progressions in men with mild lower urinary tract symptoms of bladder outlet obstruction and identify the predictors for progression in this group of men. Methods A total of 397 men who presented to the urology clinics with mild symptoms of bladder outlet obstruction (International Prostate Symptom Score less than 8) were analyzed in this longitudinal study conducted during a 4-year period. They began with the watchful waiting protocol and were followed up every 3 months for 48 months. Age, International Prostate Symptom Score (IPSS), divided into obstructive symptom score and irritative symptom score, serum prostate-specific antigen level, total prostate volume, transitional zone volume, urinary flow rates, and postvoid residual urine volume were documented. Results The cumulative incidence of clinical progression, defined as worsening of the IPSS with migration to the moderate symptom group (IPSS 8 to 18) or severe symptom group (IPSS 19 to 35) and an increase in IPSS of more than 2 points, was 6%, 13%, 15%, 24%, 28%, and 31% at 6, 12, 18, 24, 36, and 48 months, respectively. Nineteen patients (4.9%) developed acute urinary retention within the 48-month follow-up period. Of these 19 patients, only 2 (0.6%) required transurethral resection of the prostate. The variables of importance for disease progression in the artificial neural network analysis were, in order of statistical significance, prostate-specific antigen level, obstructive symptom score, and transitional zone volume. Conclusions The risk for men with mild symptoms of bladder outlet obstruction to progress clinically and develop complications such as acute retention of urine is moderate. Prostate-specific antigen, obstructive symptom score, and transitional zone volume were identified as important risk factors.

Gene Alert--a sequence search results keyword parser.

Similarity searching is an important tool to many biological scientists. Various computer implementations (BLAST, FASTA, Smith-Waterman) are used by scientists to analyze their sequences of interest to identify identities (perfect matches) or similarities (statistically significant matches) between their query sequences and large databases such as GenBank. Search engines currently return brief annotations and alignments ranked in order of statistical significance or raw similarity score. However, it is frequently not the top-scoring similarities that bring important new information to the investigating scientist, but the content of the annotation or similarity hits at any significant score. The Gene Alert algorithm applies additional filtering and a user weighted keyword search to the BLAST output to parse the output into a form customized to the user. There are three components to the Gene Alert implementation as it is currently operating: an organized file structure, a BLAST engine, and a parser written in the PERL scripting language. The file structure was designed to place code and database components in logical positions and to facilitate future complete automation of the Gene Alert and similarity search system. Shown here is the file structure within the UNIX environment.

Diagnostic and Prognostic Relevance of the Immunophenotype in Acute Myelocytic Leukemia

The immunophenotype of 72 cases with acute myelocytic leukemia was investigated with a panel of monoclonal antibodies. When the morphologic criteria of the FAB classification was compared with the normal myeloid and erythroid pathway of differentiation identified by MoAbs, a relationship was found with FAB M5 and M6. Moreover, a constant negativity to HLA-DR and CD15 antigens in M3 and the contemporaneous expression of HLA-DR and CD11b antigens on the M4 and M5 leukemic cells were observed. We identified phenotypically distinct groups of patients with different responses to therapy. In fact, patients whose leukemic cells did not express the HLA-DR antigen showed, in a univariate analysis, a significantly higher percentage of complete remissions than did HLA-DR-positive patients. Multivariate discriminant analysis, in line with this result, showed that the parameters of discriminant capacity were, in order of statistical significance, young age, low WBC count and the lack of DR expression, respectively. A trend for a better response to therapy, without any statistical relevance, was also observed in CD11b-negative and CD33-positive cases. Similar results were detected in patients who expressed either DR or CD11b, or none of these markers. These findings indicate that immunophenotype may identify some FAB subtypes. Moreover, in some cases the phenotypic profile can provide useful information about the clinical outcome.

Perinatal bacterial infection after prolonged rupture of amniotic membranes: An analysis of risk and management

Chi-square and logistic stepwise multiple regression analysis of perinatal determinants of infant bacterial infection following prolonged rupture of amniotic membranes for 24 hours or more prior to delivery was applied in 33 infected infants and 66 matched control infants from the NINCDS Collaborative Project. In order of statistical significance, the most important variables were placental inflammation (P = 0.002), gestational age less than 34 weeks (P = 0.008), gestational age 34 to 37 weeks (P = 0.013), male sex (P = 0.015), Apgar score less than 6 at 5 minutes (P = 0.023), and clinical amnionitis (maternal fever, fetal tachycardia, or amniotic or gastric fluid leukocytes or bacteria) (P = 0.044). Duration of labor during PROM, race, and maternal age and parity were insignificant. Using these predictive variables, identification of infected infants for either microbial surveillance (superficial and systemic cultures) or microbial surveillance and anticipatory antibiotic therapy (discontinued after 3 days of negative cultures) was highly significant (P = 0.0001). Incorporating these variables and derived coefficients from multivariate analysis, a mathematical model was used for evaluation and prediction of perinatal bacterial infection with a sensitivity of 82% and specificity of 70%. Analysis of 46 infants prior to and 310 infants after implementation of this process at Harbor-UCLA Medical Center indicated significant improvement in the appropriate management of these infants at risk (from 59% to 87% of the population, P less than 0.05). Inappropriate antibiotic therapy decreased from 35% to 10% (P less than 0.05). In the absence of a shift in the median days of hospitalization of non-PROM infants, determination of the grand median days of PROM infant hospital stay showed a decrease (P less than 0.01) after initiation of this evaluation and management scheme.

Influences on the Migration of Canadian Professionals

The human capital approach has increased our understanding of migration as an act of investment and highlighted the importance of geographical movements by capital-laden professional manpower. This article analyzes some determinants of migration for such personnel and gauges the relative importance of costs and benefits for professional manpower migrating between Canada and the U.S. Determinants of migration, in order of statistical significance, were U.S. education, highest degree, employment mobility, ethnicity, and region of origin. An important conclusion is that sending Canadians to the U.S. for graduate education entails a high risk of nonreturn. The results also cast doubt on the view of Canada as a bridge in the migrational flow from the rest of the world to the U.S.