Associations between the Personality Inventory for DSM-5 trait facets and aggression among outpatients with personality disorder: A multimethod study.

BACKGROUND: Most research on the Personality Inventory for DSM-5 (PID-5) was conducted with self-reports. One of the specific areas for which a multimethod design has yet to be implemented is for the PID-5's associations with aggression. The main objectives of this study were to (a) compare the PID-5 associations with self-reported and file-rated aggression, (b) compare these associations between women and men, and (c) identify the relative importance of PID-5 facet predictors. METHODS: A sample of outpatients with personality disorder (N = 285) was recruited in a specialized public clinic to complete questionnaires, and a subsample was assessed for file-rated aggression (n = 227). Multiple regression analyses were performed with PID-5 facets as statistical predictors but using distinct operationalizations of aggression (self-reported vs. file-rated). Moderation analyses were performed to identify the moderating effect of biological sex. Dominance analyses were computed to identify the relative importance of predictors. RESULTS: PID-5 facet predictors of self-reported and file-rated aggression were very consistent in both conditions. However, the amount of explained variance was reduced in the latter case (from 39% to 14%), especially for women (from 40% to 2%). The most important predictors were Hostility, Risk Taking, and Callousness. CONCLUSION: Pertaining to the statistically significant facets associated with aggression, strong evidence of multimethod replication was found. The women-men discrepancies were not most obvious in their specific associations with aggression, but rather in their amount of explained variance, maybe reflecting examiners' or patients' implicit biases, and/or different manifestations of aggression between women and men.

Preliminary Steps Toward Extracting the Specific Alternative Model for Personality Disorders Diagnoses From Criteria A and B Self-Reports.

The Alternative DSM-5 Model for Personality Disorders (AMPD) retains six specific personality disorders (PDs) that can be diagnosed based on Criterion A level of impairment and Criterion B maladaptive facets. Those specific diagnoses are still underresearched, despite the preference expressed by most PD scholars for a mixed/hybrid classification. This study explores the possibility of using Criterion A and B self-report questionnaires to extract the specific AMPD diagnoses. Plausible prevalence estimates were found in three samples (outpatient PD, private practice, community; N = 766) using the facet score ≥ 2 and t score > 65 methods for determining the presence of a Criterion B facet; diagnoses had meaningful correlations with external variables. This study provides evidence-albeit preliminary-that the extraction of the specific AMPD PDs from self-report questionnaires might be a viable avenue. Ultimately, it could promote the use and dissemination of those diagnoses for screening purposes in clinical and research settings.

Analysis of the interaction between personality dysfunction and traits in the statistical prediction of physical aggression: Results from outpatient and community samples.

The Alternative Model for Personality Disorders (AMPD), included in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) and the World Health Organization's International Classification of Diseases (11th ed.; ICD-11) are, respectively, hybrid categorical-dimensional and dimensional frameworks for personality disorders (PDs). Both models emphasize personality dysfunction and personality traits. Previous studies investigating the links between the AMPD and ICD-11, and self-reported physical aggression have mostly focused on traits and did not take into account the potential interaction between personality dysfunction and traits. Thus, the aim of this study is to identify dysfunction*trait interactions using regression-based analysis. Outpatients with personality disorder from a specialized public clinic (N = 285) and community participants (N = 995) were recruited to complete self-report questionnaires. Some small-size, albeit significant and clinically/conceptually meaningful personality dysfunction*trait interactions were found to predict physical aggression in both samples. Interaction analyses might further inform, to some degree, about the current discussion pertaining to the potential redundancy between dysfunction and traits, the optimal personality dysfunction structure (in the case of the AMPD), as well as clinical assessment based on AMPD/ICD-11 PD frameworks.

[Validation of a screening procedure for borderline personality disorder based on the Alternative DSM-5 Model for Personality Disorders]. / Validation d'une procédure de dépistage du trouble de personnalité limite selon le Modèle alternatif pour les troubles de la personnalité du DSM-5.

Objectives The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) includes an Alternative Model for Personality Disorders (DSM-5), which defines personality disorders based on two dimensional criteria. Criterion A corresponds to the severity of personality dysfunction in the areas of self and interpersonal functioning, while Criterion B comprises five pathological domains including a total of 25 facets. Six specific disorders, including borderline personality disorder (BPD), are defined in the AMPD based on Criteria A and B. However, there is currently very little data on these diagnoses as they are operationalized in the MATP. This study aims to present data on this recent operationalization of BPD. More specifically, we will first introduce a procedure, based on self-reported questionnaires covering the two main MATP criteria, implemented to generate the BPD diagnosis from the AMPD. Then, we will assess its validity (a) by documenting its prevalence in a clinical sample; (b) by determining its degree of correspondence with the "traditional" BPD categorical diagnosis and with a dimensional measure of borderline symptomatology; (c) by presenting convergent validity data with constructs relevant to the study of BPD (impulsivity, aggression); and (d) by determining the incremental validity of the proposed procedure in contrast with a simplified approach where only Criterion B would be considered. Method Data from 287 patients recruited as part of the admission process at the Centre de traitement le Faubourg Saint-Jean of the CIUSSS-Capitale-Nationale were analyzed. The BPD diagnosis from the MATP was generated based on two validated self-report questionnaires, in their French version, namely the Self and Interpersonal Functioning Scale (Criterion A) and the Personality Inventory for DSM-5-Faceted Brief Form (Criterion B). Results The BPD diagnosis, as operationalized in the AMPD, had a prevalence of 39.7% in the sample. A moderate fit with the clinician's diagnosis of BPD according to the traditional DSM-5 categorical model was observed, as well as a strong correlation with a dimensional measure of borderline symptomatology. Nomological network analysis revealed high and theoretically expected correlations between the disorder and measures of aggression and impulsivity. The proposed diagnostic extraction procedure, which uses Criteria A and B, showed incremental validity in the statistical prediction of external variables (borderline symptomatology, aggression, impulsivity) compared to a simplified procedure using only Criterion B. Conclusions The proposed procedure for generating the BPD diagnosis according to the MATP definition yields promising results and could allow screening for the disorder based on this contemporary conceptualization of personality pathologies.

[Perpetrators and victims of intimate partner violence: Personological profiles of people with borderline personality disorder]. / Violence conjugale commise et subie : profils personnologiques de personnes avec un trouble de personnalité limite.

Objective Personality disorders and intimate partner violence (IPV) are two problems recognized as major public health issues associated with serious individual and societal repercussions. Several studies have documented the links between borderline personality disorder (BPD) and IPV; however, we know very little about the specific pathological traits contributing to IPV. The study aims to document the phenomenon of IPV committed and suffered in persons with BPD and to draw profiles from the personality facets of the DSM-5 Alternative Model for Personality Disorders (AMPD). Method One hundred and eight BPD participants (83.3% female; Mage = 32.39, SD = 9.00) referred to a day hospital program following a crisis episode completed a battery of questionnaires including the French versions of the Revised Conflict Tactics Scales, evaluating physical and psychological IPV committed and suffered, and the Personality Inventory for the DSM-5- Faceted Brief Form, evaluating 25 pathological facets of personality. Results Among the participants, 78.7% report having committed psychological IPV, while 68.5% have been victims, which is more than the estimates published by the World Health Organization (27%). In addition, 31.5% would have committed physical IPV, while 22.2% would have been victims. IPV appears to be bidirectional since 85.9% of participants who are perpetrators of psychological IPV also report suffering from it and 52.9% of participants who are perpetrators of physical IPV report being also victims. Nonparametric group comparisons indicate that Hostility, Suspiciousness, Duplicity, Risk-Taking, and Irresponsibility facets distinguish physically and psychologically violent participants from nonviolent participants. High results on Hostility, Callousness, Manipulation, and Risk-taking facets characterize participants who are victims of psychological IPV, while an elevation in Hostility, Withdrawal, Avoidance of intimacy, and Risk-taking facets and a low result on the Submission facet distinguish participants who are victims of physical IPV from non-victims. Regression analyzes show that the Hostility facet alone explains a significant variance in the results of IPV perpetrated, while the Irresponsibility facet contributes substantially to the variance of the results of IPV experienced. Conclusion Results show the high prevalence of IPV in a sample of persons with BPD, as well as its bidirectional nature. Beyond the diagnosis of BPD, certain specific facets of the personality (including Hostility and Irresponsability) make it possible to target persons at greater risk of committing and suffering from psychological and physical IPV.

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for a soluble glycoprotein vaccine to prevent disease caused by Nipah or Hendra viruses.

Auro Vaccines LLC has developed a protein vaccine to prevent disease from Nipah and Hendra virus infection that employs a recombinant soluble Hendra glycoprotein (HeV-sG) adjuvanted with aluminum phosphate. This vaccine is currently under clinical evaluation in a Phase 1 study. The Benefit-Risk Assessment of VAccines by TechnolOgy Working Group (BRAVATO; ex-V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of protein vaccines. This will help key stakeholders to assess potential safety issues and understand the benefit-risk of such a vaccine platform. The structured and standardized assessment provided by the template may also help contribute to improved public acceptance and communication of licensed protein vaccines.

Safety and Efficacy of Using Fracture Tables for Prosthetic Hip Dislocations.

The incidence of prosthetic hip dislocation continues to increase because of the overall increase in volume of total hip replacement surgery. Closed reduction is often the preferred treatment, particularly in the first few months after surgery. No matter the closed reduction technique, linear traction is a requirement, thus posing a physically demanding stress opening both surgeon and patient to potential injury. We describe a fracture table closed reduction technique along with outcomes and safety data for a sample of patients. In all 10 reduction procedures, reduction was achieved quickly and without fracture or anesthetic complication. The use of a fracture table for reduction of prosthetic hip dislocation is a viable option, particularly when the surgeon may not have the physical requirements and/or qualified assistance necessary for reduction in the emergency department.

A Proposed Classification of ICD-11 Severity Degrees of Personality Pathology Using the Self and Interpersonal Functioning Scale.

Background: The 11th version of the World Health Organization's International Classification of Diseases (ICD-11) has adopted a dimensional approach to personality disorder (PD) nosology. Notably, it includes an assessment of PD degree of severity, which can be classified according to five categories. To date, there is no gold standard measure for assessing degree of PD severity based on the ICD-11 model, and there are no empirically-based anchor points to delineate the proposed categories. With the operationalization of PD degrees of severity in the ICD-11 PD model now being closely aligned with Criterion A of the DSM-5 Alternative Model for Personality Disorders (AMPD), sharing a focus on self and interpersonal dysfunction, self-report instruments developed for the latter model might prove useful as screening tools to determine degrees of severity in the former. Methods: The Self and Interpersonal Functioning Scale, a brief validated self-report questionnaire originally designed to assess level of personality pathology according to the AMPD framework, was used to derive anchor points to delineate the five severity degrees from the ICD-11 PD model. Data from five clinical and non-clinical samples (total N = 2,240) allowed identifying anchor points for classification, based on Receiver Operating Characteristic curve analysis, Latent Class Analysis, and data distribution statistics. Categories were validated using multiple indices pertaining to externalizing and internalizing symptoms relevant to PD. Results: Analyses yielded the following anchor points for PD degrees of severity: No PD = 0-1.04; Personality Difficulty = 1.05-1.29; Mild PD = 1.30-1.89; Moderate PD = 1.90-2.49; and Severe PD = 2.50 and above. A clear gradient of severity across the five categories was observed in all samples. A high number of significant contrasts among PD categories were also observed on external variables, consistent with the ICD-11 PD degree of severity operationalization. Conclusions: The present study provides potentially useful guidelines to determine severity of personality pathology based on the ICD-11 model. The use of a brief self-report questionnaire as a screening tool for assessing PD degrees of severity should be seen as a time-efficient support for clinical decision and treatment planning.

Latent profiles of patients with borderline pathology based on the alternative DSM-5 model for personality disorders.

BACKGROUND: There have been multiple attempts to try to parse out heterogeneity within borderline pathology by identifying patient subtypes; thus far, these works have yielded few consistent results. Recent developments in the operationalization of borderline pathology may provide new opportunities to identify clinically and conceptually meaningful subgroups of patients. The Alternative DSM-5 Model for Personality Disorders (AMPD) offers a categorical-dimensional operationalization of Borderline personality disorder (BPD) that has yet to be tested for identification of patient subgroups. The purpose of the present study is to test whether the combination of the Criterion A elements (pertaining to level of severity) and the seven pathological facets from Criterion B that define BPD in the AMPD can yield meaningful patient profiles. METHODS: A total of 211 outpatients from a specialized PD treatment program (133 women, Mage = 33.66, SD = 10.97) were selected based on the presence of at least moderate borderline pathology according to cutoffs recently proposed for the Borderline Symptom List-23. Valid Criterion A (Self and Interpersonal Functioning Scale) and B (Personality Inventory for DSM-5 Faceted Brief Form) self-reports were administered to measure elements and facets that define BPD in the AMPD model; these variables were used as indicators in a latent profile analysis (LPA). RESULTS: The optimal solution generated by LPA yielded four distinct profiles: (a) Borderline traits; (b) Moderate pathology with Impulsivity; (c) Moderate pathology with Identity problems and Depressivity; and (d) Severe pathology. Clinically meaningful distinctions emerged among profiles on AMPD indicators and external variables relevant to PD, especially aggression and impulsivity. CONCLUSIONS: Profiles reflected both the "severity" and "style" components imbedded within Criterion A and B of the AMPD, as they were mainly distinguished by a continuum of severity but also by some meaningful qualitative differences that may have important clinical implications for treatment planning and contracting. Results also suggest that the four Criterion A elements have independent value to identify important differences in patients with borderline pathology. They also highlight that some Criterion B facets that define BPD in the AMPD may be especially important to identify subgroups of patients, mainly Impulsivity and Depressivity.

Safety and immunogenicity of a highly attenuated rVSVN4CT1-EBOVGP1 Ebola virus vaccine: a randomised, double-blind, placebo-controlled, phase 1 clinical trial.

BACKGROUND: The safety and immunogenicity of a highly attenuated recombinant vesicular stomatitis virus (rVSV) expressing HIV-1 gag (rVSVN4CT1-HIV-1gag1) was shown in previous phase 1 clinical studies. An rVSV vector expressing Ebola virus glycoprotein (EBOV-GP) in place of HIV-1 gag (rVSVN4CT1-EBOVGP1) showed single-dose protection from lethal challenge with low passage Ebola virus in non-human primates. We aimed to evaluate the safety and immunogenicity of the rVSVN4CT1-EBOVGP1 vaccine in healthy adults. METHODS: We did a randomised double-blind, placebo-controlled, phase 1 dose-escalation study at a single clinical site (Optimal Research) in Melbourne, FL, USA. Eligible participants were healthy men and non-pregnant women aged 18-60 years, with a body-mass index (BMI) of less than 40 kg/m2, no history of filovirus infection, VSV infection, or receipt of rVSV in previous studies, and who had not visited regions where Ebola virus outbreaks have occurred. Three cohorts were enrolled to assess a low (2·5 × 104 plaque forming units [PFU]), intermediate (2 × 105 PFU), or high dose (1·8 × 106 PFU) of the vaccine. Participants within each cohort were randomly allocated (10:3) to receive vaccine or placebo by intramuscular injection in a homologous prime and boost regimen, with 4 weeks between doses. All syringes were masked with syringe sleeves; participants and study site staff were not blinded to dose level but were blinded to active vaccine and placebo. The primary outcomes were safety and tolerability; immunogenicity, assessed as GP-specific humoral immune response (at 2 weeks after each dose) and cellular immune response (at 1 and 2 weeks after each dose), was a secondary outcome. All randomised participants were included in primary and safety analyses. This trial is registered with ClinicalTrials.gov, NCT02718469. FINDINGS: Between Dec 22, 2015, and Sept 15, 2016, 39 individuals (18 [46%] men and 21 [54%] women, mean age 51 years [SD 10]) were enrolled, with ten participants receiving the vaccine and three participants receiving placebo in each of three cohorts. One participant in the intermediate dose cohort was withdrawn from the study because of a diagnosis of invasive ductal breast carcinoma 24 days after the first vaccination, which was considered unrelated to the vaccine. No severe adverse events were observed. Solicited local adverse events occurred in ten (26%) of 39 participants after the first dose and nine (24%) of 38 participants after the second dose; the events lasted 3 days or less, were predominantly injection site tenderness (17 events) and injection site pain (ten events), and were either mild (19 events) or moderate (ten events) in intensity. Systemic adverse events occurred in 13 (33%) of 39 participants after the first dose and eight (21%) of 38 participants after the second dose; the events were mild (45 events) or moderate (11 events) in severity, and the most common events were malaise or fatigue (13 events) and headache (12 events). Arthritis and maculopapular, vesicular, or purpuric rash distal to the vaccination site(s) were not reported. A GP-specific IgG response was detected in all vaccine recipients after two doses (and IgG response frequency was 100% after a single high dose), and an Ebola virus neutralising response was detected in 100% of participants in the high-dose cohort. INTERPRETATION: The rVSVN4CT1-EBOVGP1 vaccine was well tolerated at all dose levels tested and was immunogenic despite a high degree of attenuation. The combined safety and immunogenicity profile of the rVSVN4CT1-EBOVGP1 vaccine vector support phase 1-2 clinical evaluation. FUNDING: US Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense: Joint Project Manager for Chemical, Biological, Radiological and Nuclear Medical.

Deep genealogical analysis of a large cohort of participants in the CARTaGENE project (Quebec, Canada).

BACKGROUND: Genealogical analysis helps to better understand the genetic structure of populations. The population of Quebec (Canada) often serves as a model for this type of analysis, having one of the world's most complete genealogical databases. AIM: The main objective of this study was to reconstruct, analyse and compare the ascending genealogies of participants to CARTaGENE, a project that aims at building a database on various aspects of public health. SUBJECTS AND METHODS: In total, 5110 genealogies from four Quebec regions were reconstructed. Distribution of ancestors, completeness and depth of the genealogies, characteristics of immigrant ancestors and kinship and inbreeding coefficients were analysed. RESULTS: Most genealogies go back to the 17th century, with a mean genealogical depth of 10 generations. Origins of immigrant ancestors are more diverse in the Montreal region, resulting in lower inbreeding and kinship among the participants from this region. Inbreeding and kinship values are mainly explained by remote genealogical links (from 6 to 11 generations). CONCLUSION: Deep genealogies allowed for a precise measurement of the geographic origins of the participants' immigrant ancestors, as well as inbreeding and kinship ties in the population, which may be crucial for studies aiming to identify genetic variations associated with Mendelian or complex diseases.

Fixation for metacarpal neck fracture: a biomechanical study.

BACKGROUND: There is no robust evidence of the best operative treatment for displaced unstable metacarpal neck fractures. Numerous constructs are used in the fixation of metacarpal neck fractures. Currently, two common methods are dorsal locking plate and K-wire fixation. A new metacarpal sled fixation system for metacarpal neck fracture was designed to provide fracture stability but limit dissection and avoid exposed hardware. The purpose of this study was to compare the biomechanical integrity of the metacarpal sled versus standard locking plate fixation and retrograde K-wire fixation in a simulated porcine metacarpal fracture model. METHODS: Transverse metacarpal neck fractures were created in 30 porcine second metacarpals. The specimens were randomly fixed with locking plates, metacarpal sleds, or retrograde K-wires. Constructs were then loaded to failure in three-point bending. Stiffness and peak load were measured from the load-to-failure deflection curve. Data were analyzed via ANOVA, followed by Tukey-Kramer's post hoc pairwise comparison. RESULTS: The K-wire group had the highest initial stiffness followed by the sled group and then the plate group. Statistical difference was only found between K-wires and plate. Peak load for the K-wire group was lowest, followed by sled, and then by plate. A statistically significant difference was observed between the peak loads of the K-wires and plate, as well as the sled and plate. However, a difference in peak load was not detected between the K-wires and sled. CONCLUSIONS: For transverse metacarpal neck fractures, a metacarpal sled construct provides similar fixation to K-wires with limited dissection and without exposed hardware or the potential for soft tissue tethering. The new low profile construct using a minimally invasive technique would be suitable for unstable metacarpal neck fractures.

First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Vesicular Stomatitis Virus Human Immunodeficiency Virus-1 gag Vaccine (HVTN 090).

Background. We report the first-in-human safety and immunogenicity evaluation of a highly attenuated, replication-competent recombinant vesicular stomatitis virus (rVSV) human immunodeficiency virus (HIV)-1 vaccine. Methods. Sixty healthy, HIV-1-uninfected adults were enrolled in a randomized, double-blinded, placebo-controlled dose-escalation study. Groups of 12 participants received rVSV HIV-1 gag vaccine at 5 dose levels (4.6 × 10(3) to 3.4 × 10(7) particle forming units) (N = 10/group) or placebo (N = 2/group), delivered intramuscularly as bilateral injections at 0 and 2 months. Safety monitoring included VSV cultures from blood, urine, saliva, and swabs of oral lesions. Vesicular stomatitis virus-neutralizing antibodies, T-cell immunogenicity, and HIV-1 specific binding antibodies were assessed. Results. Local and systemic reactogenicity symptoms were mild to moderate and increased with dose. No severe reactogenicity or product-related serious adverse events were reported, and all rVSV cultures were negative. All vaccine recipients became seropositive for VSV after 2 vaccinations. gag-specific T-cell responses were detected in 63% of participants by interferon-γ enzyme-linked immunospot at the highest dose post boost. Conclusions. An attenuated replication-competent rVSV gag vaccine has an acceptable safety profile in healthy adults. This rVSV vector is a promising new vaccine platform for the development of vaccines to combat HIV-1 and other serious human diseases.

Effects of Right Lower Limb Orthopedic Immobilization on Braking Function: An On-The-Road Experimental Study With Healthy Volunteers.

Little is known about how immobilization of the right lower limb might affect driving. The purpose of the present study was to evaluate the effect of 2 types of immobilization on the emergency braking time of healthy subjects during actual driving conditions. The emergency braking times of 14 healthy volunteers were assessed in a closed circuit under 3 conditions: wearing running shoes, wearing an Aircast Walker(®), or wearing a walking cast on their right lower limb. An instrumented car was used to measure the emergency braking times during braking tests with and without a distractor. The foot movement times were significantly increased with both immobilization devices compared with the running shoe (p < .01). The median total braking time with the running shoe during emergency braking without a distractor was 0.452 (interquartile range, 25th to 75th [IQR], 0.413 to 0.472) second. The results obtained with the Aircast Walker(®) or the walking cast were significantly longer (p < .01), at 0.480 (IQR, 0.431 to 0.537) second and 0.512 (IQR, 0.451 to 0.535) second, respectively. When a distractor was added, the total braking time with the running shoe, Aircast Walker(®), and walking cast was 0.489 (IQR, 0.429 to 0.575), 0.516 (IQR, 0.459 to 0.586), and 0.510 (IQR, 0.469 to 0.570) second, respectively, with no statistically significant differences among these 3 conditions. Wearing an immobilization device on the right lower limb minimally lengthens the emergency braking time in healthy drivers under actual driving conditions. Clinicians must nonetheless exercise caution when advising a driver wearing an orthopedic immobilization, because driving a motor vehicle is a complex psychomotor task that goes well beyond the emergency braking time.

Genealogical analysis as a new approach for the investigation of drug intolerance heritability.

Genealogical analysis has proven a useful method to understand the origins and frequencies of hereditary diseases in many populations. However, this type of analysis has not yet been used for the investigation of drug intolerance among patients suffering from inherited disorders. This study aims to do so, using data from familial hypercholesterolemia (FH) patients receiving high doses of statins. The objective is to measure and compare various genealogical parameters that could shed light on the origins and heritability of muscular intolerance to statins using FH as a model. Analysis was performed on 224 genealogies from 112 FH subjects carrying either the low-density lipoprotein receptor (LDLR) prom_e1 deletion>15 kb (n=28) or c.259T>G (p.Trp87Gly) (n=84) mutations and 112 non-FH controls. Number of ancestors, geographical origins and genetic contribution of founders, inbreeding and kinship coefficients were calculated using the S-Plus-based GENLIB software package. For both mutations, repeated occurrences of the same ancestors are more frequent among the carriers' genealogies than among the controls', but no difference was observed between tolerant and intolerant subjects. Founders who may have introduced both mutations in the population appear with approximately the same frequencies in all genealogies. Kinship coefficients are higher among carriers, with no difference according to statins tolerance. Inbreeding coefficients are slightly lower among >15-kb deletion carriers than among c.259 T>G carriers, but the differences between tolerants and intolerants are not significant. These findings suggest that although muscular intolerance to statins shows a family aggregation, it is not transmitted through the same Mendelian pattern as LDLR mutations.

Labeling individual neurons in the brains of live Xenopus tadpoles by electroporation of dyes or DNA.

This protocol describes the targeted introduction of fluorophore in the form of a dye or genetic material into single cells. This method has the advantage of producing true single-cell chimeric animals in which to study the effects of overexpression or knockdown of a gene in an otherwise entirely wild-type background.

In vivo time-lapse imaging of neuronal development in Xenopus.

In vivo fluorescence imaging of cells in the developing nervous system is greatly facilitated in specimens in which cells are brightly but sparsely labeled. In this article, we describe a number of techniques that can be used for delivering fluorophore to neurons in the albino Xenopus laevis tadpole. Fluorescent dye or DNA that encodes a fluorescent protein can be delivered to single cells by electroporation. Alternatively, multiple cells can be labeled with fluorescent dye introduced by local iontophoresis or with plasmid DNA introduced by bulk electroporation. Technical considerations and analysis methods for time-lapse imaging in living tissue are also discussed.

Dye labeling retinal ganglion cell axons in live Xenopus tadpoles.

Individual neurons in the developing nervous system can be visualized by the targeted delivery of a fluorophore. In this article, we describe a method for introducing a fluorescent dye via iontophoresis into retinal ganglion cell (RGC) axons in albino Xenopus laevis tadpoles. Iontophoresis is the enhanced permeation of molecules across biological membranes under the influence of an electrical field. Lipophilic dyes such as DiI are well suited to this method--being insoluble in the aqueous environment of the eye, they precipitate instantaneously, and only cells in contact with the dye crystal are labeled as the dye diffuses through the plasma membrane. A dissection stereomicroscope is used to allow a wide range of approach angles for the micropipette. The goal is to introduce a small bolus of dye into the neural retina where the ganglion cell somata are located and the axons course, with the expectation that it will be taken up by a small enough number of axons to allow individual cells to be distinguished. Because RGC axons will typically be imaged in the tectum far from the injection site, a relatively large injection can be made, increasing the probability of labeling axons without obscuring their visualization at the target. This approach is particularly useful under conditions in which it might be too difficult to perform juxtacellular electroporation because of limited visibility or access.

Bulk electroporation of retinal ganglion cells in live Xenopus tadpoles.

Individual neurons in the developing nervous system of Xenopus laevis can be visualized by the targeted delivery of a fluorophore. The fluorophore can be delivered as a fluorescent dye or DNA that encodes a fluorescent protein. Local iontophoresis is a method that works well for transfer of fluorescent dye to retinal ganglion cells (RGCs) in the eye, but it does not give a high yield for delivery of DNA. This is largely because the degree of pigmentation of the eyes, even in albino strains, makes it difficult to visualize RGC somata during pipette positioning. Bulk retinal electroporation is a better approach for delivery of plasmid DNA to RGC. The method described here works best in tadpoles older than stage 42.

Admixed ancestry and stratification of Quebec regional populations.

Population stratification results from unequal, nonrandom genetic contribution of ancestors and should be reflected in the underlying genealogies. In Quebec, the distribution of Mendelian diseases points to local founder effects suggesting stratification of the contemporary French Canadian gene pool. Here we characterize the population structure through the analysis of the genetic contribution of 7,798 immigrant founders identified in the genealogies of 2,221 subjects partitioned in eight regions. In all but one region, about 90% of gene pools were contributed by early French founders. In the eastern region where this contribution was 76%, we observed higher contributions of Acadians, British and American Loyalists. To detect population stratification from genealogical data, we propose an approach based on principal component analysis (PCA) of immigrant founders' genetic contributions. This analysis was compared with a multidimensional scaling of pairwise kinship coefficients. Both methods showed evidence of a distinct identity of the northeastern and eastern regions and stratification of the regional populations correlated with geographical location along the St-Lawrence River. In addition, we observed a West-East decreasing gradient of diversity. Analysis of PC-correlated founders illustrates the differential impact of early versus latter founders consistent with specific regional genetic patterns. These results highlight the importance of considering the geographic origin of samples in the design of genetic epidemiology studies conducted in Quebec. Moreover, our results demonstrate that the study of deep ascending genealogies can accurately reveal population structure.