Small Business: Referral Information on Programs to Assist Women and Minorities in Establishing and Expanding Small Businesses, Revised October 2000

Small Business: Referral Information on Programs to Assist Women and Minorities in Establishing and Expanding Small Businesses

IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes.

Genetic polymorphisms near IL28B are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with IL28B polymorphisms has yet to be fully appreciated. We analyzed the association of IL28B polymorphisms with histological and follow-up features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n = 1,098), fibrosis (n = 1,527), fibrosis progression rate (n = 1,312), and hepatocellular carcinoma development (n = 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at IL28B marker rs8099917-previously shown to be at risk of treatment failure-was associated with lower activity (P = 0.04), lower fibrosis (P = 0.02) with a trend toward lower fibrosis progression rate (P = 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (P = 0.003 for activity, P = 0.001 for fibrosis, and P = 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with IL28B genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively. IL28B polymorphisms were not predictive of the development of hepatocellular carcinoma. CONCLUSION: In chronic hepatitis C, IL28B variants associated with poor response to interferon therapy may predict slower fibrosis progression, especially in patients infected with non-1 HCV genotypes.

Early postnatal hospital discharge: the consequences of reducing length of stay for women and newborns

The objective of this study is to examine the literature and identify most salient outcomes of early postnatal discharge for women, newborns and the health system. An electronic search strategy was designed including the following sources: Web of Science, Scopus, ProQuest and PubMed/MEDLINE, using the following terms: (early AND discharge) OR (length AND stay) AND (postpartum OR postnatal) AND (effect* OR result OR outcome). Content analysis was used to identify and summarise the findings and methods of the research papers. The evidence available is not enough to either reject or support the practice of early postnatal discharge; different studies have reported different outcomes for women and newborns. The need of systematic clinical research is discussed.

A Study of Women and Poverty in Iowa

Information on women and poverty in Iowa based on the perspectives of women who have experienced poverty in Iowa as well as the perspectives of direct service providers.

Cumulative Vulnerability: A Case Study on intrafamilial violence, Drug Addiction and Adolescent Pregnancy

A pregnant adolescent’s vulnerability increases when she is a victim of intrafamilial violence and drug addiction, which cause physical and biopsychosocial damage to the mother and her baby. Objective Present and analyze the case of an adolescent who is addicted to drugs, pregnant and the victim of lifelong intrafamilial violence. Method A case study based on a semi-structured interview conducted in the Obstetrics Emergency Unit at the Teaching Hospital of the University of São Paulo. The data were interpreted and analyzed using Content Analysis. Results intrafamilial violence experienced at the beginning of the adolescent’s early relationships seriously affected her emotional maturity, triggering the development of psychopathologies and leaving her more susceptible to the use and abuse of alcohol and other drugs. The adolescent is repeating her history with her daughter, reproducing the cycle of violence. Conclusion Adolescent pregnancy combined with intrafamilial violence and drug addiction and multiplies the adolescent’s psychosocial vulnerability increased the adolescent’s vulnerability.

The (un)receptive experiences of female rape victims who seek healthcare services

OBJECTIVE To know the structure and functioning of healthcare services from the perspective of women who have suffered rape. METHOD A qualitative study conducted with 11 women who experienced rape, monitored in a maternity in the state of Alagoas, Brazil. Data were systematically based on content analysis. RESULTS It allowed for understanding the path taken by women in search of support from health services, as well as the limitations and capabilities of these services. CONCLUSION The assistance received in healthcare services leans towards a revictimization process of women who already carry trauma from the rape. It is necessary to reflect about care practices aimed at sexually victimized women.

Addiction: l'égalité face aux substances [Addiction: are women and men equal?]

When illicit drugs are taken, men and women have a different biological response to drug used. Likewise, gender differences show more stigmas, more complex familial environment, and more history of sexual abuse for drug addicted women. The expression of psychiatric co-morbidities differs according to gender, with increased mood disorders, eating disorders, anxiety, and post traumatic disorders among drug addicted women.

Unique spectrum of activity of prosimian TRIM5alpha against exogenous and endogenous retroviruses.

Lentiviruses, the genus of retrovirus that includes HIV-1, rarely endogenize. Some lemurs uniquely possess an endogenous lentivirus called PSIV ("prosimian immunodeficiency virus"). Thus, lemurs provide the opportunity to study the activity of host defense factors, such as TRIM5α, in the setting of germ line invasion. We characterized the activities of TRIM5α proteins from two distant lemurs against exogenous retroviruses and a chimeric PSIV. TRIM5α from gray mouse lemur, which carries PSIV in its genome, exhibited the narrowest restriction activity. One allelic variant of gray mouse lemur TRIM5α restricted only N-tropic murine leukemia virus (N-MLV), while a second variant restricted N-MLV and, uniquely, B-tropic MLV (B-MLV); both variants poorly blocked PSIV. In contrast, TRIM5α from ring-tailed lemur, which does not contain PSIV in its genome, revealed one of the broadest antiviral activities reported to date against lentiviruses, including PSIV. Investigation into the antiviral specificity of ring-tailed lemur TRIM5α demonstrated a major contribution of a 32-amino-acid expansion in variable region 2 (v2) of the B30.2/SPRY domain to the breadth of restriction. Data on lemur TRIM5α and the prediction of ancestral simian sequences hint at an evolutionary scenario where antiretroviral specificity is prominently defined by the lineage-specific expansion of the variable loops of B30.2/SPRY.

Amine-reactive OVA multimers for auto-vaccination against cytokines and other mediators: perspectives illustrated for GCP-2 in L. major infection.

Anticytokine auto-vaccination is a powerful tool for the study of cytokine functions in vivo but has remained rather esoteric as a result of numerous technical difficulties. We here describe a two-step procedure based on the use of OVA multimers purified by size exclusion chromatography after incubation with glutaraldehyde at pH 6. When such polymers are incubated with a target protein at pH 8.5 to deprotonate reactive amines, complexes are formed that confer immunogenicity to self-antigens. The chemokine GCP-2/CXCL6, the cytokines GM-CSF, IL-17F, IL-17E/IL-25, IL-27, and TGF-β1, and the MMP-9/gelatinase B are discussed as examples. mAb, derived from such immunized mice, have obvious advantages for in vivo studies of the target proteins. Using a mAb against GCP-2, obtained by the method described here, we provide the first demonstration of the major role played by this chemokine in rapid neutrophil mobilization after Leishmania major infection. Pre-activated OVA multimers reactive with amine residues thus provide an efficient carrier for auto-vaccination against 9-90 kDa autologous proteins.

Literature and Mythology in Tennessee Williams's "Suddenly Last Summer": Fighting against Venus and Oedipus

The aim of this article is to analyze accurately the role played by two classical references, Venus and Oedipus, in Tennessee Williams Suddenly Last Summer, in accordance with the usual nature of studies on Classical Tradition a Greek and Roman- and focusing in this case on the relationship between literature and mythology. It is thanks to Venus and Oedipus that the playwright succeeds in showing the magnitude of mens and womens tragedy, which from his point of view is simply that they have failed to see either kindness in the face of God or to feel his loving and fatherly providence.

TNF deficiency fails to protect BAFF transgenic mice against autoimmunity and reveals a predisposition to B cell lymphoma.

TNF is well characterized as a mediator of inflammatory responses. TNF also facilitates organization of secondary lymphoid organs, particularly B cell follicles and germinal centers, a hallmark of T-dependent Ab responses. TNF also mediates defense against tumors. We examined the role of TNF in the development of inflammatory autoimmune disorders resembling systemic lupus erythematosus and Sjögren's syndrome induced by excess B cell-activating factor belonging to the TNF family (BAFF), by generating BAFF-transgenic (Tg) mice lacking TNF. TNF(-/-) BAFF-Tg mice resembled TNF(-/-) mice, in that they lacked B cell follicles, follicular dendritic cells, and germinal centers, and have impaired responses to T-dependent Ags. Nevertheless, TNF(-/-) BAFF-Tg mice developed autoimmune disorders similar to that of BAFF-Tg mice. Disease in TNF(-/-) BAFF-Tg mice correlates with the expansion of transitional type 2 and marginal zone B cell populations and enhanced T-independent immune responses. TNF deficiency in BAFF-Tg mice also led to a surprisingly high incidence of B cell lymphomas (>35%), which most likely resulted from the combined effects of BAFF promotion of neoplastic B cell survival, coupled with lack of protective antitumor defense by TNF. Thus, TNF appears to be dispensable for BAFF-mediated autoimmune disorders and may, in fact, counter any proneoplastic effects of high levels of BAFF in diseases such as Sjögren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis.

Multidimensionnalité des violences envers les femmes. La Suisse en regard des États-Unis: pertinence et validité d'une comparaison

Summary : International comparisons in the area of victimization, particularly in the field of violence against women, are fraught with methodological problems that previous research has not systematically addressed, and whose answer does not seem to be agreed up~n. For obvious logistic and financial reasons, international studies on violence against women (i.e. studies that administer the same instrument in different countries). are seldom; therefore, researchers are bound to resort to secondary comparisons. Many studies simply juxtapose their results to the ones of previous wòrk or to findings obtained in different contexts, in order to offer an allegedly comparative perspective to their conclusions. If, most of the time, researchers indicate the methodological limitations of a direct comparison, it is not rare that these do not result in concrete methodological controls. Yet, many studies have shown the influence of surveys methodological parameters on findings, listing recommendations fora «best practice» of research. Although, over the past decades, violence against women surveys have become more and more similar -tending towards a sort of uniformization that could be interpreted as a passive consensus -these instruments retain more or less subtle differences that are still susceptible to influence the validity of a comparison. Yet, only a small number of studies have directly worked on the comparability of violence against women data, striving to control the methodological parameters of the surveys in order to guarantee the validity of their comparisons. The goal of this work is to compare data from two national surveys on violence against women: the Swiss component of the International Violence Against Women Survey [CH-IVAWS] and the National Violence Against Women Survey [NVAWS] administered in the United States. The choice of these studies certainly ensues from the author's affiliations; however, it is far from being trivial. Indeed, the criminological field currently endows American and Anglo-Saxon literature with a predominant space, compelling researchers from other countries to almost do the splits to interpret their results in the light of previous work or to develop effective interventions in their own context. Turning to hypotheses or concepts developed in a specific framework inevitably raises the issue of their applicability to another context, i.e. the Swiss context, if not at least European. This problematic then takes on an interest that goes beyond the particular topic of violence against women, adding to its relevance. This work articulates around three axes. First, it shows the way survey characteristics influence estimates. The comparability of the nature of the CH-IVAWS and NVAWS, their sampling design and the characteristics of their administration are discussed. The definitions used, the operationalization of variables based on comparable items, the control of reference periods, as well as the nature of the victim-offender relationship are included among controlled factors. This study establishes content validity within and across studies, presenting a systematic process destined to maximize the comparability of secondary data. Implications of the process are illustrated with the successive presentation of comparable and non-comparable operationalizations of computed variables. Measuring violence against. women in Switzerland and the United-States, this work compares the prevalence of different forms (threats, physical violence and sexual violence) and types of violence (partner and nonpartner violence). Second, it endeavors to analyze concepts of multivictimization (i.e. experiencing different forms of victimization), repeat victimization (i.e. experiencing the same form of violence more than once), and revictimization (i.e. the link between childhood and adulthood victimization) in a comparative -and comparable -approach. Third, aiming at understanding why partner violence appears higher in the United States, while victims of nonpartners are more frequent in Switzerland, as well as in other European countries, different victimization correlates are examined. This research contributes to a better understanding of the relevance of controlling methodological parameters in comparisons across studies, as it illustrates, systematically, the imposed controls and their implications on quantitative data. Moreover, it details how ignoring these parameters might lead to erroneous conclusions, statistically as well as theoretically. The conclusion of the study puts into a wider perspective the discussion of differences and similarities of violence against women in Switzerland and the United States, and integrates recommendations as to the relevance and validity of international comparisons, whatever the'field they are conducted in. Résumé: Les comparaisons internationales dans le domaine de la victimisation, et plus particulièrement en ce qui concerne les violences envers les femmes, se caractérisent par des problèmes méthodologiques que les recherches antérieures n'ont pas systématiquement adressés, et dont la réponse ne semble pas connaître de consensus. Pour des raisons logistiques et financières évidentes, les études internationales sur les violences envers les femmes (c.-à-d. les études utilisant un même instrument dans différents pays) sont rares, aussi les chercheurs sont-ils contraints de se tourner vers des comparaisons secondaires. Beaucoup de recherches juxtaposent alors simplement leurs résultats à ceux de travaux antérieurs ou à des résultats obtenus dans d'autres contextes, afin d'offrir à leurs conclusions une perspective prétendument comparative. Si, le plus souvent, les auteurs indiquent les limites méthodologiques d'une comparaison directe, il est fréquent que ces dernières ne se traduisent pas par des contrôles méthodologiques concrets. Et pourtant, quantité de travaux ont mis en évidence l'influence des paramètres méthodologiques des enquêtes sur les résultats obtenus, érigeant des listes de recommandations pour une «meilleure pratique» de la recherche. Bien que, ces dernières décennies, les sondages sur les violences envers les femmes soient devenus de plus en plus similaires -tendant, vers une certaine uniformisation que l'on peut interpréter comme un consensus passif-, il n'en demeure pas moins que ces instruments possèdent des différences plus ou moins subtiles, mais toujours susceptibles d'influencer la validité d'une comparaison. Pourtant, seules quelques recherches ont directement travaillé sur la comparabilité des données sur les violences envers les femmes, ayant à coeur de contrôler les paramètres méthodologiques des études utilisées afin de garantir la validité de leurs comparaisons. L'objectif de ce travail est la comparaison des données de deux sondages nationaux sur les violences envers les femmes: le composant suisse de l'International Violence Against Women Survey [CHIVAWSj et le National Violence Against Women Survey [NVAWS) administré aux États-Unis. Le choix de ces deux études découle certes des affiliations de l'auteure, cependant il est loin d'être anodin. Le champ criminologique actuel confère, en effet, une place prépondérante à la littérature américaine et anglo-saxonne, contraignant ainsi les chercheurs d'autres pays à un exercice proche du grand écart pour interpréter leurs résultats à la lumière des travaux antérieurs ou développer des interventions efficaces dans leur propre contexte. Le fait de recourir à des hypothèses et des concepts développés dans un cadre spécifique pose inévitablement la question de leur applicabilité à un autre contexte, soit ici le contexte suisse, sinon du moins européen. Cette problématique revêt alors un intérêt qui dépasse la thématique spécifique des violences envers les femmes, ce qui ajoute à sa pertinence. Ce travail s'articule autour de trois axes. Premièrement, il met en évidence la manière dont les caractéristiques d'un sondage influencent les estimations qui en découlent. La comparabilité de la nature du CH-IVAWS et du NVAWS, de leur processus d'échantillonnage et des caractéristiques de leur administration est discutée. Les définitions utilisées, l'opérationnalisation des variables sur la base d'items comparables, le contrôle des périodes de référence, ainsi que la nature de la relation victime-auteur figurent également parmi les facteurs contrôlés. Ce travail établit ainsi la validité de contenu intra- et inter-études, offrant un processus systématique destiné à maximiser la comparabilité des données secondaires. Les implications de cette démarche sont illustrées avec la présentation successive d'opérationnalisations comparables et non-comparables des variables construites. Mesurant les violences envers les femmes en Suisse et aux États-Unis, ce travail compare la prévalence de plusieurs formes (menaces, violences physiques et violences sexuelles) et types de violence (violences partenaires et non-partenaires). 11 s'attache également à analyser les concepts de multivictimisation (c.-à-d. le fait de subir plusieurs formes de victimisation), victimisation répétée (c.-à.-d. le fait de subir plusieurs incidents de même forme) et revictimisation (c.-à-d. le lien entre la victimisation dans l'enfance et à l'âge adulte) dans une approche comparative - et comparable. Dans un troisième temps, cherchant à comprendre pourquoi la violence des partenaires apparaît plus fréquente aux États-Unis, tandis que les victimes de non-partenaires sont plus nombreuses en Suisse, et dans d'autres pays européens, différents facteurs associés à la victimisation sont évalués. Cette recherche participe d'une meilleure compréhension de la pertinence du contrôle des paramètres méthodologiques dans les comparaisons entre études puisqu'elle illustre, pas à pas, les contrôles imposés et leurs effets sur les données quantitatives, et surtout comment l'ignorance de ces paramètres peut conduire à des conclusions erronées, tant statistiquement que théoriquement. La conclusion replace, dans un contexte plus large, la discussion des différences et des similitudes observées quant à la prévalence des violences envers les femmes en Suisse et aux États-Unis, et intègre des recommandations quant à la pertinence et à la validité des comparaisons internationales, cela quel que soit le domaine considéré.

Endocytosis, autophagy and JNK inhibition in neuroprotection against excitotoxicity and neonatal cerebral ischemia

Abstract : Neonatal stroke occurs in 1 out of 4000 live births and usually leads to serious motor and cognitive disabilities. Ischemic brain injury results from a complex of pathophysiological events that evolve over space and time making it difficult to devise successful therapy. To date, there are no effective treatments for perinatal brain damage. Most clinical trials of neuroprotectaot drugs have failed because of their side-effects. For this reason it is important to find ways to target drugs specifically into the stressed cells. In this study we plan to contribute to the development of an efficient neuroprotective strategy against excitotoxic cell death in the neonate. In order to achieve this goal, several strategies were followed. A recently described phenomenon of induced endocytosis associated with excitotoxicity was more deeply investigated. As a simplified model we used dissociated cortical neurons exposed to an excitotoxic dose of NMDA, and we showed that this phenomenon depends on clathrin and dynamin. Using a model of neonatal focal cerebral ischemia, we demonstrated that the excitotoxicity-related endocytosis targets molecules such as TAT peptides into stressed neurons. These appear to be viable, raising the possibility of using this phenomenon as a doorway for neuroprotection. One part of the project was devoted to the study of the TAT-conjugated JNK inhibitory peptide, D-JNKI1. Adose-response study showed strong neuroprotection over a wide dose-range in the case of delayed administration (either intravenous or intraperitoneal). Since D-JNKI1 is aTAT-linked peptide, we investigated the role of its own NMDA-induced endocytosis in its neuroprotective efficacy. Furthermore, we showed that this endocytosis is JNK dependent, and that D-JNKI1 regulates its own uptake. We additionally studied the different types of cell death involved in a model of neonatal focal cerebral ischemia. Necrosis occurred rapidly in the center of the lesion whereas apoptosis and autophagic cell death occurred late at the lesion border. Inhibiting apoptosis was not protective, but use of autophagy inhibitor 3methyladenine provided a strong neuroprotection. Finally, combining two neuroprotectants that target different intracellular pathways was neuroprotective in a severe model of cerebral ischemia where neither of the drugs was efficient when administered individually. Résumé : L'ischémie néonatale connaît une incidence de 1 naissance sur 4000, entraînant généralement de sérieux dysfonctionnements moteurs et cognitifs. L'ischémie cérébrale résulte d'évènements physiopathologiques complexes qui évoluent dans l'espace et le temps rendant difficile la conception de thérapies efficaces. A l'heure actuelle, aucun traitement n'existe pour lutter contre les accidents vasculaires cérébraux qui se produisent autour de la naissance. La plupart des essais cliniques concernant des molécules neuroprotectrices ont échoué du fait de leurs effets secondaires néfastes. Pour cette raison, il est important de trouver des moyens de cibler les drogues dans les cellules stressées spécifiquement. Dans cette étude nous visons à participer au développement d'une stratégie neuroprotectrice efficace contre l'ischémie cérébrale chez le nouveau-né. Dans ce but, plusieurs stratégies ont été poursuivies. Un nouveau phénomène d'endocytose induite par un stimulus excitotoxique a été récemment décrit. Une partie de cette étude va consister à mieux comprendre ce phénomène. Pour céla, nous avons utilisé comme modèle d'étude simplifié des cultures dissociées de neurones corticaux exposées à une dose excitotoxique de NMDA. Nous avons ainsi montré que cette endocytose associée à l'excitotoxicité dépend de la clathrine et de la dynamine. A l'aide d'un modèle d'ischémie cérébrale focale chez le raton de 12 jours, nous avons démontré que cette endocytose induite par l'excitotoxicité permet de cibler des molécules diverses et en particulier les peptides TAT dans les neurones stressés. Ces neurones fortement endocytiques apparaissent comme étant encore viables, ouvrant la possibilité d'utiliser cette endocytose comme moyen d'entrée pour des molécules thérapeutiques. Une partie du projet a été consacrée à l'étude d'un inhibiteur de la voie JNK, couplé au TAT, appelé D-JNKI1. Des études de dose réponse du D-JNKI1 ont été réalisées chez l'animal, testant les effets d'une administration retardée en injection intraveineuse ou intra péritonéale. Ces études démontrent qu'une large gamme de dose permet d'obCenir une réduction de la taille de la lésion. Comme D-JNK11 est couplé au peptide TAT, nous avons étudié la contribution que sa propre endocytose lors de l'excitotoxicité apporte à ses effets protecteurs. Par ailleurs, nous avons montré que cette endocytose induite par l'excitotoxicité dépend de la voie de signalisation JNK et que D-JNK11 est donc capable de réguler sa propre entrée. Nous avons en parallèle étudié les différents types de mort cellulaires impliqués dans le développement de la lésion dans un modèle sévère d'ischémie cérébrale chez le raton nouveau-né. La mort cellulaire par nécrose se développe rapidement dans le centre de la lésion alors que les morts cellulaires par apoptose et autophagique vont apparaître plus tard et au bord de la lésion. Inhiber l'apoptose n'a pas permis de réduire la taille de la lésion alors que l'utilisation d'un inhibiteur d'autophagie, la 3-méthyladénine, procure une forte neuroprotection. Finalement, la combinaison de deux peptides qui ciblent différentes voies de signalisation intracellulaire permet d'obtenir une bonne protection dans le modèle d'ischémie sévère dans lequel aucun des deux peptides administré séparément n'a donné d'effets bénéfiques.