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In Malawi, Africa, the median age at first marriage is among the lowest on the continent and adolescent fertility rates are among the highest. Using high-frequency panel data from the country designed to follow single women and men into marriage, we examine the extent to which premarital fertility is associated with the timing of marriage. Two notable findings emerge. First, premarital fertility typically leads to a more rapid transition into marriage, compared to not having had a premarital conception or birth, and this effect is as strong for men as it is for women. Second, among women with premarital fertility, those who are wealthier, and those who have two parents alive, have lower odds of not marrying. Among men with premarital fertility, however, no patterns predict their subsequent marital outcomes. This study contributes to the literature on fertility and marriage in sub-Saharan Africa by including men in the analysis.

Ethiopia has made remarkable economic progress over the past decade, achieving high gross domestic product (GDP) growth and dramatically reducing poverty. Despite this success, current gender gaps show that challenges remain to realizing inclusive growth and the full potential of women’s economic empowerment. In Ethiopia, women still lag men on several important economic indicators, including employment rate, agricultural productivity, earnings from self-employment, and wage income. While the Government of Ethiopia has already made significant commitments and investments aiming to close the country’s gender gaps, new data offer an opportunity to generate critical evidence to strategically target these investments. For this reason, the Africa gender innovation lab’s (GIL) Ethiopia gender diagnostic report provides innovative analysis on the root causes and drivers of gender inequality in Ethiopia. Using data from the latest round of the Ethiopia socioeconomic survey (2015-2016) and an established statistical approach, the report examines the country’s gender gaps in employment, agricultural productivity, and income from self- and wage employment. It presents specific policy areas for the government to target in addressing the constraints faced by female workers, farmers, and business owners. The key findings and policy recommendations are discussed in the report.

Why have African men been largely overlooked in HIV policy and programs, while poor women are almost always targeted? Men are more likely to die of AIDS than women, and multiple studies in Africa find that wealthier men are more likely to be infected with HIV than are poor men. We draw on survey and ethnographic data from rural Malawi, a country in southeastern Africa that has experienced a major AIDS epidemic, to examine this puzzle of the “missing men.” Using longitudinal survey data collected at the height of Malawi’s epidemic, we find that not only are wealthy urban men more likely to be HIV positive, but so too are rural men who are wealthy by rural standards. We further advance our argument using ethnographic data to show that rural Malawians understand that men with money are a risk, both to themselves and others. We then systematically analyze HIV policies and documents from the World Health Organization (WHO), UNAIDS, and the President’s Emergency Program for AIDS Relief (PEPFAR)—large international organizations at the forefront of responding to AIDS—to identify the extent to which women and men and poverty and wealth appear as targets. We present evidence showing that women, who appear in these documents more than twice than do men, are framed as unquestionably vulnerable and in need of aid, whereas men are overlooked. We argue that the international discourse on AIDS in Africa cannot be conceived of as separate from the broader discourses of economic development. The campaigns by international donors and NGOs to protect poor women while sidelining men with money gives an incomplete picture of AIDS epidemics.

Cet article se base sur une recension des écrits dans le cadre d’un projet d’intervention à la maîtrise en service social. Il propose une réflexion critique sur les interventions réalisées auprès de jeunes victimes d’intimidation en milieu scolaire. La recension amène à constater la concentration des objectifs des différents programmes d’intervention autour de la diminution des facteurs de risque d’être victime et de l’acquisition d’habiletés sociales. Malgré la pertinence de ces objectifs, les programmes semblent s’en tenir à une compréhension limitée, et très individuelle, de la problématique. Pour pallier ces limites, l’empowerment, qui permet une analyse des aspects macro-sociaux, est proposée comme approche alternative. Les obstacles possibles à son application en milieu scolaire viennent conclure la réflexion critique., This article is based on a review of the literature that is a part of a master intervention project in social work with groups. It proposes a critical reflection on interventions with young victims of bullying in schools. The review leads to find that most of the objectives of various intervention programs are concentrated around social skills training and the reduction of risk factors of being a bullying victim. Despite the relevance of these goals, the programs seem to stick to a limited understanding, and very personal, issues. To overcome these limitations, empowerment, enabling an analysis of macro-social aspects, is proposed as an alternative approach. Possible resistances to its application in schools close the critical reflection.

Inclusive growth and poverty reduction requires an understanding of the constraints to increasing productivity of the informal sector, which employs the majority of Zambians. Zambians working in this sector are poor, have little education, die young from avoidable diseases, and live predominantly in rural areas. Even if more opportunities for formal employment currently existed, this population would not be qualified for these jobs. Their productive inclusion in society, and making sure they can invest in their children’s futures to break the intergenerational transmission of poverty, requires rural investment that can help unlock constraints to informal sector productivity. A recent review of the constraints that women face, relative to men, reveal that women’s business performance is affected by a combination of contextual factors and gender differences. This qualitative study sought to understand : (a) the key livelihood strategies used by women and men in Zambia; (b) the key constraints that women and men face; (c) how these constraints shape the strategies that are available; and (d) what women and men understand about human rights. The research had a specific focus on identifying responses that could help to increase women’s economic empowerment.

This article focuses on Malawian sex workers’ understandings of exchange and intimacy, showing how multiple historically emergent categories and specific work pragmatics produce specific patterns of relational meanings. As we show, sex workers make sense of their relationships with clients through two categories. The first is sex work; the second is the chibwenzi, an intimate premarital relational category that emerged from pre-colonial transformations in courtship practices. These categories, in turn, are also shaped differently in different work settings. We use narratives from in-depth interviews with 45 sex workers and bar managers in southern Malawi to describe how the everyday pragmatics of two forms of sex work—performed by “bargirls” and “freelancers”—foster distinct understandings of relationships between them and men they have sex with. Bargirls, who work and live in bars, blurred the boundaries between “regulars” and chibwenzi; freelancers, who are not tethered to a specific work environment, often subverted the meanings of the chibwenzi, presenting these relationships as both intimate and emotionally distant. Through this comparison, we thus refine an approach to the study of the intimacy-exchange nexus, and use it to capture the complexities of gender relations in post-colonial Malawi.

In many African countries, the timing of important life events -- such as school-leaving, first marriage, and entry into the labor market -- is thought to be strongly tied to migration. This paper investigates the relationship between major life events, household characteristics, and migration among adolescents and young adults in contemporary Malawi. The specific research questions are twofold. First, what are the socio-economic and demographic determinants of migration? Second, how do school attendance, first marriage, and employment-seeking relate to migration patterns? The study uses panel data collected from a survey designed specifically to explore socioeconomic and demographic aspects of youth transitions to adulthood and which tracked respondents as they moved to new dwellings. Among the sample, they find that moves are not uncommon, and the predominant reasons for moves are non-economic. Although historically ethnic traditions in this area have held that girls and women usually did not move upon marrying, the data show that women were more likely to move between survey rounds than boys and men, and that marriage was the main reason for doing so. Closer ties to the head of the household are associated with less movement for both women and men.

PurposeWhen introducing new health technologies, decision makers must integrate research evidence with local operational management information to guide decisions about whether and under what conditions the technology will be used. Multi‐criteria decision analysis can support the adoption or prioritization of health interventions by using criteria to explicitly articulate the health organization's needs, limitations, and values in addition to evaluating evidence for safety and effectiveness. This paper seeks to describe the development of a framework to create agreed‐upon criteria and decision tools to enhance a pre‐existing local health technology assessment (HTA) decision support program.Design/methodology/approachThe authors compiled a list of published criteria from the literature, consulted with experts to refine the criteria list, and used a modified Delphi process with a group of key stakeholders to review, modify, and validate each criterion. In a workshop setting, the criteria were used to create decision tools.FindingsA set of user‐validated criteria for new health technology evaluation and adoption was developed and integrated into the local HTA decision support program. Technology evaluation and decision guideline tools were created using these criteria to ensure that the decision process is systematic, consistent, and transparent.Practical implicationsThis framework can be used by others to develop decision‐making criteria and tools to enhance similar technology adoption programs.Originality/valueThe development of clear, user‐validated criteria for evaluating new technologies adds a critical element to improve decision‐making on technology adoption, and the decision tools ensure consistency, transparency, and real‐world relevance.

In this article we compare how AIDS in Malawi is represented in two sources of data, newspaper articles and conversational field journals that depict local interpretations of the epidemic, over the ten-year period 1999–2008. In each of these discursive fields we focus on “moral vocabularies”—the sets of instructions about what people should and should not do to reduce their personal risks or to mitigate the burdens of HIV infection. During this decade, international AIDS organizations came to define the epidemic in the global South as a crisis to be managed less by individual effort than by interactions with bureaucratic institutions. In Malawi, these include Government of Malawi health facilities that provide testing, treatment, and other forms of medical care, as well as nongovernmental organizations (NGOs) and associations that support people living with HIV or AIDS (PLWHA) and orphans. In 1995 there were 12 NGOs registered as implementing AIDS activities; by 2005, there were approximately 300, most of them small but formalized community-based organizations in rural areas (Wangel 1995; National AIDS Commission 2005; Swidler and Watkins 2009). Correspondingly, we found a shift in the moral vocabularies deployed in response to AIDS, from injunctions about individual behavioral choices toward those that require engagement with formal institutions. By comparing the moral vocabularies in media accounts and informal conversations, we uncover striking differences. While the frequency of injunctions to engage with specialized institutions increased in both sources

Ecological comparisons in sub-Saharan Africa show that HIV prevalence is lower where men are generally circumcised than where they are not. Randomized controlled trials have found a 50-60% reduction in HIV acquisition for newly circumcised men. Yet in Malawi, HIV prevalence is highest in several districts in the Southern Region, where men are commonly circumcised. We draw upon a population-based sample of ever-married women to explore this unexpected finding. Our data show that in the southern district of Balaka, women with circumcised spouses have a lower probability of HIV infection compared to those with uncircumcised spouses. However, the strength of this effect is conditioned by specific marital histories: among women with circumcised spouses, those with multiple marriages and an absence of spousal co-residence have a higher probability of HIV infection than do those married once and those who have never lived apart from their spouses. The history of marital turnover and female-headed households among the ethnic groups of Balaka offer insight into the district's elevated HIV levels. 1. Introduction A trio of randomized controlled trials conducted in South Africa, Kenya, and Uganda during the last decade found male circumcision to reduce a man's risk of acquiring HIV from an infected partner by 50% to 60% (Auvert et al. 2005; Bailey et al. 2007; Gray et al. 2007). These trials established male circumcision as one of the few procedures known to curb infection with HIV (see also Doyle et al. 2010).3 In response, donor organizations such as the President's Emergency Plan for AIDS Relief (PEPFAR), the Global Fund, and the Bill and Melinda Gates Foundation have provided funding to numerous other countries in sub-Saharan Africa adopting male circumcision policies (Dickson 2010; WHO/UNAIDS 2010). One country that has hesitated in accepting male circumcision as an effective intervention to prevent HIV transmission is Malawi. Country officials claim that no "scientific evidence" has shown that the procedure effectively curbs the epidemic (Washington Post 2010). On the face of it, such claims appear logical: the most recent Malawi Demographic and Health Survey (MDHS) found that a greater percentage of circumcised (13.2%) than uncircumcised (9.5%) men were HIV positive, leading the authors of the 2004 Final Report to conclude that "the relationship between HIV prevalence and circumcision status is not in the expected direction" (MDHS 2005, p. 235). Population-based data from the 2004 wave of the Malawi Diffusion and Ideational Change Project (MDICP) show a similar correlation. HIV prevalence was found to be highest in the southern district of Balaka, at 9.6%, which was surprising given that 83% of the sample of men affirmed that they were circumcised. While circumcision is rarely practiced in the districts of Mchinji in the Central Region and Rumphi in the Northern Region, HIV prevalence is lower in these two settings (at 7.8% and 5.1%, respectively) than in the South (Table 1). This study aims to better understand this seeming paradox. Since male circumcision greatly reduces a man's risk of new infection, and in Balaka District men commonly circumcise, other sources of infection must contribute to the district's relatively higher levels of HIV. One of Southern Malawi's striking demographic features is the regular occurrence of marital turnover, attributable to specific forms of social organization associated with matrilineality and matrilocality (Kaler 2001; Mitchell 1951; Mitchell 1956; Peters 1997; Vaughan 1983; see Ferguson 1999 for Zambia). In contemporary Balaka about half of all marriages dissolve within 20 years and, upon divorce, women and men remarry quickly, making these rates among the highest in all of Africa (Reniers 2003). This paper therefore considers, as a backdrop, whether Balaka-specific marital practices contribute to the district's high HIV levels. In this study we direct our attention to HIV infection among women, to whether and how key aspects of women's marital lives reduce the likelihood of HIV infection or, alternatively, are consequential in other ways. …

We explore how marital aspirations are related to the sexual behaviors of adolescents and young adults in Malawi, where HIV/AIDS prevalence among adults exceeds 10%. We also consider whether the specter of AIDS is shaping ideals about marriage. By combining survey data (N = 1,087) and in-depth interviews (N = 133) with young Malawians from the Malawi Diffusion and Ideational Change Project, we show that looking for and finding a suitable spouse are linked to sexual behaviors and, thus, HIV risks. Moreover, concerns about contracting HIV are closely tied to the ideal characteristics of a future spouse. Our findings draw long-overdue attention to the importance of marital aspirations in understanding adolescent sexual behaviors and risks in the era of AIDS.

Women are frequently depicted as the face of AIDS in sub-Saharan Africa (SAA) [1–3] where they comprise nearly 58% of all reported HIV infections [4]. Donor dollars, policies, and HIV programs have followed suit, resulting in a near-exclusive focus on women [e.g. 5]. Although African women are represented as particularly vulnerable to HIV infection [6], it is men, not women, who are more likely to die of AIDS [7–9]. AIDS prevalence may have the face of a woman, but AIDS mortality has the face of a man.

Limited evidence suggests renin-angiotensin-aldosterone system (RAAS) polymorphisms alter the blood pressure (BP) response to aerobic exercise training. We examined if RAAS polymorphisms influenced postexercise hypotension in men with high normal to Stage 1 hypertension. Forty-seven men (44.2+/-1.4 years, 145.1+/-1.6/85.5+/-1.1 mmHg) randomly completed three experiments: seated rest (control) and two cycle exercise bouts at 40% (LITE) and 60% (MOD) of maximal oxygen consumption. Ambulating BP was measured for 14 h after each experiment. RAAS polymorphisms associated with hypertension (i.e. angiotensin converting I enzyme, ACE I/D; angiotensin II type 1 receptor, AT1R A/C; and intron 2 of aldosterone synthase, Int2 W/C) were analyzed using polymerase chain reaction and restriction enzyme digestion. Repeated measure ANOVA tested if BP differed between experimental conditions by RAAS genotypes. Compared to men with 0-2 variant alleles, men withor =3 combined RAAS variant alleles had lower average systolic BP (SBP) (P=0.030) and lower average diastolic BP (DBP) (P=0.009) for 14 h only after LITE. In contrast, average BP was not different for MOD and control between RAAS variant allele groups over this time period (Por =0.05). LITE reduced BP in men withor =3 variant RAAS alleles for 14 h, whereas MOD had no influence on BP in these men. In order to optimally prescribe exercise for its BP lowering benefits in those with hypertension, additional knowledge of how genetic variation affects the BP response to exercise is needed.

It has been speculated that autoimmune diseases are caused by failure of central tolerance. However, this remains controversial. We have suggested that CD40 expression identifies autoaggressive T cells in the periphery of autoimmune prone mice. In this study, we report that CD40 was cloned from autoaggressive T cells and that engagement induces expression and nuclear translocation of the recombinases, recombination activating gene (RAG) 1 and RAG2 in the autoaggressive, but not in the nonautoaggressive, peripheral T cell population. Furthermore, we demonstrate that CD40 engagement induces altered TCR Vα, but not Vβ, expression in these cells. Therefore, CD40-regulated expression of RAG1 and RAG2 in peripheral T cells may constitute a novel pathway for the generation of autoaggressive T cells.

We have produced a panel of cloned T cell lines from the BDC-2.5 TCR transgenic (Tg) mouse that exhibit a Th2 cytokine phenotype in vitro but are highly diabetogenic in vivo. Unlike an earlier report in which T cells obtained from the Tg mouse were cultured for 1 wk under Th2-promoting conditions and were found to induce disease only in NOD.scid recipients, we found that long-term T cell clones with a fixed Th2 cytokine profile can transfer disease only to young nonobese diabetic (NOD) mice and never to NOD.scid recipients. Furthermore, the mechanism by which diabetes is transferred by a Tg Th2 T cell clone differs from that of the original CD4+ Th1 BDC-2.5 T cell clone made in this laboratory. Whereas the BDC-2.5 clone rapidly causes disease in NOD.scid recipients less than 2 wk old, the Tg Th2 T cell clones can do so only when cotransferred with other diabetogenic T cells, suggesting that the Th2 T cell requires the presence of host T cells for initiation of disease.

To investigate host leukocytes recruited to the pancreas by diabetogenic T cells, we administered islet-specific CD4(+) T cell clones to 2-week-old nonobese diabetic (NOD) mice and examined the resulting pancreatic infiltrate by flow cytometry. Two different Vbeta4(+)CD4(+) T cell clones, BDC 2.5 and BDC 6.9, were found to recruit a heterogeneous T cell population as determined by staining with a panel of anti-TCR Vbeta monoclonal antibodies. The majority of the diabetes-initiating, Vbeta4(+) T cell clones migrated to the spleen whereas only 5-8% of the T cell population infiltrating the pancreas was Vbeta4(+). Anti-IL-2 receptor staining indicated that fewer than 10% of the total population of infiltrating lymphocytes within the pancreas were in a highly activated state. We have further found that normal splenic T cells from the NOD mouse proliferate poorly to IL-2 in vitro, yet secrete IFN-gamma in response to IL-2 stimulation. These results suggest that the recruited host T cells in our disease transfer system are not directly pathogenic but, rather, are responding to the small numbers of inflammatory T cell clones by providing cytokines that facilitate the disease process.

Brewer Potterat Roberts and Brody (BPRB) provide the latest in a series of papers encouraging researchers to explore nonsexual routes of human immunodeficiency virus (HIV) transmission in sub-Saharan Africa (SSA). Whereas recent findings demonstrate that circumcision provides a substantial protective effect against contracting HIV BPRB suggest tempering the enthusiasm for any interventions based on these findings until hygienic means to obtaining circumcisions can be guaranteed. They highlight levels of HIV prevalence among self-reported virgins in several SSA countries and assess variation in these countries in light of male and female circumcision practices - which they suggest add to the mounting evidence supporting iatrogenic transmission routes. We agree that medical practitioners should take care in implementing any new strategies (i.e. hygienic circumcision should be the goal not just circumcision). Furthermore we recognize that identifying routes of HIV transmission in SSA is an empiric question demanding rigorous exploration - that transmission routes should not be a foregone conclusion. But in light of our experience collecting data in this context and assessing data quality we contend that the evidence in BPRB calls for an alternate interpretation. (excerpt)

We study how considerations of male circumcision as both a favourable practice and as protective against HIV are linked with ethnicity in sub-Saharan Africa, where many ethnic groups do not traditionally circumcise. We focus on Malawi, a country with a high HIV prevalence but low male circumcision prevalence. Survey data from a population-based random sample in rural Malawi (N=3400) was analysed for ethnoregional patterns in attitudes toward male circumcision. We used logit regression models to measure how reported circumcision status, region of residence, and ethnic identity relate to attitudes toward circumcision. Overall, Malawians reported more negative than positive opinions about male circumcision, but attitudes toward circumcision varied by ethnicity and region. The implications for agencies and governments aggressively scaling up the provision of male circumcision are clear: acceptance of circumcision as a tool for HIV prevention could be low in societies divided by ethnoregional identities that also shape the practice of circumcision.

This article explores the role of social capital. The authors develop a theoretical framework intended to facilitate systematic investigation of the contributions public libraries may make to democratization.

Objective: To explore how sexual and marital trajectories are associated with HIV infection among ever-married women in rural Malawi. Methods: Retrospective survey data and HIV biomarker data for 926 ever-married women interviewed in the Malawi Diffusion and Ideational Change Project were used. The associations between HIV infection and four key life course transitions considered individually (age at sexual debut, premarital sexual activity, entry into marriage and marital disruption by divorce or death) were examined. These transitions were then sequenced to construct trajectories that represent the variety of patterns in the data. The association between different trajectories and HIV prevalence was examined, controlling for potentially confounding factors such as age and region. Results: Although each life course transition taken in isolation may be associated with HIV infection, their combined effect appeared to be conditional on the sequence in which they occurred. Although early sexual debut, not marrying one’s first sexual partner and having a disrupted marriage each increased the likelihood of HIV infection, their risk was not additive. Women who both delayed sexual debut and did not marry their first partner are, once married, more likely to experience marital disruption and to be HIV-positive. Women who marry their first partner but who have sex at a young age, however, are also at considerable risk. Conclusions: These findings identify the potential of a life course perspective for understanding why some women become infected with HIV and others do not, as well as the differentials in HIV prevalence that originate from the sequence of sexual and marital transitions in one’s life. The analysis suggests, however, the need for further data collection to permit a better examination of the mechanisms that account for variations in life course trajectories and thus in lifetime probabilities of HIV infection.

New-onset Crohn's disease and acute flares are often associated with viral infections. The aim of this study was to search for evidence of persistent or recurrent viruses in patients. Tissue blocks were obtained from surgical specimens from patients and a control population. 111 samples were tested by PCR or RT-PCR, for EBV, CMV, HSV 1, HSV 2, HHV 8, pestiviruses, and enteroviruses. Additionally, seven sets of serum samples, including pre-operative and post-operative samples, from CD patients were analyzed serologically for antibodies to EBV. The tests revealed evidence of EBV nucleic acid in tissues of 11 patients from a total of 70 tested (15.7%) and in tissues of 3 of 41 control subjects (7.3%). Evidence of pestivirus was found in one CD patient, while one patient and one control were positive for CMV. No HSV 1 or 2, HHV 8 or enteroviruses were found. The serologic tests revealed that five of seven CD patients had antibodies against the early protein, the capsid protein and the EBV nuclear antigen (EBNA). The titers were not significantly altered post-surgically. None of the patients had antibodies of the IgM isotype. Our findings vary from those of Ruther et al. who demonstrated evidence of EBV in tissues from 7 of 11 (64%) German CD patients. Antibodies to early EBV viral antigen and to nuclear antigen in five of seven Belgian patients suggest persistent active viral infection.

For young adults living in countries with AIDS epidemics, getting an HIV test may influence near-term decisions, such as when to leave school, when to marry, and when to have a first child. These behaviors, which define the transition from adolescence to adulthood, have long-term implications for well-being and directly affect a person's risk of contracting HIV. Using an experimental design embedded in a panel survey from Malawi, this study assesses how HIV voluntary counseling and testing of young adults affects these decisions. The results show a negligible intent-to-treat effect of HIV testing on behaviors. There is some suggestive evidence, however, of a differential response by wealth and by prior beliefs about one's HIV status.

The ability to generate, maintain, and use cloned lines of T cells reactive for self-antigens has opened up a new avenue of investigation for researchers. These T-cell clones allow the rapid induction of tissue-specific autoimmunity with the intent of dissecting the contribution of the different cell types involved. T cells from the diabetes-prone nonobese diabetic mouse are proving to be a vital asset for understanding the T-cell-mediated pathogenesis that leads to overt beta-cell destruction. T-cell clone adoptive transfer protocols have been developed for use in immunodeficient strains, thus reducing the complexity of mechanism of disease initiation. Furthermore, these T-cell clones have been used to derive T-cell receptor transgenic (TCR-Tg) animals carrying only self-reactive T cells. The use of these TCR-Tg animals to study pathogenesis has also evolved from the ability to generate, maintain, and use T-cell cloned lines. This chapter focuses on primary culture for the generation of T-cell lines and clones, their long-term maintenance, and their use in disease transfer for studying the pathogenesis of end-organ autoimmunity.

The ability to generate, maintain, and use cloned lines of T cells reactive for self-antigens has opened up a new avenue of investigation for researchers. These T-cell clones allow the rapid induction of tissue-specific autoimmunity with the intent of dissecting the contribution of the different cell types involved. T cells from the diabetes-prone nonobese diabetic mouse are proving to be a vital asset for understanding the T-cell-mediated pathogenesis that leads to overt beta-cell destruction. T-cell clone adoptive transfer protocols have been developed for use in immunodeficient strains, thus reducing the complexity of mechanism of disease initiation. Furthermore, these T-cell clones have been used to derive T-cell receptor transgenic (TCR-Tg) animals carrying only self-reactive T cells. The use of these TCR-Tg animals to study pathogenesis has also evolved from the ability to generate, maintain, and use T-cell cloned lines. This chapter focuses on primary culture for the generation of T-cell lines and clones, their long-term maintenance, and their use in disease transfer for studying the pathogenesis of end-organ autoimmunity.

Juvenile diabetes (type 1) is an autoimmune disease in which CD4+T cells play a major role in pathogenesis characterized by insulitis and β cell destruction leading to clinical hyperglycemia. To date, no marker for autoimmune T cells has been described, although it was previously demonstrated that autoimmune mice have a large population of CD4+cells that express CD40. We show here that established, diabetogenic T cell clones of either the Th1 or Th2 phenotype are CD40-positive, whereas nondiabetogenic clones are CD40-negative. CD40 functionally signals T cell clones, inducing rapid activation of the transcription factor NFκB. We show that autoimmune diabetes-prone nonobese diabetic mice have high levels of CD40+CD4+T cells in the thymus, spleen, and importantly, in the pancreas. Finally, as demonstrated by adoptive transfers, CD4+CD40+cells infiltrate the pancreatic islets causing β-cell degranulation and ultimately diabetes.

Paule Poulin,1 Lea Austen,1 Catherine M Scott,2 Michelle Poulin,1 Nadine Gall,2 Judy Seidel,3 René Lafrenière1 1Department of Surgery, 2Knowledge Management, 3Public Health Innovation and Decision Support, Alberta Health Services, Calgary, AB, Canada Purpose: Introducing new health technologies, including medical devices, into a local setting in a safe, effective, and transparent manner is a complex process, involving many disciplines and players within an organization. Decision making should be systematic, consistent, and transparent. It should involve translating and integrating scientific evidence, such as health technology assessment (HTA) reports, with context-sensitive evidence to develop recommendations on whether and under what conditions a new technology will be introduced. However, the development of a program to support such decision making can require considerable time and resources. An alternative is to adapt a preexisting program to the new setting. Materials and methods: We describe a framework for adapting the Local HTA Decision Support Program, originally developed by the Department of Surgery and Surgical Services (Calgary, AB, Canada), for use by other departments. The framework consists of six steps: 1) development of a program review and adaptation manual, 2) education and readiness assessment of interested departments, 3) evaluation of the program by individual departments, 4) joint evaluation via retreats, 5) synthesis of feedback and program revision, and 6) evaluation of the adaptation process. Results: Nine departments revised the Local HTA Decision Support Program and expressed strong satisfaction with the adaptation process. Key elements for success were identified. Conclusion: Adaptation of a preexisting program may reduce duplication of effort, save resources, raise the health care providers' awareness of HTA, and foster constructive stakeholder engagement, which enhances the legitimacy of evidence-informed recommendations for introducing new health technologies. We encourage others to use this framework for program adaptation and to report their experiences. Keywords: health technology assessment, evidence-based medicine, program development, program adaptation

Recent studies demonstrated that engagement of cytotoxic T lymphocyte antigen 4 (CTLA-4)/(CD152) generates an inhibitory signal to T cells which arrests an on-going immune response. Since aberrant CD152 activity is thought to contribute to autoimmunity, we examined the effect of CD152-mediated inhibitory signals on the response to self and foreign antigens in autoimmune, diabetes-prone NOD and non-autoimmune BALB/c mice. The interaction of CD152 with its ligand B7 was prevented by treating the mice with anti-CD152 blocking antibody, before and following immunization of the mice with the self-antigen, syngeneic islet cells, or the foreign antigen, key-hole limpet hemocyanin (KLH). CD152 blockade in BALB/c mice stimulated a robust islet-specific T cell-mediated immune response compared to control antibody-treated mice. The augmentation of T cell responses in BALB/c mice was consistent with the role proposed for CD152 as a down-regulator of T cell activation responses. Furthermore, CD152 blockade unmasked islet cell specific autoreactive T cells in the non-autoimmune BALB/c mouse. Conversely, CD152 blockade in NOD mice failed to regulate islet-specific auto-reactive T cell responses. However, CD152 blockade enhanced the T cell response to the exogenous, foreign antigen KLH in both non-autoimmune BALB/c and autoimmune NOD mice. Collectively, these results suggest that there is not a global defect in CD152-mediated regulation of peripheral T cell immune responses in NOD autoimmune mice but rather, a defect specific to T cells recognizing self antigen.