Multiple Sclerosis Performance Test: Technical Development and Usability.

INTRODUCTION: In the clinic, the assessment of patients with multiple sclerosis (MS) is typically qualitative and non-standardized. OBJECTIVES: To describe the MS Performance Test (MSPT), an iPad Air® 2 (Apple, Cupertino, CA, USA)-based neurological assessment platform allowing patients to input relevant information without the aid of a medical technician, creating a longitudinal, clinically meaningful, digital medical record. To report results from human factor (HF) and usability studies, and the initial large-scale implementation in a practice setting. METHODS: The HF study examined use-error patterns in small groups of MS patients and healthy controls (n = 14), the usability study assessed the effectiveness of patient interaction with the tool by patients with a range of MS disability (n = 60) in a clinical setting, and the implementation study deployed the MSPT across a diverse population of patients (n = 1000) in a large MS center for routine clinical care. RESULTS: MSPT assessments were completed by all users in the HF study; minor changes to design were recommended. In the usability study, 73% of patients with MS completed the MSPT, with an average administration time of 32 min; 85% described their experience with the tool as satisfactory. In the initial implementation for routine care, 84% of patients with MS completed the MSPT, with an average administration time of 28 min. CONCLUSION: Patients with MS with varying disability levels completed the MSPT with minimal or no supervision, resulting in comprehensive, efficient, standardized, quantitative, clinically meaningful data collection as part of routine medical care, thus allowing for large-scale, real-world evidence generation. FUNDING: Biogen. TRIAL REGISTRATION: NCT02664324.

A qualitative analysis of decision-making among women with sexual violence-related pregnancies in conflict-affected eastern Democratic Republic of the Congo.

BACKGROUND: Sexual violence is prevalent in conflict-affected settings and may result in sexual violence-related pregnancies (SVRPs). There are limited data on how women with SVRPs make decisions about pregnancy continuation or termination, especially in contexts with limited or restricted access to comprehensive reproductive health services. METHODS: A qualitative study was conducted in Bukavu, Democratic Republic of the Congo (DRC) as part of a larger mixed methods study in 2012. Utilizing respondent-driven sampling (RDS), adult women who self-reported sexual violence and a resultant SVRP were enrolled into two study subgroups: 1) women currently raising a child from an SVRP (parenting group) and 2) women who terminated an SVRP (termination group). Trained female research assistants conducted semi-structured interviews with a subset of women in a private setting and responses were manually recorded. Interview notes were translated and uploaded to a qualitative software program, coded, and thematic content analysis was conducted. RESULTS: A total of 55 women were interviewed: 38 in the parenting group and 17 in the termination group. There were a myriad of expressed attitudes, beliefs, and emotional responses toward SVRPs and the termination of SVRPs with three predominant influences on decision-making, including: 1) the biologic, ethnic, and social identities of the fetus and/or future child; 2) social reactions, including fear of social stigmatization and/or rejection; and 3) the power of religious beliefs and moral considerations on women's autonomy in the decision-making process. CONCLUSION: Findings from women who continued and women who terminated SVRPs reveal the complexities of decision-making related to SVRPs, including the emotional reasoning and responses, and the social, moral, and religious dimensions of the decision-making processes. It is important to consider these multi-faceted influences on decision-making for women with SVRPs in conflict-affected settings in order to improve provision of health services and to offer useful insights for subsequent programmatic and policy decisions.

A qualitative analysis of psychosocial outcomes among women with sexual violence-related pregnancies in eastern Democratic Republic of Congo.

BACKGROUND: Sexual violence is prevalent in eastern Democratic Republic of Congo (DRC) and has potentially devastating psychosocial consequences. Previous studies have reported on sexual violence and its impact on the mental health of survivors, but there are few studies conducted among women with sexual violence-related pregnancies (SVRPs). Women with SVRPs may be at greater risk of complex psychosocial outcomes, including social stigmatization. This study aimed to describe psychosocial outcomes among this subgroup of sexual violence survivors in order to inform future interventions. METHODS: A mixed methods study was conducted in Bukavu, DRC in 2012 among adult women who self-reported an SVRP and either (1) were currently raising a child from an SVRP (parenting group) or (2) had terminated an SVRP (termination group). This manuscript presents qualitative findings from the mixed methods study. Participants were recruited using respondent-driven sampling and a proportion engaged in semi-structured qualitative interviews conducted by trained female interviewers. Thematic content analysis was conducted and key themes were identified. RESULTS: In total, 55 women were interviewed, of whom 38 were in the parenting group and 17 in the termination group. Women with SVRPs experienced a myriad of emotional responses as they navigated their social environments following the SVRPs. Negative reactions, including social stigmatization and/or social rejection, toward women with SVRPs and toward children born from SVRPs were important influences on psychological well-being. Women expressed both internalized emotionality intertwined with externalized experiences in the social environment. Many women demonstrated resilience, or what could be termed post-traumatic growth, identifying avenues of agency to advance the social conditions for women. CONCLUSIONS: The findings from the qualitative study, and in particular, the respondents' needs and suggested strategies, may be useful to inform future research, programs, and policies for women with SVRPs in eastern DRC. Future research could move beyond cross-sectional assessments to utilize innovative research methodologies to assess processes of psychological adaptation among women with SVRPs. Multi-dimensional psychosocial programs for women with SVRPs should consider basic needs such as shelter, food, and health care within the broader framework of trauma-informed care. Participatory programming, guided by beneficiaries, could provide further avenues for agency to advance social conditions for women with SVRPs in eastern DRC.

A Qualitative Analysis of Disclosure Patterns among Women with Sexual Violence-Related Pregnancies in Eastern Democratic Republic of Congo.

The Democratic Republic of the Congo (DRC) has experienced nearly two decades of civil conflict in the Eastern regions of North and South Kivu. This conflict has been notorious for the use of sexual violence as a weapon of war, leading in many cases to pregnancy after rape. The objectives of this analysis were: 1) to describe patterns of sexual violence-related pregnancy (SVRP) disclosure; 2) to consider why survivors chose to disclose to particular individuals; and 3) to examine the dialogue around SVRPs between women with SVRPs and their confidants. In South Kivu Province, Democratic Republic of Congo, two sub-groups of sexual violence survivors completed qualitative interviews, those currently raising a child from an SVRP (parenting group, N = 38) and those who had terminated an SVRP (termination group, N = 17). The findings show that a majority of SVRPs were conceived when participants were held in sexual captivity for prolonged periods of time. The SVRPs were disclosed to friends, family members, other sexual violence survivors, community members, spouses, health care providers, or perpetrators. The confidants were most often chosen because they were perceived by the participants as being discreet, trusted, and supportive. The confidants often provided advice about continuing or terminating the SVRP. Trust and discretion are the most important factors determining to whom women with SVRPs disclose their pregnancies. The vital role of confidants in giving support after disclosure cannot be overlooked. Providing opportunities for survivors to safely disclose their SVRPs, including to health care providers, is a necessary first step in allowing them to access safe and comprehensive post-assault care and services.

A neutralizing anti-Nogo66 receptor monoclonal antibody reverses inhibition of neurite outgrowth by central nervous system myelin.

The Nogo66 receptor (NgR1) is a neuronal, leucine-rich repeat (LRR) protein that binds three central nervous system (CNS) myelin proteins, Nogo, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein, and mediates their inhibitory effects on neurite growth. Although the LRR domains on NgR1 are necessary for binding to the myelin proteins, the exact epitope(s) involved in ligand binding is unclear. Here we report the generation and detailed characterization of an anti-NgR1 monoclonal antibody, 7E11. The 7E11 monoclonal antibody blocks Nogo, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein binding to NgR1 with IC50 values of 120, 14, and 4.5 nm, respectively, and effectively promotes neurite outgrowth of P3 rat dorsal root ganglia neurons cultured on a CNS myelin substrate. Further, we have defined the molecular epitope of 7E11 to be DNAQLR located in the third LRR domain of rat NgR1. Our data demonstrate that anti-NgR1 antibodies recognizing this epitope, such as 7E11, can neutralize CNS myelin-dependent inhibition of neurite outgrowth. Thus, specific anti-NgR1 antibodies may represent a useful therapeutic approach for promoting CNS repair after injury.

Crystal structure of extracellular human BAFF, a TNF family member that stimulates B lymphocytes.

B cell activating factor (BAFF), a ligand belonging to the tumor necrosis factor (TNF) family, plays a critical role in regulating survival and activation of peripheral B cell populations and has been associated with autoimmune disease. BAFF is known to interact with three receptors, BCMA, TACI and BAFF-R, that have distant similarities with other receptors of the TNF family. We have determined the crystal structure of the TNF-homologous domain of BAFF at 2.8 A resolution. The structure reveals significant differences when compared to other TNF family members, including an unusually long D-E loop that participates in the formation of a deep, concave and negatively charged region in the putative receptor binding site. The BAFF structure was further used to generate a homology model of APRIL, a closely related TNF family ligand that also binds to BCMA and TACI, but not BAFF-R. Analysis of the putative receptor binding sites of BAFF and APRIL suggests that differences in the D-E loop structure and electrostatic surface potentials may be important for determining binding specificities for BCMA, TACI and BAFF-R.