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Background False positivity may hinder the utility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests in sub-Saharan Africa. Methods From 312 Malian samples collected before 2020, we measured antibodies to the commonly tested SARS-CoV-2 antigens and 4 other betacoronaviruses by enzyme-linked immunosorbent assay (ELISA). In a subset of samples, we assessed antibodies to a panel of Plasmodium falciparum antigens by suspension bead array and functional antiviral activity by SARS-CoV-2 pseudovirus neutralization assay. We then evaluated the performance of an ELISA using SARS-CoV-2 spike protein and receptor-binding domain developed in the United States using Malian positive and negative control samples. To optimize test performance, we compared single- and 2-antigen approaches using existing assay cutoffs and population-specific cutoffs. Results Background reactivity to SARS-CoV-2 antigens was common in prepandemic Malian samples. The SARS-CoV-2 reactivity varied between communities, increased with age, and correlated negligibly/weakly with other betacoronavirus and P falciparum antibodies. No prepandemic samples demonstrated functional activity. Regardless of the cutoffs applied, test specificity improved using a 2-antigen approach. Test performance was optimal using a 2-antigen assay with population-specific cutoffs (sensitivity, 73.9% [95% confidence interval {CI}, 51.6–89.8]; specificity, 99.4% [95% CI, 97.7–99.9]). Conclusions We have addressed the problem of SARS-CoV-2 seroassay performance in Africa by using a 2-antigen assay with cutoffs defined by performance in the target population.

Malaria may affect the reliability of SARS-CoV-2 seroassay performance and limit understanding of SARS-CoV-2 epidemiology in malaria-endemic regions. We present our experience conducting SARS-CoV-2 serosurveillance in seasonal malaria-affected communities in Mali and discuss relevant literature regarding the effect of malaria on the performance of SARS-CoV-2 serodiagnostics, including approaches to minimize the effect of malaria-associated assay interference.

To quantify the effect of cataract on color vision as measured by the low-vision Cambridge Colour Test (lvCCT; Cambridge Research Systems) and to understand whether different types and severities of cataract have different effects on color vision.Cohort study.Patients aged 18 to 95 undergoing routine cataract surgery at the Oxford Eye Hospital.The lvCCT was performed to measure color sensitivity in both eyes both before and after surgery. The crystalline lens was examined and graded according to the Lens Opacities Classification System III to determine the type and severity of cataract. Measures of repeatability were performed for the data to explore test-retest bias using Bland-Altman analysis. The Wilcoxon signed-rank test was performed to assess the effect of cataract on color vision by comparing control and surgical test measurements. Three multiple linear regressions were performed to relate cataract grading or severity to color vision measurements.Color discrimination along each of the protan, deutan, and tritan confusion lines.The Wilcoxon signed-rank test showed a statistically significant difference in both the protan (Cataract surgery has a statistically significant effect on color vision in both the protan and tritan axes. The effects of specific subtypes of cataract and different severities could not be elucidated because of the high prevalence of patients with mixed cataract. The lvCCT color sensitivity measurements are used regularly as outcome measures in clinical gene therapy trials involving vitreoretinal surgery, and vitrectomy accelerates cataract formation. Therefore, it is important to quantify the effect of cataract on color vision measurements so that it may be taken into account when used as an outcome measure in clinical trials. We were unable to derive a precise correction factor for cataract on color vision measurements.

Preerythrocytic vaccines prevent malaria by targeting parasites in the clinically silent sporozoite and liver stages and preventing progression to the virulent blood stages. The leading preerythrocytic vaccine, RTS,S/AS01E (Mosquirix), entered implementation programs in 2019 and targets the major sporozoite surface antigen, circumsporozoite protein (CSP). However, in phase III clinical trials, RTS,S conferred partial protection with limited durability, indicating a need to improve CSP-based vaccination. Previously, we identified highly expressed liver-stage proteins that could potentially be used in combination with CSP; they are referred to as preerythrocytic vaccine antigens (PEVAs). Here, we developed heterologous prime-boost CSP vaccination models to confer partial sterilizing immunity against Plasmodium yoelii (protein prime-adenovirus 5 [Ad5] boost) and Plasmodium berghei (DNA prime-Ad5 boost) in mice. When combined as individual antigens with P. yoelii CSP (PyCSP), three of eight P. yoelii PEVAs significantly enhanced sterile protection against sporozoite challenge, compared to PyCSP alone. Similar results were obtained when three P. berghei PEVAs and P. berghei CSP were combined in a single vaccine regimen. In general, PyCSP antibody responses were similar after CSP alone versus CSP plus PEVA vaccinations. Both P. yoelii and P. berghei CSP plus PEVA combination vaccines induced robust CD8(+) T cell responses, including signature gamma interferon (IFN-γ) increases. In the P. berghei model system, IFN-γ responses were significantly higher in hepatic versus splenic CD8(+) T cells. The addition of novel antigens may enhance the degree and duration of sterile protective immunity conferred by a human vaccine such as RTS,S.

Background Seasonal malaria chemoprevention (SMC) is a novel strategy to reduce malaria infections in children. Infection with Plasmodium falciparum results in immune dysfunction characterized by elevated expression of markers associated with exhaustion, such as PD1 and LAG3, and regulatory CD4+FOXP3+ T cells. Methods In the current study, the impact of seasonal malaria chemoprevention on malaria-induced immune dysfunction, as measured by markers associated with exhaustion and regulatory T cells, was explored by flow cytometry. Results Children that received seasonal malaria chemoprevention had fewer malaria episodes and showed significantly lower fold changes in CD4+PD1+ and CD4+PD1+LAG3+ compared to those that did not receive SMC. Seasonal malaria chemoprevention had no observable effect on fold changes in CD8 T cells expressing PD1 or CD160. However, children receiving SMC showed greater increases in CD4+FOXP3+ T regulatory cells compared to children not receiving SMC. Conclusions These results provide important insights into the dynamics of malaria-induced changes in the CD4 T-cell compartment of the immune system and suggest that the reduction of infections due to seasonal malaria chemoprevention may also prevent immune dysfunction. Clinical Trials Registration NCT02504918.

Background Immunity that limits malarial disease is acquired over time, but adults living in endemic areas continue to become infected and can require treatment for clinical illness. Gamma delta (γδ) T cells, particularly the Vδ2+ subset, have been associated with development of clinical malaria in children. In this study, the dynamics of total γδ T cells, Vδ2+ and Vδ2− T cells were measured during a malaria transmission season in Malian adults. Methods This study explored γδ T cell dynamics and Plasmodium falciparum infection outcomes over the course of the malaria transmission season in Malian adults enrolled in the placebo arm of a double-blind randomized vaccine trial. All volunteers were treated with anti-malarial drugs prior to the start of the transmission season and blood smears were assessed for P. falciparum infection every 2 weeks from July 2014 to January 2015. The study participants were stratified as either asymptomatic infections or clinical malaria cases. Vδ2+ and Vδ2− γδ T cell frequencies and activation (as measured by CD38 expression) were measured in all study participants at baseline and then every 2 months using a whole blood flow cytometry assay. Results Forty of the forty-three subjects became infected with P. falciparum and, of those, 21 individuals were diagnosed with clinical malaria at least once during the season. The γδ T cell percentage and activation increased over the duration of the transmission season. Both the Vδ2+ and Vδ2− γδ T cells were activated by P. falciparum infection. Conclusion γδ T cells increased during a malaria transmission season and this expansion was noted in both the Vδ2+ and Vδ2− γδ T cells. However, neither expansion or activation of either γδ T cell subsets discriminated study participants that had asymptomatic infections from those that had clinical malaria cases.

BACKGROUND: The extent of SARS-CoV-2 exposure and transmission in Mali and the surrounding region is not well understood, although infection has been confirmed in nearly 14,000 symptomatic individuals and their contacts since the first case in March 2020. We aimed to estimate the cumulative incidence of SARS-CoV-2 in three Malian communities, and understand factors associated with infection. METHODS: Between 27 July 2020 and 29 January 2021, we collected blood samples along with demographic, social, medical and self-reported symptoms information from residents aged 6 months and older in three study communities at two study visits. SARS-CoV-2 antibodies were measured using a highly specific two-antigen ELISA optimized for use in Mali. We calculated cumulative adjusted seroprevalence for each site and evaluated factors associated with serostatus at each visit by univariate and multivariate analysis. FINDINGS: Overall, 94.8% (2533/2672) of participants completed both study visits. A total of 50.3% (1343/2672) of participants were male, and 31.3% (837/2672) were aged

Background The extent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure and transmission in Mali and the surrounding region is not well understood. We aimed to estimate the cumulative incidence of SARS-CoV-2 in 3 communities and understand factors associated with infection. Methods Between July 2020 and January 2021, we collected blood samples and demographic, social, medical, and self-reported symptoms information from residents aged 6 months and older over 2 study visits. SARS-CoV-2 antibodies were measured using a highly specific 2-antigen enzyme-linked immunosorbent assay optimized for use in Mali. We calculated cumulative adjusted seroprevalence for each community and evaluated factors associated with serostatus at each visit by univariate and multivariate analysis. Results Overall, 94.8% (2533/2672) of participants completed both study visits. A total of 31.3% (837/2672) were aged, This study demonstrates a large, previously unquantified burden of SARS-COV-2 infection in the community in West Africa. In this young study population, there was limited evidence of severe illness and seropositivity rates that may approach hypothetical “herd immunity.”

Serological tests are an indispensable tool to understand the epidemiology of the SARS-CoV-2 pandemic, particularly in areas where molecular diagnostics are limited. Poor assay performance may hinder the utility of these tests, including high rates of false-positivity previously reported in sub-Saharan Africa. From 312 Malian samples collected prior to 2020, we measured antibodies to the commonly tested SARS-CoV-2 antigens and four other betacoronaviruses by ELISA, and assessed functional cross-reactivity in a subset by SARS-CoV-2 pseudovirus neutralization assay. We then evaluated the performance of an ELISA developed in the US, using two-antigen SARS-CoV-2 spike protein and receptor-binding domain. To optimize test performance, we compared single and two-antigen approaches using existing assay cutoffs and population-specific cutoffs for Malian control samples (positive and negative). Background reactivity to SARS-CoV-2 antigens was common in pre-pandemic samples compared to US controls (43.4% (135/311) for spike protein, 22.8% (71/312) for RBD, and 33.9% (79/233) for nucleocapsid protein). SARS-CoV-2 reactivity correlated weakly with other betacoronavirus reactivity, varied between Malian communities, and increased with age. No pre-pandemic samples demonstrated functional activity. Regardless of the cutoffs applied, specificity improved using a two-antigen approach. Test performance was optimal using a two-antigen assay with population-specific cutoffs derived from ROC curve analysis [Sensitivity: 73.9% (51.6-89.8), Specificity: 99.4% (97.7-99.9)]. In the setting of high background reactivity, such as sub-Saharan Africa, SARS-CoV-2 serological assays need careful qualification is to characterize the epidemiology of disease, prevent unnecessary harm, and allocate resources for targeted control measures.

Genetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with clearance of hepatitis C virus. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we genotyped functional variants IFNL4-rs368234815, IFNL4-rs117648444, and IFNL3-rs4803217 and analyzed episodes of malaria, gastrointestinal, and respiratory infections recorded at 30,626 clinic visits from birth up to 5 years of age. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), rs368234815-dG allele was most strongly associated with an earlier time-to-first episode of gastrointestinal infections (p = 0.003). The risk of experiencing an infection episode during the follow-up was also significantly increased with rs368234815-dG allele, with OR = 1.53, 95%CI (1.13–2.07), p = 0.005 for gastrointestinal infections and OR = 1.30, 95%CI (1.02–1.65), p = 0.033 for malaria. All the associations for the moderately linked rs4803217 (r2 = 0.78 in this set) were weaker and lost significance after adjusting for rs368234815. We also analyzed all outcomes in relation to IFN-λ4-P70S groups. Our results implicate IFN-λ4 and not IFN-λ3 as the primary functional cause of genetic associations with increased overall risk and younger age at first clinical episodes but not with recurrence or intensity of several common pediatric infections.

Choroideremia is an X-linked recessive retinal degeneration predominantly affecting hemizygous males. It is caused by mutations in the CHM gene that encodes the Rab escort protein-1. Characteristic features include early nyctalopia followed by progressive constriction of peripheral visual fields and sparing of the central vision until late in life with a distinct fundoscopic appearance. We present the case of a 17-year-old male with a c.282delT in exon 4 of CHM that has not previously been reported. Phenotypically this patient presented with an atypical choroideremia phenotype of early central macular degeneration in addition to the classic peripheral fundus characteristic findings.

Genetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with impaired clearance of hepatitis C virus (HCV) infection. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we analyzed episodes of malaria, gastrointestinal and respiratory infections using information for 30,626 clinic visits from birth through up to 5 years of follow-up. Genetic polymorphisms IFNL4-rs368234815 and IFNL3-rs4803217 that functionally affect type III interferons were genotyped with TaqMan assays. For both genetic variants and each infection, we evaluated time-to-first episode and calculated odds ratios (ORs) for the risk of an infection episode during follow-up, controlling for relevant covariates. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), each copy of the rs368234815-dG allele was associated with an earlier first episode of a gastrointestinal infection (p=0.003) and respiratory infection (p=0.045). The risk of experiencing an infection episode during the follow-up was also significantly increased with each copy of the rs368234815-dG allele – for gastrointestinal infections (OR=1.53, 95%CI (1.13-2.07), p=0.005) and malaria (OR=1.30, 95%CI (1.02-1.65), p=0.033). IFNL4-rs368234815 and IFNL3-rs4803217 were in moderate linkage disequilibrium in this population (r2=0.78), and all the associations for rs4803217 were weaker and lost significance after adjusting for rs368234815, implicating IFN-λ4 and not IFN-λ3 as the primary cause of these associations. We conclude that the ability to produce IFN-λ4 may have broad health-related implications by negatively affecting the immune response and clinical outcomes of several common infections.

Plasmodium vivaxmalaria incidence has increased in Latin America and Asia and is responsible for nearly 74.1% of malaria cases in Latin America. Immune responses toP. vivaxare less well characterized than those toP. falciparum, partly becauseP. vivaxis more difficult to cultivate in the laboratory. While antibodies are known to play an important role inP. vivaxdisease control, few studies have evaluated responses toP. vivaxsexual stage antigens. We collected sera or plasma samples fromP. vivax-infected subjects from Brazil (n= 70) and Cambodia (n= 79) to assess antibody responses to domain 1 of the gametocyte/gamete stage protein Pvs230 (Pvs230D1M). We found that 27.1% (19/70) and 26.6% (21/79) of subjects from Brazil and Cambodia, respectively, presented with detectable antibody responses to Pvs230D1M antigen. The most frequent subclasses elicited in response to Pvs230D1M were IgG1 and IgG3. Although age did not correlate significantly with Pvs230D1M antibody levels overall, we observed significant differences between age strata. Hemoglobin concentration inversely correlated with Pvs230D1M antibody levels in Brazil, but not in Cambodia. Additionally, we analyzed the antibody response against Pfs230D1M, theP. falciparumortholog of Pvs230D1M. We detected antibodies to Pfs230D1M in 7.2 and 16.5% of Brazilian and CambodianP. vivax-infected subjects. Depletion of Pvs230D1M IgG did not impair the response to Pfs230D1M, suggesting pre-exposure toP. falciparum, or co-infection. We also analyzed IgG responses to sporozoite protein PvCSP (11.4 and 41.8% in Brazil and Cambodia, respectively) and to merozoite protein PvDBP-RII (67.1 and 48.1% in Brazil and Cambodia, respectively), whose titers also inversely correlated with hemoglobin concentration only in Brazil. These data establish patterns of seroreactivity to sexual stage Pvs230D1M and show similar antibody responses amongP. vivax-infected subjects from regions of differing transmission intensity in Brazil and Cambodia.

The global spread of artemisinin resistance brings with it the threat of incurable malaria. Already, this disease threatens over 219 million lives per year and causes 5-6% losses in GDP in endemic areas, even with current advances in prevention and treatment. This chapter discusses the currently tenuous position we are in globally, and the impact that could be seen if artemisinin treatment is lost, whether due to the unchecked spread of K13 mutations or poor global investment in treatment and prevention advances. Artemisinin is the backbone of current ACT treatment programs and severe malarial treatment; without it, the success of future malaria eradication programs will be in jeopardy.

The global spread of artemisinin resistance brings with it the threat of incurable malaria. Already, this disease threatens over 219 million lives per year and causes 5-6% losses in GDP in endemic areas, even with current advances in prevention and treatment. This chapter discusses the currently tenuous position we are in globally, and the impact that could be seen if artemisinin treatment is lost, whether due to the unchecked spread of K13 mutations or poor global investment in treatment and prevention advances. Artemisinin is the backbone of current ACT treatment programs and severe malarial treatment; without it, the success of future malaria eradication programs will be in jeopardy.

During pregnancy, Plasmodium falciparum-infected erythrocytes (IE) accumulate in the intervillous spaces of the placenta by binding to chondroitin sulfate A (CSA) and elicit inflammatory responses that are associated with poor pregnancy outcomes. Primigravidae lack immunity to IE that sequester in the placenta and thus are susceptible to placental malaria (PM). Women become resistant to PM over successive pregnancies as antibodies to placental IE are acquired. Here, we assayed plasma collected at delivery from Malian and Tanzanian women of different parities for total antibody levels against recombinant VAR2CSA antigens (FCR3 allele), and for surface reactivity and binding inhibition and opsonizing functional activities against IE using two CSA-binding laboratory isolates (FCR3 and NF54). Overall, antibody reactivity to VAR2CSA recombinant proteins and to CSA-binding IE was higher in multigravidae than in primigravidae. However, plasma from Malian gravid women reacted more strongly with FCR3 whereas Tanzanian plasma preferentially reacted with NF54. Further, acquisition of functional antibodies was variant dependent: binding inhibition of P. falciparum strain NF54 (P < 0.001) but not of the strain FCR3 increased significantly with parity, while only opsonizing activity against FCR3 (P < 0.001) increased significantly with parity. In addition, opsonizing and binding inhibition activities of plasma of multigravidae were significantly correlated in assays of FCR3 (r = 0.4, P = 0.01) but not of NF54 isolates; functional activities did not correlate in plasma from primigravidae. These data suggest that IE surface-expressed epitopes involved in each functional activity differ among P. falciparum strains. Consequently, geographic bias in circulating strains may impact antibody functions. Our study has implications for the development of PM vaccines aiming to achieve broad protection against various parasite strains.

Objective:To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF).Methods:We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations.Results:The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment.Conclusion:The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.

Background: High temperatures are associated with risk of Heat-Related Illness (HRI) and other acute clinical outcomes. Information on HRI risk factors is rarely place-based; decision-makers need l...

BACKGROUND AND OBJECTIVES: In 2000, the US Congress authorized the National Institutes of Health to conduct a prospective national longitudinal study of environmental influences on children’s health and development from birth through 21 years. Several recruitment methodologies were piloted to determine the optimal strategy for a main National Children’s Study. METHODS: After an initial pilot recruitment that used a household enumeration strategy performed poorly, the National Children’s Study Vanguard Study developed and evaluated the feasibility, acceptability, and cost of 4 alternate strategies to recruit a large prospective national probability sample of pregnant women and their newborn children. We compare household-based recruitment, provider-based recruitment, direct outreach, and provider-based sampling (PBS) strategies with respect to overall recruitment success, efficiency, cost, and fulfillment of scientific requirements. RESULTS: Although all 5 strategies achieved similar enrollment rates (63%–81%) among eligible women, PBS achieved the highest recruitment success as measured by the ratio of observed-to-expected newborn enrollees per year of 0.99, exceeding those of the other strategies (range: 0.35–0.48). Because PBS could reach the enrollment target through sampling of high volume obstetric provider offices and birth hospitals, it achieved the lowest ratio of women screened to women enrolled and was also the least costly strategy. With the exception of direct outreach, all strategies enrolled a cohort of women whose demographics were similar to county natality data. CONCLUSIONS: PBS demonstrated the optimal combination of recruitment success, efficiency, cost, and population representativeness and serves as a model for the assembly of future prospective probability-based birth cohorts.

The research presented in this paper highlights the rising incidents of family violence in Aboriginal communities and the lasting and damaging effects of colonialism on the Aboriginal peoples and promotes awareness for those individuals who work closely with the Aboriginal communities. In addition, this paper presents an overview of two primary theories related to Aboriginal family violence, so as to emphasize the complexities surrounding this issue. Family violence within Aboriginal communities has specifically seen a paradigm shift from pre-colonialism to post-colonialism, moving from a rare occurrence to one that has been estimated to impact approximately 65 % of the Aboriginal populations in Canada. Factors such as a transient lifestyle, substance abuse, economic status, and gender inequality have been found to increase the risk of experiencing family violence or domestic abuse. These factors, in addition to a long history of colonialism, have created a state in which Aboriginal families are more vulnerable to the occurrence of family violence. The epidemic of family violence in Aboriginal families is further compounded by underlying racism, lack of cultural competency, and a general misunderstanding of Aboriginal worldviews by service providers.

The disease burden of Wuchereria bancrofti and Plasmodium falciparum malaria is high, particularly in Africa, and co-infection is common. However, the effects of filarial infection on the risk of severe malaria are unknown. We used the remaining serum samples from a large cohort study in Muheza, Tanzania to describe vector-borne filarial sero-reactivity among young children and to identify associations between exposure to filarial parasites and subsequent severe malaria infections. We identified positive filarial antibody responses (as well as positive antibody responses to Strongyloides stercoralis) among infants as young as six months. In addition, we found a significant association between filarial seropositivity at six months of age and subsequent severe malaria. Specifically, infants who developed severe malaria by one year of age were 3.9 times more likely (OR = 3.9, 95% CI: 1.2, 13.0) to have been seropositive for filarial antigen at six months of age compared with infants who did not develop severe malaria., Author summary In this paper, we used a multiplexed, serologic assessment to identify children with previous or current exposure to or infection with filarial parasites or S. stercoralis (a soil transmitted helminth), enhancing our understanding of co-infections in early childhood. We identified an increasing prevalence of filarial antibodies over time in a population of children as young as 6 months old. In addition, we found a significant association between filarial seropositivity at six months of age and subsequent severe malaria.

Identifying factors associated with B lymphocyte depletion and recovery may aid the development of individualized treatment regimens, optimizing therapy for patients with autoimmune disease. In this study, 12 patients with active SLE were monitored at baseline and monthly following treatment with rituximab. The number and phenotype of peripheral blood B lymphocytes, T lymphocytes and natural killer cells were correlated with the extent and longevity of B lymphocyte depletion. This analysis generated three candidate biomarkers for lymphocyte monitoring in patients with autoimmune disease who are treated with rituximab: circulating transitional B cells, the kappa:lambda ratio and natural killer cells. Further refinement of these potential biomarkers may lead to a better understanding of the role of B cells in disease pathogenesis and a more rational use of B cell depletion therapies.

Objective To evaluate the validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) for use by rheumatologists via reliability testing, and to extend the validation for dermatologists. Methods Fourteen subjects with cutaneous lupus erythematosus (CLE; n = 10), a mimicker skin disease only (a cutaneous lesion that may appear clinically similar to CLE; n = 1), or both (n = 3) were rated with the CLASI by academic-based dermatologists (n = 5) and rheumatologists (n = 5). Results The dermatology intraclass correlation coefficient (ICC) was 0.92 for activity and 0.82 for damage; for rheumatology the ICC was 0.83 for activity and 0.86 for damage. For intrarater reliability, the dermatology Spearman's rho was 0.94 for activity and 0.97 for damage; for rheumatology the Spearman's rho was 0.91 for activity and 0.99 for damage. Conclusion Our data confirm the reliability of the CLASI when used by dermatologists and support the CLASI as a reliable instrument for use by rheumatologists.

A revolution in the treatment of rheumatoid arthritis has occurred in recent years. This holds particularly true for B-cell-directed therapies for rheumatoid arthritis. The approval of rituximab for the treatment of rheumatoid arthritis has not only expanded the armamentarium of therapies for rheumatologists, but it has also led the way to better understanding of the biologic sequelae of these treatments as well as the potential to better understand the etiology of autoimmune diseases. This review updates the latest B-cell therapies in rheumatoid arthritis.

Desmoid fibromatosis, or aggressive fibromatosis, is a monoclonal proliferation of fibroblastic cells arising from fascial or musculoaponeurotic tissue. Although desmoid tumours do not metastasise,...

Background Recent emphasis in medical education has focussed on interprofessional learning and teaching, training, and appraisal skills. 1 Learning with other students enhances communication skills, develops professional respect for colleagues and improves team performance. 2 All professions need to work together and be able to professionally challenge each other, learning to receive positive and negative feedback. We set up a scheme to provide interprofessional students with the skills of teaching and learning in feedback and assessment. Methodology A one-day conference was organised, bringing together students and academics from University of Leicester and De Montfort University in a range of backgrounds: medicine, nursing, physiotherapy, speech and language therapy, pharmacy. Experienced lecturers agreed to add content on interprofessional communication, assessment and feedback. The student team designed a range of activities supported by the JASME Teaching Toolkit, to replicate patient management/discharge, and several skills-based activities 3 to apply the morning theory-based lectures, so students could practise and receive real-time feedback from each other. The student team organised the conference day. Outcomes Out of 23 reserved places, 15 attended. 14 recorded an improvement in skills on giving and receiving feedback; 13 rated the activities as very good/excellent as they allowed for collaborative practice and insight into the health disciplines. Delegates particularly praised the feedback element of the sessions and everyone concluded this was an event they would recommend to colleagues. Potential impact Students appreciated the friendly environment to foster interprofessional collaboration and an insight into holistic care. Most recognised that giving and receiving feedback was challenging, but this was a safe place to practise. The experience provided them more empathy towards teachers and acknowledgement how difficult giving negative criticism can be. We aim to improve the event this year by gaining official recognition from the university and involving more interprofessional student groups in writing the simulations. References General Medical Council. Good Medical Practice. London: GMC; 2009 Thistlethwaite J. Interprofessional education: a review of context, learning and the research agenda. Med Educ 2012 Jan;46(1):58–70 Miller GE. The assessment of clinical skills/competence/performance. Acad Med 1990 Sep;65(9 Suppl):S63–7

ObjectiveTo examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.DesignLongitudinal study.SettingInformation about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.SubjectsInfants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.ResultsDaily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.ConclusionsMost of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.

Introduction Remote ischaemic preconditioning (rIPC) is postulated to involve the generation of a humoral signal possibly involving an endothelial signalling pathway. Our lab and others have demonstrated the cardioprotective effects of serum collected from healthy volunteers subjected to rIPC of an arm. This study aims to determine whether cardioprotection from rIPC is preserved in menopause given its association with endothelial and vascular dysfunction, and whether cardioprotection can be restored with oestrogen replacement therapy (ORT). Methods Blood was taken from healthy male and female volunteers and menopausal women before and after 3 months ORT, after 4 cycles of 5 min of upper arm cuff inflation/deflation and the isolated rIPC-serum applied to adult ventricular myocytes (AVM) for 30 mins to simulate rIPC. Ischaemia/reperfusion injury was induced in AVM by incubating cells in a hypoxic chamber (99.5% N 2 ; 0.5% O 2 ), removal of metabolic substrates and the addition of 2-deoxyglucose (10 mM), for 150 mins. Reperfusion was achieved by the addition of pyruvate (5 mM) and reoxygenation for 60 mins. Cell injury was assessed using calcein and propidium iodide staining and fluorescence microscopy. All serum samples were repeated 3–4 × . Data are mean ± s.e.m. Statistical analysis performed using one-way ANOVA, with Tukey’s test; significance taken at p Results Hypoxia/reoxygenation resulted in necrotic injury in control AVM of 58.7 ± 2.3% (n = 36) and this was significantly reduced to 35.1 ± 3.3% (n = 20; p Conclusions Our data show significant cardioprotection by rIC-serum from healthy male and female volunteers. This cardioprotection is absent in women with long standing menopause (>1 yr). ORT over 3 months results in some recovery of cardioprotection but this was not significant. This suggests that although ORT improves endothelium-dependent vasodilatory function, 1 it may not improve other endothelial or vascular functions important for rIPC. It is possible that baseline oestrogen levels are responsible for greater cardioprotection seen in healthy female serum collected before rIPC. Reference 1 Lieberman EH, Gerhard MD, Uehata A, Walsh BW, Selwyn AP, Ganz P, et al . Estrogen Improves Endothelium-Dependent, Flow-Mediated Vasodilation in Postmenopausal Women. Annals of Internal Medicine 1994 December 15;121(12):936–941