Variants in EMX2 and PTEN do not contribute to risk of endometriosis

Endometriosis has a genetic component, and significant linkage has been found to a region on chromosome 10q. Two candidate genes, EMX2 and PTEN, implicated in both endometriosis and endometrial cancer, lie on chromosome 10q. We hypothesized that variation in EMX2 and/or PTEN could contribute to the risk of endometriosis and may account for some of the linkage signal on 10q. We genotyped single nucleotide polymorphisms (SNPs) in a case-control design to evaluate association between endometriosis and common variations in these two genes. The genotyping and statistical analysis were based on samples collected from Australian volunteers. The cases were 768 unrelated women with surgically confirmed endometriosis selected from affected sister pair (ASP) families participating in the Australian Genes behind Endometriosis Study. The controls were 768 female participants in twin studies who, based on screening questions, did not have a diagnosis of endometriosis. Genotypes of 22 SNPs in the EMX2 gene and 15 SNPs in the PTEN gene were the main outcome measures. Statistical analysis provided measures of linkage disequilibrium and association. Permutation testing showed no globally significant association between any SNPs or haplotypes and endometriosis for either gene. It is unlikely that the EMX2 or PTEN gene variants investigated contribute to risk for initiation and/or development of endometriosis.

The cost-effectiveness of the MobileMums intervention to increase physical activity among mothers with young children: A Markov model informed by a randomised controlled trial

Objectives: To determine the cost-effectiveness of the MobileMums intervention. MobileMums is a 12-week programme which assists mothers with young children to be more physically active, primarily through the use of personalised SMS text-messages. Design: A cost-effectiveness analysis using a Markov model to estimate and compare the costs and consequences of MobileMums and usual care. Setting: This study considers the cost-effectiveness of MobileMums in Queensland, Australia. Participants: A hypothetical cohort of over 36 000 women with a child under 1 year old is considered. These women are expected to be eligible and willing to participate in the intervention in Queensland, Australia. Data sources: The model was informed by the effectiveness results from a 9-month two-arm community-based randomised controlled trial undertaken in 2011 and registered retrospectively with the Australian Clinical Trials Registry (ACTRN12611000481976). Baseline characteristics for the model cohort, treatment effects and resource utilisation were all informed by this trial. Main outcome measures: The incremental cost per quality-adjusted life year (QALY) of MobileMums compared with usual care. Results: The intervention is estimated to lead to an increase of 131 QALYs for an additional cost to the health system of 1.1 million Australian dollars (AUD). The expected incremental cost-effectiveness ratio for MobileMums is 8608 AUD per QALY gained. MobileMums has a 98% probability of being cost-effective at a cost-effectiveness threshold of 64 000 AUD. Varying modelling assumptions has little effect on this result. Conclusions: At a cost-effectiveness threshold of 64 000 AUD, MobileMums would likely be a cost-effective use of healthcare resources in Queensland, Australia. Trial registration number: Australian Clinical Trials Registry; ACTRN12611000481976.

The impact of a streamlined funding application process on application time: Two cross-sectional surveys of Australian researchers

Objective: To examine if streamlining a medical research funding application process saved time for applicants. Design: Cross-sectional surveys before and after the streamlining. Setting: The National Health and Medical Research Council (NHMRC) of Australia. Participants: Researchers who submitted one or more NHMRC Project Grant applications in 2012 or 2014. Main outcome measures: Average researcher time spent preparing an application and the total time for all applications in working days. Results: The average time per application increased from 34 working days before streamlining (95% CI 33 to 35) to 38 working days after streamlining (95% CI 37 to 39; mean difference 4 days, bootstrap p value <0.001). The estimated total time spent by all researchers on applications after streamlining was 614 working years, a 67-year increase from before streamlining. Conclusions: Streamlined applications were shorter but took longer to prepare on average. Researchers may be allocating a fixed amount of time to preparing funding applications based on their expected return, or may be increasing their time in response to increased competition. Many potentially productive years of researcher time are still being lost to preparing failed applications.

Analysis of body composition in individuals with high bone mass reveals a marked increase in fat mass in women but not men

Context: High bone mass (HBM), detected in 0.2% of dual-energy x-ray absorptiometry (DXA) scans, is characterized by raised body mass index, the basis for which is unclear. Objective: To investigate why body mass index is elevated in individuals with HBM, we characterized body composition and examined whether differences could be explained by bone phenotypes, eg, bone mass and/or bone turnover. Design, Setting, and Participants: We conducted a case-control study of 153 cases with unexplained HBM recruited from 4 UK centers by screening 219 088 DXA scans. Atotal of 138 first-degree relatives (of whom 51 had HBM) and 39 spouses were also recruited. Unaffected individuals served as controls. Main Outcome Measures: We measured fat mass, by DXA, and bone turnover markers. Results: Amongwomen, fat mass was inversely related to age in controls (P<.01), but not in HBM cases (P<.96) in whom mean fat mass was 8.9 [95% CI 4.7, 13.0] kg higher compared with controls (fully adjusted mean difference, P<.001). Increased fat mass in male HBM cases was less marked (gender interaction P = .03). Compared with controls, lean mass was also increased in female HBM cases (by 3.3 [1.2, 5.4] kg; P<.002); however, lean mass increases wereless marked than fat mass increases, resulting in 4.5% lower percentage lean mass in HBM cases (P<.001). Osteocalcin was also lower in female HBM cases compared with controls (by 2.8 [0.1, 5.5]μg/L; P = .04). Differences in fat mass were fully attenuated after hip bone mineral density (BMD) adjustment (P = .52) but unchanged after adjustment for bone turnover (P < .001), whereas the greater hip BMD in female HBM cases was minimally attenuated by fat mass adjustment (P<.001). Conclusions: HBM is characterized by a marked increase in fat mass in females, statistically explained by their greater BMD, but not by markers of bone turnover. Copyright © 2013 by The Endocrine Society.

The role of 25-hydroxyvitamin D deficiency in promoting insulin resistance and inflammation in patients with chronic kidney disease: A randomised controlled trial

BACKGROUND Approximately 50% of patients with stage 3 Chronic Kidney Disease are 25-hydroxyvitamin D insufficient, and this prevalence increases with falling glomerular filtration rate. Vitamin D is now recognised as having pleiotropic roles beyond bone and mineral homeostasis, with the vitamin D receptor and metabolising machinery identified in multiple tissues. Worryingly, recent observational data has highlighted an association between hypovitaminosis D and increased cardiovascular mortality, possibly mediated via vitamin D effects on insulin resistance and inflammation. The main hypothesis of this study is that oral Vitamin D supplementation will ameliorate insulin resistance in patients with Chronic Kidney Disease stage 3 when compared to placebo. Secondary hypotheses will test whether this is associated with decreased inflammation and bone/adipocyte-endocrine dysregulation. METHODS/DESIGN This study is a single-centre, double-blinded, randomised, placebo-controlled trial. Inclusion criteria include; estimated glomerular filtration rate 30-59 ml/min/1.73 m(2); aged >or=18 on entry to study; and serum 25-hydroxyvitamin D levels <75 nmol/L. Patients will be randomised 1:1 to receive either oral cholecalciferol 2000IU/day or placebo for 6 months. The primary outcome will be an improvement in insulin sensitivity, measured by hyperinsulinaemic euglycaemic clamp. Secondary outcome measures will include serum parathyroid hormone, cytokines (Interleukin-1beta, Interleukin-6, Tumour Necrosis Factor alpha), adiponectin (total and High Molecular Weight), osteocalcin (carboxylated and under-carboxylated), peripheral blood mononuclear cell Nuclear Factor Kappa-B p65 binding activity, brachial artery reactivity, aortic pulse wave velocity and waveform analysis, and indirect calorimetry. All outcome measures will be performed at baseline and end of study. DISCUSSION To date, no randomised controlled trial has been performed in pre-dialysis CKD patients to study the correlation between vitamin D status with supplementation, insulin resistance and markers of adverse cardiovascular risk. We remain hopeful that cholecalciferol may be a safe intervention, with health benefits beyond those related to bone-mineral homeostasis. TRIAL REGISTRATION Australian and New Zealand Clinical Trials Registry ACTRN12609000246280.

Efficacy of family mediation and the role of family violence: Study protocol

Background Family law reforms in Australia require separated parents in dispute to attempt mandatory family dispute resolution (FDR) in community-based family services before court attendance. However, there are concerns about such services when clients present with a history of high conflict and family violence. This study protocol describes a longitudinal study of couples presenting for family mediation services. The study aims to describe the profile of family mediation clients, including type of family violence, and determine the impact of violence profiles on FDR processes and outcomes, such as the type and durability of shared parenting arrangements and clients’ satisfaction with mediated agreements. Methods A mixed method, naturalistic longitudinal design is used. The sampling frame is clients presenting at nine family mediation centres across metropolitan, outer suburban, and regional/rural sites in Victoria, Australia. Data are collected at pre-test, completion of mediation, and six months later. Self-administered surveys are administered at the three time points, and a telephone interview at the final post-test. The key study variable is family violence. Key outcome measures are changes in the type and level of acrimony and violent behaviours, the relationship between violence and mediated agreements, the durability of agreements over six months, and client satisfaction with mediation. Discussion Family violence is a major risk to the physical and mental health of women and children. This study will inform debates about the role of family violence and how to manage it in the family mediation context. It will also inform decision-making about mediation practices by better understanding how mediation impacts on parenting agreements, and the implications for children, especially in the context of family violence.

After interpretation.

Using 58 audio recorded sessions of psychoanalysis (coming from two analysts and three patients) as data and conversation analysis as method, this paper shows how psychoanalysts deal with patients’ responses to interpretations. After the analyst offers an interpretation, the patient responds: at that point (in the “third position”), the analysts recurrently modify the tenor of the description from what it was in the patients’ responses. They intensify the emotional valence of the description, or they reveal layers of the patients’ experience other than those that the patient reported. Both are usually accomplished in an implicit, non-marked way, and they discreetly index possible opportunities for the patients to modify their understandings of the initial interpretation. Although the patients usually do not fully endorse these modifications, the data available suggests that during the sessions that follow, the participants do work with the aspects of patients’ experience that the analyst highlighted. In discussion, it is suggested that actions that the psychoanalysts produce in therapy, such as choices of turn design in third position, may be informed by working understanding of the minds and mental conflicts of individual patients, alongside the more general therapeutic model of mind they hold to.

The role of androgens in fetal growth: observational study in two genetic models of disordered androgen signalling.

OBJECTIVE: To examine the role of androgens on birth weight in genetic models of altered androgen signalling. SETTING: Cambridge Disorders of Sex Development (DSD) database and the Swedish national screening programme for congenital adrenal hyperplasia (CAH). PATIENTS: (1) 29 girls with XY karyotype and mutation positive complete androgen insensitivity syndrome (CAIS); (2) 43 girls and 30 boys with genotype confirmed CAH. MAIN OUTCOME MEASURES: Birth weight, birth weight-for-gestational-age (birth weight standard deviation score (SDS)) calculated by comparison with national references. RESULTS: Mean birth weight SDS in CAIS XY infants was higher than the reference for girls (mean, 95% CI: 0.4, 0.1 to 0.7; p=0.02) and was similar to the national reference for boys (0.1, -0.2 to 0.4). Birth weight SDS in CAH girls was similar to the national reference for girls (0.0, -0.2 to 0.2) and did not vary by severity of gene mutation. Birth weight SDS in CAH boys was also similar to the national reference for boys (0.2, -0.2 to 0.6). CONCLUSION: CAIS XY infants have a birth weight distribution similar to normal male infants and birth weight is not increased in infants with CAH. Alterations in androgen signalling have little impact on birth weight. Sex dimorphism in birth size is unrelated to prenatal androgen exposure.

Investigating the relationships between user capabilities and product demands for older and disabled users

This paper presents the results of a study that specifically looks at the relationships between measured user capabilities and product demands in a sample of older and disabled users. An empirical study was conducted with 19 users performing tasks with four consumer products (a clock-radio, a mobile phone, a blender and a vacuum cleaner). The sensory, cognitive and motor capabilities of each user were measured using objective capability tests. The study yielded a rich dataset comprising capability measures, product demands, outcome measures (task times and errors), and subjective ratings of difficulty. Scatter plots were produced showing quantified product demands on user capabilities, together with subjective ratings of difficulty. The results are analysed in terms of the strength of correlations observed taking into account the limitations of the study sample. Directions for future research are also outlined. © 2011 Springer-Verlag.

Effects of Naotan Pill on repair of neural cells and cognitive disorders in juvenile rats following hypoxia and ischemia

BACKGROUND: Hypoxia and ischemia induce neuronal damage, decreased neuronal numbers and synaptophysin levels, and deficits in learning and memory functions. Previous studies have shown that lycium barbarum polysaccharide, the most effective component of barbary wolfberry fruit, has protective effects on neural cells in hypoxia-ischemia. OBJECTIVE: To investigate the effects of Naotan Pill on glutamate-treated neural cells and on cognitive function in juvenile rats following hypoxia-ischemia. DESIGN, TIME AND SETTING: The randomized, controlled, in vivo study was performed at the Cell Laboratory of Lanzhou University, Lanzhou Institute of Modern Physics of Chinese Academy of Sciences, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from December 2005 to August 2006. The cellular neurobiology, in vitro experiment was conducted at the Institute of Human Anatomy, Histology, Embryology and Neuroscience, School of Basic Medical Sciences, Lanzhou University, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from March 2007 to January 2008. MATERIALS: Naotan Pill, composed of barbary wolfberry fruit, danshen root, grassleaf sweetflag rhizome, and glossy privet fruit, was prepared by Gansu Provincial Rehabilitation Center, China. Rabbit anti-synaptophysin, choline acetyl transferase polyclonal antibody, streptavidin-biotin complex kit and diaminobenzidine kit (Boster, Wuhan, China), as well as glutamate (Hualian, Shanghai, China) were used in this study. METHODS: Cortical neural cells were isolated from neonatal Wistar rats. Neural cell damage models were induced using glutamate, and administered Naotan Pill prior to and following damage. A total of 54 juvenile Wistar rats were equally and randomly assigned into model, Naotan Pill, and sham operation groups. The left common carotid artery was ligated, and then rat models of hypoxic-ischemic injury were assigned to the model and Naotan Pill groups. At 2 days following model induction, rats in the Naotan Pill group were administered Naotan Pill suspension for 21 days. In the model and sham operation groups, rats received an equal volume of saline. MAIN OUTCOME MEASURES: Neural cell morphology was observed using an inverted phase contrast microscope. Survival rate of neural cells was measured by MTT assay. Synaptophysin and choline acetyl transferase expression was observed in the hippocampal CA1 region of juvenile rats using immunohistochemistry. Cognitive function was tested by the Morris water maze. RESULTS: Pathological changes were detected in glutamate-treated neural cells. Neural cell morphology remained normal after Naotan Pill intervention. Absorbance and survival rate of neural cells were significantly greater following Naotan Pill intervention, compared to glutamate-treated neural cells (P < 0.05). Synaptophysin and choline acetyl transferase expression was lowest in the hippocampal CA1 region in the model group and highest in the sham operation group. Significant differences among groups were observed (P < 0.05). Escape latency and swimming distance were significantly longer in the model group compared to the Naotan Pill group (P < 0.05). CONCLUSION: Naotan Pill exhibited protective and repair effects on glutamate-treated neural cells. Naotan Pill upregulated synaptophysin and choline acetyl transferase expression in the hippocampus and improved cognitive function in rats following hypoxia-ischemia.

Prevalence of overweight and obesity among nurses in Scotland: A cross-sectional study using the Scottish Health Survey.

Background Increasing prevalence of overweight and obesity represents a global pandemic. As the largest occupational group in international healthcare systems nurses are at the forefront of health promotion to address this pandemic. However, nurses own health behaviours are known to influence the extent to which they engage in health promotion and the public's confidence in advice offered. Estimating the prevalence of overweight and obesity among nurses is therefore important. However, to date, prevalence estimates have been based on non-representative samples and internationally no studies have compared prevalence of overweight and obesity among nurses to other healthcare professionals using representative data. Objectives To estimate overweight and obesity prevalence among nurses in Scotland, and compare to other healthcare professionals and those working in non-heath related occupations. Design Cross-sectional study using a nationally representative sample of five aggregated annual rounds (2008-2012) of the Scottish Health Survey. Setting Scotland. Participants: 13,483 adults aged 17 to 65 indicating they had worked in the past 4 weeks, classified in four occupational groups: nurses (n = 411), other healthcare professionals (n = 320), unqualified care staff (n = 685), and individuals employed in non-health related occupations (n = 12,067). Main outcome measures: Prevalence of overweight and obesity defined as Body Mass Index ≥ 25.0. Methods Estimates of overweight and obesity prevalence in each occupational group were calculated with 95% confidence intervals (CI). A logistic regression model was then built to compare the odds of being overweight or obese with not being overweight or obese for nurses in comparison to the other occupational categories. Data were analysed using SAS 9.1.3. Results 69.1% (95% CI 64.6,73.6) of Scottish nurses were overweight or obese. Prevalence of overweight and obesity was higher in nurses than other healthcare professionals (51.3%, CI 45.8,56.7), unqualified care staff (68.5%, CI 65.0,72.0) and those in non-health related occupations (68.9%, CI 68.1,69.7). A logistic regression model adjusted for socio-demographic composition indicated that, compared to nurses, the odds of being overweight or obese was statistically significantly lower for other healthcare professionals (Odds Ratio [OR] 0.45, CI 0.33,0.61) and those in non-health related occupations (OR 0.78, CI 0.62,0.97). Conclusions Prevalence of overweight and obesity among Scottish nurses is worryingly high, and significantly higher than those in other healthcare professionals and non-health related occupations. High prevalence of overweight and obesity potentially harms nurses’ own health and hampers the effectiveness of nurses’ health promotion role. Interventions are therefore urgently required to address overweight and obesity among the Scottish nursing workforce.

WHO guidelines for antimicrobial treatment in children admitted to hospital in an area of intense Plasmodium falciparum transmission: prospective study.

OBJECTIVES: To assess the performance of WHO's "Guidelines for care at the first-referral level in developing countries" in an area of intense malaria transmission and identify bacterial infections in children with and without malaria. DESIGN: Prospective study. SETTING: District hospital in Muheza, northeast Tanzania. PARTICIPANTS: Children aged 2 months to 13 years admitted to hospital for febrile illness. MAIN OUTCOME MEASURES: Sensitivity and specificity of WHO guidelines in diagnosing invasive bacterial disease; susceptibility of isolated organisms to recommended antimicrobials. RESULTS: Over one year, 3639 children were enrolled and 184 (5.1%) died; 2195 (60.3%) were blood slide positive for Plasmodium falciparum, 341 (9.4%) had invasive bacterial disease, and 142 (3.9%) were seropositive for HIV. The prevalence of invasive bacterial disease was lower in slide positive children (100/2195, 4.6%) than in slide negative children (241/1444, 16.7%). Non-typhi Salmonella was the most frequently isolated organism (52/100 (52%) of organisms in slide positive children and 108/241 (45%) in slide negative children). Mortality among children with invasive bacterial disease was significantly higher (58/341, 17%) than in children without invasive bacterial disease (126/3298, 3.8%) (P<0.001), and this was true regardless of the presence of P falciparum parasitaemia. The sensitivity and specificity of WHO criteria in identifying invasive bacterial disease in slide positive children were 60.0% (95% confidence interval 58.0% to 62.1%) and 53.5% (51.4% to 55.6%), compared with 70.5% (68.2% to 72.9%) and 48.1% (45.6% to 50.7%) in slide negative children. In children with WHO criteria for invasive bacterial disease, only 99/211(47%) of isolated organisms were susceptible to the first recommended antimicrobial agent. CONCLUSIONS: In an area exposed to high transmission of malaria, current WHO guidelines failed to identify almost a third of children with invasive bacterial disease, and more than half of the organisms isolated were not susceptible to currently recommended antimicrobials. Improved diagnosis and treatment of invasive bacterial disease are needed to reduce childhood mortality.

The distribution of sales revenues from pharmaceutical innovation.

OBJECTIVE: This report updates our earlier work on the returns to pharmaceutical research and development (R&D) in the US (1980 to 1984), which showed that the returns distributions are highly skewed. It evaluates a more recent cohort of new drug introductions in the US (1988 to 1992) and examines how the returns distribution is emerging for drugs with life cycles concentrated in the 1990s versus the 1980s. DESIGN AND SETTING: Methods were described in detail in our earlier reports. The current sample included 110 new drug entities (including 28 orphan drugs), and sales data were obtained for the period 1988 to 1998, which represented between 7 and 11 years of sales for the drugs included. 20 years was chosen as the expected market life for this cohort, and a 2-step procedure was used to project future sales for the drugs--during the period until patent expiry and then beyond patent expiry until the 20-year time-horizon was completed. Thus, the values in the first half of the life cycle are essentially based on realised sales, while those in the second half are projected using information on patent expiry and other inputs. MAIN OUTCOME MEASURES AND RESULTS: Peak annual sales for the top decile of drugs introduced between 1988 and 1992 in the US amounted to almost $US1.1 billion compared with peak sales of less than $US175 million (1992 values) for the mean compound. In particular, the top decile accounted for 56% of overall sales revenue. Although the sales distributions were skewed in both our earlier and current analysis, the top decile in the later time-period exhibited more rapid rates of growth after launch, a peak that was more than 50% greater in real terms than for the 1980 to 1984 cohort, and a faster rate of expected decline in sales after patent expiry. One factor contributing to the distribution of sales revenues becoming more skewed over time is the orphan drug phenomenon (i.e. most of the orphan drugs are concentrated at the bottom of the distribution). CONCLUSION: The distribution of sales revenues for new drug compounds is highly skewed in nature. In this regard, the top decile of new drugs accounts for more than half of the total sales generated by the 1988 to 1992 cohort analysed. Furthermore, the distribution of sales revenues for this cohort is more skewed than that of the 1980 to 1984 cohort we analysed in previous research.

Economic return of clinical trials performed under the pediatric exclusivity program.

CONTEXT: In 1997, Congress authorized the US Food and Drug Administration (FDA) to grant 6-month extensions of marketing rights through the Pediatric Exclusivity Program if industry sponsors complete FDA-requested pediatric trials. The program has been praised for creating incentives for studies in children and has been criticized as a "windfall" to the innovator drug industry. This critique has been a substantial part of congressional debate on the program, which is due to expire in 2007. OBJECTIVE: To quantify the economic return to industry for completing pediatric exclusivity trials. DESIGN AND SETTING: A cohort study of programs conducted for pediatric exclusivity. Nine drugs that were granted pediatric exclusivity were selected. From the final study reports submitted to the FDA (2002-2004), key elements of the clinical trial design and study operations were obtained, and the cost of performing each study was estimated and converted into estimates of after-tax cash outflows. Three-year market sales were obtained and converted into estimates of after-tax cash inflows based on 6 months of additional market protection. Net economic return (cash inflows minus outflows) and net return-to-costs ratio (net economic return divided by cash outflows) for each product were then calculated. MAIN OUTCOME MEASURES: Net economic return and net return-to-cost ratio. RESULTS: The indications studied reflect a broad representation of the program: asthma, tumors, attention-deficit/hyperactivity disorder, hypertension, depression/generalized anxiety disorder, diabetes mellitus, gastroesophageal reflux, bacterial infection, and bone mineralization. The distribution of net economic return for 6 months of exclusivity varied substantially among products (net economic return ranged from -$8.9 million to $507.9 million and net return-to-cost ratio ranged from -0.68 to 73.63). CONCLUSIONS: The economic return for pediatric exclusivity is variable. As an incentive to complete much-needed clinical trials in children, pediatric exclusivity can generate lucrative returns or produce more modest returns on investment.

Characterization of B cells in muscle-specific kinase antibody myasthenia gravis.

OBJECTIVE: To characterize B-cell subsets in patients with muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG). METHODS: In accordance with Human Immunology Project Consortium guidelines, we performed polychromatic flow cytometry and ELISA assays in peripheral blood samples from 18 patients with MuSK MG and 9 healthy controls. To complement a B-cell phenotype assay that evaluated maturational subsets, we measured B10 cell percentages, plasma B cell-activating factor (BAFF) levels, and MuSK antibody titers. Immunologic variables were compared with healthy controls and clinical outcome measures. RESULTS: As expected, patients treated with rituximab had high percentages of transitional B cells and plasmablasts and thus were excluded from subsequent analysis. The remaining patients with MuSK MG and controls had similar percentages of total B cells and naïve, memory, isotype-switched, plasmablast, and transitional B-cell subsets. However, patients with MuSK MG had higher BAFF levels and lower percentages of B10 cells. In addition, we observed an increase in MuSK antibody levels with more severe disease. CONCLUSIONS: We found prominent B-cell pathology in the distinct form of MG with MuSK autoantibodies. Increased BAFF levels have been described in other autoimmune diseases, including acetylcholine receptor antibody-positive MG. This finding suggests a role for BAFF in the survival of B cells in MuSK MG, which has important therapeutic implications. B10 cells, a recently described rare regulatory B-cell subset that potently blocks Th1 and Th17 responses, were reduced, which suggests a potential mechanism for the breakdown in immune tolerance in patients with MuSK MG.