Demographically Adjusted Normative Standards for New Indices of Performance on the Paced Auditory Serial Addition Task (PASAT)

Logical grammatical structures comprehension is the ability to understand the relations between objects, actions, and qualities in spoken and written sentences. The Logical Grammatical Structures Test (LGST) was especially devised to assess these abilities in children and adolescents. In the present study the LGST was administered to 405 healthy Dutch children and adolescents. The aims of the present study were (i) to evaluate the psychometric properties of the LGST (using an Item Response Theory framework), and (ii) to establish demographically corrected normative data. The results showed that there was a strong curvilinear relationship between age and LGST performance, i.e., the relative improvement in ability level was much more pronounced for younger children (aged below 14 years) than for older children (aged above 14 years). Level of parental education was positively associated with the LGST performance. Normative data that took the relevant demographic variables into account were established, and it was shown that the LGST had sound psychometric properties.     

The internet is parents' main source of information about psychiatric manifestations of 22q11.2 deletion syndrome (22q11.2DS)

With advances in laboratory technology, an increasing number of potentially pathogenic CNVs is recognised. The phenotypic effects of some CNVs are well characterised, however, it remains unclear how much information reaches the parents of affected children and by what route. The 22q11.2 deletion syndrome (del22q11.2) is caused by the deletion of approximately 40 genes from the long arm of chromosome 22 and was first described in 1955 [1]. Our study reports the extent to which parents of an affected child are aware of the various manifestation of the condition and describes how they first learned about these potential problems.     

Meningococcal Polysaccharide A O-Acetylation Levels Do Not Impact the Immunogenicity of the Quadrivalent Meningococcal Tetanus Toxoid Conjugate Vaccine: Results from a Randomized,Controlled Phase III Study of Healthy Adults Aged 18 to 25 Years

In this study, we compared the immunogenicities of two lots of meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) that differed in serogroup A polysaccharide (PS) O-acetylation levels and evaluated their immunogenicities and safety in comparison to a licensed ACWY polysaccharide vaccine (Men-PS). In this phase III, partially blinded, controlled study, 1,170 healthy subjects aged 18 to 25 years were randomized (1:1:1) to receive one dose of MenACWY-TT lot A (ACWY-A) (68% O-acetylation), MenACWY-TT lot B (ACWY-B) (92% O-acetylation), or Men-PS (82% O-acetylation). Immunogenicity was evaluated in terms of serum bactericidal activity using rabbit complement (i.e., rabbit serum bactericidal activity [rSBA]). Solicited symptoms, unsolicited adverse events (AEs), and serious AEs (SAEs) were recorded. The immunogenicities, in terms of rSBA geometric mean titers, were comparable for both lots of MenACWY-TT. The vaccine response rates across the serogroups were 79.1 to 97.0% in the two ACWY groups and 73.7 to 94.1% in the Men-PS group. All subjects achieved rSBA titers of ≥1:8 for all serogroups. All subjects in the two ACWY groups and 99.5 to 100% in the Men-PS group achieved rSBA titers of ≥1:128. Pain was the most common solicited local symptom and was reported more frequently in the ACWY group (53.9 to 54.7%) than in the Men-PS group (36.8%). The most common solicited general symptoms were fatigue and headache, which were reported by 28.6 to 30.3% and 26.9 to 31.0% of subjects, respectively. Two subjects reported SAEs; one SAE was considered to be related to vaccination (blighted ovum; ACWY-B group). The level of serogroup A PS O-acetylation did not affect vaccine immunogenicity. MenACWY-TT (lot A) was not inferior to Men-PS in terms of vaccine response and was well tolerated.     

American society of cytopathology workload recommendations for automated pap test screening: Developed by the productivity and quality assurance in the era of automated screening task force

Based on current literature and the best available research to date, the current FDA workload limits for automated image‐assisted screening, including the ThinPrep Imaging System and the FocalPoint GS, of 100 slides/day (imaged only slides counted as 0.5) are extremely high and may be associated with significant reduction in sensitivity. This task force has proposed six recommendations relating to cytotechnologist (CT) workload in automated image‐guided Pap test screening, which have already been endorsed by major pathology professional societies. These evidence‐based recommendations, however, pertain only to gynecologic specimens with image‐assisted screening, as there is no current available data to justify modifying screening practices regarding non‐gynecologic specimens. The proposed recommendations are as follow: 1) CT workday should not include more than 7 hours of Pap test screening in a 24‐hr period, and an 8‐hr shift day must include at least 2 paid mini‐breaks of 15 minutes each and a 30‐minute lunch break. 2) Future Studies examining CT workload should use actual hours of screening rather than lesser number of hours extrapolated to 8‐hour days. 3) Average laboratory CT workload should NOT exceed 70 slides/day (slides counted per 2010 FDA bulletin). 4) Proportion of imaged slides that undergo full manual review should be at least either 15%, or twice (2×) the epithelial cell abnormality (ECA) rate, whichever is greater. 5) ECA‐adjusted workload measure is a promising method for calculating and monitoring CT workload, but further studies of this method are necessary before full endorsement. 6) CT productivity and workload limits are just one aspect of a good quality assurance program in a cytology laboratory, so other quality indicators to assess CT performance are essential. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.     

Urban legends series: Sjögren’s syndrome

Oral Diseases (2012) 19 , 46–58 Sjögren’s syndrome (SjS) is one of the most common autoimmune rheumatic diseases, clinically characterized by xerostomia and keratoconjunctivitis sicca. We investigated the following controversial topics: (i) Do we have reliable ways of assessing saliva production? (ii) How important are the quantity and quality of saliva? (iii) Are only anti‐SSA/Ro and anti‐SSB/La relevant for the diagnosis of SjS? (iv) Are the American‐European Consensus criteria (AECC) the best way to diagnose SjS? Results from literature searches suggested the following: (i) Despite the fact that numerous tests are available to assess salivation rates, direct comparisons among them are scarce with little evidence to suggest one best test. (ii) Recent developments highlight the importance of investigating the composition of saliva. However, more research is needed to standardize the methods of analysis and collection and refine the quality of the accumulating data. (iii) In addition to anti‐Ro/La autoantibodies, anti α‐fodrin IgA and anti‐MR3 autoantibodies seem to be promising diagnostic markers of SjS, but more studies are warranted to test their sensitivity and specificity. (iv) AECC are classification, not diagnostic criteria. Moreover, recent innovations have not been incorporated into these criteria. Consequently, treatment directed to patients diagnosed using the AECC might exclude a significant proportion of patients with SjS.     

Transient B-Cell Depletion Combined With Apoptotic Donor Splenocytes Induces Xeno-Specific T- and B-Cell Tolerance to Islet Xenografts

Peritransplant infusion of apoptotic donor splenocytes cross-linked with ethylene carbodiimide (ECDI-SPs) has been demonstrated to effectively induce allogeneic donor-specific tolerance. The objective of the current study is to determine the effectiveness and additional requirements for tolerance induction for xenogeneic islet transplantation using donor ECDI-SPs. In a rat-to-mouse xenogeneic islet transplant model, we show that rat ECDI-SPs alone significantly prolonged islet xenograft survival but failed to induce tolerance. In contrast to allogeneic donor ECDI-SPs, xenogeneic donor ECDI-SPs induced production of xenodonor-specific antibodies partially responsible for the eventual islet xenograft rejection. Consequently, depletion of B cells prior to infusions of rat ECDI-SPs effectively prevented such antibody production and led to the indefinite survival of rat islet xenografts. In addition to controlling antibody responses, transient B-cell depletion combined with ECDI-SPs synergistically suppressed xenodonor-specific T-cell priming as well as memory T-cell generation. Reciprocally, after initial depletion, the recovered B cells in long-term tolerized mice exhibited xenodonor-specific hyporesponsiveness. We conclude that transient B-cell depletion combined with donor ECDI-SPs is a robust strategy for induction of xenodonor-specific T- and B-cell tolerance. This combinatorial therapy may be a promising strategy for tolerance induction for clinical xenogeneic islet transplantation.Pancreatic islet transplantation is a promising treatment option for type 1 diabetes (1). However, a major limitation to its widespread clinical application is the shortage of human donor pancreata (2,3). Xenogeneic sources of islets are an attractive alternative. Currently, porcine islets are considered the best suitable substitute for human transplantation because of the unlimited donor source and their functional compatibility in humans (4). Moreover, they may be resistant to recurrent autoimmunity that is potentially present in recipients of islet transplantation (5,6). Unfortunately, the need for aggressive immunosuppression to control xenogeneic rejection is currently prohibitive for its application as a standard therapy for β-cell replacement in humans (7,8). Therefore, effective tolerance strategies for xenogeneic transplantation are urgently needed.Early studies in xenogeneic transplant models point to a critical role of T-cell–mediated processes in xenograft rejection (7–10). However, B cells are increasingly recognized for their role in xenogeneic immunity (11,12). In addition to mediating humoral responses by differentiating into antibody-producing plasma cells, B cells have also been shown to influence T-cell priming, expansion, and differentiation through a variety of mechanisms, including antigen presentation, costimulation, and cytokine production (13–16). Consequently, B-cell deficiency or depletion ameliorates autoimmune diseases, including type 1 diabetes, multiple sclerosis, and rheumatoid or collagen-induced arthritis (17–19). Likewise, B-cell depletion has been demonstrated to prolong allogeneic and xenogeneic graft survival in nonhuman primates (12,20).We have previously shown that intravenous infusion of donor splenocytes cross-linked with ethylene carbodiimide (ECDI-SPs) induces donor-specific tolerance to allogeneic islet and heart grafts (21–23), and the mechanisms of graft protection in these models involve deletion, anergy, and regulation of T cells of direct and indirect allo-specificities (24).In the current study, we tested donor ECDI-SPs in a concordant (rat-to-mouse) xenogeneic islet transplant model. We show that although ECDI-SPs alone significantly prolong islet xenograft survival, additional transient B-cell depletion is required to promote xenogeneic tolerance and indefinite islet xenograft survival. Furthermore, transient B-cell depletion significantly impairs xenogeneic T-cell priming and memory T-cell generation. Reciprocally, during B-cell reconstitution after transient B-cell depletion, the recovered B cells exhibit xenoantigen-specific unresponsiveness in the long-term tolerized hosts. Collectively, our findings establish a novel and effective tolerance therapy for xenogeneic islet transplantation and underscore the critical role of B-cell depletion in this process.