Ashcroft v. Iqbal: The Question of a Heightened Standard of Pleading in Qualified Immunity Cases

Background We have previously shown that Lactobacillus reuteri supplementation from pregnancy week 36 and to the infant through the first year of life decreased the prevalence of IgE-associated eczema at 2 years. The underlying immunological mechanisms are unknown, however. Objective To investigate the immunomodulatory effect of probiotic supplementation on allergen- and mitogen-induced immune responses in children until 2 years of age. Methods Blood mononuclear cells were collected at birth, 6, 12 and 24 months from 61 children (29 probiotic and 32 placebo treated) and cultured with ovalbumin, birch and cat extract and Phytohaemagglutinin (PHA). Cytokine and chemokine secretion was determined using an in-house multiplexed Luminex assay and ELISA. Real-time PCR was performed to investigate the Ebi3, Foxp3, GATA-3 and T-bet mRNA expression. Results Probiotic treatment was associated with low cat-induced Th2-like responses at 6 months (IL-5, P = 0.01, and IL-13, P = 0.009), with a similar trend for IL-5 at 12 months (P = 0.09). Cat-induced IFN-γ responses were also lower after probiotic than after placebo treatment at 24 months (P = 0.007), with similar findings for the anti-inflammatory IL-10 at birth (P = 0.001) and at 12 months (P = 0.009). At 24 months, Th2-associated CCL22 levels were lower in the probiotic than in the placebo group after birch stimulation (P = 0.02), with a similar trend after ovalbumin stimulation (P = 0.07). Lower CCL22 levels were recorded at 12 and 24 months (P = 0.03 and P = 0.01) after PHA stimulation. Conclusion and Clinical Relevance Lactobacillus reuteri supplementation decreases allergen responsiveness and may enhance immunoregulatory capacity during infancy. L. reuteri supplementation from week 36 and during the first year of life significantly decreases IgE-associated eczema and lowers allergen and mitogen responsiveness.Funding Agencies|Swedish Research Council|K2011-56X-21854-01-06|Ekhaga Foundation||Olle Engkvist Foundation||Heart and Lung foundation||Research Council for the South-East Sweden|F2000-106|Swedish Asthma and Allergy Association||Cancer and Allergy Association||BioGaia AB, Stockholm, Sweden||University Hospital of Linkoping, Sweden||</p

Marked improvement of overall survival in mantle cell lymphoma: a population based study from the Swedish Lymphoma Registry.

Abstract In recent years, more intensive chemotherapy regimens for mantle cell lymphoma (MCL) have been associated with prolongation of survival. In this study, our aim was to investigate prognostic factors and evaluate improvement in survival in MCL on a population level. The cohort included all patients diagnosed with MCL from 1 January 2000 to 31 March 2010 in the Swedish Lymphoma Registry. At total of 785 patients with MCL were identified. Age, performance status, and B-symptoms were significant prognostic factors for overall survival (OS) in multivariate analysis. In addition, OS was markedly improved (hazard ratio 0.8, 95% confidence interval 0.7-0.9) for patients diagnosed during the latest time period, 2006-2010, also when corrected for prognostic factors as above. Estimated OS at 3 years was 62%, compared to 47% for patients diagnosed earlier (p < 0.01). The reasons for this dramatic improvement in OS are not yet clear, but may be due to the introduction of specific and more potent therapeutic regimens

Partial validation of the Vcheck canine pancreatic lipase assay

Measurement of canine pancreatic lipase immunoreactivity (cPLI) is used for diagnosing pancreatitis in dogs. Because pancreatitis can be a life-threatening disease with severe complications, an in-house cPLI test would be valuable to obtain rapid test results. The aim of this study was to evaluate a point-of-care cPLI test, Vcheck cPL. Precision, determined according to EP15, and linearity under dilution were determined and judged against preset quality goals. Results from the Vcheck cPL were compared with a previously validated cPLI ELISA, Spec cPL. In a retrospective study, cPLI results from dogs with and without acute pancreatitis, as determined by pancreatic ultrasound examination, were investigated to assess the performance of the assay in a clinical setting. Statistical analysis included the Mann-Whitney test, Chi-square test, and Passing-Bablok regression analysis with a significance level of 0.05. Precision of the assay was acceptable, with intra-, inter-, and total coefficients of variation (CV%) less than 12.1%, 6.4%, and 12.1%, respectively. Results from the linearity study indicated that the method was acceptably linear at lower concentrations but not in the high-concentration range. The method comparison study revealed that Vcheck generally measured higher concentrations compared with Spec cPL, and that the methods should not be used interchangeably. Dogs with acute pancreatitis had significantly higher cPLI concentrations compared with dogs without pancreatitis (P < 0.01), but there was a marked overlap in cPL concentrations between the two groups

Drivers and Barriers for Inland Waterway Transportation

Inland waterway transportation (IWT) in Sweden could be a substitute for road transports with the prospects of improving the environmental performance. Sweden currently has no systematic strategies or policies for transports on inland waterways (IWW), and despite available capacity the waterways are barely utilized. In the Netherlands, for example, the IWW capacity is embedded in the transport system and utilized to a large extent. For a successful modal shift it is important to understand the drivers and barriers for the shift and develop strategies to leverage the drivers and mitigate the barriers. This study aims to identify drivers and barriers for IWT based on successful benchmark cases in the Netherlands. Furthermore, based on the learning from these benchmarks the study aims to point out strategic actions for Sweden regarding IWT. The data for this study was collected from IWT organizations, shippers and local administrations in the Netherlands. The results showed that main drivers for IWT are congestion relief, cost reduction and lower environmental impact. On the other hand, main barriers are slow pace of development, high investment costs and poor hinterland connectivity. For a successful modal shift in Sweden, it is crucial to prepare governmental support, a change in stakeholders’ mindset, decisive attitude to modal shift process and a strong long-term perspective

Pre‐ and postnatal administration of <i>Lactobacillus reuteri</i> decreases TLR2 responses in infants

BACKGROUND: Mice models indicate that intact Toll like receptor (TLR) signaling may be essential for the allergy protective effects of diverse bacterial exposure observed in clinical trials and epidemiological studies. Probiotic supplementation with Lactobacillus reuteri from pregnancy week 36 and to the infant through the first year of life decreased the prevalence of IgE-associated eczema at two years (ClinicalTrials.gov NCT01285830). The effect of this supplementation on innate immune responses to bacterial products and the expression of associated TLRs were explored. METHODS: Blood mononuclear cells were collected at birth, 6, 12 and 24 months from 61 infants and cultured with TLR2, 4 and 9 ligands. Cytokine and chemokine secretion was determined as well as TLR2, 4 and 9 mRNA expression. RESULTS: Probiotic supplementation was associated with decreased LTA (lipoteichoic acid) induced CCL4, CXCL8, IL-1β and IL-6 responses at 12 months and decreased CCL4 and IL-1β secretion at 24 months. TLR2 mRNA expression was not affected by probiotic treatment. CONCLUSIONS: Decreased responses to TLR2, the main receptor for LTA from Gram positive bacteria, in probiotic treated children seem to be dependent on factors downstream of TLR mRNA expression

High-affinity antibodies specific to the core region of the tau protein exhibit diagnostic and therapeutic potential for Alzheimer’s disease

We would like to thank the South West Dementia Brain Bank (SWDBB) and donors for the human brain tissue provided for this study. We would like to acknowledge the University of Aberdeen core facilities of Microscopy and Histology, Iain Fraser Cytometry Centre, and Proteomics for their support with microscopy, flow cytometry and surface plasmon resonance, respectively.Peer reviewe

DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML)

Pediatric acute myeloid leukemia (AML) is a heterogeneous disease composed of clinically relevant subtypes defined by recurrent cytogenetic aberrations. The majority of the aberrations used in risk grouping for treatment decisions are extensively studied, but still a large proportion of pediatric AML patients remain cytogenetically undefined and would therefore benefit from additional molecular investigation. As aberrant epigenetic regulation has been widely observed during leukemogenesis, we hypothesized that DNA methylation signatures could be used to predict molecular subtypes and identify signatures with prognostic impact in AML. To study genome-wide DNA methylation, we analyzed 123 diagnostic and 19 relapse AML samples on Illumina 450k DNA methylation arrays. We designed and validated DNA methylation-based classifiers for AML cytogenetic subtype, resulting in an overall test accuracy of 91%. Furthermore, we identified methylation signatures associated with outcome in t(8;21)/RUNX1-RUNX1T1, normal karyotype, and MLL/KMT2A-rearranged subgroups (p < 0.01). Overall, these results further underscore the clinical value of DNA methylation analysis in AML

DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML)

Pediatric acute myeloid leukemia (AML) is a heterogeneous disease composed of clinically relevant subtypes defined by recurrent cytogenetic aberrations. The majority of the aberrations used in risk grouping for treatment decisions are extensively studied, but still a large proportion of pediatric AML patients remain cytogenetically undefined and would therefore benefit from additional molecular investigation. As aberrant epigenetic regulation has been widely observed during leukemogenesis, we hypothesized that DNA methylation signatures could be used to predict molecular subtypes and identify signatures with prognostic impact in AML. To study genome-wide DNA methylation, we analyzed 123 diagnostic and 19 relapse AML samples on Illumina 450k DNA methylation arrays. We designed and validated DNA methylation-based classifiers for AML cytogenetic subtype, resulting in an overall test accuracy of 91%. Furthermore, we identified methylation signatures associated with outcome in t(8;21)/RUNX1-RUNX1T1, normal karyotype, and MLL/KMT2A-rearranged subgroups (p < 0.01). Overall, these results further underscore the clinical value of DNA methylation analysis in AML