CCR4-bearing T cells participate in autoimmune diabetes.

Chemokine receptor expression is exquisitely regulated on T cell subsets during the course of their migration to inflammatory sites. In the present study we demonstrate that CCR4 expression marks a pathogenic population of autoimmune T cells. CCR4 was found exclusively on memory CD4(+) T cells during the progression of disease in NOD mice. Cells expressing the CCR4 ligand TARC (thymus- and activation-regulated chemokine) were detected within infiltrated islets from prediabetic mice. Interestingly, neutralization of macrophage-derived chemokine (MDC) with Ab caused a significant reduction of CCR4-positive T cells within the pancreatic infiltrates and inhibited the development of insulitis and diabetes. Furthermore, enhanced recruitment of CCR4-bearing cells in NOD mice resulting from transgenic expression of MDC resulted in acceleration of clinical disease. Cumulatively, the results demonstrate that CCR4-bearing T cells participate in the development of such tissue-driven autoimmune reactions

Winter distribution of Calanus finmarchicus in the Northeast Atlantic

Data from plankton sampling and Optical Plankton Counter deployments during six cruises between December of 1994 and 1999 have been used to derive a composite three-dimensional distribution of the abundance of Calanus finmarchicus during winter (December-January) in the Norwegian Sea and Northeast Atlantic. There are two centres of abundance, one in the eastern Norwegian Sea and Faroe-Shetland Channel, associated with the interface between Norwegian Sea Deep Water and Intermediate Water layers, and another in the Irminger Sea southwest of Iceland in association with Labrador Sea Water. In the open Northeast Atlantic, the concentration of wintering animals is around 30% of that in the Norwegian Sea and the vertical distribution ismore diffuse and on average deeper. Modelling studies have shown that the overwinter distribution and transport are key factors determining the spatial persistence of C. finmarchicus but, apart from the data presented here, there is little knowledge of these large-scale properties

International chronic inflammatory demyelinating polyneuropathy outcome study (ICOS) : Protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous immune-mediated disorder with extensive variation in clinical presentation, electrophysiological phenotype, treatment response and long-term outcome. This heterogeneity may reflect the existence of distinct subtypes of CIDP with a different pathogenesis that require personalized treatment. The International CIDP Outcome Study (ICOS) is a prospective, observational, multicenter cohort study that aims to describe this variation and to define clinical and biological determinants and predictors of these subtypes, disease activity, treatment response and outcome. All patients fulfilling the European Federation of Neurological Societies/Peripheral Nerve Society 2010 diagnostic criteria for CIDP can participate, independent of age, duration and severity of the disease or treatment. We collect data on the clinical presentation, diagnostics, validated clinical outcome measures, (response to) treatment, and we collect biomaterials (DNA, cerebrospinal fluid and serial serum samples). We aim to include at least 1000 CIDP patients with a follow-up of at least 2 years. ICOS started in November 2015 in three academic medical centers in The Netherlands and by October 2018 169 patients are included: 69 new and 100 prevalent cases. ICOS is based on the format of the International Guillain-Barré syndrome (GBS) Outcome Study (IGOS). Dutch centers are invited to participate in ICOS that will continue as an independent national registry. International centers will be able to collect data and biomaterials according to the ICOS protocol by using the optional ICOS module within the INCbase infrastructure. ICOS will help to standardize the collection of data and biosamples for future research in CIDP

Drought-2018 CO2 molar fraction product from Lutjewad

Public release of the observational data product for atmospheric CO2 molar fraction at Lutjewa

Dating Lake Sediments Using Compound‐Specific 14

Abstract Lake sediments in volcanic regions contain continuous records of past eruptions and their environmental consequences. However, the frequent scarcity of plant material in lake sediments makes it difficult to provide robust age estimates. In this study, we performed compound‐specific radiocarbon analysis (CSRA) of fatty acids in a sediment core from Lake Kawaguchi in the Mount Fuji volcanic region, Japan, to assess their potential for dating sediments. The C16 fatty acid in the core top sediments exhibits an almost identical age (983 ± 56 years BP) to that of dissolved inorganic carbon in the modern lake surface water, which confirms that the carbon of this compound is derived from lake phytoplankton. Comparison of the 14C age between the C16 fatty acid and a plant leaf at the widespread (Amagi‐Kawagodaira) tephra layer revealed a lake reservoir age of 1,003 ± 73 14C years at ca. 3,150 cal BP, which is consistent with the modern lake reservoir age and the 14C age of the C16 fatty acid in the core top sediments, within error. The reservoir‐corrected 14C age of the C16 fatty acid yielded a modeled age of 2,837 ± 78 cal BP for the Mount Fuji Tephra (Omuro scoria‐fall deposit) in the core. This age is in good agreement with the age determined from plant remains in the same core (2,938 ± 29 cal BP), indicating that CSRA of C16 fatty acid has the potential to date lake sediments after reservoir age correction, even in sediments with limited occurrence of plant macrofossils

Iron deficiency anaemia and delayed diagnosis of colorectal cancer: a retrospective cohort study

Aim:  The extent to which different referral pathways following a primary care diagnosis of iron deficiency anaemia (IDA) are associated with delay in diagnosis of colorectal cancer (CRC) was determined. Method:  Eligible patients aged 40 or more years, with IDA diagnosed in primary care, and a subsequent diagnosis of CRC, were studied retrospectively. Referral pathways were identified using the specialty of first recorded GP referral following IDA diagnosis. Differences in time to diagnosis of CRC were assessed by referral specialty. Differences in the proportion of cases referred before and after the re-issue of the NICE urgent referral guidelines for suspected lower gastrointestinal (GI) cancer were also assessed. Results: Of 628 882 eligible patients, 3.1% (n = 19 349) were diagnosed with IDA during the study period; 3.0% (n = 578) were subsequently diagnosed with CRC. Two hundred and fifty-nine (44.8%) patients had no recorded referral or a referral unrelated to anaemia or the GI tract. Only 35% (n = 201) of patients were referred to a relevant specialty. Median time to CRC diagnosis ranged from 2.5 months (referral to a relevant surgical specialty) to 31.9 months (haematology). Time to diagnosis was longer in patients referred to a medical compared with a relevant surgical specialty (P = 0.024). There was no significant difference in time to CRC diagnosis before and after the NICE guidelines were re-issued in 2005. Conclusion:  Significant differences exist between referral specialties in time to CRC diagnosis following a primary care diagnosis of IDA. Despite NICE referral recommendations, a significant proportion of patients are still not managed within recommended care pathways to CRC diagnosis

Open, randomized, multicentre italian trial on PEG-IFN plus ribavirin versus PEG-IFN monotherapy for chronic hepatitis C in HIV-coinfected patients on HAART

BACKGROUND: Chronic hepatitis C is common and aggressive in HIV-positive patients, so the development of a well-tolerated HCV therapy is a priority. We evaluated the efficacy and safety of pegylated interferon alpha2b (PEG-IFN) plus ribavirin (RBV) versus PEG-IFN monotherapy in HIV/HCV-coinfected patients undergoing highly active antiretroviral therapy (HAART), and analysed the predictive factors of response. METHODS: An Italian, multicentre, open-label trial including 135 coinfected patients, randomized to PEG-IFN 1.5 microg/kg/week plus RBV 400 mg twice daily (n=69, arm A) or PEG-IFN 1.5 microg/kg/week (n=66, arm B) for 48 weeks. We assessed the predictive values of early virological response (EVR) at week 8 (HCV-RNA drop >2 log10 compared with baseline or undetectable levels) on sustained virological response (SVR). RESULTS: Fifty-five patients (28 from arm A and 27 from arm B) completed 48 weeks of therapy. At the end of treatment, 20/28 patients in arm A and 11/27 in arm B had HCV-RNA <50 IU/ml. In a per-protocol analysis, SVR was reached by 54% of patients in arm A (genotype 2-3, 11/16; genotype 1-4, 4/12) and 22% in arm B (genotype 2-3, 3/15; genotype 1-4, 3/12). In an intention-to-treat analysis, the SVR was 22% in arm A (genotype 2-3, 11/32; genotype 1-4, 4/37) versus 9% in arm B (genotype 2-3, 3/32; genotype 1-4, 3/34). The best predictors of SVR were the use of combination therapy, infection with HCV genotype 3 versus genotype 1, and EVR at week 8. Thirty patients (15 from arm A and 15 from arm B) dropped out of the trial prematurely due to side effects. The positive predictive value of EVR at week 8 was 65%, the negative predictive value was 86%. CONCLUSIONS: PEG-IFN plus RBV can be considered a solid option for the treatment of HIV/HCV-coinfected patients. The key to successfully improving efficacy is strong compliance through strict overall patient monitoring, in order to best manage drug toxicity. EVR assessment at week 8 may become a useful stategy in the management of therapy