Vaccination of COPD patients with a pneumococcus type 6B tetanus toxoid conjugate vaccine

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThis paper examines how pneumococcal type 6B polysaccharide conjugated to tetanus toxoid (Pn6B-TT) compares to a 23 valent pneumococcal vaccine (pneumococcal polysaccharide (PPS)-23) with respect to immunogenicity and serum opsonic activity in patients with chronic obstructive pulmonary disease (COPD). Patients with COPD aged 55-75 yrs were vaccinated with Pn6B-TT (n=10) or with PPS-23 (n=9). Healthy young adults (HA) were vaccinated with Pn6B-TT as controls. Total antibodies to serotype 6B polysaccharide were measured by radioimmunoassay and immunoglobulin (Ig)G antibodies by enzyme-linked immunosorbent assay. Opsonic activity was measured by a phagocytosis assay using human neutrophils as effector cells. The patient groups were comparable by age, smoking history, lung function and use of steroids. COPD patients vaccinated with Pn6B-TT or PPS-23 showed an increase in IgG antibodies and a nonsignificant increase in opsonic activity. This was similar to the increase in IgG and opsonic activity seen in HA. There was a significant correlation between antibody levels and opsonic activity in COPD patients vaccinated both with Pn6B-TT and PPS-23. Pneumococcal antibodies have been shown to confer protection from infection. The results of the present study indicate that protective immunity can be expected in elderly chronic obstructive pulmonary disease patients vaccinated with conjugate vaccines

Kinematic structure and dynamics of the Denmark Strait Overflow from ship-based observations

Author Posting. © American Meteorological Society, 2020. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 50(11), (2020): 3235–3251, https://doi.org/10.1175/JPO-D-20-0095.1.The dense outflow through Denmark Strait is the largest contributor to the lower limb of the Atlantic meridional overturning circulation, yet a description of the full velocity field across the strait remains incomplete. Here we analyze a set of 22 shipboard hydrographic–velocity sections occupied along the Látrabjarg transect at the Denmark Strait sill, obtained over the time period 1993–2018. The sections provide the first complete view of the kinematic components at the sill: the shelfbreak East Greenland Current (EGC), the combined flow of the separated EGC, and the North Icelandic Jet (NIJ), and the northward-flowing North Icelandic Irminger Current (NIIC). The total mean transport of overflow water is 3.54 ± 0.29 Sv (1 Sv ≡ 106 m3 s−1), comparable to previous estimates. The dense overflow is partitioned in terms of water mass constituents and flow components. The mean transports of the two types of overflow water—Atlantic-origin Overflow Water and Arctic-origin Overflow Water—are comparable in Denmark Strait, while the merged NIJ–separated EGC transports 55% more water than the shelfbreak EGC. A significant degree of water mass exchange takes place between the branches as they converge in Denmark Strait. There are two dominant time-varying configurations of the flow that are characterized as a cyclonic state and a noncyclonic state. These appear to be wind-driven. A potential vorticity analysis indicates that the flow through Denmark Strait is subject to symmetric instability. This occurs at the top of the overflow layer, implying that the mixing/entrainment process that modifies the overflow water begins at the sill.Funding for the study was provided by National Science Foundation (NSF) Grants OCE-1259618, OCE-1756361, and OCE-1558742. The German research cruises were financially supported through various EU Projects (e.g. THOR, NACLIM) and national projects (most recently TRR 181 “Energy Transfer in Atmosphere and Ocean” funded by the German Research Foundation and RACE II “Regional Atlantic Circulation and Global Change” funded by the German Federal Ministry for Education and Research). GWKM acknowledges the support of the Natural Sciences and Engineering Research Council of Canada. LP was supported by NSF Grant OCE-1657870

Revised circulation scheme North of the Denmark Strait

Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of Elsevier Ltd. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part I: Oceanographic Research Papers 79 (2013): 20-39, doi:10.1016/j.dsr.2013.05.007.The circulation and water mass transports north of the Denmark Strait are investigated using recently collected and historical in-situ data along with an idealized numerical model and atmospheric reanalysis fields. Emphasis is placed on the pathways of dense water feeding theDenmark StraitOverflowWater plume as well as the upper-layer circulation of freshwater. It is found that the East Greenland Current (EGC) bifurcates at the northern end of the Blosseville Basin, some 450 km upstream of the Denmark Strait, advecting overflow water and surface freshwater away from the boundary. This “separated EGC” flows southward adjacent to the previously identified North Icelandic Jet, indicating that approximately 70% of the Denmark Strait Overflow Water approaches the sill along the Iceland continental slope. Roughly a quarter of the freshwater transport of the EGC is diverted offshore via the bifurcation. Two hypotheses are examined to explain the existence of the separated EGC. The atmospheric fields demonstrate that flow distortion due to the orography of Greenland imparts significant vorticity into the ocean in this region. The negative wind stress curl, together with the closed bathymetric contours of the Blosseville Basin, is conducive for spinning up an anti-cyclonic gyre whose offshore branch could represent the separated EGC. An idealized numerical simulation suggests instead that the current is primarily eddy-forced. In particular, baroclinic instability of the model EGC spawns large anticyclones that migrate offshore and coalesce upon reaching the Iceland continental slope, resulting in the separated EGC. Regardless of the formation mechanism, the recently obtained shipboard data and historical hydrography both indicate that the separated EGC is a permanent feature of the circulation north of the Denmark Strait.Support for this work was provided by the Norwegian Research Council (KV), the European Union 7th Framework Programme (FP7 2007-2013) under grant agreement n.308299 NACLIM Project (KV), US National Science Foundation grants OCE-0959381 (RP, MS, DT) and OCE-0850416 (MS), and the Natural Sciences and Engineering Research Council of Canada (KM)

The North Icelandic Jet and its relationship to the North Icelandic Irminger Current

Author Posting. © The Authors, 2017. This article is posted here by permission of Sears Foundation for Marine Research for personal use, not for redistribution. The definitive version was published in Journal of Marine Research 75 (2017): 605-639, doi:10.1357/002224017822109505.Shipboard hydrographic and velocity sections are used to quantify aspects of the North Icelandic Jet (NIJ), which transports dense overflow water to Denmark Strait, and the North Icelandic Irminger Current (NIIC), which imports Atlantic water to the Iceland Sea. The mean transports of the two currents are comparable, in line with previous notions that there is a local overturning cell in the Iceland Sea that transforms the Atlantic water to dense overflow water. As the NIJ and NIIC flow along the north side of Iceland, they appear to share a common front when the bottom topography steers them close together, but even when they are separate there is a poleward flow inshore of the NIJ. The interannual variability in salinity of the inflowing NIIC is in phase with that of the outflowing NIJ. It is suggested, however, that the NIIC signal does not dictate that of the NIJ. Instead, the combination of liquid and solid freshwater flux from the east Greenland boundary can account for the observed net freshening of the NIIC to the NIJ for the densest half of the overturning circulation in the northwest Iceland Sea. This implies that the remaining overturning must occur in a different geographic area, consistent with earlier model results. The year-to-year variability in salinity of the NIJ can be explained by applying annual anomalies of evaporation minus precipitation over the Iceland Sea to a one-dimensional mixing model. These anomalies vary in phase with the wind stress curl over the North Atlantic subpolar gyre, which previous studies have shown drives the interannual variation in salinity of the inflowing NIIC.Funding for the project was provided by the National Science Foundation under grants OCE-1558742 (RSP, MAS, DJT, CN), OCE-1433170 (MAS), and OCE-0959381 (DM); the Norwegian Research Council under grant agreement no. 231647 (KV); the Bergen Research Foundation (KV); the European Union Seventh Framework Programme (FP7 2007-2013) under grant agreement 308299 (NACLIM project, KV, HV, and SJ); and the Natural Sciences and Engineering Research Council of Canada (GWKM)

Water mass transformation in the Iceland Sea : Contrasting two winters separated by four decades

Dense water masses formed in the Nordic Seas flow across the Greenland–Scotland Ridge and contribute substantially to the lower limb of the Atlantic Meridional Overturning Circulation. Originally considered an important source of dense water, the Iceland Sea gained renewed interest when the North Icelandic Jet — a current transporting dense water from the Iceland Sea into Denmark Strait — was discovered in the early 2000s. Here we use recent hydrographic data to quantify water mass transformation in the Iceland Sea and contrast the present conditions with measurements from hydrographic surveys conducted four decades earlier. We demonstrate that the large-scale hydrographic structure of the central Iceland Sea has changed significantly over this period and that the locally transformed water has become less dense, in concert with a retreating sea-ice edge and diminished ocean-to-atmosphere heat fluxes. This has reduced the available supply of dense water to the North Icelandic Jet, but also permitted densification of the East Greenland Current during its transit through the presently ice-free western Iceland Sea in winter. Together, these changes have significantly altered the contribution from the Iceland Sea to the overturning in the Nordic Seas over the four decade period.Peer reviewe

Upstream sources of the Denmark Strait Overflow : observations from a high-resolution mooring array

© The Author(s), 2016. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Deep Sea Research Part I: Oceanographic Research Papers 112 (2016): 94-112, doi:10.1016/j.dsr.2016.02.007.We present the first results from a densely instrumented mooring array upstream of the Denmark Strait sill, extending from the Iceland shelfbreak to the Greenland shelf. The array was deployed from September 2011 to July 2012, and captured the vast majority of overflow water denser than 27.8 kgm-3 approaching the sill. The mean transport of overflow water over the length of the deployment was 3.54 ± 0.16 Sv. Of this, 0.58 Sv originated from below sill depth, revealing that aspiration takes place in Denmark Strait. We confirm the presence of two main sources of overflow water: one approaching the sill in the East Greenland Current and the other via the North Icelandic Jet. Using an objective technique based on the hydrographic properties of the water, the transports of these two sources are found to be 2.54 ± 0.17 Sv and 1.00 ± 0.17 Sv, respectively. We further partition the East Greenland Current source into that carried by the shelfbreak jet (1.50 ± 0.16 Sv) versus that transported by a separated branch of the current on the Iceland slope (1.04 ± 0.15 Sv). Over the course of the year the total overflow transport is more consistent than the transport in either branch; compensation takes place among the pathways that maintains a stable total overflow transport. This is especially true for the two East Greenland Current branches whose transports vary out of phase with each other on weekly and longer time scales. We argue that wind forcing plays a role in this partitioning.The mooring and analysis work was supported by NSF OCE research grants OCE-0959381 and OCE-1433958, by the European Union 7th Framework Programme (FP7 2007-2013) under grant agreement n. 308299 NACLIM, and and by the Research Council of Norway through the Fram Centre Flaggship project 6606-299.2017-03-2

Upstream sources of the Denmark Strait Overflow : observations from a high-resolution mooring array

© The Author(s), 2016. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Deep Sea Research Part I: Oceanographic Research Papers 112 (2016): 94-112, doi:10.1016/j.dsr.2016.02.007.We present the first results from a densely instrumented mooring array upstream of the Denmark Strait sill, extending from the Iceland shelfbreak to the Greenland shelf. The array was deployed from September 2011 to July 2012, and captured the vast majority of overflow water denser than 27.8 kgm-3 approaching the sill. The mean transport of overflow water over the length of the deployment was 3.54 ± 0.16 Sv. Of this, 0.58 Sv originated from below sill depth, revealing that aspiration takes place in Denmark Strait. We confirm the presence of two main sources of overflow water: one approaching the sill in the East Greenland Current and the other via the North Icelandic Jet. Using an objective technique based on the hydrographic properties of the water, the transports of these two sources are found to be 2.54 ± 0.17 Sv and 1.00 ± 0.17 Sv, respectively. We further partition the East Greenland Current source into that carried by the shelfbreak jet (1.50 ± 0.16 Sv) versus that transported by a separated branch of the current on the Iceland slope (1.04 ± 0.15 Sv). Over the course of the year the total overflow transport is more consistent than the transport in either branch; compensation takes place among the pathways that maintains a stable total overflow transport. This is especially true for the two East Greenland Current branches whose transports vary out of phase with each other on weekly and longer time scales. We argue that wind forcing plays a role in this partitioning.The mooring and analysis work was supported by NSF OCE research grants OCE-0959381 and OCE-1433958, by the European Union 7th Framework Programme (FP7 2007-2013) under grant agreement n. 308299 NACLIM, and and by the Research Council of Norway through the Fram Centre Flaggship project 6606-299.2017-03-2

HLA-Cw*0602 associates with a twofold higher prevalence of positive streptococcal throat swab at the onset of psoriasis: a case control study

<p>Abstract</p> <p>Background</p> <p>The influence of streptococcal infections in the pathogenesis of psoriasis is not yet understood. <it>In vitro </it>data suggest that streptococcal factors influence T-cell function in psoriasis in a HLA-dependent manner, but studies designed to measure the HLA-C/Streptococci interaction are lacking. In the present study, we hypothesized that there is a statistical interaction between the result of streptococcal throat cultures and the presence of the HLA-Cw*0602 allele in psoriasis patients.</p> <p>Methods</p> <p>We performed a case control study using the "Stockholm Psoriasis Cohort" consisting of patients consecutively recruited within 12 months of disease onset (Plaque psoriasis = 439, Guttate psoriasis = 143), matched to healthy controls (n = 454) randomly chosen from the Swedish Population Registry. All individuals underwent physical examination including throat swabs and DNA isolation for HLA-Cw*0602 genotyping.</p> <p>The prevalence of positive streptococcal throat swabs and HLA-Cw*0602 was compared between patients and controls and expressed as odds ratios with 95% confidence intervals. Associations were evaluated separately for guttate and plaque psoriasis by Fisher's exact test.</p> <p>Results</p> <p>Regardless of disease phenotype, the prevalence of positive streptococcal throat swabs in HLA-Cw*0602 positive patients was twice the prevalence among HLA-Cw*0602 negative patients (OR = 5.8 C.I. = 3.57–9.67, p < 0.001), while no difference was observed among Cw*0602 positive versus negative controls.</p> <p>The corresponding odds ratios for the guttate and plaque psoriasis phenotypes were 3.5 (CI = 1.5–8.7, p = 0.01) and 2.3 (CI = 1.0–5.1, p = 0.02) respectively.</p> <p>Conclusion</p> <p>These findings suggest that among HLA-Cw*0602 positive psoriasis patients, streptococci may contribute to the onset or exacerbation of the inflammatory process independent of the disease phenotype. However, studies on the functional interaction between HLA-C and streptococcal factors are needed.</p

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

&lt;p&gt;Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.&lt;/p&gt; &lt;p&gt;Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.&lt;/p&gt; &lt;p&gt;Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p&#60;5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.&lt;/p&gt; &lt;p&gt;Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.&lt;/p&gt

The mode of school transportation in pre-pubertal children does not influence the accrual of bone mineral or the gain in bone size - two year prospective data from the paediatric osteoporosis preventive (POP) study

<p>Abstract</p> <p>Background</p> <p>Walking and cycling to school are one source of regular physical activity. The aim of this two years observational study in pre-pubertal children was to evaluate if walking and cycling to school was associated with higher total amount of physical activity and larger gain in bone mineral content (BMC) and bone width than when going by car or bus.</p> <p>Methods</p> <p>133 boys and 99 girls aged 7-9 years were recruited to the Malmö Prospective Paediatric Osteoporosis Prevention (POP) study. BMC (g) was measured by dual X-ray absorptiometry (DXA) in total body, lumbar spine (L2-L4) and femoral neck (FN) at baseline and after 24 months. Bone width was measured in L2-L4 and FN. Skeletal changes in the 57 boys and 48 girls who consistently walked or cycled to school were compared with the 24 boys and 17 girls who consistently went by bus or car. All children remained in Tanner stage I. Level of everyday physical activity was estimated by accelerometers worn for four consecutive days and questionnaires. Comparisons were made by independent student's t-tests between means and Fisher's exact tests. Analysis of covariance (ANCOVA) was used to adjust for group differences in age at baseline, duration of organized physical activity, annual changes in length and BMC or bone width if there were differences in these traits at baseline.</p> <p>Results</p> <p>After the adjustments, there were no differences in the annual changes in BMC or bone width when comparing girls or boys who walked or cycled to school with those who went by car or bus. Furthermore, there were no differences in the levels of everyday physical activity objectively measured by accelerometers and all children reached above the by the United Kingdom Expert Consensus Group recommended level of 60 minutes moderate to vigorous physical activity per day.</p> <p>Conclusion</p> <p>A physical active transportation to school for two years is in pre-pubertal children not associated with a higher accrual of BMC or bone width than a passive mode of transportation, possibly due to the fact that the everyday physical activity in these pre-pubertal children, independent of the mode of school transportation, was high.</p