A Study of Human Serum Sickness

Twelve patients with bone marrow failure, who were undergoing therapy with daily intravenous infusions of horse antithymocyte globulin, were studied for the development of serum sickness. Eleven of 12 patients developed typical signs and symptoms of serum sickness 8-13 days after the initiation of treatment. These included fever, malaise, cutaneous eruptions, arthralgias, gastrointestinal disturbances, and lymphadenopathy. Eleven of 12 patients developed high levels of circulating immune complexes during serum sickness. All 12 patients also had concomitant decreases of serum C3 and C4 levels. In addition to urticarial and/or morbilliform eruptions, 8 of 11 patients also developed a serpiginous band of erythema along the sides of the fingers, hands, toes, or feet as an early cutaneous sign of serum sickness. Direct immunofluorescence of lesional skin biopsies during serum sickness revealed deposits of immunoglobulin or complement in the walls of small cutaneous blood vessels in 3 of 5 patients. These findings indicate that circulating immune complexes play a central role in the pathophysiology of human serum sickness

1-2-3-flavor color superconductivity in compact stars

We suggest a scenario where the three light quark flavors are sequentially deconfined under increasing pressure in cold asymmetric nuclear matter, e.g., as in neutron stars. The basis for our analysis is a chiral quark matter model of Nambu--Jona-Lasinio (NJL) type with diquark pairing in the spin-1 single flavor (CSL) and spin-0 two/three flavor (2SC/CFL) channels, and a Dirac-Brueckner Hartree-Fock (DBHF) approach in the nuclear matter sector. We find that nucleon dissociation sets in at about the saturation density, n_0, when the down-quark Fermi sea is populated (d-quark dripline) due to the flavor asymmetry imposed by beta-equilibrium and charge neutrality. At about 3n_0 u-quarks appear forming a two-flavor color superconducting (2SC) phase, while the s-quark Fermi sea is populated only at still higher baryon density. The hybrid star sequence has a maximum mass of 2.1 M_sun. Two- and three-flavor quark matter phases are found only in gravitationally unstable hybrid star solutions.Comment: 4 pages, 2 figures, to appear in the proceedings of Quark Matter 2008: 20th International Conference on Ultra-Relativistic Nucleus Nucleus Collisions (QM 2008), Jaipur, India, 4-10 Feb 200

Cold uniform matter and neutron stars in the quark-mesons-coupling model

A new density dependent effective baryon-baryon interaction has been recently derived from the quark-meson-coupling (QMC) model, offering impressive results in application to finite nuclei and dense baryon matter. This self-consistent, relativistic quark-level approach is used to construct the Equation of State (EoS) and to calculate key properties of high density matter and cold, slowly rotating neutron stars. The results include predictions for the maximum mass of neutron star models, together with the corresponding radius and central density, as well the properties of neutron stars with mass of order 1.4 $M_\odot$. The cooling mechanism allowed by the QMC EoS is explored and the parameters relevant to slow rotation, namely the moment of inertia and the period of rotation investigated. The results of the calculation, which are found to be in good agreement with available observational data, are compared with the predictions of more traditional EoS. The QMC EoS provides cold neutron star models with maximum mass 1.9--2.1 M$_\odot$, with central density less than 6 times nuclear saturation density ($n_{0}= 0.16 {\rm fm}^{-3}$) and offers a consistent description of the stellar mass up to this density limit. In contrast with other models, QMC predicts no hyperon contribution at densities lower than $3n_0$, for matter in $\beta$-equilibrium. At higher densities, $\Xi^{-,0}$ and $\Lambda$ hyperons are present

Effect of isovector-scalar meson on neutron star matter in strong magnetic fields

We study the effects of isovector-scalar meson $\delta$ on the equation of state (EOS) of neutron star matter in strong magnetic fields. The EOS of neutron-star matter and nucleon effective masses are calculated in the framework of Lagrangian field theory, which is solved within the mean-field approximation. From the numerical results one can find that the $\delta$-field leads to a remarkable splitting of proton and neutron effective masses. The strength of $\delta$-field decreases with the increasing of the magnetic field and is little at ultrastrong field. The proton effective mass is highly influenced by magnetic fields, while the effect of magnetic fields on the neutron effective mass is negligible. The EOS turns out to be stiffer at $B < 10^{15}$G but becomes softer at stronger magnetic field after including the $\delta$-field. The AMM terms can affect the system merely at ultrastrong magnetic field($B > 10^{19}$G). In the range of $10^{15}$ G -- $10^{18}$ G the properties of neutron-star matter are found to be similar with those without magnetic fields.Comment: 26 pages, 9 figure

Accuracy of dopaminergic imaging as a biomarker for mild cognitive impairment with Lewy bodies.

BACKGROUND: Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain. AIMS: To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies. METHOD: We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard. RESULTS: At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52-77%), specificity 88% (76-95%) and accuracy 76% (68-84%), with positive likelihood ratio 5.3. CONCLUSIONS: It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically

Mild cognitive impairment with Lewy bodies: blood perfusion with arterial spin labelling

This is the final version. Available on open access from via the DOI in this recordObjective: To use arterial spin labelling (ASL) to investigate differences in perfusion in mild cognitive impairment with Lewy bodies (MCI-LB) compared to Alzheimer type MCI (MCI-AD) and healthy controls. Methods: We obtained perfusion images on 32 MCI-LB, 30 MCI-AD and 28 healthy subjects of similar age. Perfusion relative to cerebellum was calculated, and we aimed to examine differences in relative perfusion between MCI-LB and the other groups. This included whole brain voxelwise comparisons, as well as using predefined region-of-interest ratios of medial occipital to medial temporal, and posterior cingulate to precuneus. Differences in occipital perfusion in eyes open vs eyes closed conditions were also examined. Results: Compared to controls, the MCI-LB showed reduced perfusion in the precuneus, parietal, occipital and fusiform gyrus regions. In our predefined regions, the ratio of perfusion in occipital / medial temporal was significantly lower, and the posterior cingulate / precuneus ratio significantly higher in MCI-LB compared to controls. Overall, the occipital perfusion was greater in the eyes open vs closed condition, but this did not differ between groups. Conclusion: We found patterns of altered perfusion in MCI-LB which are similar to those seen in dementia with Lewy bodies, with reduction in posterior parietal and occipital regions, but relatively preserved posterior cingulate.Alzheimer’s Research UKNational Institute for Health Research (NIHR

Neuropsychological Impairments and their cognitive architecture in Mild Cognitive Impairment (MCI) with Lewy Bodies and MCI-Alzheimer’s Disease

This is the final version. Available on open access from Cambridge University Press via the DOI in this recordObjective: The present study aimed to clarify the neuropsychological profile of the emergent diagnostic category of Mild Cognitive Impairment with Lewy bodies (MCI-LB) and determine whether domain-specific impairments such as in memory were related to deficits in domain-general cognitive processes (executive function or processing speed). Method: Patients (n=83) and healthy age- and sex-matched controls (n=34) underwent clinical and imaging assessments. Probable MCI-LB (n=44) and MCI-AD (n=39) were diagnosed following National Institute on Aging-Alzheimer’s Association (NIA-AA) and DLB consortium criteria. Neuropsychological measures included cognitive and psychomotor speed, executive function, working memory, and verbal and visuospatial recall. Results: MCI-LB scored significantly lower than MCI-AD on processing speed (Trail Making Test B: p=0.03, g=0.45; Digit Symbol Substitution Test [DSST]: p=0.04, g=0.47; DSST Error Check: p.05) Conclusions: MCI-LB was characterised by executive dysfunction and slowed processing speed but did not show the visuospatial dysfunction expected, whilst MCI-AD displayed an amnestic profile. However, there was considerable neuropsychological profile overlap and processing speed mediated performance in both MCI subtypes.Alzheimer’s Research UKMedical Research Council (MRC)GE HealthcareAlzheimer’s SocietyNational Institute for Health Research (NIHR

A human gut bacterial genome and culture collection for improved metagenomic analyses

Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional analyses. We present the Human Gastrointestinal Bacteria Culture Collection (HBC), a comprehensive set of 737 whole-genome-sequenced bacterial isolates, representing 273 species (105 novel species) from 31 families found in the human gastrointestinal microbiota. The HBC increases the number of bacterial genomes derived from human gastrointestinal microbiota by 37%. The resulting global Human Gastrointestinal Bacteria Genome Collection (HGG) classifies 83% of genera by abundance across 13,490 shotgun-sequenced metagenomic samples, improves taxonomic classification by 61% compared to the Human Microbiome Project (HMP) genome collection and achieves subspecies-level classification for almost 50% of sequences. The improved resource of gastrointestinal bacterial reference sequences circumvents dependence on de novo assembly of metagenomes and enables accurate and cost-effective shotgun metagenomic analyses of human gastrointestinal microbiota

Uniformity of cardiac 123I-MIBG uptake on SPECT images in older adults with normal cognition and patients with dementia.

INTRODUCTION: Some studies report that assessing regional 123I-cardiac MIBG uptake can aid in the diagnosis of Lewy body disease, but others report heterogeneity in healthy controls. We aimed to evaluate regional cardiac MIBG uptake patterns in healthy older adults and patients with dementia. METHODS: 31 older adults with normal cognition, 15 Alzheimer's disease (AD), and 17 Dementia with Lewy bodies (DLB) patients were recruited. 5 individuals had previous myocardial infarction. Participants with sufficient cardiac uptake for regional SPECT analysis (29/31 controls, 15/15 AD, 5/17 DLB) had relative uptake pattern recorded. Controls were assessed for risk of future cardiovascular events using QRISK2, a validated online tool. RESULTS: In controls uptake was reduced in the inferior wall (85%), apex (23%), septum (15%), and lateral wall (8%). AD and DLB showed similar patterns to controls. Lung or liver interference was present in 61% of cases. Myocardial infarction cases showed regional reductions in uptake, but normal/borderline planar uptake. In controls, there was no relationship between cardiovascular risk score and uptake pattern. CONCLUSIONS: Significant variability of regional cardiac 123I-MIBG uptake is common in cases with normal planar cardiac uptake. Heterogeneity of regional uptake appears non-specific and unlikely to aid in the diagnosis of Lewy body disease

Olfactory impairment in mild cognitive impairment with Lewy bodies and Alzheimer’s disease

This is the author accepted manuscript. The final version is available from Cambridge University Press via the DOI in this recordObjectives: Impaired olfaction may be a biomarker for early Lewy body disease but its value in Mild Cognitive Impairment with Lewy bodies (MCI-LB) is unknown. We compared olfaction in MCI-LB with MCI due to Alzheimer’s disease (MCI-AD) and healthy older adults. We hypothesised that olfactory function would be worse in probable MCI-LB than in both MCI- AD and healthy comparison subjects (HC). Design: Cross-sectional study assessing olfaction using Sniffin’ Sticks 16 (SS-16) in MCI-LB, MCI- AD and HC with longitudinal follow-up. Differences were adjusted for age and receiver operating characteristic curves were used for discriminating MCI-LB from MCI-AD andHC. Setting: Participants were recruited from Memory Services in the North East of England Participants: 38 probable MCI-LB, 33 MCI-AD, 19 possible MCI-LB and 32HC. Measurements: Olfaction was assessed using SS-16 and a questionnaire. Results: Participants with probable MCI-LB had worse olfaction than both MCI-AD (Age-adjusted mean difference (B)=2.05,95% CI:0.62-3.49, p=.005) and HC (B=3.96, 95% CI:2.51–5.40, p<.001). The previously-identified cut-off score for the SS-16 of ≤ 10 had 84% sensitivity for probable MCI-LB (95% CI: 69-94%) but 30% specificity vs MCI-AD. ROC analysis found a lower cut-off of ≤ 7 was better (63% sensitivity for MCI-LB, with 73% specificity vs MCI-AD and 97% vsHC). Asking about olfactory impairments was not useful in identifying them. Conclusions: MCI-LB had worse olfaction than MCI-AD and normal ageing. A lower cut-off score of ≤ 7 is required when using SS-16 in such patients. Olfactory testing may have value in identifying early LB disease in memory services.Alzheimer’s Research UKNational Institute for Health Research (NIHR