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Memory Concerns, Memory Performance and Risk of Dementia in Patients with Mild Cognitive Impairment
(2014)
Background: Concerns about worsening memory (“memory concerns”; MC) and impairment in memory performance are both predictors of Alzheimer's dementia (AD). The relationship of both in dementia prediction at the pre-dementia disease stage, however, is not well explored. Refined understanding of the contribution of both MC and memory performance in dementia prediction is crucial for defining at-risk populations. We examined the risk of incident AD by MC and memory performance in patients with mild cognitive impairment (MCI).
Methods: We analyzed data of 417 MCI patients from a longitudinal multicenter observational study. Patients were classified based on presence (n = 305) vs. absence (n = 112) of MC. Risk of incident AD was estimated with Cox Proportional-Hazards regression models.
Results: Risk of incident AD was increased by MC (HR = 2.55, 95%CI: 1.33–4.89), lower memory performance (HR = 0.63, 95%CI: 0.56–0.71) and ApoE4-genotype (HR = 1.89, 95%CI: 1.18–3.02). An interaction effect between MC and memory performance was observed. The predictive power of MC was greatest for patients with very mild memory impairment and decreased with increasing memory impairment.
Conclusions: Our data suggest that the power of MC as a predictor of future dementia at the MCI stage varies with the patients' level of cognitive impairment. While MC are predictive at early stage MCI, their predictive value at more advanced stages of MCI is reduced. This suggests that loss of insight related to AD may occur at the late stage of MCI.
Ongoing liver inflammation in patients with chronic hepatitis C and sustained virological response
(2017)
Background: Novel direct-acting antiviral DAA combination therapies tremendously improved sustained virologic response (SVR) rates in patients with chronic HCV infection. SVR is typically accompanied by normalization of liver enzymes, however, hepatic inflammation, i.e. persistently elevated aminotransferase levels may persist despite HCV eradication. Aim: To investigate prevalence and risk factors for ongoing hepatic inflammation after SVR in two large patient cohorts.
Methods: This post-hoc analysis was based on prospectively collected demographic and clinical data from 834 patients with SVR after HCV treatment with either PegIFN- or DAA-based treatment regimens from the PRAMA trial (n = 341) or patients treated at our outpatient clinic (n = 493).
Results: We observed an unexpected high prevalence of post-SVR inflammation, including patients who received novel IFN-free DAA-based therapies. Up to 10% of patients had ongoing elevation of aminotransferase levels and another 25% showed aminotransferase activity above the so-called healthy range. Several baseline factors were independently associated with post-SVR aminotransferase elevation. Among those, particularly male gender, advanced liver disease and markers for liver steatosis were strongly predictive for persistent ALT elevation. The use of IFN-based antiviral treatment was independently correlated with post-SVR inflammation, further supporting the overall benefit of IFN-free combination regimens.
Conclusion: This is the first comprehensive study on a large patient cohort investigating the prevalence and risk factors for ongoing liver inflammation after eradication of HCV. Our data show a high proportion of patients with ongoing hepatic inflammation despite HCV eradication with potential implications for the management of approximately one third of all patients upon SVR.
Background: While the use of plastic materials has generated huge societal benefits, the "plastic age" comes with downsides: One issue of emerging concern is the accumulation of plastics in the aquatic environment. Here, so-called microplastics (MP), fragments smaller than 5 mm, are of special concern because they can be ingested throughout the food web more readily than larger particles. Focusing on freshwater MP, we briefly review the state of the science to identify gaps of knowledge and deduce research needs.
State of the science: Environmental scientists started investigating marine (micro)plastics in the early 2000s. Today, a wealth of studies demonstrates that MP have ubiquitously permeated the marine ecosystem, including the polar regions and the deep sea. MP ingestion has been documented for an increasing number of marine species. However, to date, only few studies investigate their biological effects. The majority of marine plastics are considered to originate from land-based sources, including surface waters. Although they may be important transport pathways of MP, data from freshwater ecosystems is scarce. So far, only few studies provide evidence for the presence of MP in rivers and lakes. Data on MP uptake by freshwater invertebrates and fish is very limited.
Knowledge gaps: While the research on marine MP is more advanced, there are immense gaps of knowledge regarding freshwater MP. Data on their abundance is fragmentary for large and absent for small surface waters. Likewise, relevant sources and the environmental fate remain to be investigated. Data on the biological effects of MP in freshwater species is completely lacking. The accumulation of other freshwater contaminants on MP is of special interest because ingestion might increase the chemical exposure. Again, data is unavailable on this important issue.
Conclusions: MP represent freshwater contaminants of emerging concern. However, to assess the environmental risk associated with MP, comprehensive data on their abundance, fate, sources, and biological effects in freshwater ecosystems are needed. Establishing such data critically depends on a collaborative effort by environmental scientists from diverse disciplines (chemistry, hydrology, ecotoxicology, etc.) and, unsurprisingly, on the allocation of sufficient public funding.
We compute the static-light baryon spectrum with Nf = 2 flavors of sea quarks using Wilson twisted mass lattice QCD. As light valence quarks we consider quarks, which have the same mass as the sea quarks with corresponding pion masses in the range 340MeV<∼ mPS<∼ 525MeV, as well as partially quenched quarks, which have the mass of the physical s quark. We extract masses of states with isospin I = 0,1/2,1, with strangeness S = 0,−1,−2, with angular momentum of the light degrees of freedom j = 0,1 and with parity P = +,−. We present a preliminary extrapolation in the light u/d and an interpolation in the heavy b quark mass to the physical point and compare with available experimental results.
We study the light scalar mesons a_0(980) and kappa using N_f = 2+1+1 flavor lattice QCD. In order to probe the internal structure of these scalar mesons, and in particular to identify, whether a sizeable tetraquark component is present, we use a large set of operators, including diquark-antidiquark, mesonic molecule and two-meson operators. The inclusion of disconnected diagrams, which are technically rather challenging, but which would allow us to extend our work to e.g. the f_0(980) meson, is introduced and discussed.
Background: Hypoxia is a key driver for infiltrative growth in experimental gliomas. It has remained elusive whether tumor hypoxia in glioblastoma patients contributes to distant or diffuse recurrences. We therefore investigated the influence of perioperative cerebral ischemia on patterns of progression in glioblastoma patients.
Methods: We retrospectively screened MRI scans of 245 patients with newly diagnosed glioblastoma undergoing resection for perioperative ischemia near the resection cavity. 46 showed relevant ischemia nearby the resection cavity. A control cohort without perioperative ischemia was generated by a 1:1 matching using an algorithm based on gender, age and adjuvant treatment. Both cohorts were analyzed for patterns of progression by a blinded neuroradiologist.
Results: The percentage of diffuse or distant recurrences at first relapse was significantly higher in the cohort with perioperative ischemia (61.1%) compared to the control cohort (19.4%). The results of the control cohort matched well with historical data. The change in patterns of progression was not associated with a difference in survival.
Conclusions: This study reveals an unrecognized association of perioperative cerebral ischemia with distant or diffuse recurrence in glioblastoma. It is the first clinical study supporting the concept that hypoxia is a key driver of infiltrative tumor growth in glioblastoma patients.
We perform a detailed study of the adjoint static potential in the pseudoparticle approach, which is a model for SU(2) Yang-Mills theory. We find agreement with the Casimir scaling hypothesis and there is clear evidence for string breaking. At the same time the potential in the fundamental representation is linear for large separations. Our results are in qualitative agreement with results from lattice computations.
Nucleation and growth of aerosol particles from atmospheric vapors constitutes a major source of global cloud condensation nuclei (CCN). The fraction of newly formed particles that reaches CCN sizes is highly sensitive to particle growth rates, especially for particle sizes <10 nm, where coagulation losses to larger aerosol particles are greatest. Recent results show that some oxidation products from biogenic volatile organic compounds are major contributors to particle formation and initial growth. However, whether oxidized organics contribute to particle growth over the broad span of tropospheric temperatures remains an open question, and quantitative mass balance for organic growth has yet to be demonstrated at any temperature. Here, in experiments performed under atmospheric conditions in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN), we show that rapid growth of organic particles occurs over the range from −25 ∘C to 25 ∘C. The lower extent of autoxidation at reduced temperatures is compensated by the decreased volatility of all oxidized molecules. This is confirmed by particle-phase composition measurements, showing enhanced uptake of relatively less oxygenated products at cold temperatures. We can reproduce the measured growth rates using an aerosol growth model based entirely on the experimentally measured gas-phase spectra of oxidized organic molecules obtained from two complementary mass spectrometers. We show that the growth rates are sensitive to particle curvature, explaining widespread atmospheric observations that particle growth rates increase in the single-digit-nanometer size range. Our results demonstrate that organic vapors can contribute to particle growth over a wide range of tropospheric temperatures from molecular cluster sizes onward.
Purpose: Diffuse cortical damage in relapsing–remitting multiple sclerosis (RRMS) is clinically relevant but cannot be directly assessed with conventional MRI. In this study, it was aimed to use diffusion tensor imaging (DTI) techniques with optimized intrinsic eddy current compensation to quantify and characterize cortical mean diffusivity (MD) and fractional anisotropy (FA) changes in RRMS and to analyze the distribution of these changes across the cortex.
Materials and Methods: Three-Tesla MRI acquisition, mapping of the MD providing information about the integrity of microstructural barriers and of the FA reflecting axonal density and surface-based analysis with Freesurfer were performed for 24 RRMS patients and 25 control subjects.
Results: Across the whole cortex, MD was increased in patients (p < 0.001), while surface-based analysis revealed focal cortical FA decreases. MD and FA changes were distributed inhomogeneously across the cortex, the MD increase being more widespread than the FA decrease. Cortical MD correlated with the Expanded Disability Status Scale (EDSS, r = 0.38, p = 0.03).
Conclusion: Damage of microstructural barriers occurs inhomogeneously across the cortex in RRMS and might be spatially more widespread than axonal degeneration. The results and, in particular, the correlation with the clinical status indicate that DTI might be a promising technique for the monitoring of cortical damage under treatment in larger clinical studies.
Semi-dry grasslands were once widely distributed communities, but today they represent some of the most vulnerable habitats in Central Europe. European and national legislation and non-governmental organizations have managed to protect some of the remaining fragments. However, despite their status as Natura 2000 habitats, they are often endangered due to improper management, fragmentation and edge effects from adjacent croplands. By using a sample of 44 semi-dry hay meadows in the south-eastern Alpine Foreland of Styria, we investigated how species-richness and trait composition of semi-dry grassland species respond to variation in patch size, connectivity, abiotic site factors and management regimes. We used linear regression models to identify the most important drivers for richness of typical semi-dry grassland species and thus conservation value. The number of typical semi-dry grassland species was highest in well-connected fragments, i.e. units that shared two or more borders with neighbouring species-rich grasslands. Furthermore, large semi-dry grasslands (> 8000 m²) had highest numbers of semi-dry grassland species and highest relevance for conservation; no difference was found among smaller fragment sizes. Unregular management was associated with increased presence of competitive species which replaced stress-tolerant specialists. Our study indicates that under eutrophication, small fragment size and isolation, only large semi-dry grasslands can sustain a high number of species with high conservation value. The conservation value of smaller semi-dry grassland fragments could be improved by buffer zones, adapted mowing treatments and periodical sheep grazing.