To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
To examine the impact of determinants of incident dementia in three different old age groups (75–79, 80–84, 85+years) in Germany.
Multicenter prospective AgeCoDe/AgeQualiDe cohort study with baseline and nine follow-up assessments at 1.5-year intervals.
Primary care medical record registry sample.
General practitioners’ (GPs) patients aged 75+years at baseline.
Conduction of standardized interviews including neuropsychological assessment and collection of GP information at each assessment wave. We used age-stratified competing risk regression models (accounting for the competing event of mortality) to assess determinants of incident dementia and age-stratified ordinary least square regressions to quantify the impact of identified determinants on the age at dementia onset.
Among 3027 dementia-free GP patients, n = 704 (23.3%) developed dementia during the 13-year study period. Worse cognitive performance and subjective memory decline with related worries at baseline, and the APOE ε4 allele were associated independently with increased dementia risk in all three old age groups. Worse cognitive performance at baseline was also associated with younger age at dementia onset in all three age groups. Other well-known determinants were associated with dementia risk and age at dementia onset only in some or in none of the three old age groups.
This study provides further evidence for the age-specific importance of determinants of incident dementia in old age. Such specifics have to be considered more strongly particularly with regard to potential approaches of early detection and prevention of dementia.
Karlsruhe Institute of Technology (KIT) is doing research and development in the field of megawatt-class radio frequency (RF) sources (gyrotrons) for the Electron Cyclotron Resonance Heating (ECRH) systems of the International Thermonuclear Experimental Reactor (ITER) and the DEMOnstration Fusion Power Plant that will follow ITER. In the focus is the development and verification of the European coaxial-cavity gyrotron technology which shall lead to gyrotrons operating at an RF output power significantly larger than 1 MW CW and at an operating frequency above 200 GHz. A major step into that direction is the final verification of the European 170 GHz 2 MW coaxial-cavity pre-prototype at longer pulses up to 1 s. It bases on the upgrade of an already existing highly modular short-pulse (ms-range) pre-prototype. That pre-prototype has shown a world record output power of 2.2 MW already. This paper summarizes briefly the already achieved experimental results using the short-pulse pre-prototype and discusses in detail the design and manufacturing process of the upgrade of the pre-prototype toward longer pulses up to 1 s.
Subjective cognitive decline (SCD), the potentially earliest notable manifestation of preclinical Alzheimer's disease and other dementias, was consistently associated with lower quality of life in cross-sectional studies. The aim of this study was to investigate whether such an association persists longitudinally – particularly with health-related quality of life (HRQoL) in older individuals without cognitive impairment.
Data were derived from follow-up 2–6 of the prospective Germany Study on Ageing, Cognition and Dementia in Primary Care (AgeCoDe) covering a total six-year observation period. We used linear mixed effects models to estimate the effect of SCD on HRQoL measured by the EQ-5D visual analogue scale (EQ VAS).
Of 1,387 cognitively unimpaired individuals aged 82.2 years (SD = 3.2) on average, 702 (50.6%) reported SCD and 230 (16.6%) with SCD-related concerns. Effect estimates of the linear mixed effects models revealed lower HRQoL in individuals with SCD (unadjusted: –3.7 points on the EQ VAS, 95%CI = –5.3 to –2.1; SE = 0.8; p < 0.001; adjusted: –2.9 points, 95%CI = –3.9 to –1.9; SE = 0.5; p < 0.001) than in individuals without SCD. The effect was most pronounced in SCD with related concerns (unadjusted: –5.4, 95%CI = –7.6 to –3.2; SE = 1.1; p < 0.001; adjusted: –4.3, 95%CI = –5.8 to –2.9, SE = 0.7; p < 0.001).
SCD constitutes a serious issue to older cognitively unimpaired individuals that is depicted in persisting lower levels of HRQoL beyond depressive symptoms and functional impairment. Therefore, SCD should be taken seriously in clinical practice.
Chitinous arm hooks (onychites) of belemnoid coleoid cephalopods are widely distributed in Mesozoic sediments. Due to their relative abundance and variable morphology compared with the single, bullet-shaped, belemnite rostrum, arm hooks came into the focus of micropaleontologists as a promising index fossil group for the Jurassic–Cretaceous rock record and have been the target of functional, ecological, and phylogenetic interpretations in the past. Based on three well-preserved arm crowns of the Toarcian diplobelid Chondroteuthis wunnenbergi, we analyzed the shape of a total of 87 micro-hooks. The arm crown of Chondroteuthis is unique in having uniserial rather than biserial hooks. The first application of elliptic Fourier shape analysis to the arm weapons of belemnoid coleoids allows for the distinction of four micro-hook morphotypes and the quantification of shape variation within these morphotypes. Based on the best-preserved arm crown, we reconstructed the distribution of morphotypes within the arm crown and along a single arm. Our quantitative data support former observations that smaller hooks were found close to the mouth and at the most distal arm parts, while the largest hooks were found in the central part of the arm crown. Furthermore, we found a distinct arm differentiation, as not every arm was equipped with the same hook morphotype. Here, we report the functional specialization of the belemnoid arm crown for the first time and speculate about the potential function of the four morphotypes based on comparisons with modern cephalopods. Our analyses suggest a highly adapted functional morphology and intra-individual distribution of belemnoid hooks serving distinct purposes mainly during prey capture.
Most of the previous studies attempted to disentangle the relationship between disability and depressive symptoms were limited to observation periods of only few years. Moreover, evidence is missing regarding the complex co-occurrence of disability and depressive symptoms in old age in Germany. In order to close the research gap, we aimed at disentangling the complex co-occurrence of disability and depressive symptoms in old age in Germany over a longer time frame.
Based on data from a representative survey of the German general population aged 75 years and older, the course of disability as well as depressive symptoms was observed every 1.5 years over six waves. While disability was quantified by the Lawton and Brody Instrumental Activities of Daily Living scale, the Geriatric Depression Scale was used to measure depressive symptoms. Taking into account the complex co-occurrence of depressive symptoms and disability, a panel vector autoregressive model was used. By taking the first differences, unobserved heterogeneity was taken into account.
In the total sample and in both sexes, we revealed a robust positive association between an initial change in depressive symptoms and subsequent changes in disability. No robust association between an initial change in disability and a subsequent change in depressive symptoms was detected.
Our findings highlight the importance of changes in depressive symptoms for future changes in disability in old age.
A number of laser facilities coming online all over the world promise the capability of high-power laser experiments with shot repetition rates between 1 and 10 Hz. Target availability and technical issues related to the interaction environment could become a bottleneck for the exploitation of such facilities. In this paper, we report on target needs for three different classes of experiments: dynamic compression physics, electron transport and isochoric heating, and laser-driven particle and radiation sources. We also review some of the most challenging issues in target fabrication and high repetition rate operation. Finally, we discuss current target supply strategies and future perspectives to establish a sustainable target provision infrastructure for advanced laser facilities.
Plant sterols (PS) lower LDL-cholesterol, an established risk factor for CHD. Endothelial dysfunction and low-grade inflammation are two important features in the development of atherosclerosis. Whether PS affect biomarkers of endothelial function and low-grade inflammation is not well studied. The aim of the present study was to investigate the effect of regular intake of PS on biomarkers of endothelial dysfunction and low-grade inflammation. In a double-blind, randomised, placebo-controlled, parallel-group study, which was primarily designed to investigate the effect of PS intake on vascular function (clinicaltrials.gov: NCT01803178), 240 hypercholesterolaemic but otherwise healthy men and women consumed a low-fat spread with added PS (3 g/d) or a placebo spread for 12 weeks. Endothelial dysfunction biomarkers (both vascular and intracellular adhesion molecules 1 and soluble endothelial-selectin) and low-grade inflammation biomarkers (C-reactive protein, serum amyloid A, IL-6, IL-8, TNF-α and soluble intercellular adhesion molecule-1) were measured using a multi-array detection system based on electrochemiluminescence technology. Biomarkers were combined using z-scores. Differences in changes from baseline between the PS and the placebo groups were assessed. The intake of PS did not significantly change the individual biomarkers of endothelial dysfunction and low-grade inflammation. The z-scores for endothelial dysfunction (−0·02; 95 % CI −0·15, 0·11) and low-grade inflammation (−0·04; 95 % CI −0·16, 0·07) were also not significantly changed after PS intake compared with placebo. In conclusion, biomarkers of endothelial dysfunction and low-grade inflammation were not affected by regular intake of 3 g/d PS for 12 weeks in hypercholesterolaemic men and women.
We describe a hybrid pixel array detector (electron microscope pixel array detector, or EMPAD) adapted for use in electron microscope applications, especially as a universal detector for scanning transmission electron microscopy. The 128×128 pixel detector consists of a 500 µm thick silicon diode array bump-bonded pixel-by-pixel to an application-specific integrated circuit. The in-pixel circuitry provides a 1,000,000:1 dynamic range within a single frame, allowing the direct electron beam to be imaged while still maintaining single electron sensitivity. A 1.1 kHz framing rate enables rapid data collection and minimizes sample drift distortions while scanning. By capturing the entire unsaturated diffraction pattern in scanning mode, one can simultaneously capture bright field, dark field, and phase contrast information, as well as being able to analyze the full scattering distribution, allowing true center of mass imaging. The scattering is recorded on an absolute scale, so that information such as local sample thickness can be directly determined. This paper describes the detector architecture, data acquisition system, and preliminary results from experiments with 80–200 keV electron beams.
Reconstructing the evolution of arid landscapes is challenged by limited availability of appropriate environmental archives. A widespread surface feature — stone pavement — traps aeolian fines and forms a special accretionary archive. Seven stone pavement-covered sections on basalt flows in the eastern Mojave Desert are condensed into a composite section, comprising five sedimentological units supported by an OSL-based chronology. Three of the units are of accretionary nature and each is covered by a stone pavement. They were deposited > 50.9–36.6 ka, < 36.6–14.2 ka and < 14.2 ka, and they are intimately coupled with the history of nearby Lake Mojave, which advances the current understanding of regional aeolian activity. End-member modeling analysis of grain-size distributions yielded seven sediment transport regimes. The accretionary system operates in two modes: A) episodic formation of a stone pavement by lateral processes once a vesicular horizon has formed on a barren surface; and B) accretion of dust and eventual burial of the clast layer. These findings improve current concepts about stone pavement evolution and their environmental proxy function in arid landscapes. Stone pavement-covered accretionary deposits are a new key archive that allows quantifying the relative importance of dust accretion, slope processes, soil formation and vegetation cover.
The role of self generated magnetic fields in the transport of a heat wave following a nanosecond laser irradiation of a solid target is investigated. Magnetic fields are expected to localize the electron carrying the heat flux but at the same time are affected in their evolution by the heat flux itself. We performed simultaneous measurements of heat wave propagation velocity within the target and magnetic fields developing on the target surface. These were compared to results obtained by numerical magneto-hydrodynamic modeling, including self-generated B fields. The comparison shows that longitudinal heat flow is overestimated in the simulations. Similarly, but most notably, the radial expansion of the magnetic fields is underestimated by the modeling. The two are likely linked, the more pronounced radial drift of B-fields induces a rotation of heat flux in the radial direction, and corresponding longitudinal heat flux inhibition. This suggests the need for improving present modeling of self-generated magnetic fields evolution in high power laser-matter interaction.
As physical activity may modify the effect of the apolipoprotein E (APOE) ε4 allele on the risk of dementia and Alzheimer's disease (AD) dementia, we tested for such a gene–environment interaction in a sample of general practice patients aged ⩾75 years.
Data were derived from follow-up waves I–IV of the longitudinal German study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe). The Kaplan–Meier survival method was used to estimate dementia- and AD-free survival times. Multivariable Cox regression was used to assess individual associations of APOE ε4 and physical activity with risk for dementia and AD, controlling for covariates. We tested for gene–environment interaction by calculating three indices of additive interaction.
Among the randomly selected sample of 6619 patients, 3327 (50.3%) individuals participated in the study at baseline and 2810 (42.5%) at follow-up I. Of the 2492 patients without dementia included at follow-up I, 278 developed dementia (184 AD) over the subsequent follow-up interval of 4.5 years. The presence of the APOE ε4 allele significantly increased and higher physical activity significantly decreased risk for dementia and AD. The co-presence of APOE ε4 with low physical activity was associated with higher risk for dementia and AD and shorter dementia- and AD-free survival time than the presence of APOE ε4 or low physical activity alone. Indices of interaction indicated no significant interaction between low physical activity and the APOE ε4 allele for general dementia risk, but a possible additive interaction for AD risk.
Physical activity even in late life may be effective in reducing conversion to dementia and AD or in delaying the onset of clinical manifestations. APOE ε4 carriers may particularly benefit from increasing physical activity with regard to their risk for AD.
We investigate the hydrodynamic interactions of spherical colloidal nano particles and nano tetrahedra near a planar wall by means of molecular dynamics (MD) simulations of rigid particles within an all-atom solvent. For both spherical and nano-tetrahedral particles, we find that the parallel and perpendicular components of the local diffusion coefficient and viscosity, show good agreement with hydrodynamic theory of Faxén and Brenner. This provides further evidence that low perturbations from sphericality of a nanoparticle’s shape has little influence on its local diffusive behaviour, and that for this particular case, the continuum theory fluid dynamics is valid even down to molecular scales.
Whether late-onset depression is a risk factor for or a prodrome of dementia remains unclear. We investigated the impact of depressive symptoms and early- v. late-onset depression on subsequent dementia in a cohort of elderly general-practitioner patients (n = 2663, mean age = 81.2 years).
Risk for subsequent dementia was estimated over three follow-ups (each 18 months apart) depending on history of depression, particularly age of depression onset, and current depressive symptoms using proportional hazard models. We also examined the additive prediction of incident dementia by depression beyond cognitive impairment.
An increase of dementia risk for higher age cut-offs of late-onset depression was found. In analyses controlling for age, sex, education, and apolipoprotein E4 genotype, we found that very late-onset depression (aged ⩾70 years) and current depressive symptoms separately predicted all-cause dementia. Combined very late-onset depression with current depressive symptoms was specifically predictive for later Alzheimer's disease (AD; adjusted hazard ratio 5.48, 95% confidence interval 2.41–12.46, p < 0.001). This association was still significant after controlling for cognitive measures, but further analyses suggested that it was mediated by subjective memory impairment with worries.
Depression might be a prodrome of AD but not of dementia of other aetiology as very late-onset depression in combination with current depressive symptoms, possibly emerging as a consequence of subjectively perceived worrisome cognitive deterioration, was most predictive. As depression parameters and subjective memory impairment predicted AD independently of objective cognition, clinicians should take this into account.
Polycrystalline samples of the single-layered cobaltate La2-xCaxCoO4 were prepared in a wide doping range of 0 ≤ x ≤ 1.5. Structural properties were characterized at room temperature. The orthorhombic distorted structure of the mother compound La2CoO4 changes to a tetragonal structure for x = 0.5 and then becomes orthorhombic again for x > 0.5. The magnetic properties were investigated in the temperature range from 5 K ≤ T ≤ 300 K. With increasing hole-doping a successive decrease of antiferromagnetic exchange is observed for x ≤ 0.5 whereas an increase of ferromagnetic exchange evolves for x ≥ 0.5.
Epidemiological, clinical and post mortem studies indicate that inflammatory and immune reactions are involved in the pathomechanisms of affective and schizophrenic spectrum disorders. However, in psychiatric patients, only sporadic investigation on immunochemistry has been performed and information about immunofunction derived by investigation of immunocompetent cells in the CSF is not available to date.
Here we present an interdisciplinary work of neurologists, psychiatrists and hemato-immunologists focusing on the immunology of psychiatric and neurological disorders. In a first study including 63 patients with therapy resistant affective and schizophrenic spectrum disorders we applied conventional, validated neurological CSF investigation such as analysis of albumin, IgG, IgA, IgM, oligoclonal IgG and specific antibodies, cell count and interpreted the data by Reibergrams.
In a second study, we applied the highly sensitive and specific multicolour flowcytometry of paired samples of CSF and peripheral blood cells to characterize the immunostatus of psychiatric and neurological patients. We demonstrate that flowcytometry technology constitutes an appropriate method to investigate subsets of lymphocytes even with low CSF cell numbers, and therefore as a promising diagnostic tool for routine purposes in the differential diagnosis of psychiatric diseases. Furthermore, knowledge of the frequencies of T cell subsets such as the T regulatory cell type might open new avenues to models of psychiatric and neurological diseases as well as diagnostic and monitoring implications.
Three hundred and seventy-six patients attending their general practitioner with cutaneous warts at five health centres in Northern Ireland were screened for human papilloma virus (HPV) types 1 and 2 IgM antibody using an indirect immunofluorescence test. Eighty-eight (23·4%) patients were positive for HPV type 1 IgM and 156 (41·5%) for HPV type 2 IgM. HPV 1 IgM antibody was significantly more likely to be associated with plantar warts than warts elsewhere (P 0·0001). HPV 2 IgM was present in 45 (34·1%) patients with plantar warts and 99 (45·6%) patients with warts at other sites (P=0·1). Evidence of multiple infection by HPV types 1 and 2 was demonstrated by the finding of HPV 1 and 2 IgM antibodies in the sera of 16 (4·3%). HPV 4 was found in only 1 out of 30 biopsies and HPV 4 IgM was undetectable in 50 randomly chosen sera.
At the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B) Dhaka we studied the trends in cholera for the period January 1992 to May 1995. Vibrio cholerae O139 Bengal emerged as a second aetiologic agent of cholera in Dhaka in January 1993. In 1993, the majority of cholera cases was due to V. cholerae O139, with V. cholerae O1 accounting for a small proportion of cases. During the latter part of the study period (Jan 1994–May 1995), V. cholerae O1 re-emerged as the predominant cholera strain. The predominant age group affected in endemic cholera due to V. cholerae O1 was children 2–9 years old, and the organism was isolated from more females than from males at all ages. In contrast, cholera due to V. cholerae O139 caused disease mostly in adults 15 years and older, which indicated that this organism was new in this population. As with V. cholerae O1, V. cholerae O139 was isolated from more females than males. The initial rapid emergence and predominance of V. cholerae O139 was considered possibly to herald the start of the eighth pandemic of cholera. However, just after a year, the prevalence of V. cholerae O139 decreased dramatically with V. cholerae O1 resuming the role of the dominant cholera strain. The factor(s) contributing to the dramatic decline in prevalence of V. cholerae O139 is not well understood.