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 firstname.lastname@example.org
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.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Serosurveys have established data about the distribution of immunoglobulin G (IgG)-antibodies to pertussis toxin (PT) in various populations. We tried to detect whether small serosurveys in blood donors could serve as a simple and inexpensive means to collect information about the circulation of Bordetella pertussis. We screened every donation in 307 adult blood donors aged 19–69 years for IgG-anti-PT by standardised enzyme-linked immunosorbent assays (ELISA), and the donors were followed between 2014 and 2016 for a total of 426 person-years. When we used a vertical survey with cut-offs of 100, 62.5 and 40 IU/ml, respectively, as an indicator for recent contacts with B. pertussis, nine (2.9%), 22 (7.2%) and 54 (17.6%) of donors had IgG-anti-PT titres above the respective levels. During the horizontal observation period of 426 person years, six significant increases and two conversions were found, which lead to an estimate of 1878 contacts/100.000 person-years (1.9% per year). Median and mean IgG-anti-PT concentrations remained relatively stable from year to year during the observation period. Our findings show that small serosurveys of blood donors offer a simple and cheap method for the surveillance of B. pertussis.
Olfactory disorders increase with age and often affect elderly people who have pre-dementia or dementia. Despite the frequent occurrence of olfactory changes at the early stages of neurodegenerative disorders such as Alzheimer's disease, olfactory disorders are rarely assessed in daily clinical practice, mainly due to a lack of standardised assessment tools. The aims of this review were to (1) summarise the existing literature on olfactory disorders in ageing populations and patients with neurodegenerative disorders; (2) present the strengths and weaknesses of current olfactory disorder assessment tools; and (3) discuss the benefits of developing specific olfactory tests for neurodegenerative diseases.
A systematic review was performed of literature published between 2000 and 2015 addressing olfactory disorders in elderly people with or without Alzheimer's disease or other related disorders to identify the main tools currently used for olfactory disorder assessment.
Olfactory disorder assessment is a promising method for improving both the early and differential diagnosis of Alzheimer's disease. However, the current lack of consensus on which tests should be used does not permit the consistent integration of olfactory disorder assessment into clinical settings.
Otolaryngologists are encouraged to use olfactory tests in older adults to help predict the development of neurodegenerative diseases. Olfactory tests should be specifically adapted to assess olfactory disorders in Alzheimer's disease patients.
Traditionally, it is understood that dizygotic (DZ) twins always have a dichorionic placenta. However, with 8% blood chimerism in DZ twins, placental sharing is probably more common than previously has been recognized. In this article, we will review all available cases of monochorionic dizygotic (MCDZ) twins. A total of 31 twins have been described in literature. A monochorionic diamniotic placenta is reported in all cases. Assisted reproductive technology is responsible for the origin of the pregnancy in 82.1% of the cases. In 15.4% of the sex-discordant twins, a genital anomaly was reported in one of the twins. Chimerism is demonstrable in 90.3% of the twins, leading to various diagnostic difficulties. As this review shows that most MCDZ twins are discovered by accident, it can be argued that it is far more common than has been assumed until now. However, the prevalence is still unclear. Awareness of MCDZ twinning is important, with subsequently correct medical strategies. Similarly, the resulting (blood) chimerism is essential to consider in diagnostic procedures, pre- and postnatally. More research on the effect of placental transfusion between sex-discordant twins is required.
In the last decade, small and compact accelerator mass spectrometry (AMS) systems became available operating at terminal voltages of 1 MV and below. This new category of instruments has become competitive for radiocarbon detection to larger tandem accelerators and many of these instruments are successfully used for 14C dating or biomedical applications. The AMS group at ETH Zurich has demonstrated that small instruments can be built, which allow measurements also of other radionuclides such as 10Be, 26Al, 129I, and the actinides. 41Ca measurements can be performed with sufficient sensitivity for biomedical applications. A summary of recent developments made at the 500kV Pelletron in Zurich is given and its performance is compared with that of a commercial compact instrument from the company High Voltage Engineering Europe (HVEE) in Amersfoort, the Netherlands, operating at 1MV at CNA in Seville, Spain, as well as with that of larger AMS facilities. It turns out that the ion optics, stripper design, and the detection system are critical for the performance.
Feedback learning is essential for behavioral development. We investigated feedback learning in relation to behavior problems after pediatric traumatic brain injury (TBI).
Children aged 6–13 years diagnosed with TBI (n = 112; 1.7 years post-injury) were compared with children with traumatic control (TC) injury (n = 52). TBI severity was defined as mild TBI without risk factors for complicated TBI (mildRF− TBI, n = 24), mild TBI with ⩾1 risk factor for complicated TBI (mildRF+ TBI, n = 51) and moderate/severe TBI (n = 37). The Probabilistic Learning Test was used to measure feedback learning, assessing the effects of inconsistent feedback on learning and generalization of learning from the learning context to novel contexts. The relation between feedback learning and behavioral functioning rated by parents and teachers was explored.
No evidence was found for an effect of TBI on learning from inconsistent feedback, while the moderate/severe TBI group showed impaired generalization of learning from the learning context to novel contexts (p = 0.03, d = −0.51). Furthermore, the mildRF+ TBI and moderate/severe TBI groups had higher parent and teacher ratings of internalizing problems (p's ⩽ 0.04, d's ⩾ 0.47) than the TC group, while the moderate/severe TBI group also had higher parent ratings of externalizing problems (p = 0.006, d = 0.58). Importantly, poorer generalization of learning predicted higher parent ratings of externalizing problems in children with TBI (p = 0.03, β = −0.21) and had diagnostic utility for the identification of children with TBI and clinically significant externalizing behavior problems (area under the curve = 0.77, p = 0.001).
Moderate/severe pediatric TBI has a negative impact on generalization of learning, which may contribute to post-injury externalizing problems.
Laboratory tests in adult outpatients with longer lasting coughs to identify a potential causal pathogen are rarely performed, and there is no gold standard for these diagnostic tests. While the diagnostic validity of serological tests for pertussis is well established their potential contribution for diagnosing adenovirus and influenza virus A and B infections is unclear. A sentinel study into the population-based incidence of longer lasting coughs in adults was done in Rostock (former East Germany) and Krefeld (former West Germany). A total of 971 outpatients who consulted general practitioners or internists were included. Inclusion criteria were coughing for ⩾1 week and no chronic respiratory diseases. We evaluated the performance of polymerase chain reaction (PCR) as well as IgG and IgA serology, applying a latent class model for diagnosing infections with adenovirus, B. pertussis, and influenza virus A and B. The adult outpatients first sought medical attention when they had been coughing for a median of 3 weeks. In this situation, direct detection of infectious agents by PCR had a low sensitivity. Modelling showed that additional serological tests equally improved sensitivity and specificity for diagnosis for adenovirus, B. pertussis and influenza virus A and B infections. The combination of serology and PCR may improve the overall performance of diagnostic tests for B. pertussis and also for adenovirus, and influenza virus A and B infections.
High temporal resolution (three hours) records of temperature, wind speed and sea level pressure recorded at Antarctic research station Neumayer (70°S, 8°W) during 1982–2011 are analysed to identify oscillations from daily to intraseasonal timescales. The diurnal cycle dominates the three-hourly time series of temperature during the Antarctic summer and is almost absent during winter. In contrast, the three-hourly time series of wind speed and sea level pressure show a weak diurnal cycle. The dominant pattern of the intraseasonal variability of these quantities, which captures the out-of-phase variation of temperature and wind speed with sea level pressure, shows enhanced variability at timescales of ∼ 40 days and ∼ 80 days, respectively. Correlation and composite analysis reveal that these oscillations may be related to tropical intraseasonal oscillations via large-scale eastward propagating atmospheric circulation wave-trains. The second pattern of intraseasonal variability, which captures in-phase variations of temperature, wind and sea level pressure, shows enhanced variability at timescales of ∼ 35, ∼ 60 and ∼ 120 days. These oscillations are attributed to the Southern Annular Mode/Antarctic Oscillation (SAM/AAO) which shows enhanced variability at these timescales. We argue that intraseasonal oscillations of tropical climate and SAM/AAO are related to distinct patterns of climate variables measured at Neumayer.
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.
Neuroimaging studies have demonstrated an association between lithium (Li) treatment and brain structure in human subjects. A crucial unresolved question is whether this association reflects direct neurochemical effects of Li or indirect effects secondary to treatment or prevention of episodes of bipolar disorder (BD).
To address this knowledge gap, we compared manually traced hippocampal volumes in 37 BD patients with at least 2 years of Li treatment (Li group), 19 BD patients with <3 months of lifetime Li exposure over 2 years ago (non-Li group) and 50 healthy controls. All BD participants were followed prospectively and had at least 10 years of illness and a minimum of five episodes. We established illness course and long-term treatment response to Li using National Institute of Mental Health (NIMH) life charts.
The non-Li group had smaller hippocampal volumes than the controls or the Li group (F2,102 = 4.97, p = 0.009). However, the time spent in a mood episode on the current mood stabilizer was more than three times longer in the Li than in the non-Li group (t51 = 2.00, p = 0.05). Even Li-treated patients with BD episodes while on Li had hippocampal volumes comparable to healthy controls and significantly larger than non-Li patients (t43 = 2.62, corrected p = 0.02).
Our findings support the neuroprotective effects of Li. The association between Li treatment and hippocampal volume seems to be independent of long-term treatment response and occurred even in subjects with episodes of BD while on Li. Consequently, these effects of Li on brain structure may generalize to patients with neuropsychiatric illnesses other than BD.
This study aimed to explore if natural dizygotic (DZ) twinning is associated with earlier menopause and lower anti-Mullerian hormone (AMH) values. We investigated if advanced biological reproductive aging, which can be responsible for the multiple follicle growth in familial twinning, is similar to mechanisms that occur in normal ovarian aging, reflected by earlier menopause in mothers of DZ twins and lower levels of AMH. A total of 16 mothers of DZ twins enrolled with the Netherlands Twin Register (average age at first assessment: 35.9 ± 3.0 years) and 14 control mothers (35.1 ± 3 years) took part in a prospective study. Fifteen years after entry into the study, which included follicle-stimulating hormone (FSH) assessment, AMH was measured in stored serum samples and menopause status was evaluated. Average AMH levels were not significantly different between DZ twin mothers and controls (2.1 ± 2.4 μg/L vs. 1.9 ± 1.9 μg/L). Among the 16 mothers of twins, 7 had an elevated (FSH) value over 10 U/L at first assessment. Their AMH levels were lower than the nine twin mothers with normal FSH values: 0.6 ± 0.4 versus 3.4 ± 2.6 μg/L (p = .01). Of the mothers of twins, eight mothers had entered menopause at the second assessment compared with only one control mother (p = .07). Thus, slightly more DZ mothers were in menopause than the control mothers, although this difference was not significant. The subgroup of DZ twin mothers who had an increased FSH concentration 15 years ago had a limited ovarian reserve as reflected by lower AMH levels. These data indicate that advanced ovarian aging can be a feature in familial DZ twinning, particularly with elevated early follicular phase FSH.
It is well documented that global warming is unequivocal. Dairy production systems are considered as important sources of greenhouse gas emissions; however, little is known about the sensitivity and vulnerability of these production systems themselves to climate warming. This review brings different aspects of dairy cow production in Central Europe into focus, with a holistic approach to emphasize potential future consequences and challenges arising from climate change. With the current understanding of the effects of climate change, it is expected that yield of forage per hectare will be influenced positively, whereas quality will mainly depend on water availability and soil characteristics. Thus, the botanical composition of future grassland should include species that are able to withstand the changing conditions (e.g. lucerne and bird's foot trefoil). Changes in nutrient concentration of forage plants, elevated heat loads and altered feeding patterns of animals may influence rumen physiology. Several promising nutritional strategies are available to lower potential negative impacts of climate change on dairy cow nutrition and performance. Adjustment of feeding and drinking regimes, diet composition and additive supplementation can contribute to the maintenance of adequate dairy cow nutrition and performance. Provision of adequate shade and cooling will reduce the direct effects of heat stress. As estimated genetic parameters are promising, heat stress tolerance as a functional trait may be included into breeding programmes. Indirect effects of global warming on the health and welfare of animals seem to be more complicated and thus are less predictable. As the epidemiology of certain gastrointestinal nematodes and liver fluke is favourably influenced by increased temperature and humidity, relations between climate change and disease dynamics should be followed closely. Under current conditions, climate change associated economic impacts are estimated to be neutral if some form of adaptation is integrated. Therefore, it is essential to establish and adopt mitigation strategies covering available tools from management, nutrition, health and plant and animal breeding to cope with the future consequences of climate change on dairy farming.
The quality of SiGe/Si heterodevices recently could be improved by depositing on a SiGe buffer with a Ge grading. In house MBE grown structures reached 1.5 K mobilities of 173000 cm2/Vs. Also at room temperature (RT) the mobility is up to 4 times higher than in bulk Si or SiGe. HBTs in the discussed material system can exceed performances of conventional Si-homobipolar transistors, already with relaxed design rules. I briefly review on mesa - like SiGe HBTs with high fmax and fT around 50 GHz, owing to low base sheet resistances <1Kω□. In DC-operation high gains >400 or 13 000 at RT or 77K were obtained, n - and p - channel Si, SiGe and Ge MODFETs will be presented in more detail, n- MODFETs exhibit high transconductances above 300 mS/mm at RT and almost 1000 mS/mm at 77K. Different effects will be discussed, e.g. the influence of the gate to channel distance and effects of rapid thermal activation. Si/Ge heterosystems offer exclusive properties, e.g. the same mobility in a Si - 2DEG and a Ge - 2DHG. Complementary MODFETs (CMOD) can be envisaged. Furtheron the Si/Ge system allows the monolithic integration of heterodevices with high complexity Si - ICs (heterointegration).
The Co/Cu(100) system is the first system known where the contributions to the spin polarisation of spin-orbit coupling and the ferromagnetic overlayer were clearly distinguished experimentally. In order to get a first understanding of the photoemission data non-relativistic spin-polarized photoemission calculations are performed for one and two overlayers of Co on Cu(100).
The implementation of a wet oxidation process in an RTP system using a bubbler with deionized water is described. A special process related calibration in a wet atmosphere, by means of pyrometer and thermocouple readings, allows one to improve the temperature accuracy during the oxidation to an offset of only + 1 to 2°C. High oxide growth rates, up to a factor of 1.8 above literature data have been achieved. Wet and dry RTO oxides are compared and related to the expectations from growth models. Effects of growth time (10 s to 4 min), growth temperature (675°C-950°C), substrate orientation (100,111), preparation (e.g. HF) and bubbler temperature (20°C-90°C) are presented. The uniformity of oxides on 4 and 6 inch diameter wafers are discussed. Preferentially by the use of a silicon guard ring and by adjusting lamp power and gas flow rates excellent results concerning uniformity (standard deviations 2σ: 1-2 %) and reproducibility (variation of 0.5 to 0.75 % at least over 12 wafers) are obtained.
Early diagnosis of dementia requires knowledge about associated predictors. The aim of this study was to determine the impact of mild cognitive impairment (MCI) and impairment in instrumental activities of daily living (IADL) on the time to an incident dementia diagnosis.
Data were derived from the Leipzig Longitudinal Study of the Aged (LEILA75+), a population-based study of individuals aged ⩾75 years. Kaplan-Meier survival analysis was used to determine time to incident dementia. Cox proportional hazards models were applied to determine the impact of MCI and IADL impairment on the time to incident dementia.
In total, 180 (22.0%) of 819 initially dementia-free subjects developed dementia by the end of the study. Mean time to incident dementia was 6.7 years [95% confidence interval (CI) 6.5–6.9]. MCI combined with IADL impairment was associated with a higher conversion rate to dementia, a shorter time to clinically manifest diagnosis and a lower chance of reversibility to cognitive normal. The highest risk for a shorter time to incident dementia was found for amnestic MCI combined with IADL impairment. The mean time to incident dementia was 3.7 years (95% CI 2.9–4.4) and thus half as long as in subjects without MCI and IADL impairment.
Subjects with MCI and IADL impairment constitute a high-risk population for future dementia. The consideration of both – MCI and IADL impairment – might help to improve the prediction of dementia.
Individuals with anxiety disorders often do not receive an accurate diagnosis or adequate treatment in primary care.
To analyse the cost-effectiveness of an optimised care model for people with anxiety disorders in primary care.
In a cluster randomised controlled trial, 46 primary care practices with 389 individuals positively screened with anxiety were randomised to intervention (23 practices, 201 participants) or usual care (23 practices, 188 participants). Physicians in the intervention group received training on diagnosis and treatment of anxiety disorders combined with the offer of a psychiatric consultation–liaison service for 6 months. Anxiety, depression, quality of life, service utilisation and costs were assessed at baseline, 6-month and 9-month follow-up.
No significant differences were observed between intervention and control group on the Beck Anxiety Inventory, Beck Depression Inventory and EQ–5D during follow-up. Total costs were higher in the intervention group (€4911 v. €3453, P = 0.09). The probability of an incremental cost-effectiveness ratio <€50 000 per quality-adjusted life year was below 10%.
The optimised care model did not prove to be cost-effective.