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Profiling patients on a proposed ‘immunometabolic depression’ (IMD) dimension, described as a cluster of atypical depressive symptoms related to energy regulation and immunometabolic dysregulations, may optimise personalised treatment.
Aims
To test the hypothesis that baseline IMD features predict poorer treatment outcomes with antidepressants.
Method
Data on 2551 individuals with depression across the iSPOT-D (n = 967), CO-MED (n = 665), GENDEP (n = 773) and EMBARC (n = 146) clinical trials were used. Predictors included baseline severity of atypical energy-related symptoms (AES), body mass index (BMI) and C-reactive protein levels (CRP, three trials only) separately and aggregated into an IMD index. Mixed models on the primary outcome (change in depressive symptom severity) and logistic regressions on secondary outcomes (response and remission) were conducted for the individual trial data-sets and pooled using random-effects meta-analyses.
Results
Although AES severity and BMI did not predict changes in depressive symptom severity, higher baseline CRP predicted smaller reductions in depressive symptoms (n = 376, βpooled = 0.06, P = 0.049, 95% CI 0.0001–0.12, I2 = 3.61%); this was also found for an IMD index combining these features (n = 372, βpooled = 0.12, s.e. = 0.12, P = 0.031, 95% CI 0.01–0.22, I2= 23.91%), with a higher – but still small – effect size compared with CRP. Confining analyses to selective serotonin reuptake inhibitor users indicated larger effects of CRP (βpooled = 0.16) and the IMD index (βpooled = 0.20). Baseline IMD features, both separately and combined, did not predict response or remission.
Conclusions
Depressive symptoms of people with more IMD features improved less when treated with antidepressants. However, clinical relevance is limited owing to small effect sizes in inconsistent associations. Whether these patients would benefit more from treatments targeting immunometabolic pathways remains to be investigated.
High cognitive activity possibly reduces the risk of cognitive decline and dementia.
Aims
To investigate associations between an individual's need to engage in cognitively stimulating activities (need for cognition, NFC) and structural brain damage and cognitive functioning in the Dutch general population with and without existing cognitive impairment.
Method
Cross-sectional data were used from the population-based cohort of the Maastricht Study. NFC was measured using the Need For Cognition Scale. Cognitive functioning was tested in three domains: verbal memory, information processing speed, and executive functioning and attention. Values 1.5 s.d. below the mean were defined as cognitive impairment. Standardised volumes of white matter hyperintensities (WMH), cerebrospinal fluid (CSF) and presence of cerebral small vessel disease (CSVD) were derived from 3T magnetic resonance imaging. Multiple linear and binary logistic regression analyses were used adjusted for demographic, somatic and lifestyle factors.
Results
Participants (n = 4209; mean age 59.06 years, s.d. = 8.58; 50.1% women) with higher NFC scores had higher overall cognition scores (B = 0.21, 95% CI 0.17–0.26, P < 0.001) and lower odds for CSVD (OR = 0.74, 95% CI 0.60–0.91, P = 0.005) and cognitive impairment (OR = 0.60, 95% CI 0.48–0.76, P < 0.001) after adjustment for demographic, somatic and lifestyle factors. The association between NFC score and cognitive functioning was similar for individuals with and without prevalent cognitive impairment. We found no significant association between NFC and WMH or CSF volumes.
Conclusions
A high need to engage in cognitively stimulating activities is associated with better cognitive functioning and less presence of CSVD and cognitive impairment. This suggests that, in middle-aged individuals, motivation to engage in cognitively stimulating activities may be an opportunity to improve brain health.
The Marine20 radiocarbon (14C) age calibration curve, and all earlier marine 14C calibration curves from the IntCal group, must be used extremely cautiously for the calibration of marine 14C samples from polar regions (outside ∼ 40ºS–40ºN) during glacial periods. Calibrating polar 14C marine samples from glacial periods against any Marine calibration curve (Marine20 or any earlier product) using an estimate of ${\rm{\Delta R}}$, the regional 14C depletion adjustment, that has been obtained from samples in the recent (non-glacial) past is likely to lead to bias and overconfidence in the calibrated age. We propose an approach to calibration that aims to address this by accounting for the possibility of additional, localized, glacial 14C depletion in polar oceans. We suggest, for a specific polar location, bounds on the value of ${\rm{\Delta }}{{\rm{R}}_{20}}\left( {\rm{\theta }} \right)$ during a glacial period. The lower bound ${\rm{\Delta R}}_{20}^{{\rm{Hol}}}$ may be based on 14C samples from the recent non-glacial (Holocene) past and corresponds to a low-depletion glacial scenario. The upper bound, ${\rm{\Delta R}}_{20}^{{\rm{GS}}}$, representing a high-depletion scenario is found by increasing ${\rm{\Delta R}}_{20}^{{\rm{Hol}}}$ according to the latitude of the 14C sample to be calibrated. The suggested increases to obtain ${\rm{\Delta R}}_{20}^{{\rm{GS}}}$ are based upon simulations of the Hamburg Large Scale Geostrophic Ocean General Circulation Model (LSG OGCM). Calibrating against the Marine20 curve using the upper and lower ${\rm{\Delta }}{{\rm{R}}_{20}}$ bounds provide estimates of calibrated ages for glacial 14C samples in high- and low-depletion scenarios which should bracket the true calendar age of the sample. In some circumstances, users may be able to determine which depletion scenario is more appropriate using independent paleoclimatic or proxy evidence.
Individuals with depression have an increased dementia risk, which might be due to modifiable risk factors for dementia. This study investigated the extent to which the increased risk for dementia in depression is explained by modifiable dementia risk factors.
Methods
We used data from the English Longitudinal Study of Ageing (2008–2009 to 2018–2019), a prospective cohort study. A total of 7460 individuals were included [mean(standard deviation) age, 65.7 ± 9.4 years; 3915(54.7%) were women]. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale-8 (score ≥3) or self-reported doctor's diagnosis. Ten modifiable risk factors for dementia were combined in the ‘LIfestyle for BRAin health’ (LIBRA) score. Dementia was determined by physician diagnosis, self-reported Alzheimer's disease or the shortened version of the Informant Questionnaire on Cognitive Decline in the Elderly (average score ≥3.38). Structural equation modelling was used to test mediation of LIBRA score.
Results
During 61 311 person-years, 306 individuals (4.1%) developed dementia. Participants aged 50–70 years with depressive symptoms had higher LIBRA scores [difference(s.e.) = 1.15(0.10)] and a 3.59 times increased dementia risk [HR(95% CI) = 3.59(2.20–5.84)], adjusted for age, sex, education, wealth and clustering at the household level. In total, 10.4% of the dementia risk was mediated by differences in LIBRA score [indirect effect: HR = 1.14(1.03–1.26)], while 89.6% was attributed to a direct effect of depressive symptoms on dementia risk [direct effect: HR = 3.14(2.20–5.84)].
Conclusions
Modifiable dementia risk factors can be important targets for the prevention of dementia in individuals with depressive symptoms during midlife. Yet, effect sizes are small and other aetiological pathways likely exist.
Radiocarbon (14C) concentrations in the oceans are different from those in the atmosphere. Understanding these ocean-atmospheric 14C differences is important both to estimate the calendar ages of samples which obtained their 14C in the marine environment, and to investigate the carbon cycle. The Marine20 radiocarbon age calibration curve is created to address these dual aims by providing a global-scale surface ocean record of radiocarbon from 55,000–0 cal yr BP that accounts for the smoothed response of the ocean to variations in atmospheric 14C production rates and factors out the effect of known changes in global-scale palaeoclimatic variables. The curve also serves as a baseline to study regional oceanic 14C variation. Marine20 offers substantial improvements over the previous Marine13 curve. In response to community questions, we provide a short intuitive guide, intended for the lay-reader, on the construction and use of the Marine20 calibration curve. We describe the choices behind the making of Marine20, as well as the similarities and differences compared with the earlier Marine calibration curves. We also describe how to use the Marine20 curve for calibration and how to estimate ΔR—the localized variation in the oceanic 14C levels due to regional factors which are not incorporated in the global-scale Marine20 curve. To aid understanding, illustrative worked examples are provided.
Cognitive disturbances are common and disabling features of major depressive disorder (MDD). Previous studies provide limited insight into the co-occurrence of hot (emotion-dependent) and cold (emotion-independent) cognitive disturbances in MDD. Therefore, we here map both hot and cold cognition in depressed patients compared to healthy individuals.
Methods
We collected neuropsychological data from 92 antidepressant-free MDD patients and 103 healthy controls. All participants completed a comprehensive neuropsychological test battery assessing hot cognition including emotion processing, affective verbal memory and social cognition as well as cold cognition including verbal and working memory and reaction time.
Results
The depressed patients showed small to moderate negative affective biases on emotion processing outcomes, moderate increases in ratings of guilt and shame and moderate deficits in verbal and working memory as well as moderately slowed reaction time compared to healthy controls. We observed no correlations between individual cognitive tasks and depression severity in the depressed patients. Lastly, an exploratory cluster analysis suggested the presence of three cognitive profiles in MDD: one characterised predominantly by disturbed hot cognitive functions, one characterised predominantly by disturbed cold cognitive functions and one characterised by global impairment across all cognitive domains. Notably, the three cognitive profiles differed in depression severity.
Conclusion
We identified a pattern of small to moderate disturbances in both hot and cold cognition in MDD. While none of the individual cognitive outcomes mapped onto depression severity, cognitive profile clusters did. Overall cognition-based stratification tools may be useful in precision medicine approaches to MDD.
The snow surface roughness at centimetre and millimetre scales is an important parameter related to wind transport, snowdrifts, snowfall, snowmelt and snow grain size. Knowledge of the snow surface roughness is also of high interest for analyzing the signal from radar sensors such as SAR, altimeters and scatterometers. Unfortunately, this parameter has seldom been measured over snow surfaces. The techniques used to measure the roughness of other surfaces, such as agricultural or sand soils, are difficult to implement in polar regions because of the harsh climatic conditions. In this paper we develop a device based on a laser profiler coupled with a GPS receiver on board a snowmobile. This instrumentation was tested successfully in midre Lovénbreen, Svalbard, in April 2006. It allowed us to generate profiles of 3 km sections of the snow-covered glacier surface. Because of the motion of the snowmobile, the roughness signal is mixed with the snowmobile signal. We use a distance/frequency analysis (the empirical mode decomposition) to filter the signal. This method allows us to recover the snow surface structures of wavelengths between 4 and 50 cm with amplitudes of >1 mm. Finally, the roughness parameters of snow surfaces are retrieved. The snow surface roughness is found to be dependent on the scales of the observations. The retrieved RMS of the height distribution is found to vary between 0.5 and 9.2 mm, and the correlation length is found to be between 0.6 and 46 cm. This range of measurements is particularly well adapted to the analysis of GHz radar response on snow surfaces.
Recovery Ice Stream has multiple branches reaching far into the East Antarctic ice sheet. We use new airborne and ground-based geophysics to give the first comprehensive overview of the upper catchment and, by constraining the physical setting, to advance our understanding of the controlling mechanisms for the onset of fast flow. The 400 km wide ice stream extends towards the Recovery Subglacial Lakes, a region characterized by a crustal boundary, a change in bed roughness, a bedrock topographic step and four topographic basins (A–D), three of which (A–C) contain subglacial water. All these characteristics are considered potential causal mechanisms that contribute to the onset of fast flow. In Lakes B and C the subglacial water is located in basins with sharp downstream ridges, in contrast to the gently sloping ridge on the downstream margin of Lake A. The fastest-flowing branch of the ice stream emanates from Lake A. The presence of multiple causal mechanisms along the four Recovery Lakes allows us to identify basal water as a dominant factor for the onset of fast flow, but only if it is stored in a shallow-sided basin where it can lubricate the flow downstream. Relatively minor topographic barriers appear to inhibit streaming.
Archaeological data and research results are essential to addressing such fundamental questions as the origins of human culture; the origin, waxing, and waning of civilizations and cities; the response of societies to long-term climate changes; and the systemic relationships implicated in human-induced changes in the environment. However, we lack the capacity for acquiring, managing, analyzing, and synthesizing the data sets needed to address important questions such as these. We propose investments in computational infrastructure that would transform archaeology’s ability to advance research on the field’s most compelling questions with an evidential base and inferential rigor that have heretofore been impossible. At the same time, new infrastructure would make archaeological data accessible to researchers in other disciplines. We offer recommendations regarding data management and availability, cyberinfrastructure tool building, and social and cultural changes in the discipline. We propose funding synthetic case studies that would demonstrate archaeology’s ability to contribute to transdisciplinary research on long-term social dynamics and serve as a context for developing computational tools and analytical workflows that will be necessary to attack these questions. The case studies would explore how emerging research in computer science could empower this research and would simultaneously provide productive challenges for computer science research.
To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD.
Method
The Pubmed/Medline, EMBASE and PsycInfo electronic databases were searched up to May 2015. Two independent authors conducted searches, examined references for eligibility, and extracted data. Meta-analyses in any language examining peripheral non-genetic biomarkers in participants with BD (across different mood states) compared to unaffected controls were included.
Results
Six references, which examined 13 biomarkers across 20 meta-analyses (5474 BD cases and 4823 healthy controls) met inclusion criteria. Evidence for excess of significance bias (i.e. bias favoring publication of ‘positive’ nominally significant results) was observed in 11 meta-analyses. Heterogeneity was high for (I2 ⩾ 50%) 16 meta-analyses. Only two biomarkers met criteria for suggestive evidence namely the soluble IL-2 receptor and morning cortisol. The median power of included studies, using the effect size of the largest dataset as the plausible true effect size of each meta-analysis, was 15.3%.
Conclusions
Our findings suggest that there is an excess of statistically significant results in the literature of peripheral biomarkers for BD. Selective publication of ‘positive’ results and selective reporting of outcomes are possible mechanisms.
This article represents a systematic effort to answer the question, What are archaeology’s most important scientific challenges? Starting with a crowd-sourced query directed broadly to the professional community of archaeologists, the authors augmented, prioritized, and refined the responses during a two-day workshop focused specifically on this question. The resulting 25 “grand challenges” focus on dynamic cultural processes and the operation of coupled human and natural systems. We organize these challenges into five topics: (1) emergence, communities, and complexity; (2) resilience, persistence, transformation, and collapse; (3) movement, mobility, and migration; (4) cognition, behavior, and identity; and (5) human-environment interactions. A discussion and a brief list of references accompany each question. An important goal in identifying these challenges is to inform decisions on infrastructure investments for archaeology. Our premise is that the highest priority investments should enable us to address the most important questions. Addressing many of these challenges will require both sophisticated modeling and large-scale synthetic research that are only now becoming possible. Although new archaeological fieldwork will be essential, the greatest pay off will derive from investments that provide sophisticated research access to the explosion in systematically collected archaeological data that has occurred over the last several decades.
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).
Method
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.
Results
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.
Conclusions
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.
Contrastive phonology has been preoccupied with the phoneme concept and the isolated word. The Contrastive Structure Series demonstrates this quite clearly. In Moulton's contrastive comparison of English and German sounds (Moulton, 1962), to take a representative example of the series and of contrastive phonological studies in general, 107 pages out of 145 deal with the consonant and vowel phonemes in English and German words and with their contrastive analysis. Only 31 pages treat stress (largely word stress), intonation and the inevitable juncture, which is the epitome of word phonemics in that it looks at the incidence of boundary signals at word and morpheme boundaries, e.g. antrat and das Kitzeln with strongly aspirated stops as against Landrat and die Skizze with weakly aspirated or unaspirated stops indicating different divisions between word final and initial consonants (p. 142). I would like to mention in passing that this opposition is artificially constructed in word material by a linguist on the basis of the equally artificial codification in Siebs (de Boor et al., 1969), where again hardly any tribute is paid to segmental sentence phonology (Kohler, 1970).
Acute flaccid paralysis (AFP) surveillance data from India were analysed to examine sensitivity of poliovirus isolation from stool specimens and the added sensitivity obtained from collection of a second stool specimen. Analysis was restricted to Indian AFP cases, 1998–2000, with two adequate stool specimens. The proportion of cases confirmed with wild poliovirus isolation by the second specimen only was calculated, regardless of specimen quality. Overall specimen sensitivity (1998–2000) was 81% using the first specimen, 78% using the second, and 96% using both. Sensitivity increased from 1998 to 2000, with slightly higher sensitivity each year for the first specimen. The second specimen increased sensitivity by 15% overall and contributed more when the first specimen was collected late or was in poor condition. As wild poliovirus disappears, increased sensitivity provided by a second stool specimen may reduce the risk of missing circulating virus.
Cubic phase GaN/AlxGa1-xN Multi Quantum Well structures were grown by rf-plasma assisted molecular beam epitaxy (MBE) on GaAs (001) substrates. X-ray measurements showed a high phase purity of the epilayers and revealed an Aluminum incorporation between 9 % and 49 %, respectively. The QW luminescence was tuned between 3.25 eV and 3.4 eV by means of the variation of QW barrier Aluminum content and QW width. Strong Cathodoluminescence (CL) from the GaN QWs and the underlying cubic AlxGa1-xN bulk material was observed at room temperature. The spatial localization of the QW emission was unambiguously determined by depth-resolved CL measurements. Combined with a model of energy-dependent penetration, diffusion, and recombination, these variations indicate a value of about 20 nm for the minority carrier diffusion length within the AlxGa1-xN confinement layer. The assignment of AlxGa1-xN bulk and GaN luminescence was further supported by employing a simple effective-mass quantum mechanical model.
Recent results on the local bonding of nitrogen in dilute GaInAsN and AlGaAsN on GaAs are reviewed, revealing that bonding of nitrogen in GaInAsN is controlled by an interplay between bond cohesive energy and reduction of local strain. Thus, III-N bonding in GaInAsN can be changed from Ga-N to In-N by post-growth thermal annealing. In AlGaAsN, in contrast, nitrogen bonds preferentially to Al, i.e. Al-N bonds are formed, due to the much larger cohesive energy of the Al-N bond. Further, results on indium-rich highly strained GaInAsN quantum wells on InP substrate are reported, showing room-temperature photoluminescence at wavelengths up to 2.3 μm. This result demonstrates the potential of high indium content dilute GaInAsN for InP-based long wavelength diode lasers.
The optical properties of Carbon doped cubic GaN epilayers have been investigated by temperature and intensity dependent photoluminescence measurements. RF-plasma assisted molecular beam epitaxy equipped with an e-beam-evaporation source for carbon doping is used to grow the cubic GaN layers on GaAs (001) substrates. With increasing Carbon flux a new photoluminescence line at 3.08 eV appeared at 2K. This line is attributed to a donor acceptor transistion, which involves the shallow CN acceptor. From the spectral position the binding energy of the C acceptor is estimated to be about EC = 0.215 eV. Our experiments demonstrate that C indeed introduces a shallow acceptor in cubic GaN with an acceptor binding energy, which is about 15 meV lower than that observed for the Mg acceptor in cubic GaN. However, at high C fluxes a deep red luminescence band appeared at 2.1 eV, indicating compensation effects.
Spectroscopic ellipsometry (SE) has been used for the characterization of AlGaN/GaN and InGaN/GaN heterostructures. The resulting pseudodielectric function spectra were analyzed using a multilayer approach, describing the dielectric functions of the individual layers by a parametric oscillator model. From this analysis, the dielectric function spectra of GaN, AlxGa1−xN (x≤0.16), and In0.13Ga0.87N were deduced. Further, the dependence of the AlxGa1−xN band gap energy on the Al mole fraction was derived and compared with photoluminescence data recorded on the same material. The SE band gap data are compatible with a bowing parameter close to 1 eV for the composition dependence of the AlxGa1−xN gap energy. Finally, the parametric dielectric functions have been used to model the pseudodielectric function spectrum of a complete GaN/AlGaN/InGaN LED structure.