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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The public health measure restrictions across the world due to COVID-19 have inadvertently impacted the routines for people with Parkinson’s disease (PD) and their care partners not only in terms of compromised neurological clinical care but also drastically changing the way of life to minimize the risk of becoming infected. This study explores initial PD patients’ lived experiences to observe how quality of life and health care has been affected at the start of the COVID-19 pandemic and provide insight into the importance of patient engagement and virtual care.
Twenty-two virtual, in-depth semi-structured interviews with persons diagnosed with PD who usually attend a Movement Disorders specialty clinic in Calgary, Alberta, were completed between April 28 and May 13, 2020, and the care partners that wished to participate. Interviews were recorded and transcribed, after which transcripts were analyzed and coded into relevant themes using NVivo 12.
Impacts from the public health measures and COVID-19 results into three main themes: (1) Impacts of COVID-19 on PD Clinical Care; (2) Activities of Daily Living; (3) Attitudes and Perceptions. Participants reported worsening in motor and nonmotor symptoms and had to accommodate to clinical care via virtual means which were associated with limitations and suggestions for improvement of remote care.
This study provides a unique opportunity for researchers to better understand the lived experiences of PD patients in all aspects of their life suggesting that innovative means are needed for facilitating virtual health care medicine and increased social interaction.
This article aims to estimate the effect of expert assessments on the prices for single malt Scotch whiskies on the investment market. Our results obtained using an original dataset combining data from Jim Murray's Whisky Bible and a web trading platform specializing in whisky investment show that the quality rating is not a powerful predictor of investor ask prices, especially when controlling for distillery and bottler reputation. This finding suggests that although the Murray score may embed information of use to unsophisticated investors, its effect on price can be outperformed by a detailed knowledge of the whisky industry. (JEL Classifications: L11, L15, Q13)
It is unclear whether olfactory deficits improve after remission in depressed patients. Therefore, we aimed to assess in drug-free patients the olfactory performance of patients with major depressive episodes (MDE) and its change after antidepressant treatment.
In the DEP-ARREST-CLIN study, 69 drug-free patients with a current MDE in the context of major depressive disorder (MDD) were assessed for their olfactory performances and depression severity, before and after 1 (M1) and 3 (M3) months of venlafaxine antidepressant treatment. They were compared to 32 age- and sex-matched healthy controls (HCs). Olfaction was assessed with a psychophysical test, the Sniffin’ Sticks test (Threshold: T score; Discrimination: D score; Identification: I score; total score: T + D + I = TDI score) and Pleasantness (pleasantness score: p score; neutral score: N score; unpleasantness score: U score).
As compared to HCs, depressed patients had lower TDI olfactory scores [mean (s.d.) 30.0(4.5) v. 33.3(4.2), p < 0.001], T scores [5.6(2.6) v. 7.4(2.6), p < 0.01], p scores [7.5(3.0) v. 9.8(2.8), p < 0.001)] and higher N scores [3.5(2.6) v. 2.1(1.8), p < 0.01]. T, p and N scores at baseline were independent from depression and anhedonia severity. After venlafaxine treatment, significant increases of T scores [M1: 7.0(2.6) and M3: 6.8(3.1), p < 0.01] and p scores [M1: 8.1(3.0) and M3: 8.4(3.3), p < 0.05] were evidenced, in remitters only (T: p < 0.01; P: p < 0.01). Olfaction improvement was mediated by depression improvement.
The olfactory signature of MDE is restored after venlafaxine treatment. This olfaction improvement is mediated by depression improvement.
The determinants of quality of life (QoL) in schizophrenia are largely debated, mainly due to methodological discrepancies and divergence about the concepts concerned. As most studies have investigated bi- or tri-variate models, a multivariate model accounting for simultaneous potential mediations is necessary to have a comprehensive view of the determinants of QOL. We sought to estimate the associations between cognitive reserve, cognition, functioning, insight, depression, schizophrenic symptoms, and QoL in schizophrenia and their potential mediation relationships.
We used structural equation modeling with mediation analyses to test a model based on existing literature in a sample of 776 patients with schizophrenia from the FondaMental Foundation FACE-SZ cohort.
Our model showed a good fit to the data. We found better functioning to be positively associated with a better QoL, whereas better cognition, better insight, higher levels of depression, and schizophrenic symptoms were associated with a lower QoL in our sample. Cognitive reserve is not directly linked to QoL, but indirectly in a negative manner via cognition. We confirm the negative relationship between cognition and subjective QoL which was previously evidenced by other studies; moreover, this relationship seems to be robust as it survived in our multivariate model. It was not explained by insight as some suggested, thus the mechanism at stake remains to be explained.
The pathways to subjective QoL in schizophrenia are complex and the determinants largely influence each other. Longitudinal studies are warranted to confirm these cross-sectional findings.
The direct dating of rock paintings is not always possible due to the lack of organic carbon compounds in pigments, or because sampling from a heritage site is often restricted. To overcome these limitations, dating laboratories have to develop new approaches. In this study, we consider sampling calcium oxalate crusts covering the painted artworks as a way to indirectly date the rock art. This stratigraphic approach includes isolating and extracting pure oxalate from the crusts. The approach was tested on natural bulk accretions collected in the open-air sites of Erongo Mountains in Namibia. The accretions were separated into two phases (pure oxalate and the remaining residues) with a special pretreatment. This process removes carbonates through acidification (HCl 6N) and dissolves the oxalate into the supernatant, leaving the minerals and windblown organic compounds in the residue. The efficiency of the separation was checked on the two phases by FTIR analyses and by 14C dating and showed that pure oxalate powders were indeed obtained. AMS radiocarbon results of various accretions on the same art panels provided ages from modern periods to 2410 ± 35 BP. From these first results, more targeted sampling campaigns can be considered to provide a terminus ante quem for the rock art.
Over recent years, a new transnational conflict has been deemed to be structuring political conflict in Europe. Several scholars have posited the emergence of a new ‘demarcation’ vs. ‘integration’ cleavage, pitting the ‘losers’ and ‘winners’ of globalization against each other. This new conflict is allegedly structured along economic (free trade and globalization), cultural (immigration and multiculturalism), and institutional [European Union (EU) integration] dimensions. From an empirical viewpoint, it is still a matter of discussion whether this conflict can be interpreted as a new cleavage, which could replace or complement the traditional ones. In this context, the European Parliament (EP) elections of 2019 represent an ideal case for investigating how far this new cleavage has evolved towards structuring political competition in European party systems. In this paper, by relying on an original dataset and an innovative theoretical and empirical framework based on the study of a cleavage's lifecycle, we test whether a demarcation cleavage is structuring the European political systems. Moreover, we assess the evolution of this cleavage across the 28 EU countries since 1979 and the role it plays within each party system. The paper finds that the demarcation cleavage has emerged in most European countries, mobilizing over time a growing number of voters. In particular, this long-term trend has reached its highest peak in the 2019 EP election. However, although the cleavage has become an important (if not the main) dimension of electoral competition in many countries, it has not reached maturity yet.
Using an analysis of time series data over an extended period, this article describes the waning strength of the left-wing vote in Italy's ‘red regions’. By analysing changes to the provincial share of the vote for successive principal left-wing parties over the period 1953–2018, the degree of continuity in relation to the left's traditional territorial entrenchment is assessed. It becomes clear that after an extended period of minimal change, in more recent years there has been an increasing disruption of previous patterns. A thorough analysis of voter transitions during the 2001–19 period in Umbria, the first red region in which the left lost control of the regional government, shows that in this case the gradual weakening of the traditional left-wing ‘vote of belonging’ has experienced a dramatic acceleration during the more recent period. This has been expressed in a growing rate of abstention, vote-switching according to the type of electoral contest, and a marked propensity to vote for populist movements and parties on both the left and right.
Intermediate morphologies of a new fossil crinoid shed light on the pathway by which crinoids acquired their distinctive arms. Apomorphies originating deep in echinoderm history among early nonblastozoan pentaradiate echinoderms distinguish Tremadocian (earliest Ordovician) crinoid arms from later taxa. The brachial series is separated from the ambulacra, part of the axial skeleton, by lateral plate fields. Cover plates are arrayed in two tiers, and floor plates expressed podial basins and pores. Later during the Early Ordovician, floor plates contacted and nestled into brachials, then were unexpressed as stereom elements entirely and cover plates were reduced to a single tier. Incorporation of these events into a parsimony analysis supports crinoid origin deep in echinoderm history separate from blastozoans (eocrinoids, ‘cystoids’). Arm morphology is exceptionally well-preserved in the late Tremadocian to early Floian Athenacrinus broweri new genus new species. Character analysis supports a hypothesis that this taxon originated early within in the disparid clade. Athenacrinus n. gen. (in Athenacrinidae new family) is the earliest-known crinoid to express what is commonly referred to as ‘compound’ or ‘biradial’ morphology. This terminology is misleading in that no evidence for implied fusion or fission of radials exists, rather it is suggested that this condition arose through disproportionate growth.
The VISCACHA (VIsible Soar photometry of star Clusters in tApii and Coxi HuguA†) Survey is an ongoing project based on deep and spatially resolved photometric observations of Magellanic Cloud star clusters, collected using the SOuthern Astrophysical Research (SOAR) telescope together with the SOAR Adaptive Module Imager. So far we have used >300h of telescope time to observe ∼150 star clusters, mostly with low mass (M < 104M⊙) on the outskirts of the LMC and SMC. With this high-quality data set, we homogeneously determine physical properties using deep colour-magnitude diagrams (ages, metallicities, reddening, distances, mass, luminosity and mass functions) and structural parameters (radial density profiles, sizes) for these clusters which are used as a proxy to investigate the interplay between the Magellanic Clouds and their evolution. We present the VISCACHA survey and its initial results, based on our first two papers. The project’s long term goals and expected legacy to the community are also addressed.
This article examines the main determinants of differences in ask prices set by investors for single malt whiskies from Islay in Scotland using an original dataset collected from a web trading platform specializing in whisky investment. We find strong evidence that the vintage age (the number of years between the distillation date and the data collection date) positively affects investor asking prices. More precisely, given that the characteristics of whisky, unlike wine, do not change over time once bottled, we disentangle the vintage age effect by subdividing the vintage age into whisky age (the time spent in the cask) and bottle age (the time spent in the bottle). Our results show that whisky age has a more pronounced impact (8.9% per year on average) than bottle age (6.7%). Other findings include the significant influence of distillery reputation, with a moderating effect for independent bottling (i.e., not in-house by the distiller itself) and a positive impact for cask strength whiskies compared to diluted ones. (JEL Classifications: G11, L15, Q11)
This study presents the first documented observations of a brachyuran crab's proactive fishing behaviour in conjunction with mangrove pneumatophores which are employed as prey-localization devices. All ecological data were recorded in situ using simple behavioural observations, visual census and field experiments. Field experiments were based on stimulus-response and ecological surveys on random displacement. Assemblages of Metopograpsus messor were observed daily performing a foraging/predatory tide-related cyclic behaviour pattern in an arid mangrove ecosystem which experiences challenging environmental conditions. Prey-localizing behaviour was observed during the flood tide when pneumatophore-borne vibrations were used to identify potential prey. The prey simulation field experiment (where a single pneumatophore was stimulated by knocking) showed that in >93% of instances a crab approached the exact pneumatophore being stimulated. As water levels increased during the tidal cycle M. messor was observed climbing pneumatophores. The crabs anchored themselves to the pneumatophore just above the water level with their pereiopods. The chelipeds were positioned in a pincher-like trap, and remained in a ‘capture-position’ waiting for prey to move within striking range. This characteristic fishing behaviour was performed daily by a population of M. messor. Ecological observations suggest that both these predatory behaviours are associated with the fish Aphanius dispar dispar in a direct prey–predator relation. Evidence suggests that these fishing behaviours evolved due to characteristics within the M. messor phylogeny (foraging in intertidal zones; daily displacement following tidal levels; high sensitivity to vibrations; and an opportunist diet) and its associated environment (presence of pneumatophores and high availability of a fish resource).
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Although there is a growing interest for the effects of intermittent fasting on energy balance, this study aimed to compare appetite, energy intake and food reward responses with an energy depletion induced either by 24-h food restriction or an equivalent deficit with exercise in healthy males. In all, twelve healthy lean males (21·5 (sd 0·5) years old; BMI: 22·5 (sd 1·7) kg/m2) participated in this study. Body composition, aerobic capacity, food preferences and energy intake were assessed. They randomly completed three conditions: (i) no depletion (CON); (ii) full 24-h energy restrictions (Def-EI); and (iii) exercise condition (Def-EX). Ad libitum energy intake and food reward were assessed at the end of each session. Appetite feelings were assessed regularly. Ad libitum energy intake was higher on Def-EI (7330 (sd 2975) kJ (1752 (sd 711) kcal) compared with that on CON (5301 (sd 1205) kJ (1267 (sd 288) kcal)) (P<0·05), with no difference between CON and Def-EX (6238 (sd 1741) kJ (1491 (sd 416) kcal) (P=0·38) and between Def-EX and Def-EI (P=0·22). There was no difference in the percent energy ingested from macronutrients. Hunger was lower on CON and Def-EX compared with Def-EI (P<0·001). Satiety was higher on CON and Def-EI compared with that on Def-EX (P<0·001). There was a significant interaction condition × time for food choice fat bias (P=0·04), showing a greater preference for high-fat v. low-fat food during Def-EI and Def-EX. Although 24-h fasting leads to increased energy intake at the following test meal (without total daily energy intake difference), increased hunger profile and decreased post-meal food choice fat bias, such nutritional responses are not observed after a similar deficit induced by exercise.
Major depressive disorder (MDD) is underdiagnosed and undertreated in schizophrenia, and has been strongly associated with impaired quality of life.
To determine the prevalence and associated factors of MDD and unremitted MDD in schizophrenia, to compare treated and non-treated MDD.
Participants were included in the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment. MDD was defined by a Calgary score ≥6. Non-remitted MDD was defined by current antidepressant treatment (unchanged for >8 weeks) and current Calgary score ≥6.
613 patients were included and 175 (28.5%) were identified with current MDD. MDD has been significantly associated with respectively paranoid delusion (odds ratio 1.8; P = 0.01), avolition (odds ratio 1.8; P = 0.02), blunted affect (odds ratio 1.7; P = 0.04) and benzodiazepine consumption (odds ratio 1.8; P = 0.02). Antidepressants were associated with lower depressive symptoms score (5.4 v. 9.5; P < 0.0001); however, 44.1% of treated patients remained in non-remittance MDD. Nonremitters were found to have more paranoid delusion (odds ratio 2.3; P = 0.009) and more current alcohol misuse disorder (odds ratio 4.8; P = 0.04). No antidepressant class or specific antipsychotic were associated with higher or lower response to antidepressant treatment. MDD was associated with Metabolic syndrome (31.4 v. 20.2%; P = 0.006) but not with increased C-reactive protein.
Antidepressant administration is associated with lower depressive symptom level in patients with schizophrenia and MDD. Paranoid delusions and alcohol misuse disorder should be specifically explored and treated in cases of non-remission under treatment. MetS may play a role in MDD onset and/or maintenance in patients with schizophrenia.
Individuals with Alzheimer's disease (AD) present poor immediate primacy recall accompanied by intact or exaggerated recency, which then tends to decline after a delay. Bruno et al. (Journal of Clinical and Experimental Neuropsychology, Vol. 38, 2016, pp. 967–973) have shown that higher ratio scores between immediate and delayed recency (i.e. the recency ratio; Rr) are associated with cognitive decline in high-functioning older individuals. We tested whether Rr predicted conversion to early mild cognitive impairment (early MCI) from a cognitively healthy baseline.
Data were analyzed longitudinally with binomial regression. Baseline scores were used to predict conversion to early MCI after approximately nine years. Setting: Data were collected at the Wisconsin Registry of Alzheimer's Prevention, in Madison, Wisconsin.
For the study, 427 individuals were included in the analysis; all participants were 50 years of age or older and cognitively intact at baseline, and were native English speakers.
Memory data were collected using the Rey's Auditory Verbal Learning Test, and the early MCI diagnosis was obtained via consensus conference.
Our results showed that higher Rr scores are correlated with greater risk of later early MCI diagnosis, and this association is independent of total recall performance.
Rr is an emerging cognitive marker of cognitive decline.
The objective of this study was to assess the influence of nutritional regimens such as adequate feeding, restricted feeding, and underfeeding–refeeding on the follicle growth and development from caprine ovaries. Goats were divided into three different groups (n = 5 per group). For 24 weeks, goats received elephant grass plus concentrate to provide 1.5 (n = 5) and 0.72 (n = 10) times the energy requirements for maintenance of live weight. Underfed goats were subsequently refed for 6 weeks with the diet of the nourished group (1.5 times the energetic requirements of maintenance). Follicular morphology and morphometry, as well as granulosa cells mitotic index were assessed. Ovarian follicles were classified as small or large preantral follicles, or as small or large antral follicles. Ovarian volume was smaller in animals from both underfed and refed groups than in those animals from fed group. Although no difference in the total number of normal follicles was observed among the nutritional groups, underfed animals presented higher percentages of atretic preantral and small antral follicles when compared with fed animals. Large antral follicles from underfed and refed goats presented a lower mitotic index when compared with fed ones. In conclusion, ovaries from goats challenged with prolonged undernutrition will be functionally compromised, which is characterized by atresia of preantral and small antral follicles and decreased mitotic index of large antral follicles. Refeeding those animals will not recover ovarian function to a same level experienced by goats fed a diet with adequate energy requirements.
Sown-grass margin strips, historically established to limit pesticide drift and soil erosion, are now also promoted for enhancing floral diversity and associated ecosystem services. To better understand weed community assembly in grass margin strips, we performed floral surveys in 75 sown-grass margin strips in two regions in France and characterized each species using information from trait databases. We hypothesized that traits of dominant species would differ between newly sown-grass margin strips and older strips. Weed species were separated into functional groups based on their traits using multiple correspondence analysis and hierarchical ascendant classification. Functional group trajectories were investigated in sown-grass margin strips that differed in age using a space-for-time substitution approach. We found that geophyte, competitor, and monocotyledon species were more frequent and abundant in grass margin strips than therophyte, ruderal, and dicotyledon species. Results also showed that floral diversity was greatest in grass margin strips of intermediate age. Our findings have implications for optimizing diversity and ecosystem services on land enrolled in conservation programs and suggest that mowing later in the season and periodic soil disturbance can increase floral diversity. The analytical framework that we introduced in this research can also be used to explore weed community assembly in other systems.
The nature and timing of environmental changes throughout the last glacial-interglacial transition in the South Caucasus, and more widely in eastern Europe, are still not fully understood. According to certain pollen records, forest expansion occurred in many areas several millennia after what is considered worldwide as the onset of the Holocene. The current problem we face is that the time lag in forest expansion varies from one sequence to another, sometimes with no delay at all. Moreover, the potential forcing/controlling factors behind this complex pattern, contrary to the almost synchronous global Holocene warming, are still a matter for debate. Accordingly, we revisit the issue of forest expansion through vegetation history obtained in the South Caucasus using a new pollen record, retrieved from the Nariani paleolake (South Georgia). These data attest to a steppic phase, initially dominated by Amaranthaceae-Chenopodiaceae (12,700–10,500 cal yr BP), then by Poaceae (10,500–9000 cal yr BP), culminating with a more forested phase (9000–5000 calyrBP). Although some palaeoclimatic regional reconstructions show a wet early Holocene, we interpret the delay in forest expansion recorded in Nariani (2500 years) as the result of reduced spring precipitation, which would have limited forest development at that time.