The prevalence of loneliness across 113 countries: systematic review and meta-analysis.

OBJECTIVES: To identify data availability, gaps, and patterns for population level prevalence of loneliness globally, to summarise prevalence estimates within World Health Organization regions when feasible through meta-analysis, and to examine temporal trends of loneliness in countries where data exist. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, Medline, PsycINFO, and Scopus for peer reviewed literature, and Google Scholar and Open Grey for grey literature, supplemented by backward reference searching (to 1 September 2021) ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies based on nationally representative samples (n≥292), validated instruments, and prevalence data for 2000-19. Two researchers independently extracted data and assessed the risk of bias using the Joanna Briggs Institute checklist. Random effects meta-analysis was conducted in the subset of studies with relatively homogeneous research methods by measurement instrument, age group, and WHO region. RESULTS: Prevalence data were available for 113 countries or territories, according to official WHO nomenclature for regions, from 57 studies. Data were available for adolescents (12-17 years) in 77 countries or territories, young adults (18-29 years) in 30 countries, middle aged adults (30-59 years) in 32 countries, and older adults (≥60 years) in 40 countries. Data for all age groups except adolescents were lacking outside of Europe. Overall, 212 estimates for 106 countries from 24 studies were included in meta-analyses. The pooled prevalence of loneliness for adolescents ranged from 9.2% (95% confidence interval 6.8% to 12.4%) in South-East Asia to 14.4% (12.2% to 17.1%) in the Eastern Mediterranean region. For adults, meta-analysis was conducted for the European region only, and a consistent geographical pattern was shown for all adult age groups. The lowest prevalence of loneliness was consistently observed in northern European countries (2.9%, 1.8% to 4.5% for young adults; 2.7%, 2.4% to 3.0% for middle aged adults; and 5.2%, 4.2% to 6.5% for older adults) and the highest in eastern European countries (7.5%, 5.9% to 9.4% for young adults; 9.6%, 7.7% to 12.0% for middle aged adults; and 21.3%, 18.7% to 24.2% for older adults). CONCLUSION: Problematic levels of loneliness are experienced by a substantial proportion of the population in many countries. The substantial difference in data coverage between high income countries (particularly Europe) and low and middle income countries raised an important equity issue. Evidence on the temporal trends of loneliness is insufficient. The findings of this meta-analysis are limited by data scarcity and methodological heterogeneity. Loneliness should be incorporated into general health surveillance with broader geographical and age coverage, using standardised and validated measurement tools. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019131448

Engrailed2 modulates cerebellar granule neuron precursor proliferation, differentiation and insulin-like growth factor 1 signaling during postnatal development

BACKGROUND: The homeobox transcription factor Engrailed2 (En2) has been studied extensively in neurodevelopment, particularly in the midbrain/hindbrain region and cerebellum, where it exhibits dynamic patterns of expression and regulates cell patterning and morphogenesis. Because of its roles in regulating cerebellar development and evidence of cerebellar pathology in autism spectrum disorder (ASD), we previously examined an ENGRAILED2 association and found evidence to support EN2 as a susceptibility gene, a finding replicated by several other investigators. However, its functions at the cell biological level remain undefined. In the mouse, En2 gene is expressed in granule neuron precursors (GNPs) just as they exit the cell cycle and begin to differentiate, raising the possibility that En2 may modulate these developmental processes. METHODS: To define En2 functions, we examined proliferation, differentiation and signaling pathway activation in En2 knockout (KO) and wild-type (WT) GNPs in response to a variety of extracellular growth factors and following En2 cDNA overexpression in cell culture. In vivo analyses of cerebellar GNP proliferation as well as responses to insulin-like growth factor-1 (IGF1) treatment were also conducted. RESULTS: Proliferation markers were increased in KO GNPs in vivo and in 24-h cultures, suggesting En2 normally serves to promote cell cycle exit. Significantly, IGF1 stimulated greater DNA synthesis in KO than WT cells in culture, a finding associated with markedly increased phospho-S6 kinase activation. Similarly, there was three-fold greater DNA synthesis in the KO cerebellum in response to IGF1 in vivo. On the other hand, KO GNPs exhibited reduced neurite outgrowth and differentiation. Conversely, En2 overexpression increased cell cycle exit and promoted neuronal differentiation. CONCLUSIONS: In aggregate, our observations suggest that the ASD-associated gene En2 promotes GNP cell cycle exit and differentiation, and modulates IGF1 activity during postnatal cerebellar development. Thus, genetic/epigenetic alterations of EN2 expression may impact proliferation, differentiation and IGF1 signaling as possible mechanisms that may contribute to ASD pathogenesis

Synchronisation in Coupled Sine Circle Maps

We study the spatially synchronized and temporally periodic solutions of a 1-d lattice of coupled sine circle maps. We carry out an analytic stability analysis of this spatially synchronized and temporally periodic case and obtain the stability matrix in a neat block diagonal form. We find spatially synchronized behaviour over a substantial range of parameter space. We have also extended the analysis to higher spatial periods with similar results. Numerical simulations for various temporal periods of the synchronized solution, reveal that the entire structure of the Arnold tongues and the devil's staircase seen in the case of the single circle map can also be observed for the synchronized coupled sine circle map lattice. Our formalism should be useful in the study of spatially periodic behaviour in other coupled map lattices.Comment: uuencoded, 1 rextex file 14 pages, 3 postscript figure

The braid groups of the projective plane and the Fadell-Neuwirth short exact sequence

International audienceWe study the pure braid groups $P_n(RP^2)$ of the real projective plane $RP^2$, and in particular the possible splitting of the Fadell-Neuwirth short exact sequence $1 \to P_m(RP^2 \ {x_1,...,x_n} \to P_{n+m}(RP^2) \stackrel{p_{\ast}}{\to} P_n(RP^2) \to 1$, where $n\geq 2$ and $m\geq 1$, and $p_{\ast}$ is the homomorphism which corresponds geometrically to forgetting the last $m$ strings. This problem is equivalent to that of the existence of a section for the associated fibration $p: F_{n+m}(RP^2) \to F_n(RP^2)$ of configuration spaces. Van Buskirk proved in 1966 that $p$ and $p_{\ast}$ admit a section if $n=2$ and $m=1$. Our main result in this paper is to prove that there is no section if $n\geq 3$. As a corollary, it follows that $n=2$ and $m=1$ are the only values for which a section exists. As part of the proof, we derive a presentation of $P_n(RP^2)$: this appears to be the first time that such a presentation has been given in the literature

A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

Calcineurin and Protein kinase G regulate C. elegans behavioral quiescence during locomotion in liquid

<p>Abstract</p> <p>Background</p> <p>Most rhythmic motor behaviors in nature are episodic i.e. they alternate between different behavioral states, including quiescence. Electrophysiological studies in invertebrate behavioral switching, maintenance and quiescence have elucidated several neuronal mechanisms that generate a temporal pattern in behavior. However, the genetic bases of these processes are less well studied. We have previously uncovered a novel episodic behavior exhibited by <it>C. elegans </it>in liquid media where they alternate between distinct phases of rhythmic swimming and quiescence. Here, we have investigated the effect of several genes and their site of action on the behavioral quiescence exhibited in liquid by the nematode <it>C. elegans</it>.</p> <p>Results</p> <p>We have previously reported that high cholinergic signaling promotes quiescence and command interneurons are critical for timing the quiescence bout durations. We have found that in addition to command interneurons, sensory neurons are also critical for quiescence. We show that the protein phosphatase calcineurin homolog <it>tax-6 </it>promotes swimming whereas the protein kinase G homolog <it>egl-4 </it>promotes quiescence. <it>tax-6 </it>expression in the sensory neurons is sufficient to account for its effect. <it>egl-4 </it>also acts in multiple sensory neurons to mediate its effect on quiescence. In addition our data is consistent with regulation of quiescence by <it>egl-4 </it>acting functionally downstream of release of acetylcholine (ACh) by motor neurons.</p> <p>Conclusions</p> <p>Our study provides genetic evidence for mechanisms underlying the maintenance of a behavioral state operating at multiple neuronal levels through the activities of a kinase and a phosphatase. These results in a genetically tractable organism establish a framework for further dissection of the mechanism of quiescence during episodic behaviors.</p

Egg Production in a Coastal Seabird, the Glaucous-Winged Gull (Larus glaucescens), Declines during the Last Century

Seabirds integrate information about oceanic ecosystems across time and space, and are considered sensitive indicators of marine conditions. To assess whether hypothesized long-term foodweb changes such as forage fish declines may be reflected in a consumer's life history traits over time, I used meta-regression to evaluate multi-decadal changes in aspects of egg production in the glaucous-winged gull (Larus glaucescens), a common coastal bird. Study data were derived from literature searches of published papers and unpublished historical accounts, museum egg collections, and modern field studies, with inclusion criteria based on data quality and geographic area of the original study. Combined historical and modern data showed that gull egg size declined at an average of 0.04 cc y−1 from 1902 (108 y), equivalent to a decline of 5% of mean egg volume, while clutch size decreased over 48 y from a mean of 2.82 eggs per clutch in 1962 to 2.25 in 2009. There was a negative relationship between lay date and mean clutch size in a given year, with smaller clutches occurring in years where egg laying commenced later. Lay date itself advanced over time, with commencement of laying presently (2008–2010) 7 d later than in previous studies (1959–1986). This study demonstrates that glaucous-winged gull investment in egg production has declined significantly over the past ∼50–100 y, with such changes potentially contributing to recent population declines. Though gulls are generalist feeders that should readily be able to buffer themselves against food web changes, they are likely nutritionally constrained during the early breeding period, when egg production requirements are ideally met by consumption of high-quality prey such as forage fish. This study's results suggest a possible decline in the availability of such prey, and the incremental long-term impoverishment of a coastal marine ecosystem bordering one of North America's rapidly growing urban areas

Increased Avian Diversity Is Associated with Lower Incidence of Human West Nile Infection: Observation of the Dilution Effect

Recent infectious disease models illustrate a suite of mechanisms that can result in lower incidence of disease in areas of higher disease host diversity–the ‘dilution effect’. These models are particularly applicable to human zoonoses, which are infectious diseases of wildlife that spill over into human populations. As many recent emerging infectious diseases are zoonoses, the mechanisms that underlie the ‘dilution effect’ are potentially widely applicable and could contribute greatly to our understanding of a suite of diseases. The dilution effect has largely been observed in the context of Lyme disease and the predictions of the underlying models have rarely been examined for other infectious diseases on a broad geographic scale. Here, we explored whether the dilution effect can be observed in the relationship between the incidence of human West Nile virus (WNV) infection and bird (host) diversity in the eastern US. We constructed a novel geospatial contrasts analysis that compares the small differences in avian diversity of neighboring US counties (where one county reported human cases of WNV and the other reported no cases) with associated between-county differences in human disease. We also controlled for confounding factors of climate, regional variation in mosquito vector type, urbanization, and human socioeconomic factors that are all likely to affect human disease incidence. We found there is lower incidence of human WNV in eastern US counties that have greater avian (viral host) diversity. This pattern exists when examining diversity-disease relationships both before WNV reached the US (in 1998) and once the epidemic was underway (in 2002). The robust disease-diversity relationships confirm that the dilution effect can be observed in another emerging infectious disease and illustrate an important ecosystem service provided by biodiversity, further supporting the growing view that protecting biodiversity should be considered in public health and safety plans

Pigmentation plasticity enhances crypsis in larval newts: Associated metabolic cost and background choice behaviour

In heterogeneous environments, the capacity for colour change can be a valuable adaptation enhancing crypsis against predators. Alternatively, organisms might achieve concealment by evolving preferences for backgrounds that match their visual traits, thus avoiding the costs of plasticity. Here we examined the degree of plasticity in pigmentation of newt larvae (Lissotriton boscai) in relation to predation risk. Furthermore, we tested for associated metabolic costs and pigmentation-dependent background choice behaviour. Newt larvae expressed substantial changes in pigmentation so that light, high-reflecting environment induced depigmentation whereas dark, low-reflecting environment induced pigmentation in just three days of exposure. Induced pigmentation was completely reversible upon switching microhabitats. Predator cues, however, did not enhance cryptic phenotypes, suggesting that environmental albedo induces changes in pigmentation improving concealment regardless of the perceived predation risk. Metabolic rate was higher in heavily pigmented individuals from dark environments, indicating a high energetic requirement of pigmentation that could impose a constraint to larval camouflage in dim habitats. Finally, we found partial evidence for larvae selecting backgrounds matching their induced phenotypes. However, in the presence of predator cues, larvae increased the time spent in light environments, which may reflect a escape response towards shallow waters rather than an attempt at increasing crypsisFinancial support was provided by the Spanish Ministry of Science and Innovation (MICINN), Grant CGL2012-40044 to IGM, and by the Universidad Autónoma de Madrid, Short Stay Grant to NPC. Additional financial support was provided by the MICINN, Grant CGL2015-68670-R to NP

Dynamic displacement of normal and detached semicircular canal cupula

© 2009 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in JARO - Journal of the Association for Research in Otolaryngology 10 (2009): 497-509, doi:10.1007/s10162-009-0174-y.The dynamic displacement of the semicircular canal cupula and modulation of afferent nerve discharge were measured simultaneously in response to physiological stimuli in vivo. The adaptation time constant(s) of normal cupulae in response to step stimuli averaged 36 s, corresponding to a mechanical lower corner frequency for sinusoidal stimuli of 0.0044 Hz. For stimuli equivalent to 40–200 deg/s of angular head velocity, the displacement gain of the central region of the cupula averaged 53 nm per deg/s. Afferents adapted more rapidly than the cupula, demonstrating the presence of a relaxation process that contributes significantly to the neural representation of angular head motions by the discharge patterns of canal afferent neurons. We also investigated changes in time constants of the cupula and afferents following detachment of the cupula at its apex—mechanical detachment that occurs in response to excessive transcupular endolymph pressure. Detached cupulae exhibited sharply reduced adaptation time constants (300 ms–3 s, n = 3) and can be explained by endolymph flowing rapidly over the apex of the cupula. Partially detached cupulae reattached and normal afferent discharge patterns were recovered 5–7 h following detachment. This regeneration process may have relevance to the recovery of semicircular canal function following head trauma.Financial support was provided by the NIDCD R01 DC06685 (Rabbitt) and NASA GSRP 56000135 & NSF IGERT DGE- 9987616 (Breneman)