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Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
Clay minerals from the Indus Canyon and eastern clinoform since ~12 ka are uniformly rich in smectite and illite, similar to those from the Holocene Indus flood plains. A systematic enrichment of smectite in the proximal delta compared to the canyon and eastern clinoform argues for preferential capture of smectite close to the river mouth since ~12 ka. There is a rapid shift to a more smectite-rich assemblage in the canyon and eastern clinoform after ~5 ka. This change is probably caused by a change in sediment source, with less direct flux from the Himalaya and more erosion of older, weathered, smectite-rich sediment from the Indus River flood plains, driven by incision of the Indus and its tributaries into the floodplain as summer monsoon rains weakened. This influx of smectite is consistent with lower kaolinite/smectite values since ~5 ka. The onset of large-scale agricultural activities since ~5 ka, especially starting with the Harappan Civilization, may also have enhanced incision and erosion of floodplain sediments over the same time period. This study reports for the first time how monsoon strength variations since ~12 ka affected the clay mineral assemblages and sediment provenance in a major submarine canyon.
To assess whether a community water service is associated with the frequency of sugar-sweetened beverages (SSB) consumption, obesity, or perceived health status in rural Alaska.
We examined the cross-sectional associations between community water access and frequency of SSB consumption, body mass index categories, and perceived health status using data from the 2013 and 2015 Alaska Behavioral Risk Factor Surveillance System (BRFSS). Participants were categorized by zip code to ‘in-home piped water service’ or ‘no in-home piped water service’ based on water utility data. We evaluated the univariable and multivariable (adjusting for age, household income and education) associations between water service and outcomes using log-linear survey-weighted generalized linear models.
Rural Alaska, USA.
Eight hundred and eighty-seven adults, aged 25 years and older.
In unadjusted models, participants without in-home water reported consuming SSB more often than participants with in-home water (1·46, 95 % CI: 1·06, 2·00). After adjustment for potential confounders, the effect decreased but remained borderline significant (1·29, 95 % CI: 1·00, 1·67). Obesity was not significantly associated with water service but self-reported poor health was higher in those communities without in-home water (1·63, 95 % CI: 1·05, 2·54).
Not having access to in-home piped water could affect behaviours surrounding SSB consumption and general perception of health in rural Alaska.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Outpatient central venous catheters (CVCs) are being used more frequently; however, data describing mechanical complications and central-line–associated bloodstream infections (CLABSI) in the outpatient setting are limited. We performed a retrospective observational cohort study to understand the burden of these complications to elucidate their impact on the healthcare system.
Data were retrospectively collected on patients discharged from Vanderbilt University Medical Center with a CVC in place and admitted into the care of Vanderbilt Home Care Services. Risk factors for medically attended catheter-associated complications (CACs) and outpatient CLABSIs were analyzed.
A CAC developed in 143 patients (21.9%), for a total of 165 discrete CAC events. Among these, 76 (46%) required at least 1 visit to the emergency department or an inpatient admission, while the remaining 89 (54%) required an outpatient clinic visit. The risk for developing a CAC was significantly increased in female patients, patients with a CVC with >1 lumen, and patients receiving total parenteral nutrition. The absolute number of CLABSIs identified in the study population was small at 16, or 2.4% of the total cohort.
Medically attended catheter complications were common among outpatients discharged with a CVC, and reduction of these events should be the focus of outpatient quality improvement programs.
Bipolar disorder is a highly heritable polygenic disorder. Recent
enrichment analyses suggest that there may be true risk variants for
bipolar disorder in the expression quantitative trait loci (eQTL) in the
We sought to assess the impact of eQTL variants on bipolar disorder risk
by combining data from both bipolar disorder genome-wide association
studies (GWAS) and brain eQTL.
To detect single nucleotide polymorphisms (SNPs) that influence
expression levels of genes associated with bipolar disorder, we jointly
analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls)
and a genome-wide brain (cortical) eQTL (193 healthy controls) using a
Bayesian statistical method, with independent follow-up replications. The
identified risk SNP was then further tested for association with
hippocampal volume (n = 5775) and cognitive performance
(n = 342) among healthy individuals.
Integrative analysis revealed a significant association between a brain
eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes
factor = 5.48; bipolar disorder P =
5.85×10–5). Follow-up studies across multiple independent
samples confirmed the association of the risk SNP (rs6088662) with gene
expression and bipolar disorder susceptibility (P =
3.54×10–8). Further exploratory analysis revealed that
rs6088662 is also associated with hippocampal volume and cognitive
performance in healthy individuals.
Our findings suggest that 20q11.22 is likely a risk region for bipolar
disorder; they also highlight the informative value of integrating
functional annotation of genetic variants for gene expression in
advancing our understanding of the biological basis underlying complex
disorders, such as bipolar disorder.
Microbes (Bacteria, Archaea, and Fungi) are the most diverse and numerous organisms on earth. They are essential components of every ecosystem and occupy almost every trophic position and niche space (i.e., as heterotrophs, photoheterotrophs, chemoautotrophs, and photoautotrophs; see DeLong et al., 2014). Saprotrophic or heterotrophic species are unique in their capacity to break down and mineralize organic matter (OM) that forms the basis of the carbon, nutrient, and energy cycles. As such, they are the biochemical engineers responsible for the mobilization and mineralization of non-living OM in terrestrial and aquatic ecosystems, and they contribute extensively to the respiratory exchanges of carbon (mainly CO2 and CH4) between the biosphere and the atmosphere. The overwhelming dominance of microbes in OM decomposition has led to extensive exploration into the top-down and bottom-up processes regulating their biomass and diversity, and their consequences for biogeochemical cycling. These heterotrophic microbes form the basis of the decomposer food web, supporting a wide diversity of detritivorous invertebrates and protists, and in turn, a wide range of vertebrate and invertebrate predators.
Unlike autotrophic food webs, where living plants are the primary trophic level, detrital food webs are based on the production of non-living organic material that cannot grow in response to reduced consumption rates, but can accumulate when introduced from adjacent ecosystems. In this sense, the detritus-based food web (often referred to as the “brown” food web) is a “donor-controlled” system, relying on allochthonous inputs from the autotrophic (plant-based) sub-system. As such, these systems can never be exclusively top-down controlled, because microbial predation cannot directly affect the production of OM. Instead, top-down and bottom-up processes are on a continuum of relative importance, and ultimately, the effects of predation propagate as increased or decreased rates of OM decomposition, and thus OM accumulation. In essence, as microbial activity increases, decomposition rates (i.e., the initial loss of OM) generally increase, but when invertebrate predators (henceforth referred to as “grazers”) exert top-down control of microbial communities, their ability to decompose OM can be altered.
Studies of trade routes across Southeast Asia in prehistory have hitherto focused largely on archaeological evidence from Mainland Southeast Asia, particularly the Thai Peninsula and Vietnam. The role of Indonesia and Island Southeast Asia in these networks has been poorly understood, owing to the paucity of evidence from this region. Recent research has begun to fill this void. New excavations at Sembiran and Pacung on the northern coast of Bali have produced new, direct AMS dates from burials, and analytical data from cultural materials including pottery, glass, bronze, gold andsemi-precious stone, as well as evidence of local bronze-casting. This suggests strong links with the Indian subcontinent and Mainland Southeast Asia from the late first millennium BC, some 200 years earlier than previously thought.
Knowledge on the ecology of humpback whales in the eastern North Atlantic is lacking by comparison with most other ocean basins. Humpback whales were historically over-exploited in the region and are still found in low relative abundances. This, coupled with their large range makes them difficult to study. With the aim of informing more effective conservation measures in Ireland, the Irish Whale and Dolphin Group began recording sightings and images suitable for photo-identification of humpback whales from Irish waters in 1999. Validated records submitted by members of the public and data from dedicated surveys were analysed to form a longitudinal study of individually recognizable humpback whales. The distribution, relative abundance and seasonality of humpback whale sighting records are presented, revealing discrete important areas for humpback whales in Irish coastal waters. An annual easterly movement of humpback whales along the southern coast of Ireland is documented, mirroring that of their preferred prey: herring and sprat. Photo-identification images were compared with others collected throughout the North Atlantic (N = 8016), resulting in matches of two individuals between Ireland and Iceland, Norway and the Netherlands but no matches to known breeding grounds (Cape Verde and West Indies). This study demonstrates that combining public records with dedicated survey data is an effective approach to studying low-density, threatened migratory species over temporal and spatial scales that are relevant to conservation and management.