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The genetic contribution to the comorbidity of depression and anxiety: a multi-site electronic health records study of almost 178 000 people
- Brandon J Coombes, Isotta Landi, Karmel W Choi, Kritika Singh, Brian Fennessy, Greg D Jenkins, Anthony Batzler, Richard Pendegraft, Nicolas A Nunez, Y Nina Gao, Euijung Ryu, Priya Wickramaratne, Myrna M Weissman, Regeneron Genetics Center, Jyotishman Pathak, J John Mann, Jordan W Smoller, Lea K Davis, Mark Olfson, Alexander W Charney, Joanna M Biernacka
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- Journal:
- Psychological Medicine / Volume 53 / Issue 15 / November 2023
- Published online by Cambridge University Press:
- 05 May 2023, pp. 7368-7374
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Background
Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation.
MethodsDiagnostic codes were extracted from electronic health records for four biobanks [N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]. The outcome was a four-level variable representing the depression/anxiety diagnosis group: neither, depression-only, anxiety-only, and comorbid. Multinomial regression was used to test for association of depression and anxiety polygenic risk scores (PRSs) with the outcome while adjusting for principal components of ancestry.
ResultsIn total, 132 960 patients had neither diagnosis (74.8%), 16 092 depression-only (9.0%), 13 098 anxiety-only (7.4%), and 16 584 comorbid (9.3%). In the European meta-analysis across biobanks, both PRSs were higher in each diagnosis group compared to controls. Notably, depression-PRS (OR 1.20 per s.d. increase in PRS; 95% CI 1.18–1.23) and anxiety-PRS (OR 1.07; 95% CI 1.05–1.09) had the largest effect when the comorbid group was compared with controls. Furthermore, the depression-PRS was significantly higher in the comorbid group than the depression-only group (OR 1.09; 95% CI 1.06–1.12) and the anxiety-only group (OR 1.15; 95% CI 1.11–1.19) and was significantly higher in the depression-only group than the anxiety-only group (OR 1.06; 95% CI 1.02–1.09), showing a genetic risk gradient across the conditions and the comorbidity.
ConclusionsThis study suggests that depression and anxiety have partially independent genetic liabilities and the genetic vulnerabilities to depression and anxiety make distinct contributions to comorbid depression and anxiety.
The Pantheon+ analysis: Improving the redshifts and peculiar velocities of Type Ia supernovae used in cosmological analyses
- Anthony Carr, Tamara M. Davis, Dan Scolnic, Khaled Said, Dillon Brout, Erik R. Peterson, Richard Kessler
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 39 / 2022
- Published online by Cambridge University Press:
- 11 October 2022, e046
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We examine the redshifts of a comprehensive set of published Type Ia supernovae, and provide a combined, improved catalogue with updated redshifts. We improve on the original catalogues by using the most up-to-date heliocentric redshift data available; ensuring all redshifts have uncertainty estimates; using the exact formulae to convert heliocentric redshifts into the Cosmic Microwave Background (CMB) frame; and utilising an improved peculiar velocity model that calculates local motions in redshift-space and more realistically accounts for the external bulk flow at high-redshifts. We review 2607 supernova redshifts; 2285 are from unique supernovae and 322 are from repeat-observations of the same supernova. In total, we updated 990 unique heliocentric redshifts, and found 5 cases of missing or incorrect heliocentric corrections, 44 incorrect or missing supernova coordinates, 230 missing heliocentric or CMB frame redshifts, and 1200 missing redshift uncertainties. The absolute corrections range between $10^{-8} \leq \Delta z \leq 0.038$ , and RMS $(\Delta z) \sim 3{\times 10^{-3}}$ . The sign of the correction was essentially random, so the mean and median corrections are small: $4{\times 10^{-4}}$ and $4{\times 10^{-6}}$ respectively. We examine the impact of these improvements for $H_0$ and the dark energy equation of state w and find that the cosmological results change by $\Delta H_0 = -0.12\,\mathrm{km\,s}^{-1}\mathrm{Mpc}^{-1}$ and $\Delta w = 0.003$ , both significantly smaller than previously reported uncertainties for $H_0$ of 1.0 $\mathrm{km\,s}^{-1}\mathrm{Mpc}^{-1}$ and w of 0.04 respectively.
Can we check serum lithium levels less often without compromising patient safety?
- Adrian H. Heald, David Holland, Michael Stedman, Mark Davies, Chris J. Duff, Ceri Parfitt, Lewis Green, Jonathan Scargill, David Taylor, Anthony A. Fryer
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- Journal:
- BJPsych Open / Volume 8 / Issue 1 / January 2022
- Published online by Cambridge University Press:
- 17 December 2021, e18
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Background
Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder.
AimsThis study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases.
MethodWe included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history.
ResultsFor tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40–0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4–0.79 mmol/L group (2%), irrespective of testing frequency.
ConclusionWe propose that for those who achieve 12 months of lithium tests within the 0.40–0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80–0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.
We can check serum lithium levels less often without compromising patient safety: evidence from a multi-centre study
- Adrian Heald, David Holland, Mark Davies, Chris Duff, Ceri Parfitt, Lewis Green, Jonathan Scargill, David Taylor, Anthony Fryer
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- Journal:
- BJPsych Open / Volume 7 / Issue S1 / June 2021
- Published online by Cambridge University Press:
- 18 June 2021, pp. S29-S30
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Aims
Lithium was first found to have an acute antimanic effect in 1948 with further corroboration in the early 1950s. It took some time for lithium to become the standard treatment for relapse prevention in bipolar affective disorder. In this study, our aims were to examine the factors associated wtih the likelihood of maintaining lithium levels within the recommended therapeutic range and to look at the stability of lithium levels between blood tests. We examined this relation using clinical laboratory serum lithium test requesting data collected from three large UK centres, where the approach to managing patients with bipolar disorder and ordering lithium testing varied.
Method46,555 lithium rest requests in 3,371 individuals over 7 years were included from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where, on subsequent testing, lithium results remained in the same category or switched category. We then examined the association between testing interval and proportion remaining within target, and the effect of age, duration of lithium therapy and testing history.
ResultFor tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall 3-monthly testing was associated with 90% of lithium results remaining within range compared with 85% at 6-monthly intervals. At all test intervals, lithium test result history in the previous 12-months was associated with the proportion of next test results on target (BNF/NICE criteria), with 90% remaining within range target after 6-months if all tests in the previous 12-months were on target. Age/duration of lithium therapy had no significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) than those in the 0.40–0.79 mmolL group (2%), irrespective of testing frequency. Thus prior history in relation to stability of lithium level in the previous 12 months is a predictor of future stability of lithium level.
ConclusionWe propose that, for those who achieve 12-months of lithium tests within the 0.40–0.79mmol/L range, it would be reasonable to increase the interval between tests to 6 months, irrespective of age, freeing up resource to focus on those less concordant with their lithium monitoring. Where lithium level is 0.80–0.99mmol/L test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.
Scaling-up Health-Arts Programmes: the largest study in the world bringing arts-based mental health interventions into a national health service
- Carolina Estevao, Daisy Fancourt, Paola Dazzan, K. Ray Chaudhuri, Nick Sevdalis, Anthony Woods, Nikki Crane, Rebecca Bind, Kristi Sawyer, Lavinia Rebecchini, Katie Hazelgrove, Manonmani Manoharan, Alexandra Burton, Hannah Dye, Tim Osborn, Lucinda Jarrett, Nick Ward, Fiona Jones, Aleksandra Podlewska, Isabella Premoli, Fleur Derbyshire-Fox, Alison Hartley, Tayana Soukup, Rachel Davis, Ioannis Bakolis, Andy Healey, Carmine M. Pariante
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- Journal:
- BJPsych Bulletin / Volume 45 / Issue 1 / February 2021
- Published online by Cambridge University Press:
- 23 December 2020, pp. 32-39
- Print publication:
- February 2021
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The Scaling-up Health-Arts Programme: Implementation and Effectiveness Research (SHAPER) project is the world's largest hybrid study on the impact of the arts on mental health embedded into a national healthcare system. This programme, funded by the Wellcome Trust, aims to study the impact and the scalability of the arts as an intervention for mental health. The programme will be delivered by a team of clinicians, research scientists, charities, artists, patients and healthcare professionals in the UK's National Health Service (NHS) and the community, spanning academia, the NHS and the charity sector. SHAPER consists of three studies – Melodies for Mums, Dance for Parkinson's, and Stroke Odysseys – which will recruit over 800 participants, deliver the interventions and draw conclusions on their clinical impact, implementation effectiveness and cost-effectiveness. We hope that this work will inspire organisations and commissioners in the NHS and around the world to expand the remit of social prescribing to include evidence-based arts interventions.
Burden of Clostridium difficile Infection (CDI) Across Whole Healthcare Economies and European Borders; COMBACTE-CDI Results
- Kerrie Davies, Virginie Viprey, Duncan Ewin, William Spittal, Jon Vernon, Valerija Tkalec, Warren Fawley, Anthony Benson, Georgina Davis, Maja Rupnik, Mark Wilcox
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 41 / Issue S1 / October 2020
- Published online by Cambridge University Press:
- 02 November 2020, pp. s24-s25
- Print publication:
- October 2020
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Background: The burden of C. difficile infection (CDI) on healthcare facilities is well recognized. However, studies focusing on inpatient settings, in addition to ascertainment bias in general, have led to a paucity of data on the true burden of CDI across whole healthcare economies. Methods: Sites testing both inpatient and community samples were recruited from 12 European countries (1 site per 3 million population). On 2 selected days, all diarrheal fecal samples (regardless of tests requested) were sent to the European Coordinating Laboratory (ECL) for C. difficile toxin testing and culture. The CDI results and tests not requested at each submitting site were compared with the ECL results to determine the number of missed CDIs. Contemporaneous C. difficile isolates from food and animal sources were collected. All isolates underwent PCR ribotyping and toxinotyping; prevalences of ribotypes among regions of Europe and reservoir settings were compared. Results: Overall, 3,163 diarrheal fecal samples were received from 119 sites. The burden of CDI varied by country (positivity rates, 0–15.8%) and by European region; the highest positivity rate in Eastern Europe was 13.1%. The testing and positivity rates in community samples were 29.6% and 1.4% vs 74.9% and 5.0% in hospital samples; 16% and 55% of samples positive for CDI at ECL were not diagnosed in hospitals and the community. The most common C. difficile ribotypes from hospital samples were 027 (11%), 181 (12%), and 014 (8%), although prevalence varied by country. The highest prevalence of toxinotype IIIb (ribotypes 027, 181, and 176) was seen in Eastern Europe (55% of all isolates), which also had the lowest testing rate. For hospital samples, the proportion of toxinotype IIIb was inversely related to the testing rate (r = −0.79) (Fig. 1). The most common ribotypes from food sources were 078 (23%) and 126 (13%) (toxinotype V), and most common ribotypes from community samples were 078 (9%) and 039 (9%). Overall, 106 different ribotypes were identified: 25 in both the hospital and community and 16 in the hospital, community, and food chain. Conclusions: The diagnosed burden of CDI varies markedly among countries in both hospital and community settings. Reduced sampling/testing in Eastern Europe is inversely related to the proportion of toxinotype IIIb strains identified, suggesting that lack of suspicion leads to underdiagnosis and outbreaks of infection. The proportion of missed CDIs in the community was ~3.5× higher than in hospitals, indicating major underrecognition in the former setting. There were marked differences in ribotypes in different reservoir settings, emphasizing the complex epidemiology of C. difficile.
Funding: Proprietary organization: COMBACTE-CDI is an EU funded (Horizon2020) consortium of academic and EFPIA partners (bioMerieux, GSK, Sanofi Pasteur, Astra Zeneca, Pfizer, Da Volterra) with additional Funding: from the EFPIA partners.
Disclosures: Submitter: Kerrie Davies; the work presented is funded via the EU and EFPIA (commercial) partners in a consortium.
Rolling of non-wetting droplets down a gently inclined plane
- Ory Schnitzer, Anthony M. J. Davis, Ehud Yariv
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- Journal of Fluid Mechanics / Volume 903 / 25 November 2020
- Published online by Cambridge University Press:
- 28 September 2020, A25
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We analyse the near-rolling motion of non-wetting droplets down a gently inclined plane. Inspired by the scaling analysis of Mahadevan & Pomeau (Phys. Fluids, vol. 11, 1999, pp. 2449–2453), we focus upon the limit of small Bond numbers, where the drop shape is nearly spherical and the internal flow is approximately a rigid-body rotation except close to the flat spot at the base of the drop. In that region, where the fluid interface appears flat, we obtain an analytical approximation for the flow field. By evaluating the dissipation associated with that flow we obtain a closed-form approximation for the drop speed. This approximation reveals that the missing prefactor in the Mahadevan–Pomeau scaling law is $(3{\rm \pi} /16)\sqrt {3/2}\approx 0.72$ – in good agreement with experiments. An unexpected feature of the flow field is that it happens to satisfy the no-slip and shear-free conditions simultaneously over both the solid flat spot and the mobile fluid interface in its vicinity. Furthermore, we show that close to the near-circular contact line the velocity field lies primarily in the plane locally normal to the contact line; it is analogous there to the local solution in the comparable problem of a two-dimensional rolling drop. This analogy breaks down near the two points where the contact line propagates parallel to itself, the local flow being there genuinely three dimensional. These observations illuminate a unique ‘peeling’ mechanism by which a rolling droplet avoids the familiar non-integrable stress singularity at a moving contact line.
The Tumblagooda Sandstone revisited: exceptionally abundant trace fossils and geological outcrop provide a window onto Palaeozoic littoral habitats before invertebrate terrestrialization
- Anthony P. Shillito, Neil S. Davies
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- Journal:
- Geological Magazine / Volume 157 / Issue 12 / December 2020
- Published online by Cambridge University Press:
- 13 April 2020, pp. 1939-1970
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The establishment of permanent animal communities on land was a defining event in the history of evolution, and one for which the ichnofauna and facies of the Tumblagooda Sandstone of Western Australia have been considered an archetypal case study. However, terrestrialization can only be understood from the rock record with conclusive sedimentological evidence for non-marine deposition, and original fieldwork on the formation shows that a marine influence was pervasive throughout all trace fossil-bearing strata. Four distinct facies associations are described, deposited in fluvial, tidal and estuarine settings. Here we explain the controversies surrounding the age and depositional environment of the Tumblagooda Sandstone, many of which have arisen due to the challenges in distinguishing marine from non-marine depositional settings in lower Palaeozoic successions. We clarify the terminological inconsistency that has hindered such determination, and demonstrate how palaeoenvironmental explanations can be expanded out from unambiguously indicative sedimentary structures. The Tumblagooda Sandstone provides a unique insight into an early Palaeozoic ichnofauna that was strongly partitioned by patchy resource distribution in a littoral setting. The influence of outcrop style and quality is accounted for to contextualize this ichnofauna, revealing six distinct low-disparity groups of trace fossil associations, each related to a different sub-environment within the high-ichnodisparity broad depositional setting. The formation is compared with contemporaneous ichnofaunas to examine its continued significance to understanding the terrestrialization process. Despite not recording permanent non-marine communities, the Tumblagooda Sandstone provides a detailed picture of the realm left behind by the first invertebrate pioneers of terrestrialization.
Mineralogical and geochemical evidence of weathering in a middle to late Pleistocene paleosol sequence in the Driftless Area of Wisconsin
- Peter M. Jacobs, Anthony T. Davis
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- Journal:
- Quaternary Research / Volume 89 / Issue 3 / May 2018
- Published online by Cambridge University Press:
- 26 October 2017, pp. 756-768
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Paleosols occur in the Driftless Area of southwestern Wisconsin because this area escaped direct Pleistocene glaciation, allowing long-term loess and colluvium accumulation in selected settings. The most complete known depositional sequence at Oil City, Wisconsin, contains eight lithologic units with five paleosols, all with normal remanent magnetism (i.e., <780 ka). Previous work characterized the stratigraphy, pedology, micromorphology, and clay mineralogy of the section. We investigate chemical weathering of the 8–63 µm silt fraction using X-ray diffraction (XRD) and elemental geochemistry by portable X-ray fluorescence (pXRF). Elemental ratios TiO2/CaO, Zr/Sr, and Rb/Sr generally align with the pedological evidence of weathering. Mineral ratios plagioclase/quartz and K-feldspar/quartz display greater scatter and less certainty in interpretation. The paleosols with Bt horizons have ratios indicating greater weathering than the modern soil. The most weathered paleosol is formed in the unnamed fourth loess unit stratigraphically below the Loveland Member. The stratigraphic position and higher degree of weathering support correlation of the fourth loess with the Yarmouth Geosol and Crowley’s Ridge Silt of the Middle Mississippi valley. Geochemical indices by pXRF are more consistent with established lithologic breaks than mineralogy by XRD. Our results support the use of pXRF for stratigraphic and weathering studies of Quaternary sediments.
Meta-Analysis of Crop and Weed Growth Responses to Arbuscular Mycorrhizal Fungi: Implications for Integrated Weed Management
- Meng Li, Nicholas R. Jordan, Roger T. Koide, Anthony C. Yannarell, Adam S. Davis
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- Journal:
- Weed Science / Volume 64 / Issue 4 / December 2016
- Published online by Cambridge University Press:
- 20 January 2017, pp. 642-652
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Integrated weed management (IWM) relies upon multiple chemical, physical, or biological weed management techniques to achieve an acceptable level of weed control. Agents that selectively suppress weeds but not crops and that can be manipulated in agriculture will be promising components for inclusion in IWM. We used a meta-analytic approach to investigate the potential of arbuscular mycorrhizal fungi (AMF) to contribute to IWM. We quantified the effect of crop and weed host status (strong and weak AMF hosts are divided in this study by a 10% root length colonization threshold), AMF diversity (single vs. mixed), and soil N and P fertility management on plant mycorrhizal growth responses (MGRs). Our results indicated that weak host weeds had consistently lower MGRs than strong host crops in both controlled and field conditions. Moreover, these differences in MGRs between weak host weeds and strong host crops were more pronounced under mixed AMF inoculum and low N and P nutrient availability. In contrast, MGR of strong host weeds was not different from strong host crops in general. However, we observed a wide range of MGRs among strong host weeds, some of which had much lower MGRs than strong host crops. In addition, in the presence of N and P fertilizers, strong host crops had a stronger positive response to AMF than strong host weeds. Thus, our meta-analysis indicates that AMF have potential to contribute to weed control by direct and indirect pathways: directly suppress weak host weeds, and indirectly suppress some strong host weeds mediating by competitive effects exerted by strong host crops. We suggest that management practices affecting AMF diversity and crop and weed mycorrhizal responses could be chosen to improve the contribution of AMF to IWM. Better understanding is needed of crop–weed–AMF interactions and management practices that enhance this form of weed management.
Sedimentology and Palynology of Middle Wisconsinan Deposits in the Pecatonica River Valley, Wisconsin and Illinois
- G. Richard Whittecar, Anthony M. Davis
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- Quaternary Research / Volume 17 / Issue 2 / March 1982
- Published online by Cambridge University Press:
- 20 January 2017, pp. 228-240
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The bedrock valley of the Pecatonica River north of Freeport, Illinois, contains a thick valley-fill complex of alluvium and drift. Within the valley, loess-capped benches surround hills of silty Illinoian drift. Beneath these benches lie thick deposits of poorly sorted stony silt interbedded with thin lenses of silt, sand, and organic-rich loam. Channel deposits and peat cap the diamicton in places. We interpret the stony silts as solifluction debris shed from silty slopes within the valley-fill during the Early or Middle Wisconsinan (Altonian). Top and bottom radiocarbon dates from a 2.5-m section of peat overlying the diamicton are 26,820 ± 200 and 40,500 ± 1700 yr B.P., respectively. We informally refer to the stony silts, channel sediments, and peat as the “Martintown unit.” Geomorphic position, sediment input, and macrofossils suggest that the dated peat was deposited in a floodplain pond (oxbow?). The pollen record from the peat indicates that a boreal forest dominated this area during the Middle Wisconsinan (late Altonian and Farmdalian). Two pollen zones are recognized: a basal Zone I with Pinus slightly more abundant than Picea and with few herbs and shrubs, and an upper Zone II dominated by Picea and with a larger representation of herbaceous and shrub taxa. Little displacement of vegetation zones is indicated, even though ice advanced to within 100 km of the site during the time of peat accumulation. Because of the problems involved in clearly defining Middle Wisconsinan forest-tundra in mid-latitudes by using analogs of Holocene forest-tundra in high latitudes, caution is required in making geomorphic inferences solely from vegetation data. Together, though, pollen and sediment data indicate that during the Middle Wisconsinan, Pecatonica hillslopes progressed through a sequence of instability-stability-instability related to climatic fluctuations.
Paleoenvironmental records of water level and climatic changes from the middle to late holocene at a Lake Erie coastal wetland, Ontario, Canada
- Sarah A. Finkelstein, Anthony M. Davis
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- Journal:
- Quaternary Research / Volume 65 / Issue 1 / January 2006
- Published online by Cambridge University Press:
- 20 January 2017, pp. 33-43
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Pollen and diatom assemblages, and peat stratigraphies, from a coastal wetland on the northern shore of Lake Erie were used to analyze water level and climatic changes since the middle Holocene and their effects on wetland plant communities. Peat deposition began 4700 cal yr B.P. during the Nipissing II transgression, which was driven by isostatic rebound. At that time, a diatom-rich wild rice marsh existed at the site. Water level dropped at the end of the Nipissing rise at least 2 m within 200 yr, leading to the development of shallower-water plant communities and an environment too dry for most diatoms to persist. The sharp decline in water level was probably driven primarily by outlet incision, but climate likely played some role. The paleoecological records provide evidence for post-Nipissing century-scale transgressions occurring around 2300, 1160, 700 and 450 cal yr B.P. The chronology for these transgressions correlates with other studies from the region and implies climatic forcing. Peat inception in shallow sloughs across part of the study area around 700 cal yr B.P. coincides with the Little Ice Age. These records, considered alongside others from the region, suggest that the Little Ice Age may have resulted in a wetter climate across the eastern Great Lakes region.
A 6000-year record of ecological and hydrological changes from Laguna de la Leche, north coastal Cuba
- Matthew C. Peros, Eduard G. Reinhardt, Anthony M. Davis
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- Journal:
- Quaternary Research / Volume 67 / Issue 1 / January 2007
- Published online by Cambridge University Press:
- 20 January 2017, pp. 69-82
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Laguna de la Leche, north coastal Cuba, is a shallow (≤ 3 m), oligohaline (∼ 2.0–4.5‰) coastal lake surrounded by mangroves and cattail stands. A 227-cm core was studied using loss-on-ignition, pollen, calcareous microfossils, and plant macrofossils. From ∼6200 to ∼ 4800 cal yr BP, the area was an oligohaline lake. The period from ∼ 4800 to ∼ 4200 cal yr BP saw higher water levels and a freshened system; these changes are indicated by an increase in the regional pollen rain, as well as by the presence of charophyte oogonia and an increase in freshwater gastropods (Hydrobiidae). By ∼ 4000 cal yr BP, an open mesohaline lagoon had formed; an increase in salt-tolerant foraminifers suggests that water level increase was driven by relative sea level rise. The initiation of Laguna de la Leche correlates with a shift to wetter conditions as indicated in pollen records from the southeastern United States (e.g., Lake Tulane). This synchronicity suggests that sea level rise caused middle Holocene environmental change region-wide. Two other cores sampled from mangrove swamps in the vicinity of Laguna de la Leche indicate that a major expansion of mangroves was underway by ∼ 1700 cal yr BP.
Instability of a vortex sheet leaving a right-angled wedge
- Anthony M. J. Davis, Stefan G. Llewellyn Smith
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- Journal:
- Journal of Fluid Mechanics / Volume 803 / 25 September 2016
- Published online by Cambridge University Press:
- 15 August 2016, pp. 1-17
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We examine the dynamics of a semi-infinite vortex sheet attached not to a semi-infinite plate but instead to a rigid right-angled wedge, with the sheet aligned along one of its edges. Our approach to this problem, which was suggested by David Crighton, accords well with the fundamental ethos of Crighton’s work, which was characterized by ‘the application of rigorous mathematical approximations to fluid mechanical idealizations of practically relevant problems’ (Ffowcs Williams, Annu. Rev. Fluid Mech., vol. 34, 2002, pp. 37–49). The resulting linearised unsteady potential flow is forced by an oscillatory dipole in the uniform stream passing along the top of the wedge, while there is stagnant fluid in the remaining quadrant. Spatial instability is considered according to well-established methods: causality is enforced by allowing the frequency to become temporarily complex. The essentially quadrant-type geometry replaces the usual Wiener–Hopf technique by the Mellin transform. The core difficulty is that a first-order difference equation of period 4 requires a solution of period unity. As a result, the complex fourth roots $(\pm 1\pm \text{i})$ of $-4$ appear in the complementary function. The Helmholtz instability wave is excited and requires careful handling to obtain explicit results for the amplitude of the instability wave.
Contributors
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. 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Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- The Cambridge Dictionary of Philosophy
- Published online:
- 05 August 2015
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- 27 April 2015, pp ix-xxx
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Contributors
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- By Mari C. Jones, Sjef Barbiers, Dorothee Beermann, Bernard Bel, Matt Coler, Jeffrey E. Davis, Médéric Gasquet-Cyrus, Tjeerd de Graaf, Petr Homola, Russell Hugo, Geraint Jennings, Lysbeth Jongbloed-Faber, Aimée Lahaussois, Cecilia Odé, Nicholas Ostler, Hugh Paterson, Anthony Scott Warren, Cor van der Meer
- Edited by Mari C. Jones, University of Cambridge
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- Endangered Languages and New Technologies
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- 05 December 2014
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- 04 December 2014, pp x-xii
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Analysis of copy number variations at 15 schizophrenia-associated loci
- Elliott Rees, James T. R. Walters, Lyudmila Georgieva, Anthony R. Isles, Kimberly D. Chambert, Alexander L. Richards, Gerwyn Mahoney-Davies, Sophie E. Legge, Jennifer L. Moran, Steven A. McCarroll, Michael C. O'Donovan, Michael J. Owen, George Kirov
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- The British Journal of Psychiatry / Volume 204 / Issue 2 / February 2014
- Published online by Cambridge University Press:
- 02 January 2018, pp. 108-114
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- February 2014
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Background
A number of copy number variants (CNVs) have been suggested as susceptibility factors for schizophrenia. For some of these the data remain equivocal, and the frequency in individuals with schizophrenia is uncertain.
AimsTo determine the contribution of CNVs at 15 schizophrenia-associated loci (a) using a large new data-set of patients with schizophrenia (n = 6882) and controls (n = 6316), and (b) combining our results with those from previous studies.
MethodWe used Illumina microarrays to analyse our data. Analyses were restricted to 520 766 probes common to all arrays used in the different data-sets.
ResultsWe found higher rates in participants with schizophrenia than in controls for 13 of the 15 previously implicated CNVs. Six were nominally significantly associated (P<0.05) in this new data-set: deletions at 1q21.1, NRXN1, 15q11.2 and 22q11.2 and duplications at 16p11.2 and the Angelman/Prader–Willi Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were of maternal origin. When combined with published data, 11 of the 15 loci showed highly significant evidence for association with schizophrenia (P<4.1×10−4).
ConclusionsWe strengthen the support for the majority of the previously implicated CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9% of controls carry a large, detectable CNV at one of these loci. Routine CNV screening may be clinically appropriate given the high rate of known deleterious mutations in the disorder and the comorbidity associated with these heritable mutations.
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- By Vanessa Agnew, Gregory Barz, Michael Beckerman, Stephen Blum, Philip V. Bohlman, Salwa El-Shawan Castelo-Branco, Martin Clayton, Nicholas Cook, Timothy J. Cooley, Ruth F. Davis, Beverley Diamond, Aaron A. Fox, Keith Howard, Bernardo Illari, Travis A. Jackson, Jaime Jones, Margaret Kartomi, Sebastian Klotz, Lars-Christian Koch, Peter Manuel, Wayne Marshall, Kaley Mason, Richard Middleton, Bruno Nettl, Regula Burckhardt Qureshi, Ronald Radano, Suzel Ana Reily, Timothy Rommen, Kay Kaufman Shelemay, W. Anthony Sheppard, Jonathan P. J. Stock, Martin Stokes, Timothy D. Taylor, Bonnie C. Wade, Bennett Zon
- Edited by Philip V. Bohlman, University of Chicago
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- The Cambridge History of World Music
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- 05 December 2013
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- 12 December 2013, pp xv-xxiii
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14 - Vaughan Williams and his successors: composers’ forum
- from Part III - Activism, reception and influence
- Edited by Alain Frogley, University of Connecticut, Aidan J. Thomson, Queen's University Belfast
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- The Cambridge Companion to Vaughan Williams
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- 05 December 2013
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- 14 November 2013, pp 299-320
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- By Krista Adamek, Ana Luisa K. Albernaz, J. Marcio Ayres†, Andrew J. Baker, Karen L. Bales, Adrian A. Barnett, Christopher Barton, John M. Bates, Jennie Becker, Bruna M. Bezerra, Júlio César Bicca-Marques, Richard Bodmer, Jean P. Boubli, Mark Bowler, Sarah A. Boyle, Christini Barbosa Caselli, Janice Chism, Elena P. Cunningham, José Maria C. da Silva, Lesa C. Davies, Nayara de Alcântara Cardoso, Manuella A. de Souza, Stella de la Torre, Ana Gabriela de Luna, Thomas R. Defler, Anthony Di Fiore, Eduardo Fernandez-Duque, Stephen F. Ferrari, Wilsea M.B. Figueiredo-Ready, Tracy Frampton, Paul A. Garber, Brian W. Grafton, L. Tremaine Gregory, Maria L. Harada, Amy Harrison-Levine, Walter C. Hartwig, Stefanie Heiduck, Eckhard W. Heymann, André Hirsch, Leandro Jerusalinsky, Gareth Jones, Richard F. Kay, Martin M. Kowalewski, Shawn M. Lehman, Laura Marsh, Jesús Martinez, William A. Mason, Hope Matthews, Wynlyn McBride, Shona McCann-Wood, W. Scott McGraw, D. Jeffrey Meldrum, Sally P. Mendoza, Nohelia Mercado, Russell A. Mittermeier, Mirjam N. Nadjafzadeh, Marilyn A. Norconk, Robert Gary Norman, Marcela Oliveira, Marcelo M. Oliveira, Maria Juliana Ospina Rodríguez, Erwin Palacios, Suzanne Palminteri, Liliam P. Pinto, Marcio Port-Carvalho, Leila Porter, Carlos Portillo-Quintero, George Powell, Ghillean T. Prance, Rodrigo C. Printes, Pablo Puertas, P. Kirsten Pullen, Helder L. Queiroz, Luis Reginaldo R. Rodrigues, Adriana Rodríguez, Alfred L. Rosenberger, Anthony B. Rylands, Ricardo R. Santos, Horacio Schneider, Eleonore Z.F. Setz, Suleima S.B. Silva, José S. Silva Júnior, Andrew T. Smith, Marcelo C. Sousa, Antonio S. Souto, Wilson R. Spironello, Masanaru Takai, Marcelo F. Tejedor, Cynthia L. Thompson, Diego G. Tirira, Raul Tupayachi, Bernardo Urbani, Liza M. Veiga, Marianela Velilla, João Valsecchi, Jean-Christophe Vié, Tatiana M. Vieira, Suzanne E. Walker-Pacheco, Rob Wallace, Patricia C. Wright, Charles E. Zartman
- Edited by Liza M. Veiga, Universidade Federal do Pará, Brazil, Adrian A. Barnett, Roehampton University, London, Stephen F. Ferrari, Universidade Federal de Sergipe, Brazil, Marilyn A. Norconk, Kent State University, Ohio
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- Evolutionary Biology and Conservation of Titis, Sakis and Uacaris
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- 05 April 2013
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- 11 April 2013, pp xii-xv
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