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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.
Nearly all societies are bilingual (Appel & Muysken, 2006), a fact which places monolingualism in the minority. Multilingual individuals who live within the same national borders use the official language of the country in addition to their own to survive socially and economically. Globally, the position of English as a lingua franca has compelled people to learn it (Ur, 2010), which might suggest that in most cases, bilingualism is really understood as proficiency in English plus another language. In immigration contexts, families have to learn the dominant language—normally the most prestigious language—to be integrated to the new community, usually suppressing their minority language. According to Ferreira et al. (2016), the learners’ attitude towards the more prestigious linguistic group might have a positive impact on learning the new language, but maintaining the heritage language and culture seems to be an arduous task, even though the maintenance of heritage culture has benefits for first language (L1) literacy skills in addition to cognitive-linguistic variables, favouring a bi-dimensional model of acculturation (Berry, 1990).
Although there has been considerable scholarly interest in the nature of ancient cities, it has been difficult to identify and explore quantitative patterns in their design and amenities. Here, the authors offer a model for the relationship between the population size and infrastructural area of settlements, before testing it against measures of urban form in the Roman Empire. They advocate a more consistent approach to the investigation of settlements that is capable of not only incorporating sites with divergent physical forms and historical trajectories into the same model, but also able to expose their similarities and differences.
Geochemical and related studies have been made of near-surface sediments from the River Clyde estuary and adjoining areas, extending from Glasgow to the N, and W as far as the Holy Loch on the W coast of Scotland, UK. Multibeam echosounder, sidescan sonar and shallow seismic data, taken with core information, indicate that a shallow layer of modern sediment, often less than a metre thick, rests on earlier glacial and post-glacial sediments. The offshore Quaternary history can be aligned with onshore sequences, with the recognition of buried drumlins, settlement of muds from quieter water, probably behind an ice dam, and later tidal delta deposits. The geochemistry of contaminants within the cores also indicates shallow contaminated sediments, often resting on pristine pre-industrial deposits at depths less than 1m. The distribution of different contaminants with depth in the sediment, such as Pb (and Pb isotopes), organics and radionuclides, allow chronologies of contamination from different sources to be suggested. Dating was also attempted using microfossils, radiocarbon and 210Pb, but with limited success. Some of the spatial distribution of contaminants in the surface sediments can be related to grain-size variations. Contaminants are highest, both in absolute terms and in enrichment relative to the natural background, in the urban and inner estuary and in the Holy Loch, reflecting the concentration of industrial activity.
Significant reductions recently seen in the size of wide-bandgap power electronics have not been accompanied by a relative decrease in the size of the corresponding magnetic components. To achieve this, a new generation of materials with high magnetic saturation and permeability are needed. Here, we develop gram-scale syntheses of superparamagnetic Fe/FexOy core–shell nanoparticles and incorporate them as the magnetic component in a strongly magnetic nanocomposite. Nanocomposites are typically formed by the organization of nanoparticles within a polymeric matrix. However, this approach can lead to high organic fractions and phase separation; reducing the performance of the resulting material. Here, we form aminated nanoparticles that are then cross-linked using epoxy chemistry. The result is a magnetic nanoparticle component that is covalently linked and well separated. By using this ‘matrix-free’ approach, we can substantially increase the magnetic nanoparticle fraction, while still maintaining good separation, leading to a superparamagnetic nanocomposite with strong magnetic properties.
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.
Misidentified fossils are common in paleontology, but Platylithophycus has undergone a particularly problematic series of descriptions. The holotype of P. cretaceus comes from the Upper Cretaceous Niobrara Chalk of Kansas, and was first described as a calcareous green alga, based on the surface texture of the specimen. Later, Platylithophycus was re-identified as a sepiid cephalopod, based partly on a comparison of microstructure between P. cretaceus and the pen of modern squids. Platylithophycus then became part of the University of Nebraska teaching collection, where, according to paleontological legend, an undergraduate student suggested that the fossil’s tessellated surface looked a lot like shark cartilage. However, that interpretation has not been formally proposed until now. This work re-describes the holotype of Platylithophycus cretaceus as part of the branchial endoskeleton of an elasmobranch, based on both gross morphology and ultrastructure, including recognizable tessellated cartilage with intertesseral pores and joints.
be an elliptic curve over a field
. There is a functor
from the category of finitely presented torsion-free left
-modules to the category of abelian varieties isogenous to a power of
, and a functor
in the opposite direction. We prove necessary and sufficient conditions on
for these functors to be equivalences of categories. We also prove a partial generalization in which
is replaced by a suitable higher-dimensional abelian variety over
For the UK geological disposal facility (GDF) concept in a high strength crystalline rock, Nirex Reference Vault Backfill (NRVB) has been considered to use as a cementitious backfill material. The lifetime performance of this high pH material is required to be extremely long, and as a consequence of the interaction with the geological environment (e.g. groundwater), the backfill material will evolve and age with time. In this paper, we present the results of a leaching experiment, where NRVB is placed in contact with three different groundwater compositions representative of granitic, clay and saline groundwater for 35 days. Some differences were observed related with the mineralogy. X-ray Diffraction results showed the formation of more ettringite, mainly in the NRVB samples leached in clay and saline groundwater. An increase of the pH was also observed in the NRVB samples leached with the three different ground waters, being these results in accordance with the reactive transport modelling performed.
While our fascination with understanding the past is sufficient to warrant an increased focus on synthesis, solutions to important problems facing modern society require understandings based on data that only archaeology can provide. Yet, even as we use public monies to collect ever-greater amounts of data, modes of research that can stimulate emergent understandings of human behavior have lagged behind. Consequently, a substantial amount of archaeological inference remains at the level of the individual project. We can more effectively leverage these data and advance our understandings of the past in ways that contribute to solutions to contemporary problems if we adapt the model pioneered by the National Center for Ecological Analysis and Synthesis to foster synthetic collaborative research in archaeology. We propose the creation of the Coalition for Archaeological Synthesis coordinated through a U.S.-based National Center for Archaeological Synthesis. The coalition will be composed of established public and private organizations that provide essential scholarly, cultural heritage, computational, educational, and public engagement infrastructure. The center would seek and administer funding to support collaborative analysis and synthesis projects executed through coalition partners. This innovative structure will enable the discipline to address key challenges facing society through evidentially based, collaborative synthetic research.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
It has been an underlying assumption in many studies that near-surface layers imaged by ground-penetrating radar (GPR) can be interpreted as depositional markers or isochrones. It has been shown that GPR layers can be approximately reproduced from the measured electrical properties of ice, but these material layers are generally narrower and more closely spaced than can be resolved by typical GPR systems operating in the range 50−400 MHz. Thus GPR layers should be interpreted as interference patterns produced from closely spaced and potentially discontinuous material layers, and should not be assumed to be interpretable as precise markers of isochrones. We present 100 MHz GPR data from Lyddan Ice Rise, Antarctica, in which near-surface (<50 m deep) layers are clearly imaged. The growth of the undulations in these layers with depth is approximately linear, implying that, rather than resulting from a pattern of vertical strain rate, they do correspond to some pattern of snowfall variation. Furthermore, comparison of the GPR layers with snow-stake measurements suggests that around 80% of the rms variability in mean annual accumulation is present in the GPR layers. The observations suggest that, at least in this case, the GPR layers do approximate isochrones, and that patterns of snow accumulation over Lyddan Ice Rise are dominated by extremely persistent spatial variations with only a small residual spatial variability. If this condition is shown to be widely applicable it may reduce the period required for measurements of surface elevation change to be taken as significant indications of mass imbalance.
We use models constrained by remotely sensed data from Pine Island and Thwaites Glaciers, West Antarctica, to infer basal properties that are difficult to observe directly. The results indicate strong basal melting in areas upstream of the grounding lines of both glaciers, where the ice flow is fast and the basal shear stress is large. Farther inland, we find that both glaciers have ‘mixed’ bed conditions, with extensive areas of both bedrock and weak till. In particular, there are weak areas along much of Pine Island Glacier’s main trunk that could prove unstable if it retreats past the band of strong bed just above its current grounding line. In agreement with earlier studies, our forward ice-stream model shows a strong sensitivity to small perturbations in the grounding line position. These results also reveal a large sensitivity to the assumed bed (sliding or deforming) model, with non-linear sliding laws producing substantially greater dynamic response than earlier simulations that assume a linear-viscous till rheology. Finally, comparison indicates that our results using a plastic bed are compatible with the limited observational constraints and theoretical work that suggests an upper bound exists on maximum basal shear stress.
OBJECTIVES/SPECIFIC AIMS: Endogenous RT (eRT) is necessary for the function of retrotransposons, elements that replicate via an RNA intermediate. One source of eRT activity is long interspersed elements (LINE). LINEs, of which there are several subgroups (L1, L2, L3), are retrotransposons that regulate cellular growth and gene expression. Given their diverse and important roles, we hypothesized that L1 elements regulate functional responses in megakaryocytes and platelets; a concept not yet examined in the field. METHODS/STUDY POPULATION: To study eRT in human platelets we used RT activity assays, PCR, and Western blot approaches. Furthermore, we used an RT-inhibitor to dissect the function of eRT, analyzed RT-dependent protein synthetic capacity, and immunoprecipitated RNA-DNA hybrids. RNA-DNA hybrids were also detected by means of ICC and automated analysis using CellProfiler software. RNA-DNA hybrids were validated by PCR and eRT regulated synthesis of target proteins was analyzed using autoradiography and Western blot techniques. Platelets from patients with HIV+ were examined in parallel. RESULTS/ANTICIPATED RESULTS: We identified that highly purified, isolated platelets from healthy subjects possess eRT activity. eRT activity was blocked with the non-nucleoside RT inhibitor nevirapine at concentrations within the therapeutic drug range. L1 elements are bicistronic, containing 2 open reading frames (ORFs), ORF1 and ORF2. Thus, we next identified that human platelets express full-length L1 mRNA containing ORF1 and ORF2. In human platelets, eRT activity was localized to L1 protein containing ribonucleo particles. Platelet eRT reverse transcribed exogenous RNAs, a process inhibited by nevirapine, acting in trans using the 3′-UTR of exogenous mRNAs as a template. To dissect the function of eRT in platelets, we next examined cytoskeletal and protein synthetic events in the presence or absence of nevirapine. Inhibition of eRT in isolated platelets led to characteristically beaded platelets in appearance, strongly resembling bone marrow proplatelets. Parallel increases in platelet reactivity were also observed. As these changes occurred over hours, not minutes, we hypothesized that inhibition of eRT would affect platelet protein synthetic events. Consistent with this, RT inhibition resulted in upregulation of global platelet protein synthesis. We validated upregulation of the synthesis of specific proteins (mitofilin, p-selectin, and L26—a component of the 60S ribosomal subunit essential for mRNA translation). RNA-DNA hybrids, noncanonical nucleic acid structures that regulate gene expression, are enriched in regions where L1 is abundant. RNA-DNA hybrids were present in platelets and expression confirmed via differential digestion of RNAs (eg, with RNase A and RNAse I). Next-generation sequencing of pulled down (eg, immunoprecipitated) platelet RNA-DNA hybrids identified numerous differentially expressed transcripts and we focused on MAP1LC3B (LC3B), a primary regulator of autophagy. Hybrid sequencing results for LC3B were validated using qPCR and we confirmed that LC3B RNA binds to L1-encoded RNA binding protein. Platelets treated with nevirapine had increased total LC3B protein expression. As RT inhibition is an important mechanism to control HIV infection, we examined platelet morphology, activation, and LC3B expression in platelets from HIV+ subjects treated with nevirapine. HIV+ patients treated with RT inhibitors had higher numbers of platelets that were beaded in appearance at baseline, increased platelet reactivity, and differential LC3B expression compared with healthy controls. DISCUSSION/SIGNIFICANCE OF IMPACT: Taken together, these results demonstrate that platelets possess eRT activity that regulates platelet morphology, platelet hyperreactivity, and protein synthetic events. We postulate that eRT activity in platelets may be a new post-transcriptional regulatory checkpoint. Moreover, our findings have implications in HIV+ patients treated with RT inhibitors, where off-target effects may contribute to platelet activation and an increased risk of thrombosis.
Gamma-ray bursts are generally believed to originate in the vicinity of neutron stars, but the phenomenology is still not understood. In this paper we review the known characteristics of gamma bursts and give new observational results on temporal and spectral properties. We suggest that a class of repeating bursters exists that are spectrally harder than x-ray bursters but significantly softer than “classical” gamma bursts. The March 5, 1979, burst may be the prototype of this class of bursters.
Sphingolipids (SLs) are an integral part of all eukaryotic cellular membranes. In addition, they have indispensable functions as signalling molecules controlling a myriad of cellular events. Disruption of either the de novo synthesis or the degradation pathways has been shown to have detrimental effects. The earlier identification of selective inhibitors of fungal SL biosynthesis promised potent broad-spectrum anti-fungal agents, which later encouraged testing some of those agents against protozoan parasites. In this review we focus on the key enzymes of the SL de novo biosynthetic pathway in protozoan parasites of the Apicomplexa and Kinetoplastidae, outlining the divergence and interconnection between host and pathogen metabolism. The druggability of the SL biosynthesis is considered, alongside recent technology advances that will enable the dissection and analyses of this pathway in the parasitic protozoa. The future impact of these advances for the development of new therapeutics for both globally threatening and neglected infectious diseases is potentially profound.
The economic viability of nine representative energy conservation options for Pennsylvania greenhouse operators is examined. The analysis is done using an Internal Rate of Return procedure for four major fuels under three price escalator assumptions. The minimum energy savings per square foot per year is also calculated for each option. Wide variation is found in the economic feasibility of these options with the ones with the lowest installation costs generally providing the greatest IRR and the lowest required minimum savings per year. The results clearly indicate the need to evaluate carefully the econcmic viability of such investments beforehand.