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Understanding risk factors for death from Covid-19 is key to providing good quality clinical care. We assessed the presenting characteristics of the ‘first wave’ of patients with Covid-19 at Royal Oldham Hospital, UK and undertook logistic regression modelling to investigate factors associated with death. Of 470 patients admitted, 169 (36%) died. The median age was 71 years (interquartile range 57–82), and 255 (54.3%) were men. The most common comorbidities were hypertension (n = 218, 46.4%), diabetes (n = 143, 30.4%) and chronic neurological disease (n = 123, 26.1%). The most frequent complications were acute kidney injury (AKI) (n = 157, 33.4%) and myocardial injury (n = 21, 4.5%). Forty-three (9.1%) patients required intubation and ventilation, and 39 (8.3%) received non-invasive ventilation. Independent risk factors for death were increasing age (odds ratio (OR) per 10 year increase above 40 years 1.87, 95% confidence interval (CI) 1.57–2.27), hypertension (OR 1.72, 95% CI 1.10–2.70), cancer (OR 2.20, 95% CI 1.27–3.81), platelets <150 × 103/μl (OR 1.93, 95% CI 1.13–3.30), C-reactive protein ≥100 μg/ml (OR 1.68, 95% CI 1.05–2.68), >50% chest radiograph infiltrates (OR 2.09, 95% CI 1.16–3.77) and AKI (OR 2.60, 95% CI 1.64–4.13). There was no independent association between death and gender, ethnicity, deprivation level, fever, SpO2/FiO2, lymphopoenia or other comorbidities. These findings will inform clinical and shared decision making, including use of respiratory support and therapeutic agents.
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.
Identifying the mechanisms linking early experiences, genetic risk factors, and their interaction with later health consequences is central to the development of preventive interventions and identifying potential boundary conditions for their efficacy. In the current investigation of 412 African American adolescents followed across a 20-year period, we examined change in body mass index (BMI) across adolescence as one possible mechanism linking childhood adversity and adult health. We found associations of childhood adversity with objective indicators of young adult health, including a cardiometabolic risk index, a methylomic aging index, and a count of chronic health conditions. Childhood adversities were associated with objective indicators indirectly through their association with gains in BMI across adolescence and early adulthood. We also found evidence of an association of genetic risk with weight gain across adolescence and young adult health, as well as genetic moderation of childhood adversity's effect on gains in BMI, resulting in moderated mediation. These patterns indicated that genetic risk moderated the indirect pathways from childhood adversity to young adult health outcomes and childhood adversity moderated the indirect pathways from genetic risk to young adult health outcomes through effects on weight gain during adolescence and early adulthood.
Negative affect (NA) has been suggested to be both an antecedent and a consequence of auditory verbal hallucinations (AVH). Furthermore, negative appraisals of voices have been theorized to contribute to the maintenance of AVH. Using the experience sampling method (ESM), this study examined the bi-directional relationship between NA and AVH, and the moderating effect of negative beliefs about voices.
Forty-seven patients diagnosed with schizophrenia spectrum disorders with frequent AVH completed a clinical interview, followed by ESM for 10 times a day over 6 days on an electronic device. Time-lagged analyses were conducted using multilevel regression modeling. Beliefs about voices were assessed at baseline.
A total of 1654 data points were obtained. NA predicted an increase in AVH in the subsequent moment, and AVH predicted an increase in NA in the subsequent moment. Baseline beliefs about voices as malevolent and omnipotent significantly strengthened the association between NA and AVH within the same moment. In addition, the belief of omnipotence was associated with more hallucinatory experiences in the moment following NA. However, beliefs about voices were not associated directly with momentary levels of NA or AVH.
Experiences of NA and AVH drove each other, forming a feedback loop that maintained the voices. The associations between NA and AVH, either within the same moment or across moments, were exacerbated by negative beliefs about voices. Our results suggest that affect-improving interventions may stop the feedback loop and reduce AVH frequency.
We report a significant advance in thermally insulating transparent materials: silica-based monoliths with controlled porosity which exhibit the transparency of windows in combination with a thermal conductivity comparable to aerogels.
The lack of transparent, thermally insulating windows leads to substantial heat loss in commercial and residential buildings, which accounts for ~4.2% of primary US energy consumption annually. The present study provides a potential solution to this problem by demonstrating that ambiently dried silica aerogel monoliths, i.e., ambigels, can simultaneously achieve high optical transparency and low thermal conductivity without supercritical drying. A combination of tetraethoxysilane, methyltriethoxysilane, and post-gelation surface modification precursors were used to synthesize ambiently dried materials with varying pore fractions and pore sizes. By controlling the synthesis and processing conditions, 0.5–3 mm thick mesoporous monoliths with transmittance >95% and a thermal conductivity of 0.04 W/(m K) were produced. A narrow pore size distribution, <15 nm, led to the excellent transparency and low haze, while porosity in excess of 80% resulted in low thermal conductivity. A thermal transport model considering fractal dimension and phonon-boundary scattering is proposed to explain the low effective thermal conductivity measured. This work offers new insights into the design of transparent, energy saving windows.
Here we provide an update of the 2013 report on the Nigerian Twin and Sibling Registry (NTSR). The major aim of the NTSR is to understand genetic and environmental influences and their interplay in psychological and mental health development in Nigerian children and adolescents. Africans have the highest twin birth rates among all human populations, and Nigeria is the most populous country in Africa. Due to its combination of large population and high twin birth rates, Nigeria has one of the largest twin populations in the world. In this article, we provide current updates on the NTSR samples recruited, recruitment procedures, zygosity assessment and findings emerging from the NTSR.
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.
Functional circuits of the human brain emerge and change dramatically over the second half of gestation. It is possible that variation in neural functional system connectivity in utero predicts individual differences in infant behavioral development, but this possibility has yet to be examined. The current study examines the association between fetal sensorimotor brain system functional connectivity and infant postnatal motor ability. Resting-state functional connectivity data was obtained in 96 healthy human fetuses during the second and third trimesters of pregnancy. Infant motor ability was measured 7 months after birth using the Bayley Scales of Infant Development. Increased connectivity between the emerging motor network and regions of the prefrontal cortex, temporal lobes, posterior cingulate, and supplementary motor regions was observed in infants that showed more mature motor functions. In addition, females demonstrated stronger fetal-brain to infant-behavior associations. These observations extend prior longitudinal research back into prenatal brain development and raise exciting new ideas about the advent of risk and the ontogeny of early sex differences.
Although interstage mortality for infants with hypoplastic left heart syndrome has declined within the National Pediatric Cardiology Quality Improvement Collaborative, variation across centres persists. It remains unclear whether centres with lower interstage mortality have lower-risk patients or whether differences in care may explain this variation. We examined previously established risk factors across National Pediatric Cardiology Quality Improvement Collaborative centres with lower and higher interstage mortality rates.
Lower-mortality centres were defined as those with >25 consecutive interstage survivors. Higher-mortality centres were defined as those with cumulative interstage mortality rates >10%, which is a collaborative historic baseline rate. Baseline risk factors and perioperative characteristics were compared.
Seven lower-mortality centres were identified (n=331 patients) and had an interstage mortality rate of 2.7%, as compared with 13.3% in the four higher-mortality centres (n=173 patients, p<0.0001). Of all baseline risk factors examined, the only factor that differed between the lower- and higher-mortality centres was postnatal diagnosis (18.4 versus 31.8%, p=0.001). In multivariable analysis, there remained a significant mortality difference between the two groups of centres after adjusting for this variable: adjusted mortality rate was 2.8% in lower-mortality centres compared with 12.6% in higher-mortality centres, p=0.003. Secondary analyses identified multiple differences between groups in perioperative practices and other variables.
Variation in interstage mortality rates between these two groups of centres does not appear to be explained by differences in baseline risk factors. Further study is necessary to evaluate variation in care practices to identify targets for improvement efforts.
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.
Preliminary stable oxygen isotope data are presented from the southern North Sea Basin successions, ranging from the Lutetian to Rupelian. Analyses were performed on fish otoliths, nuculid bivalves and benthic foraminifera and are presented as bulk δ18O values relative to a well established regional sequence stratigraphic framework. The most significant positive shift in δ18O values clearly falls at the top of the regionally recognised Bassevelde 3 sequence, which base corresponds to the Eocene-Oligocene GSSP boundary. The here documented δ18O shift is closely associated with the base of the traditional Rupelian unit-stratotype and is tentatively correlated to the globally recognised Oi-1 event.
The investigation of foraminiferal assemblages from a series of Oligocene borehole sections allowed paleoenvironment and paleoclimate reconstructions for the Rupelian and Chattian (Lower and Upper Oligocene) Stages in their type region, the southern North Sea Basin. A striking feature coinciding with the Rupelian-Chattian (R-C) unconformity is the major change in paleotemperature and paleobathymetry. The shallow marine to restricted marine subtropical fauna at the base of the Chattian is in strong contrast with the deeper marine and cooler upper Rupelian assemblages. This study suggests that the early Chattian transgression is genetically related to a widespread major warming pulse, known as the Late Oligocene Warming Event.
We examined two potentially interacting, connected pathways by which parental supportiveness during early adolescence (ages 1–13) may come to be associated with later African American young adult smoking. The first pathway is between parental supportiveness and young adult stress (age 19), with stress, in turn, predicting increased smoking at age 20. The second pathway is between supportive parenting and tumor necrosis factor (TNF) gene methylation (i.e., TNFm), a proinflammatory epitype, with low levels indicating greater inflammatory potential and forecasting increased risk for smoking in response to young adult stress. In a sample of 382 African American youth residing in rural Georgia, followed from early adolescence (age 10–11) to young adulthood (age 20), supportive parenting indirectly predicted smoking via associations with young adult stress, IE = –0.071, 95% confidence interval [–0.132, –0.010]. In addition, supportive parenting was associated with TNFm measured at age 20 (r = .177, p = .001). Further, lower TNFm was associated with a significantly steeper slope (b = 0.583, p = .003) of increased smoking in response to young adult stress compared to those with higher TNFm (b = 0.155, p = .291), indicating an indirect, amplifying role for supportive parenting via TNFm. The results suggest that supportive parenting in early adolescence may play a role in understanding the emergence of smoking in young adulthood.
Eukaryotic 5S rRNA, synthesized by RNA polymerase III (Pol III), is an essential component of the large ribosomal subunit. Most organisms contain hundreds of 5S rRNA genes organized into tandem arrays. However, the genome of the protozoan parasite Leishmania major contains only 11 copies of the 5S rRNA gene, which are interspersed and associated with other Pol III-transcribed genes. Here we report that, in general, the number and order of the 5S rRNA genes is conserved between different species of Leishmania. While in most organisms 5S rRNA genes are normally associated with the nucleolus, combined fluorescent in situ hybridization and indirect immunofluorescence experiments showed that 5S rRNA genes are mainly located at the nuclear periphery in L. major. Similarly, the tandemly repeated 5S rRNA genes in Trypanosoma cruzi are dispersed throughout the nucleus. In contrast, 5S rRNA transcripts in L. major were localized within the nucleolus, and scattered throughout the cytoplasm, where mature ribosomes are located. Unlike other rRNA species, stable antisense RNA complementary to 5S rRNA is not detected in L. major.
In zebrafish embryos, distinct Ca2+ transients are localized to the early cleavage furrows during the first few cell division cycles. These transients are generated mainly by release via IP3Rs in the endoplasmic reticulum, and they are necessary for furrow positioning, propagation, deepening and apposition. We previously showed, via the use of inhibitors, that store-operated Ca2+ entry (SOCE) also appears to be essential for maintaining the IP3R-mediated elevated levels of [Ca2+]i for the extended periods required for the completion of successful furrow deepening and daughter cell apposition in these large embryonic cells. Here, newly fertilized, dechorionated embryos were fixed at various times during the first and second cell division cycles and immunolabelled with antibodies to STIM1 and/or Orai1 (key components of SOCE). We show that both of these proteins have a dynamic pattern of localization during cytokinesis of the first two cell division cycles. These new data help to support our previous inhibitor results, and provide additional evidence that SOCE contributes to the maintenance of the sustained elevated Ca2+ that is required for the successful completion of cytokinesis in the large cells of embryonic zebrafish.
This study examined subjective and objective cognitive functioning in 26 female breast cancer survivors (BCS) who received chemotherapy treatment that finished .5 to 5 years prior to testing and compared their results to 25 demographically matched women with no history of cancer. Participants were assessed on prospective memory (PM) tasks; neuropsychological tests of processing speed, attentional flexibility with greater cognitive load, executive function, and verbal memory; self-report measures of cognitive dysfunction and PM failures; and distress. The BCS group showed significantly slower speed of processing and reduced attentional flexibility, and reported significantly more cognitive complaints and PM failures than the control group on five of six self-report measures. The groups did not differ on other PM or neuropsychological measures or on a measure of distress. Subjective cognition correlated with some neuropsychological tests and with a virtual reality PM task. Objective cognitive impairments were associated with reduced quality of life in the BCS group. The results provide some evidence of both self-reported impairment and objective cognitive dysfunction following chemotherapy treatment.