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Two major outstanding questions in microbiome research ask what microbes are present in a community and how they interact with each other and their hosts. Recent, rapid improvements in nucleic acid (DNA and RNA) sequencing allow us to study the composition and function of microbiomes in unprecedented detail, leading to a step change in our understanding of host–microbe interactions. This chapter gives a broad overview of the basic toolkit available to modern microbiologists and microbial ecologists, exploring their application to key questions about microbiome structure and function. We cover tools based on nucleic acid sequencing (e.g. amplicon sequencing, metagenomics, metatranscriptomics) as well as approaches targeting larger molecules such as metabolomics and proteomics. We discuss the use of microbial culture as a means of measuring functional capacity of individual microbes, or building artificial communities to understand emergent properties of consortia. We emphasise the advantages of combining multiple techniques alongside robust experimental design to garner powerful quantitative estimates of microbiome structure, and how this relates to host–microbe interactions.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
How landscapes respond to, and evolve from, large jökulhlaups (glacial outburst floods) is poorly constrained due to limited observations and detailed monitoring. We investigate how melt of glacier ice transported and deposited by multiple jökulhlaups during the 2010 eruption of Eyjafjallajökull, Iceland, modified the volume and surface elevation of jökulhlaup deposits. Jökulhlaups generated by the eruption deposited large volumes of sediment and ice, causing significant geomorphic change in the Gígjökull proglacial basin over a 4-week period. Observation of these events enabled robust constraints on the physical properties of the floods which informs our understanding of the deposits. Using ground-based LiDAR, GPS observations and the satellite-image-derived ArcticDEMs, we quantify the post-depositional response of the 60 m-thick Gígjökull sediment package to the meltout of buried ice and other geomorphic processes. Between 2010 and 2016, total deposit volume reduced by −0.95 × 106 m3 a−1, with significant surface lowering of up to 1.88 m a−1. Surface lowering and volumetric loss of the deposits is attributed to three factors: (i) meltout of ice deposited by the jökulhlaups; (ii) rapid melting of the buried Gígjökull glacier snout; and (iii) incision of the proglacial meltwater system into the jökulhlaup deposits.
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.
Legionnaires’ disease (LD) incidence in the USA has quadrupled since 2000. Health departments must detect LD outbreaks quickly to identify and remediate sources. We tested the performance of a system to prospectively detect simulated LD outbreaks in Allegheny County, Pennsylvania, USA. We generated three simulated LD outbreaks based on published outbreaks. After verifying no significant clusters existed in surveillance data during 2014–2016, we embedded simulated outbreak-associated cases into 2016, assigning simulated residences and report dates. We mimicked daily analyses in 2016 using the prospective space-time permutation scan statistic to detect clusters of ⩽30 and ⩽180 days using 365-day and 730-day baseline periods, respectively. We used recurrence interval (RI) thresholds of ⩾20, ⩾100 and ⩾365 days to define significant signals. We calculated sensitivity, specificity and positive and negative predictive values for daily analyses, separately for each embedded outbreak. Two large, simulated cooling tower-associated outbreaks were detected. As the RI threshold was increased, sensitivity and negative predictive value decreased, while positive predictive value and specificity increased. A small, simulated potable water-associated outbreak was not detected. Use of a RI threshold of ⩾100 days minimised time-to-detection while maximizing positive predictive value. Health departments should consider using this system to detect community-acquired LD outbreaks.
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.
This paper reports on: (1) an evaluation of a common elements treatment approach (CETA) developed for comorbid presentations of depression, anxiety, traumatic stress, and/or externalizing symptoms among children in three Somali refugee camps on the Ethiopian/Somali border, and (2) an evaluation of implementation factors from the perspective of staff, lay providers, and families who engaged in the intervention.
This project was conducted in three refugee camps and utilized locally validated mental health instruments for internalizing, externalizing, and posttraumatic stress (PTS) symptoms. Participants were recruited from either a validity study or from referrals from social workers within International Rescue Committee Programs. Lay providers delivered CETA to youth (CETA-Youth) and families, and symptoms were re-assessed post-treatment. Providers and families responded to a semi-structured interview to assess implementation factors.
Children who participated in the CETA-Youth open trial reported significant decreases in symptoms of internalizing (d = 1.37), externalizing (d = 0.85), and posttraumatic stress (d = 1.71), and improvements in well-being (d = 0.75). Caregivers also reported significant decreases in child symptoms. Qualitative results were positive toward the acceptability and appropriateness of treatment, and its feasibility.
This project is the first to examine a common elements approach (CETA: defined as flexible delivery of elements, order, and dosing) with children and caregivers in a low-resource setting with delivery by lay providers. CETA-Youth may offer an effective treatment that is easier to implement and scale-up versus multiple focal interventions. A fullscale randomized clinical trial is warranted.
The majority of fast radio bursts (FRBs) are poorly localised, hindering their potential scientific yield as galactic, intergalactic, and cosmological probes. LOFT-e, a digital backend for the U.K.’s e-MERLIN seven-telescope interferometer will provide commensal search and real-time detection of FRBs, taking full advantage of its field of view (FoV), sensitivity, and observation time. Upon burst detection, LOFT-e will store raw data offline, enabling the sub-arcsecond localisation provided by e-MERLIN and expanding the pool of localised FRBs. The high-time resolution backend will additionally introduce pulsar observing capabilities to e-MERLIN.
Venous thromboembolism (VTE) is a potentially fatal condition. Hospital-associated VTE leads to more than 25,000 deaths per year in the UK. Therefore identification of at-risk patients is crucial. Psychiatric in-patients have unique factors which may affect their risk of VTE (antipsychotic prescription, restraint) however there are currently no UK guidelines which specifically address VTE risk in this population.
We assessed VTE risk among psychiatric inpatients in Cardiff and Vale university health board, Wales, UK, and whether proformas currently provided for VTE risk assessment were being completed.
All acute adult in-patient and old age psychiatric wards were assessed by a team of medical students and a junior doctor over three days. We used the UK department of health VTE risk assessment tool which was adapted to include factors specific for psychiatric patients. We also assessed if there were concerns about prescribing VTE prophylaxis (compression stockings or anticoagulants), because of a history of self-harm or ligature use.
Of the 145 patients included, 0% had a completed VTE risk assessment form. We found 38.6% to be at an increased risk of VTE and there were concerns about prescribing VTE prophylaxis in 31% of patients.
Our findings suggest that VTE risk assessment is not being carried out on psychiatric wards. Staff education is needed to improve awareness of VTE. Specific guidance for this population is needed due to the presence of unique risk factors in psychiatric in-patients and concerns regarding VTE prophylaxis.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Polygenic risk scores (PRS) incorporate many small genetic markers that are associated with conditions. This technique was first used to investigate mental illnesses in 2009. Since then, it has been widely used.
We wanted to explore how PRS have been used to the study the aetiology of psychosis, schizophrenia, bipolar disorder and depression.
We aimed to conduct a systematic review, identifying studies that have examined associations between PRS for bipolar disorder, schizophrenia/psychosis and depression and psychopathology-related outcome measures.
We searched EMBASE, Medline and PsychInfo from 06/08/2009 to 14/03/2016. We hand-searched the reference lists of related papers.
After removing duplicates, the search yielded 1043 publications. When irrelevant articles were excluded, 33 articles remained. We found 24 studies using schizophrenia PRS, three using bipolar PRS and nine using depression PRS. Many studies successfully used PRS to predict case/control status. Some studies showed associations between PRS and diagnostic sub-categories. A range of clinical phenotypes and symptoms has been explored. For example, specific PRS are associated with cognitive performance in schizophrenia, psychotic symptoms in bipolar disorder, and frequency of episodes of depression. PRS have also demonstrated genetic overlap between mental illnesses. It was difficult to assess the quality of some studies as not all reported sufficient methodological detail.
PRS have enabled us to explore the polygenic architecture of mental illness and demonstrate a genetic basis for some observed features. However, they have yet to give insights into the biology, which underpin mental illnesses.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Giant ragweed has been increasing as a major weed of row crops in the last
30 yr, but quantitative data regarding its pattern and mechanisms of spread
in crop fields are lacking. To address this gap, we conducted a Web-based
survey of certified crop advisors in the U.S. Corn Belt and Ontario, Canada.
Participants were asked questions regarding giant ragweed and crop
production practices for the county of their choice. Responses were mapped
and correlation analyses were conducted among the responses to determine
factors associated with giant ragweed populations. Respondents rated giant
ragweed as the most or one of the most difficult weeds to manage in 45% of
421 U.S. counties responding, and 57% of responding counties reported giant
ragweed populations with herbicide resistance to acetolactate synthase
inhibitors, glyphosate, or both herbicides. Results suggest that giant
ragweed is increasing in crop fields outward from the east-central U.S. Corn
Belt in most directions. Crop production practices associated with giant
ragweed populations included minimum tillage, continuous soybean, and
multiple-application herbicide programs; ecological factors included giant
ragweed presence in noncrop edge habitats, early and prolonged emergence,
and presence of the seed-burying common earthworm in crop fields. Managing
giant ragweed in noncrop areas could reduce giant ragweed migration from
noncrop habitats into crop fields and slow its spread. Where giant ragweed
is already established in crop fields, including a more diverse combination
of crop species, tillage practices, and herbicide sites of action will be
critical to reduce populations, disrupt emergence patterns, and select
against herbicide-resistant giant ragweed genotypes. Incorporation of a
cereal grain into the crop rotation may help suppress early giant ragweed
emergence and provide chemical or mechanical control options for
late-emerging giant ragweed.
Five cases of STEC O157 phage type (PT) 21/28 reported consumption of raw cows' drinking milk (RDM) produced at a dairy farm in the South West of England. STEC O157 PT21/28 was isolated from faecal specimens from milking cows on the implicated farm. Whole genome sequencing (WGS) showed that human and cattle isolates were the same strain. Further analysis of WGS data confirmed that sequences of isolates from an additional four cases (who did not report consumption of RDM when first questioned) fell within the same five single nucleotide polymorphism cluster as the initial five cases epidemiologically linked to the consumption of RDM. These four additional cases identified by WGS were investigated further and were, ultimately, associated with the implicated farm. The RDM outbreak strain encoded stx2a, which is associated with increased pathogenicity and severity of symptoms. Further epidemiological analysis showed that 70% of isolates within a wider cluster containing the outbreak strain were from cases residing in, or linked to, the same geographical region of England. During this RDM outbreak, use of WGS improved case ascertainment and provided insights into the evolution of a highly pathogenic clade of STEC O157 PT21/28 stx2a associated with the South West of England.
Cognitive dysfunction is an important aspect of depression that includes problems with thinking, concentration and memory. Research suggests that the cognitive aspect of depression is highly prevalent and has a significant impact on patient functioning. Currently, cognitive dysfunction in depression is largely unrecognised, unmonitored and untreated.
We aim to define cognitive dysfunction in clinical depression (major depressive disorder) and explore its detection and management in the UK, highlighting priority areas to be addressed.
A modified Delphi method was used as the process to gain consensus. A multi-stakeholder steering committee of depression experts (including psychiatrists, psychologists, primary care physicians, and representatives from occupational therapy and a depression charity) provided the key themes and, through round-table discussion, developed draft statements. The main areas of focus were burden, detection and management of cognitive dysfunction in depression. These statements formed a questionnaire to be reviewed by 150–200 health-care professionals with an involvement in the management of depression, with level of agreement noted as ‘strongly disagree’, ‘disagree’, ‘don’t know/uncertain’, ‘agree’ or ‘strongly agree’. Responses to the questionnaire will be analysed (very high agreement [> 66%] or very low agreement [< 33%]) and the steering committee will revise and finalise the consensus statements, and identify priority areas for future consideration. The steering committee was initiated and supported by the pharmaceutical company Lundbeck Ltd, through an educational grant. Lundbeck Ltd did not influence content.
Results of the questionnaire and the evolution of the final consensus statements will be presented.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Carbon nanotubes (CNTs) have captured the imagination of the research community because of their many superior properties. In the nearly 25 years since their novelty was recognized, however, progress toward their utility as superlightweight structural materials, especially for aerospace applications, has been disappointing. Recent advancements have revived some of the anticipation for the touted systems payoffs. The purpose of this article is to examine how close CNTs have come to fulfilling expectations for lightweight aerospace structures in the two decades since the initial report stimulated intense interest in this material. This article also proposes areas of study to bridge knowledge gaps that can realize the potential for these CNT composites to be part of the lightweight structures technology suite for aerospace use.
Mood instability is common, and an important feature of several psychiatric
disorders. We discuss the definition and measurement of mood instability,
and review its prevalence, characteristics, neurobiological correlates and
clinical implications. We suggest that mood instability has underappreciated
transdiagnostic potential as an investigational and therapeutic target.
In June 2014 Public Health England confirmed a case of Legionnaires' disease (LD) in a neonate following birth at home in a hired birthing pool incorporating a heater and a recirculation pump which had been filled in advance of labour. The case triggered a public health investigation and a microbiological survey of an additional ten heated birthing pools hired or recently hired to the general public across England. The birthing pool used by the parent of the confirmed case was identified as the source of the neonate's infection following detection of Legionella pneumophila ST48 in both patient and environmental samples. Legionella species were detected by quantitative polymerase chain reaction but not culture in a further three pools together with other opportunistic pathogens identified by culture and matrix-assisted laser desorption ionization–time of flight (MALDI–ToF) mass spectrometry. A Patient Safety Alert from NHS England and Public Health England was issued stating that heated birthing pools filled in advance of labour should not be used for home births. This recommendation remains in place. This investigation in conjunction with other recent reports has highlighted a lack of awareness regarding the microbiological safety of heated birthing pools and their potential to be a source of LD and other opportunistic infections. Furthermore, the investigation raised important considerations with regards to microbiological sampling and testing in such incidents. Public health authorities and clinicians should consider LD in the differential diagnosis of severe respiratory infection in neonates within 14 days of a water birth.