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During the past decade, genetics research has allowed scientists and clinicians to explore the human genome in detail and reveal many thousands of common genetic variants associated with disease. Genetic risk scores, known as polygenic risk scores (PRSs), aggregate risk information from the most important genetic variants into a single score that describes an individual’s genetic predisposition to a given disease. This article reviews recent developments in the predictive utility of PRSs in relation to a person’s susceptibility to breast cancer and coronary artery disease. Prognostic models for these disorders are built using data from the UK Biobank, controlling for typical clinical and underwriting risk factors. Furthermore, we explore the possibility of adverse selection where genetic information about multifactorial disorders is available for insurance purchasers but not for underwriters. We demonstrate that prediction of multifactorial diseases, using PRSs, provides population risk information additional to that captured by normal underwriting risk factors. This research using the UK Biobank is in the public interest as it contributes to our understanding of predicting risk of disease in the population. Further research is imperative to understand how PRSs could cause adverse selection if consumers use this information to alter their insurance purchasing behaviour.
We describe 14 yr of public data from the Parkes Pulsar Timing Array (PPTA), an ongoing project that is producing precise measurements of pulse times of arrival from 26 millisecond pulsars using the 64-m Parkes radio telescope with a cadence of approximately 3 weeks in three observing bands. A comprehensive description of the pulsar observing systems employed at the telescope since 2004 is provided, including the calibration methodology and an analysis of the stability of system components. We attempt to provide full accounting of the reduction from the raw measured Stokes parameters to pulse times of arrival to aid third parties in reproducing our results. This conversion is encapsulated in a processing pipeline designed to track provenance. Our data products include pulse times of arrival for each of the pulsars along with an initial set of pulsar parameters and noise models. The calibrated pulse profiles and timing template profiles are also available. These data represent almost 21 000 h of recorded data spanning over 14 yr. After accounting for processes that induce time-correlated noise, 22 of the pulsars have weighted root-mean-square timing residuals of
in at least one radio band. The data should allow end users to quickly undertake their own gravitational wave analyses, for example, without having to understand the intricacies of pulsar polarisation calibration or attain a mastery of radio frequency interference mitigation as is required when analysing raw data files.
A magnetometry survey of the Roman fort at Lake Farm, near Wimborne Minster in Dorset, first discovered in 1959, has upgraded the status of this site to a full legionary fortress: a major base of the legio II Augusta during the subjugation of the Durotriges and other tribes of south-west Britain. The interior layout of the fortress was identified for the first time, together with the original road and river connections, extensive areas of extramural activity and evidence for an earlier phase of the site as a marching camp.
The present study aims to investigate the effect of wholegrain and legume consumption on the incidence of age-related cataract in an older Australian population-based cohort. The Blue Mountains Eye Study (BMES) is a population-based cohort study of eye diseases among older adults aged 49 years or older (1992–1994, n 3654). Of 2334 participants of the second examination of the BMES (BMES 2, 1997–2000), 1541 (78·3 % of survivors) were examined 5 years later (BMES 3) who had wholegrain and legume consumption estimated from the FFQ at BMES 2. Cataract was assessed using photographs taken during examinations following the Wisconsin cataract grading system. Multivariable-adjusted logistic regression models were used to assess associations with the 5-year incidence of cataract from BMES 2 (baseline) to BMES 3. The 5-year incidence of cortical, nuclear and posterior subcapsular (PSC) cataract was 18·2, 16·5 and 5·9 %, respectively. After adjustment for age, sex and other factors, total wholegrain consumption at baseline was not associated with incidence of any type of cataract. High consumption of legumes showed a protective association for incident PSC cataract (5th quintile: adjusted OR 0·37; 95 % CI 0·15, 0·92). There was no significant trend of this association across quintiles (P = 0·08). In this older Australian population, we found no associations between wholegrain intake at baseline and the 5-year incidence of three cataract types. However, intake of legumes in the highest quintile, compared with the lowest quintile, may protect against PSC formation, a finding needing replication in other studies.
Research on psychotic illness is loosening emphasis on diagnostic stringency in favour of including a more dimensionally based conceptualization of psychopathology and pathobiology. However, to clarify these notions requires investigation of the full scope of psychotic diagnoses.
The Cavan–Monaghan First Episode Psychosis Study ascertained cases of first episode psychosis across all 12 DSM-IV psychotic diagnoses via all routes to care: public, private or forensic; home-based, outpatient or inpatient. There was no arbitrary upper age cut-off and minimal impact of factors associated with variations in social milieu, ethnicity or urbanicity. Cases were evaluated epidemiologically and assessed for psychopathology, neuropsychology, neurology, antecedent factors, insight and quality of life.
Among 432 cases, the annual incidence of any DSM-IV psychotic diagnosis was 34.1/100 000 of population and encompassed functional psychotic diagnoses, substance-induced psychopathology and psychopathology due to general medical conditions, through to psychotic illness that defied contemporary diagnostic algorithms. These 12 DSM-IV diagnostic categories, including psychotic disorder not otherwise specified, showed clinical profiles that were consistently more similar than distinct.
There are considerable similarities and overlaps across a broad range of diagnostic categories in the absence of robust discontinuities between them. Thus, psychotic illness may be of such continuity that it cannot be fully captured by operational diagnostic algorithms that, at least in part, assume discontinuities. This may reflect the impact of diverse factors each of which acts on one or more overlapping components of a common, dysfunctional neuronal network implicated in the pathobiology of psychotic illness.
Individuals with depression often do not respond to medication or psychotherapy. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting overcontrolled personality, common in refractory depression.
To compare RO DBT plus treatment as usual (TAU) for refractory depression with TAU alone (trial registration: ISRCTN 85784627).
RO DBT comprised 29 therapy sessions and 27 skills classes over 6 months. Our completed randomised trial evaluated RO DBT for refractory depression over 18 months in three British secondary care centres. Of 250 adult participants, we randomised 162 (65%) to RO DBT. The primary outcome was the Hamilton Rating Scale for Depression (HRSD), assessed masked and analysed by treatment allocated.
After 7 months, immediately following therapy, RO DBT had significantly reduced depressive symptoms by 5.40 points on the HRSD relative to TAU (95% CI 0.94–9.85). After 12 months (primary end-point), the difference of 2.15 points on the HRSD in favour of RO DBT was not significant (95% CI –2.28 to 6.59); nor was that of 1.69 points on the HRSD at 18 months (95% CI –2.84 to 6.22). Throughout RO DBT participants reported significantly better psychological flexibility and emotional coping than controls. However, they reported eight possible serious adverse reactions compared with none in the control group.
The RO DBT group reported significantly lower HRSD scores than the control group after 7 months, but not thereafter. The imbalance in serious adverse reactions was probably because of the controls' limited opportunities to report these.
In a world where the only constant is change, schools are faced with the need to adapt creatively to changing societal demands, parental expectations, and children with increasingly diverse needs. Lasting and effective change can only occur with systemic and organisational change, and this essay argues that school-based psychologists are an invaluable, but potentially overlooked, resource in driving and supporting effective, evidence-supported, organisational change in schools. It is suggested that this can occur best when school-based psychologists are able to move away from direct service models that treat individual children to a systemic model that supports whole-school change.
SPEAKING IN 2006, the Scottish writer A. L. Kennedy observed:
If you have a generally correct appreciation … of the point of view of the characters, then you have everything. You have the world, the colour of description, you have the density of description – you have this sense of genuinely being within someone else's skin or this genuine understanding of someone else. The short story is the form where you most need to have a grip of point of view or it just doesn't work.
Kennedy's observation indicates not only the extent to which one of the key organisational principles of literary Impressionism – the focus and selectivity of perspective – has become ingrained in contemporary practice but also how far it is associated with the short story form. Indeed, Edgar Allan Poe had long ago argued, with reference to Nathaniel Hawthorne's Twice-Told Tales (1842), that ‘in almost all classes of composition, the unity of effect or impression is a point of the greatest importance’. Although Poe's emphases upon concision, precision and foreshadowing prefigure key tenets of literary Impressionism, his usage echoes David Hume's association of the impression with the realm of the body, the senses and the passions. As Jesse Matz has argued, Hume's distinction forms part of a more complex negotiation between what is most memorable and most ephemeral about the impression, between profundity and banality, which destabilises the alleged philosophic roots to literary Impressionism. In charting the recent historiography of the concept, its origins, rise and fall, and subsequent dissemination into modernist techniques such as the epiphany and stream of consciousness, this chapter will argue that not only are critical attempts to define the short story in terms of Impressionism sundered by its very instability but also its range of potential meaning is complemented by the diversity of the short story form.
As several critics have emphasised, the high watermark for both Impressionist literature and its criticism was in the period from the end of the nineteenth century to the start of the 1920s. First eclipsed by the more combative and non-representational avant-garde movements such as Cubism, Futurism and Vorticism, literary Impressionism was subsequently overshadowed by the consolidation of the modernist canon during the 1940s and 50s by academics such as F. R. Leavis and the New Critics, working on either side of the Atlantic.
Paragonimiasis, human lung fluke disease, is a foodborne anthropozoonosis caused by the trematodes assigned to Paragonimus and is regarded by the World Health Organization as a Neglected Tropical Disease (NTD). The life cycle of this medically important parasite centres on a complex freshwater biological community that includes two intermediate hosts: a mollusc and a decapod, usually a brachyuran. Although there is a perception that the biology, symptoms, diagnosis and treatment of Paragonimus is well understood, in reality, this is not the case, especially in Africa. Much remains unknown concerning the life-cycle of the parasite, its transmission, the current epidemiology of the disease, diagnosis and the effectiveness of treatment. Furthermore, cases of paragonimiasis may be misdiagnosed as resistant tuberculosis (TB) because of the similar pulmonary symptoms and no remission after anti TB therapy. The endemic foci of human paragonimiasis in Africa have been reported mainly in the forest zones of Upper Guinea (Liberia, Guinea and Ivory Coast) and Lower Guinea (Nigeria, Cameroon, Equatorial Guinea and Gabon). Despite the perceived medical importance of paragonimiasis, relatively little attention has been paid to this NTD since its discovery in Africa in the 1960s. This review focuses on the current understanding of the life cycle and transmission of Paragonimus in Africa, discusses its diagnosis and public health importance and highlights many outstanding gaps in the knowledge that still exist for this NTD.
To outline the pathways a cohort of first attendees to our headache clinics had taken over the years in search of explanations and treatment for their headaches. To establish a greater awareness of the shortcomings and failures in their medical journey in the hope that better headache management will emerge in primary care.
At first attendance in primary care most headache sufferers will not receive a firm diagnosis. Treatments provided are often ineffective and so many patients embark on a somewhat random self-made journey searching for a remedy. If they reach a Headache Clinic the most common diagnoses are ‘chronic migraine’ and ‘medication overuse headache’. They are either no better or worse than when their headaches first started despite their efforts.
We undertook a prospective questionnaire-based study of over 200 patients on first attendance at each of our headache clinics, three based in District General Hospitals and one in a tertiary referral centre. We documented the patients’ headache characteristics, the ‘burden’ of their headaches, functional handicap and the financial costs incurred seeking help before referral. We also documented what our patients understood about their headache disorder and the treatments previously tried.
Most patients had not been given a formal diagnosis in primary care and many remained unconvinced of the benign nature of their headache problem and wanted further investigations. A few had sought help from headache charities. Many had unrealistic attitudes to their problem and medication overuse was rife. A few patients had been offered triptans in primary care. Key deficiencies in the primary care management of these patients included failure to provide a formal headache diagnosis, inadequate understanding of the nature and mechanism of headaches and failure to follow a resilient management strategy. We provide a more effective management pathway in primary care.
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.
Unidentified depression in primary care is a public health concern, globally. There is a need for brief, valid and easily administered tools in primary care.
To estimate reliability and validity of the newly developed Primary care Screening Questionnaire for Depression (PSQ4D), a four-item tool, with ‘yes’ or ‘no’ options.
PSQ4D was administered verbally (time required, <1 min) by primary care physicians to adult outpatients (n=827) in six primary care settings in Kerala, India. A psychiatrist evaluated each patient on the same day, using ICD-10 Diagnostic Criteria for Research, based on unstructured clinical interview.
The Cronbach's alpha for internal consistency reliability was 0.80; kappa coefficient for test-retest reliability was 0.9 and that for interrater reliability was 0.72. At a score ≥2, sensitivity was 0.96, specificity was 0.87, positive predictive value was 0.74, negative predictive value was 0.98, positive likelihood ratio was 7.4 and negative likelihood ratio was 0.05.
When physician administered, PSQ4D has good reliability. At a cut-off score of ≥2, it has high sensitivity and specificity to identify depressive disorder in primary care.
A controversy at the 2016 IUCN World Conservation Congress on the topic of closing domestic ivory markets (the 007, or so-called James Bond, motion) has given rise to a debate on IUCN's value proposition. A cross-section of authors who are engaged in IUCN but not employed by the organization, and with diverse perspectives and opinions, here argue for the importance of safeguarding and strengthening the unique technical and convening roles of IUCN, providing examples of what has and has not worked. Recommendations for protecting and enhancing IUCN's contribution to global conservation debates and policy formulation are given.