To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
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.
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.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
To achieve their conservation goals individuals, communities and organizations need to acquire a diversity of skills, knowledge and information (i.e. capacity). Despite current efforts to build and maintain appropriate levels of conservation capacity, it has been recognized that there will need to be a significant scaling-up of these activities in sub-Saharan Africa. This is because of the rapid increase in the number and extent of environmental problems in the region. We present a range of socio-economic contexts relevant to four key areas of African conservation capacity building: protected area management, community engagement, effective leadership, and professional e-learning. Under these core themes, 39 specific recommendations are presented. These were derived from multi-stakeholder workshop discussions at an international conference held in Nairobi, Kenya, in 2015. At the meeting 185 delegates (practitioners, scientists, community groups and government agencies) represented 105 organizations from 24 African nations and eight non-African nations. The 39 recommendations constituted six broad types of suggested action: (1) the development of new methods, (2) the provision of capacity building resources (e.g. information or data), (3) the communication of ideas or examples of successful initiatives, (4) the implementation of new research or gap analyses, (5) the establishment of new structures within and between organizations, and (6) the development of new partnerships. A number of cross-cutting issues also emerged from the discussions: the need for a greater sense of urgency in developing capacity building activities; the need to develop novel capacity building methodologies; and the need to move away from one-size-fits-all approaches.
It is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from ‘fundamental’ (necessary for all) to ‘specialized’ (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.
We surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by ‘fundamental’ and ‘specialized.’
There were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one’s own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).
We have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature.
The Figaro data reduction system was originally written for DEC VAXes running VMS, and little attention was paid to making it portable. Recently, however, a cooperative effort between the AAO, MSSSO, UNSW, the UK Starlink network and Caltech has resulted in a version for UNIX. This new version has been run under VMS and three different versions of UNIX. The files produced by any version may be read directly by any other version, although Figaro has a particularly complex file format which contains an extensible, self-defining, hierarchical structure of data items. This complexity has allowed the addition of error and quality data, as well as specific structures used, for example, for echelle data. Figaro is written mainly in Fortran (with numerous DEC extensions) but there is also a significant use of C. While C and Fortran are reasonably portable, the way one is called from the other is less portable and needs careful handling. Ports to other systems are possible, with effort; a Macintosh version is being considered.
The University of NSW’s Automated Patrol Telescope is a modified Baker-Nunn satellite tracking camera, now used for CCD imaging of astronomical objects. The f/1 Baker-Nunn optical design gives a 30° field of view with an approximately spherical focal surface of radius ≈500 mm. While the focal plane curvature is tolerable across the 1.4° × 1.0° field of the present CCD, it becomes unacceptable when a larger CCD is used. In addition, the use of glass filters in the highly convergent beam produces intolerable spherical aberration. We present a design modification to the original Baker-Nunn which enables a 5° diameter flat field to be produced when using B, V, R or I filters. By making this modification, we plan to perform multicolour imaging, using a new large-format CCD with a 2.9° × 1.9° field of view.
Our knowledge of the universe comes from recording the photon and particle fluxes incident on the Earth from space. We thus require sensitive measurement across the entire energy spectrum, using large telescopes with efficient instrumentation located on superb sites. Technological advances and engineering constraints are nearing the point where we are recording as many photons arriving at a site as is possible. Major advances in the future will come from improving the quality of the site. The ultimate site is, of course, beyond the Earth’s atmosphere, such as on the Moon, but economic limitations prevent our exploiting this avenue to the degree that the scientific community desires. Here we describe an alternative, which offers many of the advantages of space for a fraction of the cost: the Antarctic Plateau.
The Automated Patrol Telescope (APT) is a wide-field CCD imaging telescope operated by the University of New South Wales at Siding Spring Observatory in Australia. The optical design employed resembles that of a Schmidt, but uses a 3-element lens to achieve a wide, corrected field of view. The APT was developed by extensively modifying the optical, mechanical and electronic systems of a Baker-Nunn satellite tracking camera. Telescope motion and operation of the CCD have been placed under computer control, allowing automated observations for longterm survey and monitoring projects. The APT has 0.5 m aperture f/1 optics which produce a 5° flat field, of which a 2°×3° field is covered by the CCD currently installed. The telescope is being used for studies of stellar activity in open clusters and regions of star formation, and comet and minor planet investigations. A number of other projects for the APT are being considered, including searches for novae, supernovae in clusters of galaxies, and brown dwarfs.
The red variables whose amplitude is larger than 1.3 mag in the MOA database are studied for the LMC. Among 3 196 such stars, 532 stars are likely to be Miras or red semiregular variables. The period–colour relation of these stars is shown.
A large database of CCD photometry for 1.4 million stars towards both the LMC and the SMC, which has been established by the MOA project, is a useful resource to study variable stars. In our preliminary study, variables identified as β Lyrae type stars and Herbig Ae/Be stars have been found amongst blue stars.
A review of the MOA (Microlensing Observations in Astrophysics) project is presented. MOA is a collaboration of approximately 30 astronomers from New Zealand and Japan established with the aim of finding and detecting microlensing events towards the Magellanic Clouds and the Galactic bulge, which may be indicative of either dark matter or of planetary companions. The observing program commenced in 1995, using very wide band blue and red filters and a nine-chip mosaic CCD camera.
As a by-product of these observations a large database of CCD photometry for 1.4 million stars towards both LMC and SMC has been established. In one preliminary analysis 576 bright variable stars were confirmed, nearly half of them being Cepheids. Another analysis has identified large numbers of blue variables, and 205 eclipsing binaries are included in this sample. In addition 351 red variables (AGB stars) have been found. Light curves have been obtained for all these stars. The observations are carried out on a 61-cm f/6.25 telescope at Mt John University Observatory where a new larger CCD camera was installed in 1998 July. From this latitude (44° S) the Magellanic Clouds can be monitored throughout the year.
Population decline resulting from agricultural intensification led to contraction of the range of the cirl bunting Emberiza cirlus in the UK to a small area of south Devon. As part of the UK Biodiversity Action Plan for the species, a project to re-establish a population in suitable habitat in Cornwall was undertaken during 2006–2011, in which chicks were removed from the nest in Devon, hand-reared and then delayed-released. The survival of the birds to four time points in the year after release was analysed in relation to the effect of rearing factors, using a multivariable logistic regression model. Individuals with higher body weight at capture were more likely to survive to 1 January and 1 May in the year following release, and individuals released in June and July were more likely to survive than those released in August. Individuals released in 2006 and 2011 had a higher survival rate than those released during 2007–2010. Timing of capture, time spent at each stage in captivity, medication and the detection of parasites in the brood had no significant effect. Immunosuppressive disease, weather factors and predator activity may have led to some of the observed differences in survival. This analysis provides evidence with which to plan future translocation projects for cirl buntings and other passerine birds.
Radio interferometric observations of extragalactic radio sources have been made with antennas at the Haystack Observatory in Massachusetts and the Owens Valley Radio Observatory in California during fourteen separate experiments distributed between September 1976 and May 1978. The components of the baseline vector and the coordinates of the sources were estimated from the data from each experiment separately. The root-weighted-mean-square scatter about the weighted mean (“repeatability”) of the estimates of the length of the 3900 km baseline was approximately 7 cm, and of the source coordinates, approximately or less, except for the declinations of low-declination sources. With the source coordinates all held fixed at the best available, a posteriori, values, and the analyses repeated for each experiment, the repeatability obtained for the estimate of baseline length was 4 cm. From analyses of the data from several experiments simultaneously, estimates were obtained of changes in the x component of pole position and in the Earth's rotation (UT1). Comparison with the corresponding results obtained by the Bureau International de l'Heure (BIH) discloses systematic differences. In particular, the trends in the radio interferometric determinations of the changes in pole position agree more closely with those from the International Polar Motion Service (IPMS) and from the Doppler observations of satellites than with those from the BIH.
Background: There are no disease modifying agents for the treatment of Alzheimer’s disease (AD). Pathologically, AD is associated with the misfolding of two peptides: beta-amyloid (plaques) and tau (tangles). Methods: Using large-scale computer simulations, we modelled the misfolding of both beta-amyloid and tau, identifying a common conformational motif (CCM; i.e. an abnormal peptide shape), present in both beta-amyloid and tau, that promotes their misfolding. We screened a library of 11.8 million compounds against this in silico model of protein misfolding, identifying three novel molecular classes of putative therapeutics as anti-protein misfolding agents. We synthesized approximately 400 new chemical entity drug-like molecules in each of these three classes (i.e. 1200 potential drug candidates). These were comprehensively screened in a battery of five in vitro protein oligomerization assays. Selected compounds were next evaluated in the APP/PS1 doubly transgenic mouse model of AD. Results: Two new classes of molecules were identified with the ability to block the oligomerization of both beta-amyloid and tau. These compounds are drug-like with good pharmacokinetic properties and are brain-penetrant. They exhibit excellent efficacy in transgenic mouse models. Conclusion: Computer aided drug design has enabled the discovery of novel drug-like molecules able to inhibit both tau and beta-amyloid misfolding.
Dogs participating in endurance exercise, including herding, hunting and racing have a greater energy requirement and may be more susceptible to nutrient depletion, electrolyte imbalance and metabolic stress. The objective of the present study was to investigate the acute response to unstructured mixed exercise in American Foxhounds fed a nutrient-fortified endurance diet. Thirty-nine adult Foxhound dogs (median age: 5·0, range: 2–10 years and median body weight (BW): 36·4, range: 24·9–49·5 kg) were allotted to a standard performance diet (Control) or nutrient-fortified endurance diet for adult dogs (Test). Dogs were balanced by sex, age, BW and athletic performance between diets. All male dogs were intact, whereas all the female dogs were spayed. After 80 d on diet, blood samples were collected via jugular puncture at baseline (0 h), and at 3 and 25 h post-exercise (mean: 17·7 (sem 0·92) km run over 2–3 h). Plasma taurine concentration and complete amino acid (AA) profile, serum chemistry and creatine kinase were measured. Serum chemistry profile remained within normal ranges throughout the study. A significant (P < 0·05) diet by time interaction was observed for calcium, alkaline phosphatase and most AA. Plasma taurine and most essential AA were increased (P < 0·05) after exercise and remained greater (P < 0·05) in dogs fed the Test diet, including the branched-chain AA (isoleucine, leucine and valine). Creatine kinase increased (P = 0·01) after 3 h and returned to baseline after 25 h post-exercise, but was not altered by diet. These data indicate that dogs undergoing a moderate bout of exercise did not suffer from electrolyte imbalance, and that a nutrient-fortified diet resulted in greater plasma taurine and essential AA concentrations.