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 firstname.lastname@example.org
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.
When comparing the efficay of antipsychotics in clinical studies it would be of high practical relevance to know which doses of the respective drugs would result in equivalent blocking of dopamine-D2-receptors. This study aimed to find clinically applicable dose equivalents for haloperidol, risperidone and olanzapine.
As the occurrence of EPS correlates closely with a blockade of about 80% or more of dopamin-D2-receptors the proportion of patients developing EPS in relation to various doses of either Haloperidol (n=5252), risperidone (n=5017) or olanzapine (n =5029) was calculated. This retrospective, observational study included 20.252 inpatients from 20 hospitals with a diagnosis of schizophrenia and related disorders (ICD10 F20-25). The prescription of anticholinergic medication was utilized as surrogate parameter for the occurrence of EPS. OR, RR and NNH under different doses of AP were calculated and data entered into a probit model to predict the risk of EPS over a continuous dose range. For filtering the data ToscanaJ (FBA) was used.
1.) Same doses of risperidone and haloperidol induced the same proportion of EPS, reflected in a constant dose ratio of both drugs of ∼ 1:1 over the whole dose range.
2.) Over the whole dose range there was no linear relation between olanzapine on one hand and haloperidol and risperidone on the other hand.
3.) The results were corroborated by the probit analysis.
Previous clinical trials comparing olanzapine, risperidone and haloperidol found higher risks of EPS for Haloperidol. We propose a new model to calculate dose equivalents.
A proinflammatory state in a subgroup of depressed patients has been reported repeatedly, for example an increase in interleukin-6 and tumour necrosis factor-a is well documented. Treatment with COX-2 inhibitors down-regulate increased inflammatory markers. Therefore an adjunctive treatment of depression with COX-2 in combination with an antidepressant might lead to a better clinical outcome.
To prove or disapprove the hypothesis of a better clinical outcome in the group with add-on celecoxib to sertraline in terms of improvement of HamD-17 and MADRS scores from baseline to endpoint.
This is a dual-center, randomized, double-blind, placebo-controlled, parallel group phase IIa study to investigate the mean change in clinical outcome and in serum expression of inflammation markers from baseline to endpoint (week 6) in patients with major depression (HAMD-17 ≥ 22) treated with celecoxib in combination with sertraline compared to sertraline combined with placebo. 51 depressed patients of both gender, aged between 18 and 60 without any recent inflammatory related disease were enrolled. The study comprises six study visits (6x ratings including HAMD-17 and MADRS, 3x blood collections) during six weeks of treatment and a follow-up visit 10 weeks after baseline.
Results and Conclusion
The study was completed quite recently and the results are in progress.
Non-suicidal self-injury (NSSI) is an increasing phenomenon among adolescents. So far, comparable data on prevalence and psychosocial correlates are still rare due to different definitions, study samples, and measures.
To investigate the prevalence and associated psychosocial factors of occasional and repetitive non-suicidal self-injury (NSSI) and its relationship to suicide attempts in a representative adolescent samples from eleven European countries.
Cross sectional assessment of adolescents was performed within the European Union funded project, Saving and Empowering Young Lives in Europe (SEYLE), which was conducted in eleven European countries. The representative sample comprised 12,068 adolescents (F/M: 6,717/5,351; mean age: 14.9±0.89) recruited from randomly selected schools. Frequency of NSSI was assessed by a modified version of the Deliberate Self-Harm Inventory (DSHI) and the Paykel Suicide Scale. Additionally, a broad range of demographic, social and psychological factors was assessed.
Overall lifetime prevalence of NSSI was 27.6%; 19.7% reported occasional NSSI and 7.8% repetitive NSSI. Lifetime prevalence ranged from 17.1% to 38.6% across countries. Suicidality, anxiety and depression had the highest odds ratios for both occasional and repetitive NSSI.
Results suggest high lifetime prevalence of NSSI in European adolescents, with significant country differences. A strong association of NSSI with both psychopathology and risk-behaviours, including family-related neglect and peer-related rejection/victimization could be found. These results, combined with the observed gender and country differences, support the need for a multidimensional approach to better understand the development of NSSI and facilitate culturally adapted prevention/intervention.
The updated common rule, for human subjects research, requires that consents “begin with a ‘concise and focused’ presentation of the key information that will most likely help someone make a decision about whether to participate in a study” (Menikoff, Kaneshiro, Pritchard. The New England Journal of Medicine. 2017; 376(7): 613–615.). We utilized a community-engaged technology development approach to inform feature options within the REDCap software platform centered around collection and storage of electronic consent (eConsent) to address issues of transparency, clinical trial efficiency, and regulatory compliance for informed consent (Harris, et al. Journal of Biomedical Informatics 2009; 42(2): 377–381.). eConsent may also improve recruitment and retention in clinical research studies by addressing: (1) barriers for accessing rural populations by facilitating remote consent and (2) cultural and literacy barriers by including optional explanatory material (e.g., defining terms by hovering over them with the cursor) or the choice of displaying different videos/images based on participant’s race, ethnicity, or educational level (Phillippi, et al. Journal of Obstetric, Gynecologic, & Neonatal Nursing. 2018; 47(4): 529–534.).
We developed and pilot tested our eConsent framework to provide a personalized consent experience whereby users are guided through a consent document that utilizes avatars, contextual glossary information supplements, and videos, to facilitate communication of information.
The eConsent framework includes a portfolio of eight features, reviewed by community stakeholders, and tested at two academic medical centers.
Early adoption and utilization of this eConsent framework have demonstrated acceptability. Next steps will emphasize testing efficacy of features to improve participant engagement with the consent process.
The deviation from thermodynamic equilibrium of the ion velocity distribution functions (VDFs), as measured by the Magnetospheric Multiscale (MMS) mission in the Earth’s turbulent magnetosheath, is quantitatively investigated. Making use of the unprecedented high-resolution MMS ion data, and together with Vlasov–Maxwell simulations, this analysis aims at investigating the relationship between deviation from Maxwellian equilibrium and typical plasma parameters. Correlations of the non-Maxwellian features with plasma quantities such as electric fields, ion temperature, current density and ion vorticity are found to be similar in magnetosheath data and numerical experiments, with a poor correlation between distortions of ion VDFs and current density, evidence that questions the occurrence of VDF departure from Maxwellian at the current density peaks. Moreover, strong correlation has been observed with the magnitude of the electric field in the turbulent magnetosheath, while a certain degree of correlation has been found in the numerical simulations and during a magnetopause crossing by MMS. This work could help shed light on the influence of electrostatic waves on the distortion of the ion VDFs in space turbulent plasmas.
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.
In 2013, the national surveillance case definition for West Nile virus (WNV) disease was revised to remove fever as a criterion for neuroinvasive disease and require at most subjective fever for non-neuroinvasive disease. The aims of this project were to determine how often afebrile WNV disease occurs and assess differences among patients with and without fever. We included cases with laboratory evidence of WNV disease reported from four states in 2014. We compared demographics, clinical symptoms and laboratory evidence for patients with and without fever and stratified the analysis by neuroinvasive and non-neuroinvasive presentations. Among 956 included patients, 39 (4%) had no fever; this proportion was similar among patients with and without neuroinvasive disease symptoms. For neuroinvasive and non-neuroinvasive patients, there were no differences in age, sex, or laboratory evidence between febrile and afebrile patients, but hospitalisations were more common among patients with fever (P < 0.01). The only significant difference in symptoms was for ataxia, which was more common in neuroinvasive patients without fever (P = 0.04). Only 5% of non-neuroinvasive patients did not meet the WNV case definition due to lack of fever. The evidence presented here supports the changes made to the national case definition in 2013.
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.
We introduce a forcing technique to construct three-dimensional arrays of generic extensions through FS (finite support) iterations of ccc posets, which we refer to as 3D-coherent systems. We use them to produce models of new constellations in Cichoń’s diagram, in particular, a model where the diagram can be separated into 7 different values. Furthermore, we show that this constellation of 7 values is consistent with the existence of a
well-order of the reals.
The ability to properly assess and accurately phenotype true differences in feed efficiency among dairy cows is key to the development of breeding programs for improving feed efficiency. The variability among individuals in feed efficiency is commonly characterised by the residual intake approach. Residual feed intake is represented by the residuals of a linear regression of intake on the corresponding quantities of the biological functions that consume (or release) energy. However, the residuals include both, model fitting and measurement errors as well as any variability in cow efficiency. The objective of this study was to isolate the individual animal variability in feed efficiency from the residual component. Two separate models were fitted, in one the standard residual energy intake (REI) was calculated as the residual of a multiple linear regression of lactation average net energy intake (NEI) on lactation average milk energy output, average metabolic BW, as well as lactation loss and gain of body condition score. In the other, a linear mixed model was used to simultaneously fit fixed linear regressions and random cow levels on the biological traits and intercept using fortnight repeated measures for the variables. This method split the predicted NEI in two parts: one quantifying the population mean intercept and coefficients, and one quantifying cow-specific deviations in the intercept and coefficients. The cow-specific part of predicted NEI was assumed to isolate true differences in feed efficiency among cows. NEI and associated energy expenditure phenotypes were available for the first 17 fortnights of lactation from 119 Holstein cows; all fed a constant energy-rich diet. Mixed models fitting cow-specific intercept and coefficients to different combinations of the aforementioned energy expenditure traits, calculated on a fortnightly basis, were compared. The variance of REI estimated with the lactation average model represented only 8% of the variance of measured NEI. Among all compared mixed models, the variance of the cow-specific part of predicted NEI represented between 53% and 59% of the variance of REI estimated from the lactation average model or between 4% and 5% of the variance of measured NEI. The remaining 41% to 47% of the variance of REI estimated with the lactation average model may therefore reflect model fitting errors or measurement errors. In conclusion, the use of a mixed model framework with cow-specific random regressions seems to be a promising method to isolate the cow-specific component of REI in dairy cows.
IR spectroscopy in the range 12–230 μm with the SPace IR telescope for Cosmology and Astrophysics (SPICA) will reveal the physical processes governing the formation and evolution of galaxies and black holes through cosmic time, bridging the gap between the James Webb Space Telescope and the upcoming Extremely Large Telescopes at shorter wavelengths and the Atacama Large Millimeter Array at longer wavelengths. The SPICA, with its 2.5-m telescope actively cooled to below 8 K, will obtain the first spectroscopic determination, in the mid-IR rest-frame, of both the star-formation rate and black hole accretion rate histories of galaxies, reaching lookback times of 12 Gyr, for large statistically significant samples. Densities, temperatures, radiation fields, and gas-phase metallicities will be measured in dust-obscured galaxies and active galactic nuclei, sampling a large range in mass and luminosity, from faint local dwarf galaxies to luminous quasars in the distant Universe. Active galactic nuclei and starburst feedback and feeding mechanisms in distant galaxies will be uncovered through detailed measurements of molecular and atomic line profiles. The SPICA’s large-area deep spectrophotometric surveys will provide mid-IR spectra and continuum fluxes for unbiased samples of tens of thousands of galaxies, out to redshifts of z ~ 6.
The physical processes driving the chemical evolution of galaxies in the last ~ 11Gyr cannot be understood without directly probing the dust-obscured phase of star-forming galaxies and active galactic nuclei. This phase, hidden to optical tracers, represents the bulk of the star formation and black hole accretion activity in galaxies at 1 < z < 3. Spectroscopic observations with a cryogenic infrared observatory like SPICA, will be sensitive enough to peer through the dust-obscured regions of galaxies and access the rest-frame mid- to far-infrared range in galaxies at high-z. This wavelength range contains a unique suite of spectral lines and dust features that serve as proxies for the abundances of heavy elements and the dust composition, providing tracers with a feeble response to both extinction and temperature. In this work, we investigate how SPICA observations could be exploited to understand key aspects in the chemical evolution of galaxies: the assembly of nearby galaxies based on the spatial distribution of heavy element abundances, the global content of metals in galaxies reaching the knee of the luminosity function up to z ~ 3, and the dust composition of galaxies at high-z. Possible synergies with facilities available in the late 2020s are also discussed.
A far-infrared observatory such as the SPace Infrared telescope for Cosmology and Astrophysics, with its unprecedented spectroscopic sensitivity, would unveil the role of feedback in galaxy evolution during the last ~10 Gyr of the Universe (z = 1.5–2), through the use of far- and mid-infrared molecular and ionic fine structure lines that trace outflowing and infalling gas. Outflowing gas is identified in the far-infrared through P-Cygni line shapes and absorption blueshifted wings in molecular lines with high dipolar moments, and through emission line wings of fine-structure lines of ionised gas. We quantify the detectability of galaxy-scale massive molecular and ionised outflows as a function of redshift in AGN-dominated, starburst-dominated, and main-sequence galaxies, explore the detectability of metal-rich inflows in the local Universe, and describe the most significant synergies with other current and future observatories that will measure feedback in galaxies via complementary tracers at other wavelengths.
Background: Standardized data collection for traumatic brain injury (TBI) (including concussion) using common data elements (CDEs) has strengthened clinical care and research capacity in the United States and Europe. Currently, Ontario healthcare providers do not collect uniform data on adult patients diagnosed with concussion. Objective: The Ontario Concussion Care Strategy (OCCS) is a collaborative network of multidisciplinary healthcare providers, brain injury advocacy groups, patient representatives, and researchers with a shared vision to improve concussion care across the province, starting with the collection of standardized data. Methods: The International Framework of Functioning Disability and Health was selected as the conceptual framework to inform the selection of CDEs. The CDEs recommended by the OCCS were identified using key literature, including the National Institute of Neurological Disorders and Stroke–Zurich Consensus Statements for concussion in sport and the Ontario Neurotrauma Foundation Concussion/mTBI clinical guidelines. Results: The OCCS has recommended and piloted CDEs for Ontario that are readily available at no cost, clinically relevant, patient friendly, easy to interpret, and recognized by the international scientific community. Conclusions: The implementation of CDEs can help to shift Ontario toward internationally recognized standard data collection, and in so doing yield a more comprehensive evidence-based approach to care while also supporting rigorous research.
Social media presents an important means for social interaction, especially among adolescents, with Instagram being the most popular platform in this age-group. Pictures and communication about non-suicidal self-injury (NSSI) can frequently be found on the internet.
During 4 weeks in April 2016, n = 2826 (from n = 1154 accounts) pictures which directly depicted wounds on Instagram were investigated. Those pictures, associated comments, and user accounts were independently rated for content. Associations between characteristics of pictures and comments as well as weekly and daily trends of posting behavior were analyzed.
Most commonly, pictures depicted wounds caused by cutting on arms or legs and were rated as mild or moderate injuries. Pictures with increasing wound grades and those depicting multiple methods of NSSI generated elevated amounts of comments. While most comments were neutral or empathic with some offering help, few comments were hostile. Pictures were mainly posted in the evening hours, with a small peak in the early morning. While there was a slight peak of pictures being posted on Sundays, postings were rather evenly spread across the week.
Pictures of NSSI are frequently posted on Instagram. Social reinforcement might play a role in the posting of more severe NSSI pictures. Social media platforms need to take appropriate measures for preventing online social contagion.
Introduction: Heart failure (HF) is a common ED presentation that is associated with significant morbidity and mortality. Despite recent evidence and recommendations for early palliative care (PC) involvement in these patients, they are still significantly under-served by PC services, often resulting in multiple ED visits. We sought to evaluate use of PC services in patients with HF presenting to the ED. Secondary objectives of the study were to investigate: 1) one year mortality, ED visits, and admissions; 2) application of a novel palliative care referral score. Methods: We conducted a health records review of 500 consecutive HF patients who presented to two academic hospital EDs. We included patients aged 65 years or older who were diagnosed as having a HF exacerbation by the emergency physician (ICD-10 code 150.-). Our primary outcome was PC involvement. Secondary outcomes included one year mortality rates, ED visits, admissions to hospital, as well as the application of a novel PC referral score developed by the institutional cardiac Palliative Care Committee. The score consisted of 6 different aspects of the patient’s illness, including laboratory tests, hospital usage, and markers of decompensation. We conducted appropriate univariate analyses. Results: Patients were mean age 80.7 years, women (53.2%), and had significant comorbidities (atrial fibrillation (51.2%), diabetes (40.4%) and COPD (20.8%)). Compared to those with no PC, the 79 (15.8%) patients with PC involvement had a higher one year mortality rate (70.9% vs. 18.8%, p<0.0001), more ED visits/year for HF (0.82 vs. 0.52, p<0.0001), and more hospital admissions/year for HF (1.4 vs. 0.85, p<0.0001). Using the heart failure palliative care score criteria, 60 patients had scores >=2. Compared to those with scores <2, these patients had a higher 1-year mortality rate (50% vs. 24%, p<0.0001) and more ED visits/year for HF (0.83 vs. 0.54, p<0.01). Only 40.0% of these high risk patients had any PC involvement. Conclusion: We found that few HF patients had PC services involved in their care. Using this novel HF palliative care referral score, we were able to identify patients with a significantly greater risk of mortality and morbidity. This study provides evidence that the ED is an appropriate setting to identify and refer high risk HF patients who would likely benefit from earlier PC involvement and may be a future avenue for PC access for these patients.
Puumala virus (PUUV) causes many human infections in large parts of Europe and can lead to mild to moderate disease. The bank vole (Myodes glareolus) is the only reservoir of PUUV in Central Europe. A commercial PUUV rapid field test for rodents was validated for bank-vole blood samples collected in two PUUV-endemic regions in Germany (North Rhine-Westphalia and Baden-Württemberg). A comparison of the results of the rapid field test and standard ELISAs indicated a test efficacy of 93–95%, largely independent of the origin of the antigens used in the ELISA. In ELISAs, reactivity for the German PUUV strain was higher compared to the Swedish strain but not compared to the Finnish strain, which was used for the rapid field test. In conclusion, the use of the rapid field test can facilitate short-term estimation of PUUV seroprevalence in bank-vole populations in Germany and can aid in assessing human PUUV infection risk.