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The pharmacotherapy of epilepsy is a complex process guided by evidence-based research and clinical experience. Some patients achieve seizure freedom upon treatment with the first anti-seizure medication (ASM) prescribed, whereas others may be treated with two or three medications before one (or a combination) is found that reduces seizure frequency and/or severity with minimal side effects. Many patients demonstrate a partial response to treatment, leading to reduced seizure frequency and/or severity, but do not become completely seizure free. It is often stated that ~30% of epilepsy patients have seizures that cannot be controlled pharmacologically, and these patients are defined as having medication-resistant epilepsy (MRE). The International League Against Epilepsy (ILAE) published the following definition of MRE: ‘drug resistant epilepsy may be defined as failure of adequate trials of two tolerated and appropriately chosen and used ASM schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom’[1]. Treatment success or sustained seizure freedom is defined as one year without seizures or three times the inter-seizure interval (whichever is longer). The ILAE definition provides a useful standard from which to work, and MRE can be clinically identified in patients that fail to achieve seizure freedom after multiple ASM trials. However, the ILAE definition of successful treatment does not account for partial response to pharmacotherapy. Indeed, many partial responders have improved quality of life, even if they are not seizure-free for one year or more.
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.
Methods
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results
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).
Conclusions
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
A series of ${\left\hbox[ {{{\left\hbox( {{\rm{SnSe}}} \right\hbox)}_{1 \hbox+ \delta }}} \right\hbox]_m}{\left\hbox[ {{\rm{TiS}}{{\rm{e}}_2}} \right\hbox]_2}$ heterostructure thin films built up from repeating units of m bilayers of SnSe and two layers of TiSe2 were synthesized from designed precursors. The electronic structure of the films was investigated using X-ray photoelectron spectroscopy for samples with m = 1, 2, 3, and 7 and compared to binary samples of TiSe2 and SnSe. The observed binding energies of core levels and valence bands of the heterostructures are largely independent of m. For the SnSe layers, we can observe a rigid band shift in the heterostructures compared to the binary, which can be explained by electron transfer from SnSe to TiSe2. The electronic structure of the TiSe2 layers shows a more complicated behavior, as a small shift can be observed in the valence band and Se3d spectra, but the Ti2p core level remains at a constant energy. Complementary UV photoemission spectroscopy measurements confirm a charge transfer mechanism where the SnSe layers donate electrons into empty Ti3d states at the Fermi energy.
Atomic layer deposition (ALD) of air stable cobalt and nickel complexes based on tridentate enaminones N,N-(4,4,4-trifluorobut-1-en-3-on)-dimethylethyldiamine (Htfb-dmeda) and N,N-(4,4,4-trifluorobut-1-en-3-on)-dimethylpropyldiamine (Htfb-dmpda) successfully produced metallic cobalt and nickel thin films. Detailed X-ray photoelectron spectroscopy (XPS) studies on the binding interaction of the first precursor monolayer with the surface functional groups elucidated the chemisorption behavior of the new precursor systems. A reactive remote hydrogen plasma was used as the co-reactant to activate the precursor decomposition yielding metal hydroxide intermediates. Subsequent hydrogen plasma etching of as-deposited films resulted in phase-pure metallic films through a recrystallization process, verified by surface and sub-surface XPS. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analyses revealed pinhole-free films, with low surface roughness (0.2 ± 0.06 nm root mean square, RMS) for both, cobalt and nickel thin films. Herein, the competitive role of hydrogen as etchant and reactant was demonstrated as prolonged plasma exposure time periods resulted in the formation of metal hydrides. This is mostly due to the catalytic dissociation of molecular hydrogen on transition metal surfaces, which already occurs upon low energy input.
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.
Aims
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Method
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.
Results
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).
Conclusions
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.
In this review article, we discuss selected developments regarding the role of the equation of state in simulations of core-collapse supernovae. There are no first-principle calculations of the state of matter under supernova conditions since a wide range of conditions is covered, in terms of density, temperature, and isospin asymmetry. Instead, model equation of state are commonly employed in supernova studies. These can be divided into regimes with intrinsically different degrees of freedom: heavy nuclei at low temperatures, inhomogeneous nuclear matter where light and heavy nuclei coexist together with unbound nucleons, and the transition to homogeneous matter at high densities and temperatures. In this article, we discuss each of these phases with particular view on their role in supernova simulations.
Palliative care for nursing home residents with advanced dementia is often sub-optimal due to poor communication and limited care planning. In a cluster randomized controlled trial, registered nurses (RNs) from 10 nursing homes were trained and funded to work as Palliative Care Planning Coordinators (PCPCs) to organize family case conferences and mentor staff. This qualitative sub-study aimed to explore PCPC and health professional perceptions of the benefits of facilitated case conferencing and identify factors influencing implementation.
Method:
Semi-structured interviews were conducted with the RNs in the PCPC role, other members of nursing home staff, and physicians who participated in case conferences. Analysis was conducted by two researchers using a thematic framework approach.
Results:
Interviews were conducted with 11 PCPCs, 18 other nurses, eight allied health workers, and three physicians. Perceived benefits of facilitated case conferencing included better communication between staff and families, greater multi-disciplinary involvement in case conferences and care planning, and improved staff attitudes and capabilities for dementia palliative care. Key factors influencing implementation included: staffing levels and time; support from management, staff and physicians; and positive family feedback.
Conclusion:
The facilitated approach explored in this study addressed known barriers to case conferencing. However, current business models in the sector make it difficult for case conferencing to receive the required levels of nursing qualification, training, and time. A collaborative nursing home culture and ongoing relationships with health professionals are also prerequisites for success. Further studies should document resident and family perceptions to harness consumer advocacy.
Species with specific habitat requirements often remain within their habitat and are characterized by a very sedentary behaviour. We used radio-tracking during a 3-wk campaign to investigate the home ranges and movements of three East African passerine bird species, all adapted to cloud-forest habitats: montane white-eye Zosterops poliogaster mbuluensis, stripe-cheeked greenbul Andropadus milanjensis and white-starred robin Pogonocichla stellata macarthuri. Individuals were observed in a forest-grassland mosaic on top of Chyulu Hills, south Kenya. Based on 15 individuals with a total of 1041 fixes, we found (1) that all three species show a sedentary behaviour restricted to their home forest patch; (2) least activity during the afternoon; and (3) re-colonization into its home patch after translocation into a nearby forest patch. Our findings underline that forest-specialist bird species of the tropics show high site fidelity despite their potential movement ability.
Snow avalanche simulation software is a commonly used tool for hazard estimation and mitigation planning. In this study a depth-averaged flow model, combining a simple entrainment and friction relation, is implemented in the software SamosAT. Computational results strongly depend on the simulation input, in particular on the employed model parameters. A long-standing problem is to quantify the influence of these parameters on the simulation results. We present a new multivariate optimization approach for avalanche simulation in three-dimensional terrain. The method takes into account the entire physically relevant range of the two friction parameters (Coulomb friction, turbulent drag) and one entrainment parameter. These three flow model parameters are scrutinized with respect to six optimization variables (runout, matched and exceeded affected area, maximum velocity, average deposition depth and mass growth). The approach is applied to a documented extreme avalanche event, recorded in St Anton, Austria. The final results provide adjusted parameter distributions optimizing the simulation–observation correspondence. At the same time, the degree of parameter–variable correspondence is determined. We show that the specification of optimal values for certain model parameters is near-impossible, if corresponding optimization variables are neglected or unavailable.
Red blood cells are the subject of diverse studies. One branch is the observation and theoretical modelling of their behaviour in a shear flow. This work deals with the flow of single red cells suspended in solutions much more viscous than blood plasma. Below a critical shear rate (${\dot {\gamma } }_{t} $) the red cells rotate with little change of their resting shape. Above that value they become elongated and aligned in the shear field. We measured ${\dot {\gamma } }_{t} $ at viscosities (${\eta }_{0} $) ranging from 10.7 to 104 mPa s via observation along the vorticity of a Poiseuille flow in a glass capillary; ${\eta }_{0} {\dot {\gamma } }_{t} $ decreased steeply with increasing ${\eta }_{0} $ up to a value of 25 mPa s and remained constant for higher values. Present theoretical models are not in keeping with the measured data. Modifications of basic model assumptions are suggested.
Calcium carbonate precipitation in sea ice is thought to potentially drive significant CO2 uptake by the ocean. However, little is known about the quantitative spatial and temporal distribution of CaCO3 within sea ice, although it is hypothesized that high quantities of dissolved organic matter and/or phosphate (common in sea ice) may inhibit its formation. In this quantitative study of hydrous calcium carbonate as ikaite, sea ice cores and brine samples were collected from pack and land fast sea ice between September and December 2007 during two expeditions, one in the East Antarctic sector and the other off Terre Adélie. Samples were analysed for CaCO3, salinity, dissolved organic carbon/nitrogen, inorganic phosphate, and total alkalinity. No relationship between these parameters and CaCO3 precipitation was evident. Ikaite was found mostly in the uppermost layers of sea ice with maximum concentrations of up to 126 mg ikaite per litre melted sea ice being measured, although both the temporal and horizontal spatial distributions of ikaite were highly heterogeneous. The precipitate was also found in the snow on top of the sea ice at some of the sampling locations.