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Cross-sectional data show elevated levels of circulating cytokines in psychiatric patients. The literature is divided concerning anti-inflammatory drugs’ ability to relieve symptoms, questioning a causal link between inflammatory pathways and psychiatric conditions. We hypothesised that the development of circulating cytokine levels is related to mental distress, and that this relationship is affected by the use of anti-inflammatory drugs.
The study was a longitudinal assessment of 12-week inpatient treatment at Modum Bad Psychiatric Center, Norway. Sera and self-reported Global Severity Index (GSI) scores, which measure psychological distress, were collected at admission (T0), halfway (T1) and before discharge (T2). Other variables known to distort the neuroimmune interplay were included. These were age, gender, diagnosis of PTSD, antidepressants and anti-inflammatory drugs. A total of 128 patients (92 women and 36 men) were included, and 28 were using anti-inflammatory medication. Multilevel modelling was used for data analysis.
Patients with higher levels of IL-1RA and MCP-1 had higher GSI scores (p = 0.005 and p = 0.020). PTSD patients scored higher on GSI than non-PTSD patients (p = 0.002). These relationships were mostly present among those not using anti-inflammatory drugs (n = 99), with higher levels of IL-1RA and MCP-1 being related to higher GSI score (p = 0.023 and 0.018, respectively). Again, PTSD patients showed higher GSI levels than non-PTSD patients (p = 0.014).
Cytokine levels were associated with level of mental distress as measured by the GSI scores, but this relationship was not present among those using anti-inflammatory drugs. We found no association between cytokine levels and development of GSI score over time.
Mini-sabbaticals are formal short-term training and educational experiences away from an investigator’s home research unit. These may include rotations with other research units and externships at government research or regulatory agencies, industry and non-profit programs, and training and/or intensive educational programs. The National Institutes of Health have been encouraging training institutions to consider offering mini-sabbaticals, but given the newness of the concept, limited data are available to guide the implementation of mini-sabbatical programs. In this paper, we review the history of sabbaticals and mini-sabbaticals, report the results of surveys we performed to ascertain the use of mini-sabbaticals at Clinical and Translational Science Award hubs, and consider best practice recommendations for institutions seeking to establish formal mini-sabbatical programs.
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.
The population size of anadromous salmon in the Pacific Northwest is strongly influenced by decadal variation in watershed and oceanographic conditions and therefore should also be influenced by larger magnitude millennial-scale variations in these conditions. We studied δ15N of bulk organic matter in lake sediment from Woahink Lake, Oregon, as a proxy of marine-derived nutrients (MDN) from spawning coho salmon. We compared this site to a control lake with a natural barrier to salmon migration. From 7.5 to 5.4 ka, a dune was emplaced, breached, and emplaced again, forming Woahink Lake in a former estuary. δ15N decreased steadily since 5.4 ka at Woahink but not at the control lake. δ15N reached a minimum just prior to anthropogenic nutrient loading, which caused an increase in δ15N, thus precluding a comparison with the historical decline in salmon abundance. A mixing model of lake-water nitrate, developed to explore alternate scenarios for the observed range of δ15N, could not explain these results without invoking MDN input from at least several hundred salmon annually. Our results show a previously unreported pattern of a millennial-scale decline in salmon that has plausible linkages to parallel changes in ocean circulation and productivity.
Using new (Cycle 9) HST / WFPC2 data, we have studied a peculiar star forming region in the nearby Sc-type spiral NGC 6946. The region has a bubble-like shape and a diameter of about 600 pc. Near the centre is an extremely luminous young globular cluster with MV = −13.2 mag. The cluster has a compact core with a core radius of about 1.3 pc but is surrounded by an extended halo with a power-law luminosity profile similar to that observed for young LMC clusters. From Keck / HIRES high-dispersion spectroscopy we measure a velocity dispersion of 10 km s−1, leading to a dynamical mass estimate of about 1.7 × 106 solar masses. The dynamical mass estimate is comparable to the expectation from population synthesis modelling under the assumption of a Salpeter IMF extending down to 0.1 M⊙.
A search has been made using the Buckland Park air shower array for evidence of any excess of events from the direction of the recent supernova in the Large Magellanic Cloud. Upper limits resulting from this search and their significance are discussed in this paper.
Saturn’s largest moon Titan is the only satellite in the Solar System with a substantial atmosphere. Photolysis of methane creates a hydrocarbon haze in Titan’s atmosphere that is opaque to visible light. The new adaptive optics system on the 10–meter W. M. Keck Telescope enables us to observe Titan with a resolution of 0.04 arcseconds, or 20 resolution elements across the disk. By observing at near-infrared wavelengths that are methane band windows we can see through Titan’s hydrocarbon haze to the surface beneath. Recent adaptive optics images of Titan both in broadband (J, H, and K) filters and in narrowband filters that selectively probe Titan’s surface and atmosphere allow us to determine surface albedo and properties of the hydrocarbon haze layer. Future observations will include high-resolution spectroscopy coupled with adaptive optics to obtain spectra of individual surface features.
Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).
In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression.
Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure.
We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.
Star formation processes in strongly self-gravitating cloud cores should be similar at all redshifts, forming single or multiple stars with a range of masses determined by local magneto-hydrodynamics and gravity. The formation processes for these cores, however, as well as their structures, temperatures, Mach numbers, etc., and the boundedness and mass distribution functions of the resulting stars, should depend on environment, as should the characteristic mass, density, and column density at which cloud self-gravity dominates other forces. Because the environments for high and low redshift star formation differ significantly, we expect the resulting gas to stellar conversion details to differ also. At high redshift, the universe is denser and more gas-rich, so the active parts of galaxies are denser and more gas rich too, leading to slightly shorter gas consumption timescales, higher cloud pressures, and denser, more massive, bound stellar clusters at the high mass end. With shorter consumption times corresponding to higher relative cosmic accretion rates, and with the resulting higher star formation rates and their higher feedback powers, the ISM has greater turbulent speeds relative to the rotation speeds, thicker gas disks, and larger cloud and star complex sizes at the characteristic Jeans length. The result is a more chaotic appearance at high redshift, bridging the morphology gap between today's quiescent spirals and today's major-mergers, with neither spiral nor major-merger processes actually in play at that time. The result is also a thick disk at early times, and after in-plane accretion from relatively large clump torques, a classical bulge. Today's disks are thinner, and torque-driven accretion is slower outside of inner barred regions. This paper reviews the basic processes involved with star formation in order to illustrate its evolution over time and environment.
Communication between emergency department (ED) staff and parents of children with asthma may play a role in asthma exacerbation management. We investigated the extent to which parents of children with asthma implement recommendations provided by the ED staff. Method: We asked questions on asthma triggers, ED care (including education and discharge recommendations), and asthma management strategies used at home shortly after the ED visit and again at 6 months.
A total of 148 children with asthma were recruited. Thirty-two percent of children were not on inhaled corticosteroids prior to their ED visit. Eighty percent of parents identified upper respiratory tract infections (URTIs) as the primary trigger for their child’s asthma. No parent received or implemented any specific asthma strategies to reduce the impact of URTIs; 82% of parents did not receive any printed asthma education materials. Most (66%) parents received verbal instructions on how to manage their child’s future asthma exacerbations. Of those, one-third of families were told to return to the ED. Parents were rarely advised to bring their child to their family doctor in the event of a future exacerbation. At 6 months, parents continued to use the ED services for asthma exacerbations in their children, despite reporting feeling confident in managing their child’s asthma.
Improvements are urgently needed in developing strategies to manage pediatric asthma exacerbations related to URTIs, communication with parents at discharge in acute care, and using alternate acute care services for parents who continue to rely on EDs for the initial care of mild asthma exacerbations.
We performed a study to determine rates of reinfection in three groups followed for 2 years after successful treatment: American Indian/Alaska Native (AI/AN) persons living in urban (group 1) and rural (group 2) communities, and urban Alaska non-Native persons (group 3). We enrolled adults diagnosed with H. pylori infection based on a positive urea breath test (13C-UBT). After successful treatment was documented at 2 months, we tested each patient by 13C-UBT at 4, 6, 12 and 24 months. At each visit, participants were asked about medication use, illnesses and risk factors for reinfection. We followed 229 persons for 2 years or until they became reinfected. H. pylori reinfection occurred in 36 persons; cumulative reinfection rates were 14·5%, 22·1%, and 12·0% for groups 1, 2, and 3, respectively. Study participants who became reinfected were more likely to have peptic ulcer disease (P = 0·02), low education level (P = 0·04), or have a higher proportion of household members infected with H. pylori compared to participants who did not become reinfected (P = 0·03). Among all three groups, reinfection occurred at rates higher than those reported for other US populations (<5% at 2 years); rural AI/AN individuals appear to be at highest risk for reinfection.