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Classical stewardship efforts have targeted immunocompetent patients; however, appropriate use of antimicrobials in the immunocompromised host has become a target of interest. Cytomegalovirus (CMV) infection is one of the most common and significant complications after solid-organ transplant (SOT). The treatment of CMV requires a dual approach of antiviral drug therapy and reduction of immunosuppression for optimal outcomes. This dual approach to CMV management increases complexity and requires individualization of therapy to balance antiviral efficacy with the risk of allograft rejection. In this review, we focus on the development and implementation of CMV stewardship initiatives, as a component of antimicrobial stewardship in the immunocompromised host, to optimize the management of prevention and treatment of CMV in SOT recipients. These initiatives have the potential not only to improve judicious use of antivirals and prevent resistance but also to improve patient and graft survival given the interconnection between CMV infection and allograft function.
Predicting transition from clinical high risk (CHR) to first episode psychosis has proven difficult. Assessment of oxidative stress biomarkers and the niacin skin flush response (NSFR) may improve prediction accuracy.
To predict transition to psychosis based on combined clinical and blood biomarker.
To analyse data from patients in placebo group of a 12-week trial of omega-3 fatty acid supplementation in CHR. Transition likelihood ratios (LRs) for baseline historical risks, clinical assessments (PANSS subscales and total, GAF), NSFR and blood markers (nervonic acid, superoxide dismutase, glutathione) were calculated. Variables with the highest positive and lowest negative LRs were included in an odds ratio form of Bayes’ rule transition prediction models. Model accuracy was calculated by area under the receiver operating curves (AUROC) of each model.
1-year transition to psychosis was 28% (n=40). Historical data showed no predictability (sensitivity 30%, specificity 100% (AUROC)=0.688, p=0.085). Clinical assessments alone produced a sensitivity of 30% at a specificity of 95% (AUROC=0.83, p<0.0001). The biomarker panel alone predicted transition with 40% sensitivity and 100% specificity (AUROC=0.73, p=0.03). Combining history and clinical assessment provided no improvement above clinical data alone (sensitivity = 30%, specificity = 100%, AUROC=0.85, p< 0.0001). The combination of history, clinical assessment and biomarkers identified transition with a sensitivity of 60% and specificity of 100% (AUROC=0.87, p< 0.0001).
Probabilistic models combining biomarkers and clinical data are able to target high-risk subgroups within CHR and may help to personalise treatment.
There is community concern about the treatment of farm animals post-farm gate, particularly animal transport and slaughter. Relationships between lamb behavioural and physiological variables on farm, stockperson, dog and lamb behavioural variables pre-slaughter and plasma cortisol, glucose and lactate in lambs post-slaughter were studied in 400 lambs. The lambs were observed in three behavioural tests, novel arena, flight distance to a human and temperament tests, before transport for slaughter. Closed-circuit television video footage was used to record stockperson, dog and lamb behaviour immediately before slaughter. Blood samples for cortisol, glucose and lactate analyses were collected on farm following the three behavioural tests and immediately post-slaughter. The regression models that best predicted plasma cortisol, glucose and lactate concentrations post-slaughter included a mixture of stockperson and dog behavioural variables as well as lamb variables both on-farm and pre-slaughter. These regression models accounted for 33%, 34% and 44% of the variance in plasma cortisol, glucose and lactate concentrations post-slaughter, respectively. Some of the stockperson and dog behaviours pre-slaughter that were predictive of the stress and metabolic variables post-slaughter included the duration of negative stockperson behaviours such as fast locomotion and lifting/pulling lambs, and the duration of dog behaviours such as lunging and barking at the lamb, while some of the predictive lamb behaviour variables included the durations of jumping and fleeing. Some of the physiological and behavioural responses to the behavioural tests on farm were also predictive of the stress and metabolic variables post-slaughter. These relationships support the well-demonstrated effect of handling on fear and stress responses in livestock, and although not direct evidence of causal relationships, highlight the potential benefits of training stockpeople to reduce fear and stress in sheep at abattoirs.
The calibration hardware system of the Large Synoptic Survey Telescope (LSST) is designed to measure two quantities: a telescope’s instrumental response and atmospheric transmission, both as a function of wavelength. First of all, a “collimated beam projector” is designed to measure the instrumental response function by projecting monochromatic light through a mask and a collimating optic onto the telescope. During the measurement, the light level is monitored with a NIST-traceable photodiode. This method does not suffer from stray light effects or the reflections (known as ghosting) present when using a flat-field screen illumination, which has a systematic source of uncertainty from uncontrolled reflections. It allows for an independent measurement of the throughput of the telescope’s optical train as well as each filter’s transmission as a function of position on the primary mirror. Second, CALSPEC stars can be used as calibrated light sources to illuminate the atmosphere and measure its transmission. To measure the atmosphere’s transfer function, we use the telescope’s imager with a Ronchi grating in place of a filter to configure it as a low resolution slitless spectrograph. In this paper, we describe this calibration strategy, focusing on results from a prototype system at the Cerro Tololo Inter-American Observatory (CTIO) 0.9 meter telescope. We compare the instrumental throughput measurements to nominal values measured using a laboratory spectrophotometer, and we describe measurements of the atmosphere made via CALSPEC standard stars during the same run.
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.
This paper addresses activities carried out in a late-sixteenth or seventeenth century Maya council house (popol nah) just before its abandonment. Structure 719 at the site of Zacpeten in the central Peten lakes district is considered a noble residence remodeled into a council house with an adjacent temple. Excavations revealed quantities of de facto refuse inside the structure's two rooms and around the exterior; recent studies focused on ceramics, lithics, faunal remains, and net sinkers. The back room held abundant lithics and diverse fauna, with evidence of grinding red pigment and snapping obsidian prismatic blades into segments for fashioning arrow points. Pottery and faunal remains indicate feasting, as well as possible use of animal parts in ritual and in making ceremonial objects. The Group 719 complex served as a center of production of various goods and community ritual until its abrupt abandonment, likely in the first decade or so of the eighteenth century.
A unique approach for permeation filling of nonpermeable inertial confinement fusion target capsules with deuterium–tritium (DT) is presented. This process uses a permeable capsule coupled into the final target capsule with a 0.03-mm-diameter fill tube. Leak free permeation filling of glow-discharge polymerization (GDP) targets using this method have been successfully demonstrated, as well as ice layering of the target, yielding an inner ice surface roughness of 1-
m rms (root mean square). Finally, the measured DT ice-thickness profile for this experiment was used to validate a thermal model’s prediction of the same thickness profile.
There are advantages to performing transmission electron backscattering diffraction (tEBSD) in conjunction with focused ion beam-based specimen preparation for atom probe tomography (APT). Although tEBSD allows users to identify the position and character of grain boundaries, which can then be combined with APT to provide full chemical and orientation characterization of grain boundaries, tEBSD can also provide imaging information that improves the APT specimen preparation process by insuring proper placement of the targeted grain boundary within an APT specimen. In this report we discuss sample tilt angles, ion beam milling energies, and other considerations to optimize Kikuchi diffraction pattern quality for the APT specimen geometry. Coordinated specimen preparation and analysis of a grain boundary in a Ni-based Inconel 600 alloy is used to illustrate the approach revealing a 50° misorientation and trace element segregation to the grain boundary.