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Introduction: Optimizing naloxone dosing in the context of increasing fentanyl and ultra-potent opioid (UPO) prevalence is an important consideration for emergency health care providers. The goal of this systematic review was to evaluate the association between initial and cumulative naloxone doses on effective reversal and adverse events in undifferentiated and fentanyl/UPO overdoses. Methods: We searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials, DARE, CINAHL, Science Citation Index, reference lists, toxicology websites, and conference proceedings from July to October 2018 and back to 1972. Our search included pertinent indexing terms for UPOs. We included interventional and observational studies reporting on naloxone administration for opioid toxicity reversal in people ≥12 years old. Additionally, we accessed non-traditional evidence sources (case reports and series) given this rapidly changing field. We conducted inclusion screens, data extraction and quality assessments in duplicate. We summarized study characteristics and where reported, analyzed number of patients with clinical response. Response was defined as not receiving further naloxone doses and remaining alive. Results: We included 174 studies (108 case reports and series, 55 observational, 9 interventional) with 26,660 subjects (median age 35.1; 74.2% male). We observed lower response among patients exposed to fentanyl/UPO versus heroin for initial naloxone doses ≤0.4mg (56.8% versus 80.2%) and > 0.4mg (27.0% versus 82.1%). Mean cumulative doses were higher for fentanyl/UPO (2.10 mg, SD 1.80 mg) versus heroin (1.48 mg, SD 1.68 mg) overdoses. In North American studies the median cumulative dose used was higher for fentanyl/UPO versus heroin overdoses. A dose-response curve for fentanyl/UPO studies showed marked variability in doses among responders, indicating heterogeneity. Adverse events reporting was inconsistent; 10% of subjects experienced withdrawal based on studies in which they were reported. Conclusion: This is the first systematic review to summarize proportion of patients with clinical response by naloxone dose provided. While variable reporting, study quality, heterogeneity, and our outcome definitions limit the conclusions we can draw, it appears that higher initial doses and in some cases, higher cumulative naloxone doses were used and may be necessary to reverse toxicity due to fentanyl/UPO compared to other opioids. High-quality prospective studies assessing effectiveness and safety are needed.
According to Keven & Akins (K&A), infant orofacial gestures may not reflect imitative responses. Here, we emphasise that these actions nonetheless represent a significant feature of the infant's early sensorimotor experience, and therefore may play a key role in the development of imitative capacities. We discuss how the ideas proposed in the target article could contribute substantially to experiential accounts of imitation.
Two highly pathogenic avian influenza (HPAI) outbreaks have affected commercial egg production flocks in the American continent in recent years; a H7N3 outbreak in Mexico in 2012 that caused 70% to 85% mortality and a H5N2 outbreak in the United States in 2015 with over 99% mortality. Blood samples were obtained from survivors of each outbreak and from age and genetics matched non-affected controls. A total of 485 individuals (survivors and controls) were genotyped with a 600 k single nucleotide polymorphism (SNP) array to detect genomic regions that influenced the outcome of highly pathogenic influenza infection in the two outbreaks. A total of 420458 high quality, segregating SNPs were identified across all samples. Genetic differences between survivors and controls were analyzed using a logistic model, mixed models and a Bayesian variable selection approach. Several genomic regions potentially associated with resistance to HPAI were identified, after performing multidimensional scaling and adjustment for multiple testing. Analysis conducted within each outbreak identified different genomic regions for resistance to the two virus strains. The strongest signals for the Iowa H5N2 survivor samples were detected on chromosomes 1, 7, 9 and 15. Positional candidate genes were mainly coding for plasma membrane proteins with receptor activity and were also involved in immune response. Three regions with the strongest signal for the Mexico H7N3 samples were located on chromosomes 1 and 5. Neuronal cell surface, signal transduction and immune response proteins coding genes were located in the close proximity of these regions.
This experiment aimed to assess the effect of different indoor winter growth rates (WGR) followed by different concentrate supplementation levels at pasture on meat quality of 90 bulls. During the first winter, bulls were offered grass silage ad libitum and either 3 kg (WGR3) or 6 kg (WGR6) of concentrates. After turn-out to pasture, bulls were offered: grass without supplementation (PO), grass plus 0.2 predicted dry matter intake (DMI) as concentrates (PL) or grass plus 0.4 predicted DMI as concentrates (PH). After finishing, colour, chemical composition (unaged), instrumental texture and sensory characteristics (14 days of ageing) of longissimus thoracis were measured. WGR6 bulls had heavier carcasses than WGR3 bulls. There was an interaction between WGR and supplementation for instrumental texture and redness (a). Within WGR3, PO beef was the most tender, whereas within WRG6, PL was the most tender. However, these differences were not detected by the sensory panel. Within WGR3, redness was the lowest for PL, whereas within WRG6, PO was the least red. No differences were found for chemical composition. The multivariate analysis highlighted WGR as the main variable affecting meat quality characteristics. In conclusion, variations in growth path exerted minor effects on appearance and instrumental texture which did not affect the perception of bull beef by a trained sensory panel.
The effects of shape and thickness of a tin surface layer and of the energy of a 170 ps neodymium:yttrium-aluminum-garnet laser pulse on the conversion efficiency (CE) into extreme ultraviolet emission in the 13.5 nm region is investigated. Whereas a CE of up to 1.16% into the 2% reflection band of multilayer Mo/Si optics was measured for a bulk Sn target at a laser energy of 25 mJ, significant CE enhancement up to 1.49% is demonstrated for a 200-nm-thick Sn layer on a microstructured porous alumina substrate.
We present techniques developed to calibrate and correct Murchison Widefield Array low-frequency (72–300 MHz) radio observations for polarimetry. The extremely wide field-of-view, excellent instantaneous (u, v)-coverage and sensitivity to degree-scale structure that the Murchison Widefield Array provides enable instrumental calibration, removal of instrumental artefacts, and correction for ionospheric Faraday rotation through imaging techniques. With the demonstrated polarimetric capabilities of the Murchison Widefield Array, we discuss future directions for polarimetric science at low frequencies to answer outstanding questions relating to polarised source counts, source depolarisation, pulsar science, low-mass stars, exoplanets, the nature of the interstellar and intergalactic media, and the solar environment.
Culturomics is the study of behaviour and culture through quantitative analysis of digitised text. We aimed to apply a modern technique in this field to examine trends related to the history of psychiatry. In doing so, we aimed to explore the nature of the Google Ngram methodology.
Using Google Ngram Viewer, we studied Google’s corpus of over 4% of all published books and explored relevant trends in word usage.
An exponential growth in the use of ‘psychiatry’ between 1890 and 1984 was identified. ‘Sigmund Freud’ was mentioned more frequently than all other prominent figures in the history of psychiatry combined. Mentions of ‘suicide’ increased since 1820. The impact of several DSM editions is discussed.
This study demonstrated the potential application of the Ngram methodology to the study of the history of psychiatry. The role of textual analysis in this field merits careful, constructive consideration and is likely to expand with technological advances.
There has been relatively limited research focus on autism in the context of the criminal justice system. The relationship between autism spectrum disorder (ASD) and criminal responsibility is complex. Furthermore, the features inherent to ASD can have a significant bearing on a wide array of other issues in this context including police interviewing, fitness to be tried, culpability and the appropriateness of custodial disposal. This review explores the background to our understanding of ASD, patterns of offending behaviour and the nature of the relationship between this and characteristic ASD deficits. The clinical and legal challenges posed by ASD defendants in terms of identification, assessment and on a broader service level as they negotiate the criminal justice system are highlighted to illustrate the varied difficulties they may encounter and to draw attention to this field as a worthy area of research and training for the medical, legal and law enforcement professions.
Many medications administered to patients with schizophrenia possess anticholinergic properties. When aggregated, pharmacological treatments may result in a considerable anticholinergic burden. The extent to which anticholinergic burden has a deleterious effect on cognition and impairs ability to participate in and benefit from psychosocial treatments is unknown.
Seventy patients were followed for approximately 3 years. The MATRICS consensus cognitive battery (MCCB) was administered at baseline. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale. Ability to benefit from psychosocial programmes was measured using the DUNDRUM-3 Programme Completion Scale (D-3) at baseline and follow-up. Psychiatric symptoms were measured using the PANSS. Total antipsychotic dose was measured using chlorpromazine equivalents. Functioning was measured using the Social and Occupational Functioning Assessment Scale (SOFAS).
Mediation analysis found that the influence of anticholinergic burden on ability to participate and benefit from psychosocial programmes was completely mediated by the MCCB. For every 1-unit increase on the ACB scale, change scores for DUNDRUM-3 decreased by −0.27 points. This relationship appears specific to anticholinergic burden and not total antipsychotic dose. Moreover, mediation appears to be specific to cognition and not psychopathology. Baseline functioning also acted as mediator but only when MCCB was not controlled for.
Anticholinergic burden has a significant impact on patients’ ability to participate in and benefit from psychosocial treatment programmes. Physicians need to be mindful of the cumulative effect that medications can have on patient cognition, functional capacity and ability to benefit from psychosocial treatments.
We have successfully demonstrated optical aperture synthesis at the 4-m Anglo-Australian Telescope. By using a multi-hole mask over the (re-imaged) primary mirror and recording the resulting fringe patterns with high time resolution, diffraction-limited images of sufficiently bright objects can be reconstructed. The data processing uses closure phases to overcome the effects of atmospheric turbulence. We show an image of the double star η Oph, with component separation 0″.45.
This study was undertaken to determine the optimum approach to screening for head and neck cancer based on international experiences.
To determine whether or not head and neck cancer is suitable for screening, and, if so, what the ideal approach should be.
An electronic search of online databases up to and including May 2014 was conducted. Key search terms included ‘head and neck’, ‘cancer’, ‘screening’, ‘larynx’, ‘oropharynx’ and ‘oral’.
Subset analysis of high-risk cohorts showed statistically significant improvements in early detection of head and neck cancer via screening.
Current levels of public awareness regarding head and neck cancers are suboptimal, despite increased incidence and mortality. Scheduled and opportunistic screening, coupled with efforts to enhance education and health behaviour modification, are highly recommended for pre-defined, high-risk, targeted populations. This can enable early detection and therefore improve morbidity and mortality.
This paper describes the system architecture of a newly constructed radio telescope – the Boolardy engineering test array, which is a prototype of the Australian square kilometre array pathfinder telescope. Phased array feed technology is used to form multiple simultaneous beams per antenna, providing astronomers with unprecedented survey speed. The test array described here is a six-antenna interferometer, fitted with prototype signal processing hardware capable of forming at least nine dual-polarisation beams simultaneously, allowing several square degrees to be imaged in a single pointed observation. The main purpose of the test array is to develop beamforming and wide-field calibration methods for use with the full telescope, but it will also be capable of limited early science demonstrations.
Almost all previous studies examining the associations between glycaemic load (GL) and metabolic syndrome risk have used a daily GL value. The daily value does not distinguish between peaks of GL intake over the day, which may be more closely associated with the risk of the metabolic syndrome. The aim of the present study was to investigate the cross-sectional associations between daily and mealtime measures of GL and metabolic syndrome risk, including metabolic syndrome components, in adolescents. Adolescents participating in the 14-year follow-up of the Western Australian Pregnancy Cohort (Raine) Study completed 3 d food records and metabolic assessments. Breakfast GL, lunch GL, dinner GL and a score representing meal GL peaks over the day were determined in 516 adolescents. Logistic regression models were used to investigate whether GL variables were independent predictors of the metabolic syndrome in this population-based cohort (3·5 % prevalence of the metabolic syndrome). Breakfast GL was found to be predictive of the metabolic syndrome in girls (OR 1·15, 95 % CI 1·04, 1·27; P <0·01), but not in boys. Other meal GL values and daily GL were found to be not significant predictors of the metabolic syndrome. When breakfast GL was examined in relation to each of the components of the metabolic syndrome in girls, it was found to be negatively associated with fasting HDL-cholesterol concentrations (P= 0·037; β = − 0·004; 95 % CI − 0·008, − 0·002) and positively associated with fasting TAG concentrations (P= 0·008; exp(β) = 1·002; 95 % CI 1·001, 1·004). The results of the present study suggest that there may be an association between breakfast composition and metabolic syndrome components in adolescent girls. These findings support further investigation into including lower-GL foods as part of a healthy breakfast in adolescence, particularly for girls.
Excavations and environmental analysis of a mound and two barrows indicate that activity commenced within the range 3930–3520 cal BC with the construction of a large mound enclosed by a substantial ditch on a drumlin which had been largely cleared to grassland. A pollen sequence recovered from the fosse indicates that the drumlin remained under grassland for some time. It was still under grassland in the Iron Age when a pair of sequential barrows was constructed about the period 380 cal BC–cal AD 80. The earlier bowl barrow covered a pyre site with remains of an inhumation burial, and the later saucer barrow contained three token cremation deposits in the low mound and ditch, the last associated with the iron fittings from a wooden artefact. Pollen analysis of the ditch sequences from the barrows indicates that the drumlin remained open and heather-covered.
Vitamin D deficiency is emerging worldwide and many studies now suggest its role in the development of several chronic diseases. Due to the low level of vitamin D naturally occurring in food there is a need for supplementation and use of vitamin D-enhanced products. The aim of the present study was to determine if daily consumption of vitamin D2-enhanced mushrooms increased vitamin D status in free-living healthy adults or affected markers of the metabolic syndrome. A total of ninety volunteers (aged 40–65 years) were randomly assigned to one of two 4-week studies: mushroom study (15 µg vitamin D2 or placebo mushroom powder) and capsule study (15 µg vitamin D3 or placebo capsules). Consumption of vitamin D2-enhanced mushrooms increased serum 25-hydroxyvitamin D2 (25(OH)D2) by 128 % from baseline (3·9 (sd 1·9) nmol/l; P < 0·05). Serum 25(OH)D3 increased significantly in the vitamin D3 capsule group (a 55 % increase from a baseline of 44.0 (sd 17·1) nmol/l; P < 0·05). Vitamin D status (25(OH)D) was affected only in the vitamin D3 group. Plasminogen activator inhibitor-1 was lowered by vitamin D2 intake. Vitamin D2 from enhanced mushrooms was bioavailable and increased serum 25(OH)D2 concentration with no significant effect on 25(OH)D3 or total 25(OH)D.
Impending malignant spinal cord compression (IMSCC) may be defined as compression of the thecal sac, without any visible pressure on the spinal cord itself. Although there is a perception that IMSCC patients have a better prognosis and less severe clinical symptoms than true malignant spinal cord compression (MSCC) patients, these factors have never been documented in the literature.
To record the characteristics, management and functional outcome of a group of patients with IMSCC, who were treated with radiotherapy in our institution, and compare these parameters with similar data on MSCC patients.
Materials and methods
Data (gender, age, primary oncological diagnosis, pain, performance status and neurological status) were prospectively collected for 28 patients. Patients were then followed up post treatment to document their response to treatment and treatment-related toxicity.
The median survival of our group of IMSCC patients is similar to that of an MSCC patient. In addition, the IMSCC group exhibits significant clinical symptoms including neurological deficit.
Although further studies are necessary, we have found that IMSCC patients in this study share similar prognosis and clinical symptoms with MSCC patients. Clinicians should be aware of this when communicating with IMSCC patients and their families, and short-course radiotherapy should be considered.