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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
A survey of hospital antimicrobial stewardship programs was performed to validate core element achievement data from the National Healthcare Safety Network’s (NHSN) Patient Safety Component Annual Survey. In total, 89% of hospitals met all 7 core elements, compared to only 68% according to the NHSN survey.
Introduction: Successful resuscitation in the ED cannot occur without a viable patient, and in many cases patient viability is dependent upon optimal prehospital resuscitation performed by ad hoc teams formed in real time. Currently, little is known about the cognitive and interpersonal skills, or non-technical skills, that are essential for effective team collaboration under these conditions. We have completed a scoping review to provide a state of the literature and develop a taxonomy of the non-technical skills pertinent to ad hoc teams in prehospital settings. Methods: Our scoping review searched four databases (EMBASE, Medline, Cinahl, and Psychinfo) for articles related to resuscitation in acute care settings. No date criteria were applied, but only full text articles written in English were included. Articles underwent two-reviewer title & abstract screening, full text screening, and analysis. A quality review asked three questions: Are keywords defined? Is the article well-situated within the existing literature? Does the article contribute back to the existing body of knowledge? Although statistical analyses are not appropriate for this scoping review, analysis included a descriptive-analytical framework for organizing data. Results: Of 6932 screened articles, 38 were included in analysis, five articles examined prehospital teams, and one addressed the ad hoc nature of these teams. Only one of these articles met our three quality criteria. Nevertheless, our analysis suggests a rudimentary taxonomy whereby the primary objective of a team leader is to overcome this barrier by facilitating the development of optimal team situational awareness, fostered through timely and accurate briefings with closed-loop communication. Conclusion: This scoping review has identified that non-technical skills pertaining to resuscitation in acute care settings are becoming a widely examined phenomenon; however, few studies contribute in any meaningful way to our understanding of how non-technical skills training can be tailored to those performing as members of ad hoc prehospital resuscitation teams. As the need for interprofessional training is becoming more pressing, we anticipate this review will provide essential guidance for future inquiry as well as design for both educational models and organizational systems-based interventions.
Because standard English lacks a true a gender-neutral singular pronoun, there has long been debate over how to refer to generic persons whose genders are unknown, or those who reject binary male or female identities. Singular (or epicene) ‘they’ has a long history as a pronoun to refer to individuals of unknown gender (Balhorn, 2004), and has also been adopted as a personal pronoun by those who identify as neither male nor female. Borthen (2010) argues based on a corpus study of Norwegian that, crosslinguistically, plural pronouns allow for vague reference, and that their lexical features (e.g., number, person) need not match their interpretation in context, which makes these pronouns prime candidates to be used in gender-neutral contexts. Chen and Wu (2011) contend that this is true for both singular and plural pronouns, but Borthen (2011) disputes this, arguing that the data show that for definite plural pronouns, but not singular, the antecedent need not be activated in the speaker's or addressee's mind, and thus can be inferred.
There has recently been growing interest in various atomic and nuclear techniques for the measurement of elements in the body. This has arisen through the realisation that (a) clinically-important amounts of toxic elements can be absorbed as a result of low-level environmental exposure, and (b) important information about the nutritional status of a patient can be obtained from measurements of major body elements. Where such information can be obtained by taking samples, a very wide range of analytical techniques is available, some capable of a sensitivity measured in parts-per-billion. Sampling is not possible, however, when the whole-body content (e.g. of nitrogen) is required, and is clinically undesirable when the element in question is concentrated in particular organs, for example as lead accumulates in the bones, and cadmium and many other toxic elements accumulate in the kidneys. It is in such cases that the various in vivo techniques are particularly important.
Laboratory identification of carbapenem-resistant Enterobacteriaceae (CRE) is a key step in controlling its spread. Our survey showed that most Veterans Affairs laboratories follow VA guidelines for initial CRE identification, whereas 55.0% use PCR to confirm carbapenemase production. Most respondents were knowledgeable about CRE guidelines. Barriers included staffing, training, and financial resources.
Chronic spontaneous urticaria (CSU) has been associated with depression and can have an impact on quality of life. Therefore, researchers have suggested the potential utility of psychological interventions for targeting depression among CSU patients. Psychological interventions that may hold the most promise are those that are brief and easily transportable, such as brief behavioural activation treatment for depression. We report results of a preliminary investigation of an uncontrolled open trial of a one-session behavioural activation treatment for depression designed for patients with CSU (BATD-CSU) at a university-based allergy and immunology clinic. Participants were 11 females with chronic, poorly controlled urticaria and symptoms of depression. Following the completion of pretreatment questionnaires, participants were administered BATD-CSU primarily by non-mental health professionals trained and supervised in its delivery. One month post-BATD-CSU, participants completed follow-up questionnaires. Participants exhibited significant reductions in depression severity, avoidance/rumination, and work/school impairment. BATD-CSU was also associated with improvements in urticaria control one month post-treatment. Moreover, five of nine patients reported reliable and clinically significant improvement on at least one outcome. Results demonstrate that BATD-CSU may have benefits for CSU patients even when consisting of one session and delivered by professionals with limited background in psychological interventions, thus speaking to its feasibility and transportability.
GravityCam is a new concept of ground-based imaging instrument capable of delivering significantly sharper images from the ground than is normally possible without adaptive optics. Advances in optical and near-infrared imaging technologies allow images to be acquired at high speed without significant noise penalty. Aligning these images before they are combined can yield a 2.5–3-fold improvement in image resolution. By using arrays of such detectors, survey fields may be as wide as the telescope optics allows. Consequently, GravityCam enables both wide-field high-resolution imaging and high-speed photometry. We describe the instrument and detail its application to provide demographics of planets and satellites down to Lunar mass (or even below) across the Milky Way. GravityCam is also suited to improve the quality of weak shear studies of dark matter distribution in distant clusters of galaxies and multiwavelength follow-ups of background sources that are strongly lensed by galaxy clusters. The photometric data arising from an extensive microlensing survey will also be useful for asteroseismology studies, while GravityCam can be used to monitor fast multiwavelength flaring in accreting compact objects and promises to generate a unique data set on the population of the Kuiper belt and possibly the Oort cloud.
Important Bird and Biodiversity Areas (IBAs) are sites identified as being globally important for the conservation of bird populations on the basis of an internationally agreed set of criteria. We present the first review of the development and spread of the IBA concept since it was launched by BirdLife International (then ICBP) in 1979 and examine some of the characteristics of the resulting inventory. Over 13,000 global and regional IBAs have so far been identified and documented in terrestrial, freshwater and marine ecosystems in almost all of the world’s countries and territories, making this the largest global network of sites of significance for biodiversity. IBAs have been identified using standardised, data-driven criteria that have been developed and applied at global and regional levels. These criteria capture multiple dimensions of a site’s significance for avian biodiversity and relate to populations of globally threatened species (68.6% of the 10,746 IBAs that meet global criteria), restricted-range species (25.4%), biome-restricted species (27.5%) and congregatory species (50.3%); many global IBAs (52.7%) trigger two or more of these criteria. IBAs range in size from < 1 km2 to over 300,000 km2 and have an approximately log-normal size distribution (median = 125.0 km2, mean = 1,202.6 km2). They cover approximately 6.7% of the terrestrial, 1.6% of the marine and 3.1% of the total surface area of the Earth. The launch in 2016 of the KBA Global Standard, which aims to identify, document and conserve sites that contribute to the global persistence of wider biodiversity, and whose criteria for site identification build on those developed for IBAs, is a logical evolution of the IBA concept. The role of IBAs in conservation planning, policy and practice is reviewed elsewhere. Future technical priorities for the IBA initiative include completion of the global inventory, particularly in the marine environment, keeping the dataset up to date, and improving the systematic monitoring of these sites.
Migration was a key social process contributing to the creation of the ‘Chaco World’ between AD 800 and 1200. Dynamic social network analysis allows for evaluation of several migration scenarios, and demonstrates that Chaco’s earliest ninth-century networks show interaction with areas to the west and south, rather than migration to the Canyon from the Northern San Juan. By the late eleventh century, Chaco Canyon was tied strongly to the Middle and Northern San Juan, while a twelfth-century retraction of networks separated the Northern and Southern San Juan areas prior to regional depopulation. Understanding Chaco migration is important for comprehending both its uniqueness in U.S. Southwest archaeology and for comparison with other case studies worldwide.
Significant experimental evidence supports fat as a taste modality; however, the associated peripheral mechanisms are not well established. Several candidate taste receptors have been identified, but their expression pattern and potential functions in human fungiform papillae remain unknown. The aim of this study is to identify the fat taste candidate receptors and ion channels that were expressed in human fungiform taste buds and their association with oral sensory of fatty acids. For the expression analysis, quantitative RT-PCR (qRT-PCR) from RNA extracted from human fungiform papillae samples was used to determine the expression of candidate fatty acid receptors and ion channels. Western blotting analysis was used to confirm the presence of the proteins in fungiform papillae. Immunohistochemistry analysis was used to localise the expressed receptors or ion channels in the taste buds of fungiform papillae. The correlation study was analysed between the expression level of the expressed fat taste receptors or ion channels indicated by qRT-PCR and fat taste threshold, liking of fatty food and fat intake. As a result, qRT-PCR and western blotting indicated that mRNA and protein of CD36, FFAR4, FFAR2, GPR84 and delayed rectifying K+ channels are expressed in human fungiform taste buds. The expression level of CD36 was associated with the liking difference score (R −0·567, β=−0·04, P=0·04) between high-fat and low-fat food and FFAR2 was associated with total fat intake (ρ=−0·535, β=−0·01, P=0·003) and saturated fat intake (ρ=−0·641, β=−0·02, P=0·008).
Malignant gliomas (MG) are highly invasive and aggressive brain tumors. Despite the current standard of care, the prognosis for patients with MG is abysmal– highlighting the need for novel, more effective treatment options to combat this aggressive disease. Oncolytic virus (OV) therapy is an advancing treatment option that harnesses tumor-selective viruses to kill cancer cells while simultaneously facilitating a systemic anti-tumor immune response. Many studies have noted synergistic effects when OV’s are combined with radiotherapy in preclinical cancer models, warranting further investigation of this multi-modal approach. Image-guided radiotherapy (IGRT) uses computer-modulated imaging techniques to precisely deliver ionizing radiation to treat cancer. Despite the precision IGRT offers, cancer cells can still be ‘missed’ due to tumor microextensions or radioresistant cell populations– such as glioma stem cells or therapy-induced senescent cancer cells –and may contribute to recurrence or progression. Here we propose to combine our mCherry-tagged mutant vaccinia virus (deltaF4L-deltaJ2R-mCherry), which exhibits tumor-selectivity due to mutations in key viral nucleotide biosynthesis genes, with IGRT executed using state-of-the-art Small Animal Radiation Research Platform (SARRP) technology. We hypothesize that combining deltaF4L-deltaJ2R-mCherry with IGRT will produce better tumor control than either modality alone, by generating additive or synergistic effects in which IGRT destroys the majority of the tumor mass while our OV seeks out and targets any remaining cancer cells that have been missed or are resistant to radiotherapy.
We present a multi-frequency study of the intermediate spiral SAB(r)bc type galaxy NGC 6744, using available data from the Chandra X-Ray telescope, radio continuum data from the Australia Telescope Compact Array and Murchison Widefield Array, and Wide-field Infrared Survey Explorer infrared observations. We identify 117 X-ray sources and 280 radio sources. Of these, we find nine sources in common between the X-ray and radio catalogues, one of which is a faint central black hole with a bolometric radio luminosity similar to the Milky Way’s central black hole. We classify 5 objects as supernova remnant (SNR) candidates, 2 objects as likely SNRs, 17 as H ii regions, 1 source as an AGN; the remaining 255 radio sources are categorised as background objects and one X-ray source is classified as a foreground star. We find the star-formation rate (SFR) of NGC 6744 to be in the range 2.8–4.7 M⊙~yr − 1 signifying the galaxy is still actively forming stars. The specific SFR of NGC 6744 is greater than that of late-type spirals such as the Milky Way, but considerably less that that of a typical starburst galaxy.
Objective: To validate a case definition of multiple sclerosis (MS) using health administrative data and to provide the first province-wide estimates of MS incidence and prevalence for Saskatchewan, Canada. Methods: We used population-based health administrative data between January 1, 1996 and December 31, 2015 to identify individuals with MS using two potential case definitions: (1) ≥3 hospital, physician, or prescription claims (Marrie definition); (2) ≥1 hospitalization or ≥5 physician claims within 2 years (Canadian Chronic Disease Surveillance System [CCDSS] definition). We validated the case definitions using diagnoses from medical records (n=400) as the gold standard. Results: The Marrie definition had a sensitivity of 99.5% (95% confidence interval [CI] 92.3-99.2), specificity of 98.5% (95% CI 97.3-100.0), positive predictive value (PPV) of 99.5% (95% CI 97.2-100.0), and negative predictive value (NPV) of 97.5% (95% CI 94.4-99.2). The CCDSS definition had a sensitivity of 91.0% (95% CI 81.2-94.6), specificity of 99.0% (95% CI 96.4-99.9), PPV of 98.9% (95% CI 96.1-99.9), and NPV of 91.7% (95% CI 87.2-95.0). Using the more sensitive Marrie definition, the average annual adjusted incidence per 100,000 between 2001 and 2013 was 16.5 (95% CI 15.8-17.2), and the age- and sex-standardized prevalence of MS in Saskatchewan in 2013 was 313.6 per 100,000 (95% CI 303.0-324.3). Over the study period, incidence remained stable while prevalence increased slightly. Conclusion: We confirm Saskatchewan has one of the highest rates of MS in the world. Similar to other regions in Canada, incidence has remained stable while prevalence has gradually increased.
Thalénite-(Y), ideally Y3Si3O10F, is a heavy-rare-earth-rich silicate phase occurring in granite pegmatites that may help to illustrate rare-earth element (REE) chemistry and behaviour in natural systems. The crystal structure and mineral chemistry of thalénite-(Y) were analysed by electron microprobe analysis, X-ray diffraction and micro-Raman spectroscopy from a new locality in the peralkaline granite of the Golden Horn batholith, Okanogan County, Washington State, USA, in comparison with new analyses from the White Cloud pegmatite in the Pikes Peak batholith, Colorado, USA. The Golden Horn thalénite-(Y) occurs as late-stage sub-millimetre euhedral bladed transparent crystals in small miarolitic cavities in an arfvedsonite-bearing biotite granite. It exhibits growth zoning with distinct heavy-rare-earth element (HREE) vs. light-rare-earth element (LREE) enriched zones. The White Cloud thalénite-(Y) occurs in two distinct anhedral and botryoidal crystal habits of mostly homogenous composition. In addition, minor secondary thalénite-(Y) is recognized by its distinct Yb-rich composition (up to 0.8 atoms per formula unit (apfu) Yb). Single-crystal X-ray diffraction analysis and structure refinement reveals Y-site ordering with preferential HREE occupation of Y2 vs. Y1 and Y3 REE sites. Chondrite normalization shows continuous enrichment of HREE in White Cloud thalénite-(Y), in contrast to Golden Horn thalénite-(Y) with a slight depletion of the heaviest REE (Tm, Yb and Lu). The results suggest a hydrothermal origin of the Golden Horn miarolitic thalénite-(Y), compared to a combination of both primary magmatic followed by hydrothermal processes responsible for the multiple generations over a range of spatial scales in White Cloud thalénite-(Y).