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This chapter presents different spinal pathologies and explains how to examine each case. The specific clinical tests and clinical signs are pointed out for each case. Cases covered include kyphosis, ankylosing spondylosis, cervical myelopathy, rheumatoid spine and spondylolisthesis, amongst others.
Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.
Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation v. demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset.
PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (N = 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models.
Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence.
PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
There is increasing evidence of a strong association between sleep and mental health in both adolescents and adults. CBT for insomnia is being applied to good effect with adults with mental health difficulties but there are few studies examining its applicability to adolescents within mental health services.
We carried out a case series analysis (n = 15) looking at the feasibility, accessibility and impact of a low-intensity sleep intervention for young people (14–25 years) being seen by a secondary care Youth Mental Health team in the UK. The intervention was based on cognitive behavioural therapy for insomnia (CBTi) and acceptance and commitment therapy (ACT) approaches and involved six individual sessions delivered on a weekly basis by a graduate psychologist. Routine outcome measures were used to monitor insomnia, psychological distress and functioning with assessments at baseline, session 3, session 6 and at 4 weeks after end of intervention. All participants scored in the clinical range for insomnia at the start of the study.
High uptake, attendance and measure completion rates were observed. Large effect sizes were observed for insomnia, psychological distress and functioning. Twelve of the fifteen participants (80%) no longer scored above threshold for insomnia at follow-up. All seven under-18s no longer met threshold for clinical ‘caseness’ on the Revised Child Anxiety and Depression Scale (RCADS) at follow-up.
The findings suggest that the intervention was well accepted by young people and feasible to apply within a secondary care setting. Strong effect sizes are encouraging but are probably inflated by the small sample size, uncontrolled design and unblinded assessments.
This chapter covers the process of performing hysteroscopy, paying close attention to optimising patient comfort and maximising the effectiveness of the procedure. Tips are provided for successfully inserting the device and visualising the entire uterine cavity. The possible settings for performing a hysteroscopic investigation are outlined, with suggestions as to which setting may suit an individual patient. Oral anticoagulants have changed in recent years and the effect they may have on patients attending hysteroscopy clinics is discussed, with advice about how to avoid and manage excessive vaginal bleeding.
Prospectively acquired Canadian cerebrospinal fluid samples were used to assess the performance characteristics of three ante-mortem tests commonly used to support diagnoses of Creutzfeldt–Jakob disease. The utility of the end-point quaking-induced conversion assay as a test for Creutzfeldt–Jakob disease diagnoses was compared to that of immunoassays designed to detect increased amounts of the surrogate markers 14-3-3γ and hTau. The positive predictive values of the end-point quaking-induced conversion, 14-3-3γ, and hTau tests conducted at the Prion Diseases Section of the Public Health Agency of Canada were 96%, 68%, and 66%, respectively.
We report on the successful demonstration of a 150 J nanosecond pulsed cryogenic gas cooled, diode-pumped multi-slab Yb:YAG laser operating at 1 Hz. To the best of our knowledge, this is the highest energy ever recorded for a diode-pumped laser system.
A simple Steinberg algebra associated to an ample Hausdorff groupoid G is algebraically purely infinite if and only if the characteristic functions of compact open subsets of the unit space are infinite idempotents. If a simple Steinberg algebra is algebraically purely infinite, then the reduced groupoid $C^*$-algebra $C^*_r(G)$ is simple and purely infinite. But the Steinberg algebra seems too small for the converse to hold. For this purpose we introduce an intermediate *-algebra B(G) constructed using corners $1_U C^*_r(G) 1_U$ for all compact open subsets U of the unit space of the groupoid. We then show that if G is minimal and effective, then B(G) is algebraically properly infinite if and only if $C^*_r(G)$ is purely infinite simple. We apply our results to the algebras of higher-rank graphs.
Between 2009 and 2013, the Fly on the Wall (FLY) leaked 58% of recommendation revisions with a median delay of 27 minutes relative to the IBES announcement time. We show that FLY improves price discovery, but leaked recommendations hamper brokers’ ability to offer price improvement on trades routed through them. Three major brokers sued FLY; using key court dates, we show significant wealth and real effects to the brokerage industry. Overall, the speed with which analyst recommendations are disseminated has led to more rapid price discovery at the expense of a decline in the scope of the sell-side research industry.
This paper highlights unique sites in Ladakh, India, investigated during our 2016 multidisciplinary pathfinding expedition to the region. We summarize our scientific findings and the site's potential to support science exploration, testing of new technologies and science protocols within the framework of astrobiology research. Ladakh has several accessible, diverse, pristine and extreme environments at very high altitudes (3000–5700 m above sea level). These sites include glacial passes, sand dunes, hot springs and saline lake shorelines with periglacial features. We report geological observations and environmental characteristics (of astrobiological significance) along with the development of regolith-landform maps for cold high passes. The effects of the diurnal water cycle on salt deliquescence were studied using the ExoMars Mission instrument mockup: HabitAbility: Brines, Irradiance and Temperature (HABIT). It recorded the existence of an interaction between the diurnal water cycle in the atmosphere and salts in the soil (which can serve as habitable liquid water reservoirs). Life detection assays were also tested to establish the best protocols for biomass measurements in brines, periglacial ice-mud and permafrost melt water environments in the Tso-Kar region. This campaign helped confirm the relevance of clays and brines as interest targets of research on Mars for biomarker preservation and life detection.
We have derived absolute proper motions of stars in the Galactic bulge region combining the VVV InfraRed Astrometric Catalogue (VIRAC) and Gaia. We use the proper motions to study the kinematic structure of the bulge both integrated along the line-of-sight and in magnitude intervals using red clump stars as standard candles. In parallel we compare to a made-to-measure barred dynamical model, folding in the VIRAC selection function, to understand and interpret the structures that we observe. The barred dynamical model, which contains a boxy/peanut bulge, and has a pattern speed of 37.5 kms−1 kpc−1, is able to reproduce all structures impressively well.
Haughton crater in the Canadian Arctic has been extensively used as a Mars (and lunar) analogue over the past 20 years. Here we report on small scale, dark, semi-seasonal slope streaks formed by melt water flowing down the crater walls that we observed during the Mars Society-sponsored M160 expedition to the F-MARS facility on the NW rim of the crater. The streaks are formed by biofilms colonizing snow melt flowing from semi-permanent snow patches in Haughton crater on Devon Island and elsewhere in the Canadian Arctic. These features superficially resemble the dark slope streaks and recurring slope lineae (RSL) observed on Mars and may serve as analogues for wet models for their formation and a contrast with dry formation models. Their significance to astrobiology and planetary science is three-fold: (1) as examples of dark recurring streaks known to be associated with water they provide a benchmark to compare with Martian slope streaks and RSL. (2) The melt streaks may have potential as astrobiological analogues for wet models of slope streaks and RSL. (3) They are natural laboratories to study planetary protection issues associated with robotic and astronaut exploration of potential water-related slope features on Mars.
Liquid water on Mars might be created by deliquescence of hygroscopic salts or by permafrost melts, both potentially forming saturated brines. Freezing point depression allows these heavy brines to remain liquid in the near-surface environment for extended periods, perhaps as eutectic solutions, at the lowest temperatures and highest salt concentrations where ices and precipitates do not form. Perchlorate and chlorate salts and iron sulphate form brines with low eutectic temperatures and may persist under Mars near-surface conditions, but are chemically harsh at high concentrations and were expected to be incompatible with life, while brines of common sulphate salts on Mars may be more suitable for microbial growth. Microbial growth in saturated brines also may be relevant beyond Mars, to the oceans of Ceres, Enceladus, Europa and Pluto. We have previously shown strong growth of salinotolerant bacteria in media containing 2M MgSO4 heptahydrate (~50% w/v) at 25°C. Here we extend those observations to bacterial isolates from Basque Lake, BC and Hot Lake, WA, that grow well in saturated MgSO4 medium (67%) at 25°C and in 50% MgSO4 medium at 4°C (56% would be saturated). Psychrotolerant, salinotolerant microbes isolated from Basque Lake soils included Halomonas and Marinococcus, which were identified by 16S rRNA gene sequencing and characterized phenetically. Eutectic liquid medium constituted by 43% MgSO4 at −4°C supported copious growth of these psychrotolerant Halomonas isolates, among others. Bacterial isolates also grew well at the eutectic for K chlorate (3% at −3°C). Survival and growth in eutectic solutions increases the possibility that microbes contaminating spacecraft pose a contamination risk to Mars. The cold brines of sulphate and (per)chlorate salts that may form at times on Mars through deliquescence or permafrost melt have now been demonstrated to be suitable microbial habitats, should appropriate nutrients be available and dormant cells become vegetative.
The Norfolk Youth Service was created in 2012 in response to calls to redesign mental health services to better meet the needs of young people. The new service model transcends traditional boundaries by creating a single, ‘youth friendly’ service for young people aged 14–25 years. The aim of this study was to investigate the effect of the transition to this new model on patterns of referral, acceptance and service use. We analysed routinely collected data on young people aged 14–25 years referred for secondary mental healthcare in Norfolk before and after implementation of the youth mental health service. The number of referrals, their age and gender, proportion of referrals accepted and average number of service contacts per referral by age pre- and post-implementation were compared.
Referrals increased by 68% following implementation of the new service model, but the proportion of referrals accepted fell by 27 percentage points. Before implementation of the youth service, there was a clear discrepancy between the peak age of referral and the age of those seen by services. Following implementation, service contacts were more equitable across ages, with no marked discontinuity at age 18 years.
Our findings suggest that the transformation of services may have succeeded in reducing the ‘cliff edge’ in access to mental health services at the transition to adulthood. However, the sharp rise in referrals and reduction in the proportion of referrals accepted highlights the importance of considering possible unintended consequences of new service models.
Surveys show a lack of trust in political actors and institutions across much of the democratic world. Populist politicians and parties attempt to capitalise on this political disaffection. Commentators worry about our current 'age of anti-politics'. Focusing on the United Kingdom, using responses to public opinion surveys alongside diaries and letters collected by Mass Observation, this book takes a long view of anti-politics going back to the 1940s. This historical perspective reveals how anti-politics has grown in scope and intensity over the last half-century. Such growth is explained by citizens' changing images of 'the good politician' and changing modes of political interaction between politicians and citizens. Current efforts to reform and improve democracy will benefit greatly from the new evidence and conceptual framework set out in this important study.