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The schizophrenia polygenic risk score (SCZ-PRS) is an emerging tool in psychiatry.
We aimed to evaluate the utility of SCZ-PRS in a young, transdiagnostic, clinical cohort.
SCZ-PRSs were calculated for young people who presented to early-intervention youth mental health clinics, including 158 patients of European ancestry, 113 of whom had longitudinal outcome data. We examined associations between SCZ-PRS and diagnosis, clinical stage and functioning at initial assessment, and new-onset psychotic disorder, clinical stage transition and functional course over time in contact with services.
Compared with a control group, patients had elevated PRSs for schizophrenia, bipolar disorder and depression, but not for any non-psychiatric phenotype (for example cardiovascular disease). Higher SCZ-PRSs were elevated in participants with psychotic, bipolar, depressive, anxiety and other disorders. At initial assessment, overall SCZ-PRSs were associated with psychotic disorder (odds ratio (OR) per s.d. increase in SCZ-PRS was 1.68, 95% CI 1.08–2.59, P = 0.020), but not assignment as clinical stage 2+ (i.e. discrete, persistent or recurrent disorder) (OR = 0.90, 95% CI 0.64–1.26, P = 0.53) or functioning (R = 0.03, P = 0.76). Longitudinally, overall SCZ-PRSs were not significantly associated with new-onset psychotic disorder (OR = 0.84, 95% CI 0.34–2.03, P = 0.69), clinical stage transition (OR = 1.02, 95% CI 0.70–1.48, P = 0.92) or persistent functional impairment (OR = 0.84, 95% CI 0.52–1.38, P = 0.50).
In this preliminary study, SCZ-PRSs were associated with psychotic disorder at initial assessment in a young, transdiagnostic, clinical cohort accessing early-intervention services. Larger clinical studies are needed to further evaluate the clinical utility of SCZ-PRSs, especially among individuals with high SCZ-PRS burden.
The ‘16Up’ study conducted at the QIMR Berghofer Medical Research Institute from January 2014 to December 2018 aimed to examine the physical and mental health of young Australian twins aged 16−18 years (N = 876; 371 twin pairs and 18 triplet sets). Measurements included online questionnaires covering physical and mental health as well as information and communication technology (ICT) use, actigraphy, sleep diaries and hair samples to determine cortisol concentrations. Study participants generally rated themselves as being in good physical (79%) and mental (73%) health and reported lower rates of psychological distress and exposure to alcohol, tobacco products or other substances than previously reported for this age group in the Australian population. Daily or near-daily online activity was almost universal among study participants, with no differences noted between males and females in terms of frequency or duration of internet access. Patterns of ICT use in this sample indicated that the respondents were more likely to use online information sources for researching physical health issues than for mental health or substance use issues, and that they generally reported partial levels of satisfaction with the mental health information they found online. This suggests that internet-based mental health resources can be readily accessed by adolescent Australians, and their computer literacy augurs well for future access to online health resources. In combination with other data collected as part of the ongoing Brisbane Longitudinal Twin Study, the 16Up project provides a valuable resource for the longitudinal investigation of genetic and environmental contributions to phenotypic variation in a variety of human traits.
Predictors of new-onset bipolar disorder (BD) or psychotic disorder (PD) have been proposed on the basis of retrospective or prospective studies of ‘at-risk’ cohorts. Few studies have compared concurrently or longitudinally factors associated with the onset of BD or PDs in youth presenting to early intervention services. We aimed to identify clinical predictors of the onset of full-threshold (FT) BD or PD in this population.
Multi-state Markov modelling was used to assess the relationships between baseline characteristics and the likelihood of the onset of FT BD or PD in youth (aged 12–30) presenting to mental health services.
Of 2330 individuals assessed longitudinally, 4.3% (n = 100) met criteria for new-onset FT BD and 2.2% (n = 51) met criteria for a new-onset FT PD. The emergence of FT BD was associated with older age, lower social and occupational functioning, mania-like experiences (MLE), suicide attempts, reduced incidence of physical illness, childhood-onset depression, and childhood-onset anxiety. The emergence of a PD was associated with older age, male sex, psychosis-like experiences (PLE), suicide attempts, stimulant use, and childhood-onset depression.
Identifying risk factors for the onset of either BD or PDs in young people presenting to early intervention services is assisted not only by the increased focus on MLE and PLE, but also by recognising the predictive significance of poorer social function, childhood-onset anxiety and mood disorders, and suicide attempts prior to the time of entry to services. Secondary prevention may be enhanced by greater attention to those risk factors that are modifiable or shared by both illness trajectories.
To institute facility-wide Kamishibai card (K-card) rounding for central venous catheter (CVC) maintenance bundle education and adherence and to evaluate its impact on bundle reliability and central-line–associated bloodstream infection (CLABSI) rates.
Quality improvement project.
Inpatient units at a large, academic freestanding children’s hospital.
Data for inpatients with a CVC in place for ≥1 day between November 1, 2017 and October 31, 2018 were included.
A K-card was developed based on 7 core elements in our CVC maintenance bundle. During monthly audits, auditors used the K-cards to ask bedside nurses standardized questions and to conduct medical record documentation reviews in real time. Adherence to every bundle element was required for the audit to be considered “adherent.” We recorded bundle reliability prospectively, and we compared reliability and CLABSI rates at baseline and 1 year after the intervention.
During the study period, 2,321 K-card audits were performed for 1,051 unique patients. Overall maintenance bundle reliability increased significantly from 43% at baseline to 78% at 12 months after implementation (P < .001). The hospital-wide CLABSI rate decreased from 1.35 during the 12-month baseline period to 1.17 during the 12-month intervention period, but the change was not statistically significant (incidence rate ratio [IRR], 0.87; 95% confidence interval [CI], 0.60–1.24; P = .41).
Hospital-wide CVC K-card rounding facilitated standardized data collection, discussion of reliability, and real-time feedback to nurses. Maintenance bundle reliability increased after implementation, accompanied by a nonsignificant decrease in the CLABSI rate.
Neurocognitive impairments robustly predict functional outcome. However, heterogeneity in neurocognition is common within diagnostic groups, and data-driven analyses reveal homogeneous neurocognitive subgroups cutting across diagnostic boundaries.
To determine whether data-driven neurocognitive subgroups of young people with emerging mental disorders are associated with 3-year functional course.
Model-based cluster analysis was applied to neurocognitive test scores across nine domains from 629 young people accessing mental health clinics. Cluster groups were compared on demographic, clinical and substance-use measures. Mixed-effects models explored associations between cluster-group membership and socio-occupational functioning (using the Social and Occupational Functioning Assessment Scale) over 3 years, adjusted for gender, premorbid IQ, level of education, depressive, positive, negative and manic symptoms, and diagnosis of a primary psychotic disorder.
Cluster analysis of neurocognitive test scores derived three subgroups described as ‘normal range’ (n = 243, 38.6%), ‘intermediate impairment’ (n = 252, 40.1%), and ‘global impairment’ (n = 134, 21.3%). The major mental disorder categories (depressive, anxiety, bipolar, psychotic and other) were represented in each neurocognitive subgroup. The global impairment subgroup had lower functioning for 3 years of follow-up; however, neither the global impairment (B = 0.26, 95% CI −0.67 to 1.20; P = 0.581) or intermediate impairment (B = 0.46, 95% CI −0.26 to 1.19; P = 0.211) subgroups differed from the normal range subgroup in their rate of change in functioning over time.
Neurocognitive impairment may follow a continuum of severity across the major syndrome-based mental disorders, with data-driven neurocognitive subgroups predictive of functional course. Of note, the global impairment subgroup had longstanding functional impairment despite continuing engagement with clinical services.
Morpho-Butterfly inspired lamella structures were fabricated to make a multivariable optical sensor for measuring percent level concentrations of H2 and CO in a high temperature, zero-O2 environment. The SiO2 and Si3N4 3D structures were covered with gold nanoparticles (AuNPs) and cerium IV dioxide (CeO2) and exposed to varying concentrations of H2 and CO at 300°C. Experiments with AuNP sizes with an average diameter of 11 ± 3 nm and 3 ± 0.5 nm (larger and small AuNPs, respectively) showed that the larger AuNPs had a stronger response to the same concentrations of H2 and CO with less CO saturation and baseline drift. Further testing in the presence of 1% hydrocarbons (HCs) as an interfering gas showed excellent response to up to 17% H2 and CO in a zero-O2 environment with changes in reflected intensity of -13.1 ± 0.4% for H2 and -5.8 ± 0.3% for CO. The presence of HCs did not induce any baseline drift, with the total amount of drift being less than 0.5% over 13 hours of testing at 300°C.
Megan M. Carpenter, Megan Carpenter is Dean of the University of New Hampshire School of Law. Her research interests include intellectual property, with a particular focus on entrepreneurship, branding, and the arts.
GREAT TECHNOLOGICAL DEVELOPMENTS create a universe. The invention of the escalator was, literally, groundbreaking. It expanded our concept of space and time— and, accordingly, redefined the possibilities for commerce.
For those within the intellectual property system, the escalator is famous for its association with the phenomenon of “trademark genericide.” Trademark genericide occurs when trademarks become so famous that they cease to identify the source of goods or services in the minds of consumers and instead become names for the goods themselves. “Escalator” is right up there with “aspirin,” “cellophane,” and “kitty litter” as an example of a brand that morphed into its product. And it's true that the intellectual property story of the escalator is, in part, how Charles Seeberger's brand of moving staircases grew to symbolize the thing itself. But the larger story is about the cultural phenomenon, an invention that transformed the way we interact with the world. How people move. How sales are made. How the built world is constructed. Before the escalator was invented, commerce and transportation were largely one-dimensional. Stairs and elevators were for the committed and purposeful, their limitations constraining vertical expansion, above and below ground. Stairs require patience and effort. Elevators have a unique, precise, and tightly constrained mission. The invention of the escalator changed everything: suddenly, a constant flow of people could ascend into the air, or descend to the depths. The escalator modified architecture itself, creating fluid transitions into spaces above and below. Now, in commerce and transportation, neither the sky nor the ground would be the limit.
The first conceptual articulation of an escalator was “An Improvement in Stairs,” described in an 1859 US patent issued to Nathan Ames. Ames was an inventor with several patents, including a railroad switch, aprintingpress, and a combination knife, fork, and spoon. Ames’ patent made claim over an endless belt of steps revolving around three mechanical wheels that could be powered by hand, weights, or steam.
This version of the moving stairway didn't gain much momentum, however, and was never built.
A new protocol has been devised for determining elastic properties of natural biocomposites in the form of bivalve shells under wet and dry conditions. Four-point bending on shell slices of Mytilus edulis, Ensis siliqua, and Pecten maximus give generally lower and more reliable values of Young’s modulus, E, than those in the literature from three-point bending, due to the more even distribution of strain. Finite element analysis of the prismatic microstructure of Pinna nobilis, obtained by X-ray tomography, shows that values of E ≈ 20 GPa can be understood in terms of the real microstructure containing a small proportion of organic matrix phase with E ≈ 1 GPa and a dominant proportion of calcite with E ≈ 90 GPa. Higher values of E obtained by nanoindentation give results which are biased toward the properties of the carbonate phase rather than of the biocomposite as a whole.
The chemical enrichment of the Universe is considerably affected by the contribution of cool evolved stars. We studied the O-rich star R Peg and the C-rich star V Oph, using respectively the VLTI/GRAVITY and VLTI/MIDI instruments. We interpret the data using grids of 1-D and 3-D dynamic model atmospheres.
A natural olivenite single crystal was submitted to in situ high-temperature single-crystal X-ray diffraction from room temperature (RT) to 500°C. Unit-cell parameters were measured at regular intervals of 25°C, and complete datasets collected at T = 25, 50, 100, 150, 200, 250, 300, 400 and 500°C. Evolution of unit-cell parameters and structure refinements indicates that olivenite undergoes a structural phase transition from P21/n to Pnnm at ~200°C, and eventually becomes isostructural with the other members of the olivenite-mineral group. Volume expansion with temperature is larger in the monoclinic phase – where it follows a non-linear trend – than in the orthorhombic one. Axial and volume expansion coefficients of the orthorhombic olivenite phase are positive and linear and similar to those of the other Cu-bearing member of the mineral family, namely libethenite, but rather different from those of the Zn-analogue arsenate adamite.
Distortion of Cu polyhedra is quite high in the olivenite monoclinic phase at RT and goes towards a relative regularization with increasing T until the phase transition occurs. In the orthorhombic phase, no significant variation of the polyhedral distortion parameters is observed with increasing temperature, and maximum expansion is along the b direction and governed by corner-sharing. Landau potential provides a good representation of the macroscopic changes associated with the phase transition, coupling between the strains and the order parameter is responsible for the nearly tricritical character of the transition.
Classroom simulations have become an increasingly popular instructional method in political science to increase student engagement, interest, and learning. This article describes a simulation designed to teach students about the complexities of campaign-finance systems, particularly disclosure requirements. In the simulation, students work in groups to convince others how to vote on a pending ballot measure. After spending more than $200 on materials, groups then must register as ballot-issue committees and comply with state campaign-finance laws, including tracking contributions and expenditures and completing all required forms. The simulation ends with a debrief. Results from several years of debriefs are presented to discuss how students perceive the complexities of campaign-finance laws. Dominant themes include surprise by students in the complexities of these laws and the effects they have on political speech and association.
Firefighters represent an important population for understanding the consequences of exposure to potentially traumatic stressors.
The researchers were interested in the effects of pre-employment disaster exposure on firefighter recruits’ depression and posttraumatic stress disorder (PTSD) symptoms during the first three years of fire service and hypothesized that: (1) disaster-exposed firefighters would have greater depression and PTSD symptoms than non-exposed overall; and (2) depression and PTSD symptoms would worsen over years in fire service in exposed firefighters, but not in their unexposed counterparts.
In a baseline interview, 35 male firefighter recruits from seven US cities reported lifetime exposure to natural disaster. These disaster-exposed male firefighter recruits were matched on age, city, and education with non-exposed recruits.
A generalized linear mixed model revealed a significant exposure×time interaction (ecoef =1.04; P<.001), such that depression symptoms increased with time for those with pre-employment disaster exposure only. This pattern persisted after controlling for social support from colleagues (ecoefficient=1.05; P<.001), social support from families (ecoefficient=1.04; P=.001), and on-the-job trauma exposure (coefficient=0.06; ecoefficient=1.11; P<.001). Posttraumatic stress disorder symptoms did not vary significantly between exposure groups at baseline (P=.61).
Depression symptoms increased with time for those with pre-employment disaster exposure only, even after controlling for social support. Posttraumatic stress disorder symptoms did not vary between exposure groups.
PenningtonML, CarpenterTP, SynettSJ, TorresVA, TeagueJ, MorissetteSB, KnightJ, KamholzBW, KeaneTM, ZimeringRT, GulliverSB. The Influence of Exposure to Natural Disasters on Depression and PTSD Symptoms among Firefighters. Prehosp Disaster Med. 2018;33(1):102–108.
Transparency requires more than disclosure of data. It requires a mechanism and policy for conveying information to the public. In order for the aims of the excellent report of the FDA Transparency Working Group to be realized, a publicity initiative will need to accompany the plan of action. The FDA will need to actively convey information about the evidence concerning benefit-risk profiles of drugs, sometimes pointing out misleading claims by manufacturers or sponsors. In other cases, the FDA will need to make available its procedures, including possible conflicts of interest, not only in drug approval, but also in guidance documents and in rulemaking. Transparency as a process of letting the public see into the agency should be accompanied by a proactive strategy of distributing information about the products regulated by the agency.
The killing of Cecil the Lion in July 2015 generated considerable media attention worldwide. We measured public interest in Cecil's death to examine the degree to which this high-profile incident represented the type of focusing event that public policy scholars often emphasize as being important for triggering policy change. Finding that public interest in lion conservation spiked in the weeks immediately following the incident, we then analysed whether this focusing event led to policy changes to restrict trophy hunting in eight countries (USA, Spain, France, Russia, Canada, South Africa, Germany and Mexico) that most frequently import lion Panthera leo trophies. The surge in public attention seems to have had only a limited impact on the adoption of significant new policy, although it may have hastened changes in some countries.
OBJECTIVES/SPECIFIC AIMS: Middle ear volume (MEV) is a clinically relevant parameter in the treatment of many common conditions including otitis media, tinnitus, and conductive hearing loss. A growing number of studies have shifted from using tympanometry to 3-dimensional volume reconstruction (3DVR) to calculate MEV; however, MEV values between these methodologies have never before been directly compared. Here, our objective is to characterize agreement between MEV measurement methods across disease states and middle ear sizes. METHODS/STUDY POPULATION: Middle ears were identified from 36 patients ranging 18–89 years of age who underwent tympanometry testing during preoperative workup for tympanic membrane (TM) perforation, up to 1 month prior to a standard-of-care temporal bone computed tomography (CT) between October 15, 2005 and October 15, 2015. MEV values calculated by both tympanometry and 3DVR were analyzed for agreement using Bland and Altman plots. A correction factor was calculated where ear canal volumes were available for contralateral middle ears without TM perforation (n=12), and was applied to a second Bland and Altman plot in the corresponding patient subgroup. MEV agreement was characterized across MEV quartiles (1=smallest; 4=largest) and across increasing states of middle ear disease using Kruskal-Wallis and Wilcoxon testing with Bonferonni correction. RESULTS/ANTICIPATED RESULTS: A Bland Altman plot demonstrated significant disagreement of MEV differences as compared to a priori clinical thresholds. Absolute MEV difference was significantly greater in the average MEV fourth to first quartile (p=0.0024), fourth to second quartile (p=0.0024), third to first quartile (p=0.0048), and third to second quartile (p=0.048). Absolute MEV difference was not significantly different across varying states of middle ear disease (p=0.44). DISCUSSION/SIGNIFICANCE OF IMPACT: Statistically evident and clinically significant disagreement was demonstrated across tympanometric and 3DVR MEV estimates. This lack of agreement was most pronounced at higher average MEV and was persistent yet not appreciably different across varying severities of middle ear disease. These findings may limit the generalizability of studies of the middle ear that differ in MEV estimation methodology, particularly in pathophysiological states where MEV is increased.
We present results from a multiwavelength study of the blazar PKS 1954–388 at radio, UV, X-ray, and gamma-ray energies. A RadioAstron observation at 1.66 GHz in June 2012 resulted in the detection of interferometric fringes on baselines of 6.2 Earth-diameters. This suggests a source frame brightness temperature of greater than 2 × 1012 K, well in excess of both equipartition and inverse Compton limits and implying the existence of Doppler boosting in the core. An 8.4-GHz TANAMI VLBI image, made less than a month after the RadioAstron observations, is consistent with a previously reported superluminal motion for a jet component. Flux density monitoring with the Australia Telescope Compact Array confirms previous evidence for long-term variability that increases with observing frequency. A search for more rapid variability revealed no evidence for significant day-scale flux density variation. The ATCA light-curve reveals a strong radio flare beginning in late 2013, which peaks higher, and earlier, at higher frequencies. Comparison with the Fermi gamma-ray light-curve indicates this followed ~ 9 months after the start of a prolonged gamma-ray high-state—a radio lag comparable to that seen in other blazars. The multiwavelength data are combined to derive a Spectral Energy Distribution, which is fitted by a one-zone synchrotron-self-Compton (SSC) model with the addition of external Compton (EC) emission.