To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
As demonstrated by neuroimaging data, the human brain contains systems that control responses to threat. The revised Reinforcement Sensitivity Theory of personality predicts that individual differences in the reactivity of these brain systems produce anxiety and fear-related personality traits. Here we discuss some of the challenges in testing this theory and, as an example, present a pilot study that aimed to dissociate brain activity during pursuit by threat and goal conflict. We did this by translating the Mouse Defense Test Battery for human fMRI use. In this version, dubbed the Joystick Operated Runway Task (JORT), we repeatedly exposed 24 participants to pursuit and goal conflict, with and without threat of electric shock. The runway design of JORT allowed the effect of threat distance on brain activation to be evaluated independently of context. Goal conflict plus threat of electric shock caused deactivation in a network of brain areas that included the fusiform and middle temporal gyri, as well as the default mode network core, including medial frontal regions, precuneus and posterior cingulate gyrus, and laterally the inferior parietal and angular gyri. Consistent with earlier research, we also found that imminent threat activated the midbrain and that this effect was significantly stronger during the simple pursuit condition than during goal conflict. Also consistent with earlier research, we found significantly greater hippocampal activation during goal conflict than pursuit by imminent threat. In conclusion, our results contribute knowledge to theories linking anxiety disorders to altered functioning in defensive brain systems and also highlight challenges in this research domain.
ALKS 3831, currently under development for the treatment of schizophrenia, is composed of olanzapine (OLZ) and a fixed dose of 10mg of samidorphan. In a Phase 2 study in stable patients with schizophrenia, ALKS 3831mitigated OLZ-associated weight gain while maintaining an antipsychotic efficacy profile similar to OLZ.
To assess the efficacy and safety of ALKS 3831 in patients with acute exacerbation of schizophrenia.
This was a Phase 3, 4-week, randomized, double-blind, active and placebo (PBO)-controlled study of ALKS 3831 in patients with acute exacerbation of schizophrenia (ClinicalTrials.gov: NCT02634346). Eligible patients (N=403) were randomized 1:1:1 to receive ALKS 3831, OLZ, or PBO. Patients were treated in an inpatient setting for the first 2weeks of the study and could be treated as inpatients or outpatients for the remaining 2weeks. Patients were excluded if they received OLZ within 6months prior to screening. Antipsychotic efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression–Severity (CGI-S) and CGI–Improvement (CGI-I) scales. Safety and tolerability were assessed as adverse events (AEs).
Of 401 randomized patients who received ALKS 3831, OLZ, or PBO, 91%, 89%, and 83% of patients, respectively, completed treatment. The most common reason for discontinuation was withdrawal by patient (6% in both the ALKS 3831and PBO groups, and 7% in the OLZ group). Baseline characteristics were generally similar between groups; however, baseline mean body mass index was higher in the OLZ group than in the ALKS 3831 group. Baseline mean±standard deviation scores were 101.7±11.9 for PANSS total score and 5.1±0.7 for CGI-S scale score. The mean OLZ dose was 18.4mg/day in both active treatment arms. Least squares (LS) mean difference±standard error (SE) vs PBO from baseline to Week 4 in PANSS total score was –6.4±1.8 (P<.001) for the ALKS 3831 group and –5.3±1.8 (P=.004) for the OLZ group. LS mean difference±SE vs PBO from baseline to Week 4 in CGI-S scale score was −0.4±0.1 (P=.002) for the ALKS3831 group and −0.4±0.1 (P<.001) for the OLZ group. The percentage of patients with improvement in PANSS response (≥30% from baseline) at Week 4 was 60%, 54%, and 38% in the ALKS 3831, OLZ, and PBO groups, respectively. The percentage of patients with an improvement in CGI-I scale response (score of ≤2) at Week 4 was 58%, 51%, and 33% in the ALKS 3831, OLZ, and PBO groups, respectively. Discontinuation due to AEs was low in all groups. Common AEs (≥5% in any group) included weight gain, somnolence, dry mouth, anxiety, headache, and schizophrenia.
Treatment with ALKS 3831 was more effective than PBO, as measured by the PANSS and CGI-S scale, and its antipsychotic efficacy was similar to the active control OLZ. The safety profile of ALKS 3831 was similar toOLZ.
Funding Acknowledgements: This study was funded by Alkermes, Inc.
Antarctic silverfish (Pleuragramma antarctica Boulenger) are a keystone species in the Ross Sea. Silverfish eggs and larvae are abundant during spring amongst the sub-surface platelet ice in Terra Nova Bay. It is not known whether the eggs are spawned elsewhere and accumulate under the ice or whether there is mass migration of silverfish to coastal spawning sites in winter. To test the latter hypothesis, an upward-looking 67 kHz echo sounder was moored in Terra Nova Bay to observe potential silverfish migration. The echo sounder was deployed at 380 m in a seabed depth of 550 m and ran for 210 days from 15 May until 11 December 2015. Acoustic reflections consistent with silverfish were observed at depths of 230–380 m during 9–22 September. This timing is consistent with the presence of eggs typically observed in October. Adult silverfish were also detected with an echo sounder and camera deployed through the ice in McMurdo Sound on 10 November 2015. Juvenile silverfish, but not adults, were observed through the ice in Terra Nova Bay during 11–16 November 2017. This paper provides a proof of concept, showing that innovative use of acoustics may help fill important observation gaps in the life history of silverfish.
New excavations at the Jebel Moya cemetery in Sudan reveal extensive evidence for Meroitic-era occupation, providing valuable data on contemporaneous diet, migration, exchange and population composition in sub-Saharan Africa.
While research on conspiracy theories and those who believe them has recently undergone a renaissance, there still exists a great deal of uncertainty about the measurement of conspiratorial beliefs and orientations, and the consequences of a conspiratorial mindset for expressly political attitudes and behaviors. We first demonstrate, using data from the 2012 American National Election Study, that beliefs in a variety of specific conspiracy theories are simultaneously, but differentially, the product of both a general tendency toward conspiratorial thinking and left/right political orientations. Next, we employ unique data including a general measure of conspiratorial thinking to explore the predictors of specific conspiracy beliefs. We find that partisan and ideological self-identifications are more important than any other variable in predicting ‘birther’ beliefs, while conspiratorial thinking is most important in predicting conspiracy beliefs about the assassination of John F. Kennedy and the 9/11 terrorist attacks.
The deep subsurface of other planetary bodies is of special interest for robotic and human exploration. The subsurface provides access to planetary interior processes, thus yielding insights into planetary formation and evolution. On Mars, the subsurface might harbour the most habitable conditions. In the context of human exploration, the subsurface can provide refugia for habitation from extreme surface conditions. We describe the fifth Mine Analogue Research (MINAR 5) programme at 1 km depth in the Boulby Mine, UK in collaboration with Spaceward Bound NASA and the Kalam Centre, India, to test instruments and methods for the robotic and human exploration of deep environments on the Moon and Mars. The geological context in Permian evaporites provides an analogue to evaporitic materials on other planetary bodies such as Mars. A wide range of sample acquisition instruments (NASA drills, Small Planetary Impulse Tool (SPLIT) robotic hammer, universal sampling bags), analytical instruments (Raman spectroscopy, Close-Up Imager, Minion DNA sequencing technology, methane stable isotope analysis, biomolecule and metabolic life detection instruments) and environmental monitoring equipment (passive air particle sampler, particle detectors and environmental monitoring equipment) was deployed in an integrated campaign. Investigations included studying the geochemical signatures of chloride and sulphate evaporitic minerals, testing methods for life detection and planetary protection around human-tended operations, and investigations on the radiation environment of the deep subsurface. The MINAR analogue activity occurs in an active mine, showing how the development of space exploration technology can be used to contribute to addressing immediate Earth-based challenges. During the campaign, in collaboration with European Space Agency (ESA), MINAR was used for astronaut familiarization with future exploration tools and techniques. The campaign was used to develop primary and secondary school and primary to secondary transition curriculum materials on-site during the campaign which was focused on a classroom extra vehicular activity simulation.
Children with chronic illness often experience difficulties at school, yet little is known about the impact of the child's illness on siblings’ school experiences. This study investigated parents’ perceptions of siblings’ school experiences and school support. We conducted semi-structured telephone interviews with 27 parents of children with a chronic illness who had a sibling or siblings (4–25 years), representing the experiences of 31 siblings. Interviews were audio-recorded, transcribed, and analysed using content analysis. Parents believed that 14 of 31 (45.2%) siblings had school difficulties related to the ill child, such as increased anxiety or stress at school, lack of attention from teachers, and changes in behaviour as a result of increased carer responsibilities. Parents identified increased absenteeism due to the ill child's hospitalisation and the impact of parent absences on sibling school functioning. Parents described general and psychological support from the school, and the importance of monitoring the sibling at school and focusing on their unique needs. Overall, our findings suggest the need for a school-based sibling support model that combines psycho-education for siblings and school personnel, individualised sibling psychological support, and shared school and parent responsibility in normalising the sibling experience and providing consistent support.
The growth of Ag on ZnO was modeled using a reactive force field potential and a combination of molecular dynamics and adaptive kinetic Monte Carlo (AKMC) simulations. An adaptive lattice-based AKMC model is described as a method of extending timescales and length scales that can be simulated. Reusing previously found transitions to reduce computational time is discussed for both the lattice and off-lattice AKMC approaches. With these methods, growth of over 1 monolayer’s worth of Ag is simulated corresponding to a real deposition time of up to 0.1 s. The results show that the deposited silver aggregates on the surface through mainly single atom moves with few concerted motions. Initially silver adatoms do not agglomerate and the energy barriers for silver dimers to form are larger than for them to break apart. The first layer of silver grows as a series of connected regions rather than forming well-defined centro-symmetric islands.
The correlation between ideology and partisanship in the mass public has increased in recent decades amid a climate of persistent and growing elite polarization. Given that core values shape subsequent political predispositions, as well as the demonstrated asymmetry of elite polarization, this article hypothesizes that egalitarianism and moral traditionalism moderate the relationship between ideology and partisanship in that the latter relationship will have increased over time only among individuals who maintain conservative value orientations. An analysis of pooled American National Election Studies surveys from 1988 to 2012 supports this hypothesis. The results enhance scholarly understanding of the role of core values in shaping mass belief systems and testify to the asymmetric nature and mass public reception of elite cues among liberals and conservatives.
Collections of disaggregated snow particles were examined in a temperature-controlled microscope stage. In addition to necks that appeared to sinter in a manner congruent with the two-particle model, there also appeared unanticipated dendritic growth, which developed on some grains and grew into the pore space. These branches developed preferentially only on part of, and in different directions on, individual grains. Some of these grew enough to join with adjacent grains that were in close proximity but not initially in contact, while the surface of the adjacent grains did not show measurable growth or loss. Growth orientation is hypothesized to be due to crystal habit dependence on temperature. Columnar growth was observed at –5˚C and plate-like at –15˚C. The random growth orientation is in contrast to observed source and sink development aligned with a temperature gradient imposed using a gradient stage. In this case, a source-to-sink directionality across the pore was apparent in which faceted crystals grew at the expense of neighboring source grains. The process of mechanically disaggregating snow produces numerous broken shards and sharp-edged fracture surfaces. We hypothesize that it is the sublimation of these high-surface-energy regions that provides the excess vapor to facilitate the diffusion-limited dendritic growth observed in this ‘equitemperature’, mechanically processed snow.
To determine the scope, source, and mode of transmission of a multifacility outbreak of extensively drug-resistant (XDR) Acinetobacter baumannii.
SETTING AND PARTICIPANTS
Residents and patients in skilled nursing facilities, long-term acute-care hospital, and acute-care hospitals.
A case was defined as the incident isolate from clinical or surveillance cultures of XDR Acinetobacter baumannii resistant to imipenem or meropenem and nonsusceptible to all but 1 or 2 antibiotic classes in a patient in an Oregon healthcare facility during January 2012–December 2014. We queried clinical laboratories, reviewed medical records, oversaw patient and environmental surveillance surveys at 2 facilities, and recommended interventions. Pulsed-field gel electrophoresis (PFGE) and molecular analysis were performed.
We identified 21 cases, highly related by PFGE or healthcare facility exposure. Overall, 17 patients (81%) were admitted to either long-term acute-care hospital A (n=8), or skilled nursing facility A (n=8), or both (n=1) prior to XDR A. baumannii isolation. Interfacility communication of patient or resident XDR status was not performed during transfer between facilities. The rare plasmid-encoded carbapenemase gene blaOXA-237 was present in 16 outbreak isolates. Contact precautions, chlorhexidine baths, enhanced environmental cleaning, and interfacility communication were implemented for cases to halt transmission.
Interfacility transmission of XDR A. baumannii carrying the rare blaOXA-237 was facilitated by transfer of affected patients without communication to receiving facilities.
Remotely sensed derivation of sea-ice thickness requires sea·ice density. Sea-ice density was estimated with three techniques during the second Sea Ice Physics and Ecosystem eXperimett (SIPEX-II, September-November 2012, East Antarctica). The sea ice was first-year highly deformed, mean thicknsss 1.2 m with layers, consistent with rafting, and 6-7/10 columnar ice and 3/10 granular ice. Ice density was found to be lower than values (900-920 kg m−3 used previously to derive ice thickness,, with columnar ice mean density of 870 kg m− 3. At two different ice stations the mean density of the ice was 800 kg m–3, the lower density reflecting a high percentage of porous granular ice at the second station. Error estimates for mass/volume and liquid/solid water methods are presented. With 0.1 m long, 0.1 m core samples, the error on individual density estimates is 28 kg m-3. Errors are larger for smaller machined blocks. Errors increase to 46 kg m-3 if the liquid/solid volume method is used. The mass/vouume method has a low bias due to brine drainage of at least 5%. Bulk densities estimated from ice and snow measurements along 100 m transects were high, and likely unrealistic as the assumption of isostatcc balance is not suitable over these length scales in deformed ice.
Chemotherapy is often administered in openly designed hospital wards, where the possibility of patient–patient social influence on health exists. Previous research found that social relationships influence cancer patient's health; however, we have yet to understand social influence among patients receiving chemotherapy in the hospital. We investigate the influence of co-presence in a chemotherapy ward. We use data on 4,691 cancer patients undergoing chemotherapy in Oxfordshire, United Kingdom who average 59.8 years of age, and 44% are Male. We construct a network of patients where edges exist when patients are co-present in the ward, weighted by both patients' time in the ward. Social influence is based on total weighted co-presence with focal patients' immediate neighbors, considering neighbors' 5-year mortality. Generalized estimating equations evaluated the effect of neighbors' 5-year mortality on focal patient's 5-year mortality. Each 1,000-unit increase in weighted co-presence with a patient who dies within 5 years increases a patient's mortality odds by 42% (β = 0.357, CI:0.204,0.510). Each 1,000-unit increase in co-presence with a patient surviving 5 years reduces a patient's odds of dying by 30% (β =−0.344, CI:−0.538,0.149). Our results suggest that social influence occurs in chemotherapy wards, and thus may need to be considered in chemotherapy delivery.
Dual sequential external defibrillation (DSED) is the process of near simultaneous discharge of two defibrillators with differing pad placement to terminate refractory arrhythmias. Previously used in the electrophysiology suite, this technique has recently been used in the emergency department and prehospital setting for out-of-hospital cardiac arrest (OHCA). We present a case of successful DSED in the emergency department with neurologically intact survival to hospital discharge after refractory ventricular fibrillation (RVF) and review the putative mechanisms of action of this technique.
This article describes a formal proof of the Kepler conjecture on dense sphere packings in a combination of the HOL Light and Isabelle proof assistants. This paper constitutes the official published account of the now completed Flyspeck project.
The molecular clouds in the Central Molecular Zone of our Galaxy (CMZ; inner ~200 pc) show systematically higher gas than dust temperatures (>50 K vs <30 K) in recent H2CO line and dust continuum surveys. This discrepancy is puzzling since gas and dust temperatures should become equal over short times at the high densities observed in these clouds. In deep H2CO(3–2) and (4–3) observations of seven clouds in the CMZ, we detected not only large temperature differences between the clouds but also large gradients within the clouds. Comparing the temperatures and the main H2CO lines at 218 and 291 GHz, we found a positive correlation between those two parameters, indicating that turbulence plays an important role in the heating of the gas. As a follow-up, we mapped the temperature tracers CH3CCH and CH3CN in these seven clouds to derive multiple temperature estimates and test the accuracy of high gas temperatures.
Motivated by recent advances in direct statistical simulation (DSS) of astrophysical phenomena such as out-of-equilibrium jets, we perform a direct numerical simulation (DNS) of the helical magnetorotational instability (HMRI) under the generalised quasilinear approximation (GQL). This approximation generalises the quasilinear approximation (QL) to include the self-consistent interaction of large-scale modes, interpolating between fully nonlinear DNS and QL DNS whilst still remaining formally linear in the small scales. In this paper we address whether GQL can more accurately describe low-order statistics of axisymmetric HMRI when compared with QL by performing DNS under various degrees of GQL approximation. We utilise various diagnostics, such as energy spectra in addition to first and second cumulants, for calculations performed for a range of Reynolds and Hartmann numbers (describing rotation and imposed magnetic field strength respectively). We find that GQL performs significantly better than QL in describing the statistics of the HMRI even when relatively few large-scale modes are kept in the formalism. We conclude that DSS based on GQL (GCE2) will be significantly more accurate than that based on QL (CE2).
We address the possibility that intelligent civilizations that destroy themselves could present signatures observable by humanity. Placing limits on the number of self-destroyed civilizations in the Milky Way has strong implications for the final three terms in Drake's Equation, and would allow us to identify which classes of solution to Fermi's Paradox fit with the evidence (or lack thereof). Using the Earth as an example, we consider a variety of scenarios in which humans could extinguish their own technological civilization. Each scenario presents some form of observable signature that could be probed by astronomical campaigns to detect and characterize extrasolar planetary systems. Some observables are unlikely to be detected at interstellar distances, but some scenarios are likely to produce significant changes in atmospheric composition that could be detected serendipitously with next-generation telescopes. In some cases, the timing of the observation would prove crucial to detection, as the decay of signatures is rapid compared with humanity's communication lifetime. In others, the signatures persist on far longer timescales.