Book chapters will be unavailable on Saturday 24th August between 8am-12pm BST. This is for essential maintenance which will provide improved performance going forwards. Please accept our apologies for any inconvenience caused.
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.
Surface water can affect the properties of metal oxide nanoparticles. Investigations on several systems revealed that nanoparticles have different thermodynamic properties than their bulk counterparts due to adsorbed water on their surfaces. Some thermodynamically metastable phases of bulk metal oxides become stable when reduced to the nanoscale, partially due to interactions between high energy surfaces and surface water. Water adsorption microcalorimetry and high-temperature oxide melt solution calorimetry, low-temperature specific heat calorimetry, and inelastic neutron scattering are used to understand the interactions of surface water with metal oxide nanoparticles. Computational methods, such as molecular dynamics simulations and density functional theory calculations, have been used to study these interactions. Investigations on titania, cassiterite, and alumina illustrate the insights gained by these measurements. The energetics of water on metal oxide surfaces are different from those of either liquid water or hexagonal ice, and there is substantial variation in water interactions on different metal oxide surfaces.
To report functional recovery, symptomatic remission, and sustained symptomatic remission rates after treatment with aripiprazole once-monthly 400mg (AOM 400) administered every 4weeks for up to 52weeks as maintenance treatment in a mixed cohort of AOM 400 naïve (de novo) and experienced adults (rollover) with bipolar I disorder (BP-I).
This open-label study (NCT01710709) enrolled de novo patients with a diagnosis of BP-I and ≥1 previous manic or mixed episode and rollover patients who completed a randomized, double-blind, placebo-controlled study assessing the efficacy and safety of AOM 400 (NCT01567527). Efficacy was assessed by mean changes from baseline in Young-Mania Rating Scale (YMRS), Montgomery-Asberg Depressive Rating Scale (MADRS), and Clinical Global Impression- Bipolar Version-Severity of Illness (CGI-BP-S) scores. Sustained functional recovery was defined as a total score of ≤11 on the Functioning Assessment Short Test (FAST) for ≥8 consecutive weeks. Remission was defined as YMRS and MADRS total scores ≤12, and sustained remission was defined as meeting criteria for remission for 8 consecutive weeks. The study included a screening phase (6weeks) for de novo patients, an oral aripiprazole conversion phase (4–6weeks), an oral stabilization phase (4–12weeks), and an AOM 400 maintenance phase (up to 52weeks). Rollover patients entered directly into the AOM 400 maintenance phase.
A total of 464 subjects entered the maintenance phase and 63% (291/464) completed the trial. Of patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. The most frequent reasons for discontinuation were withdrawal of consent (11%) and adverse events (AEs) (10%). Weight increase (1.5%, 7/464) and BP-I (0.9%, 4/464) were the most common reasons for discontinuation due to AEs. Improvements in mean YMRS, MADRS, CGI-BP-S, and FAST scores achieved in previous phases were maintained over 52weeks. Treatment-emergent AEs experienced by >10% of the patients were akathisia (14.7%), weight increased (13.4%), nasopharyngitis (12.1%), and insomnia (11.0%). A high proportion of de novo patients met the criteria for symptomatic remission (87.2%, 328/376) and sustained remission (77%, 292/379) by last visit. Rollover patients’ remission rate remained stable (98.8%, 84/85) by last visit. Of the rollover patients, 35/85 (43%) and 35/116 (36%) of de novo subjects met the criteria for sustained functional recovery after study completion.
Patients treated with AOM 400 maintained symptomatic and functional stability for up to 52weeks. Importantly, more than one-third of patients achieved sustained functional recovery using a strict criterion. Overall, AOM 400 was safe and well tolerated in patients with BP-I. Results support AOM 400 as a viable once-monthlyoption for maintenance treatment of BP-I.
These data were previously presented at the 31st ECNP Congress, 2018, Barcelona,Spain.
Funding Acknowledgements: The study was supported by Otsuka Pharmaceutical Development & Commercialization, Inc.
Effective treatments for patients with high levels of negative symptoms of schizophrenia are lacking. Brexpiprazole is a serotonin–dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors, all with subnanomolar potency. Long-term treatment with brexpiprazole demonstrated broad efficacy across all five Marder factor groupings, including positive, negative, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression. This post-hoc analysis of long-term effects of brexpiprazole in patients with clinically relevant levels of negative symptoms of schizophrenia is based on data from two similarly designed short-term, placebo-controlled studies (Vector; NCT01396421 or Beacon; NCT01393613) for the brexpiprazole-treated patients who continued into an open-label extension study (Zenith; NCT01397786).
In the short-term studies, patients with acute schizophrenia were randomly assigned to fixed once-daily doses of brexpiprazole 0.25mg (Vector), 1mg (Beacon), 2mg , 4mg or placebo for 6weeks. The long-term study was an open-label, 52-week (amended to 26weeks), safety extension study with flexible-dose (1–4mg/day) brexpiprazole. The post-hoc analyses were performed on brexpiprazole-treated patients from the short-term studies who continued into the long-term study, and who had clinically relevant negative symptoms, defined as PANSS Factor Score for Negative Symptoms (PANSS-FSNS; N1, N2, N3, N4, G7, G16) of ≥24, and score of ≥4 on at least two of three core negative symptom PANSS items at randomization in the parent study. The outcome of the analysis included change from baseline to up to 58weeks in PANSS-FSNS, PANSS Total, and PSP. Safety was also assessed.
A total of 187 patients with clinically relevant levels of negative symptoms in the parent study rolled-over into the open-label extension study and were available for analysis. Eighty-three of these patients remained in the studies for 58weeks. Due to the study amendment, not all patients had the opportunity of complete 52weeks of open-label treatment. Baseline PANSS Total score was 104.4, while baseline PANSS-FSNS was 27.6 and baseline PSP Total score was 41.3. Mean change (SD) from baseline in PANSS-FSNS was –10.9 (5.0), and –44.2 (17.5) for PANSS Total score at Week 58. Change from baseline (SD) to Week 58 for PSP Total score was 24.8 (12.9) with improvement in all domains (socially useful activities, personal and social relationship, self-care, and disturbing and aggressive behaviors). The TEAEs reported ≥5% were schizophrenia (18.9%), insomnia (8.6%), weight increased (5.9%) and akathisia (5.9%).
This post-hoc analysis suggests that brexpiprazole has long-term effectiveness on negative symptoms and functioning in patients with schizophrenia and clinically relevant levels of negative symptoms.
Funding Acknowledgements: The study was funded by Otsuka Pharmaceutical Development & Commercialization Inc. and H. Lundbeck A/S
This research aims to explore the submerged landscapes of the Pilbara of western Australia, using predictive archaeological modelling, airborne LiDAR, marine acoustics, coring and diver survey. It includes excavation and geophysical investigation of a submerged shell midden in Denmark to establish guidelines for the underwater discovery of such sites elsewhere.
The increasingly negative mass balance of the Greenland ice sheet (GrIS) over the last ~25 years has been associated with enhanced surface melt and increased ice loss from marine-terminating outlet glaciers. Accelerated retreat during 2000–2010 was concentrated in the southeast and northwest sectors of the ice sheet; however, there was considerable spatial and temporal variability in the timing and magnitude of retreat both within and between these regions. This behaviour has yet to be quantified and compared for all glaciers in both regions. Furthermore, it is unclear whether retreat has continued after 2010 in the northwest, and whether the documented slowdown in the southeast post-2005 has been sustained. Here, we compare spatial and temporal patterns of frontal change in the northwest and southeast GrIS, for the period 2000–2015. Our results show near-ubiquitous retreat of outlet glaciers across both regions for the study period; however, the timing and magnitude of inter-annual frontal position change is largely asynchronous. We also find that since 2010, there is continued terminus retreat in the northwest, which contrasts with considerable inter-annual variability in the southeast. Analysis of the role of glacier-specific factors demonstrates that fjord and bed geometry are important controls on the timing and magnitude of glacier retreat.
The 2001/02 austral summer was the warmest summer on record in Taylor Valley, Antarctica, (∼78° S) since continuous records of temperature began in 1985. The highest stream-flows ever recorded in the Onyx River, Wright Valley, were also recorded that year (the record goes back to the 1969/70 austral summer). In early January 2002, a groundwater seep was observed flowing in the southwest portion of Taylor Valley. This flow has been named ‘Wormherder Creek’ (WHC) and represents an unusual event, probably occurring on a decadal time-scale. The physical characteristics of this feature suggest that it may have flowed at other times in the past. Other groundwater seeps, emanating from the north-facing slope of Taylor Valley, were also observed. Little work has been done previously on these very ephemeral seeps, and the source of water is unknown. These features, resembling recently described features on Mars, represent the melting of subsurface ice. The Martian features have been interpreted as groundwater seeps. In this paper we compare the chemistry of the WHC groundwater seep to that of the surrounding streams that flow every austral summer. The total dissolved solids content of WHC was ∼6 times greater than that of some nearby streams. The Na : Cl and SO4 : Cl ratios of the seep waters are higher than those of the streams, but the Mg : Cl and HCO3 : Cl ratios are lower, indicating different sources of solutes to the seeps compared to the streams. The enrichment of Na and SO4 relative to Cl may suggest significant dissolution of mirabilite within the previously unwetted soil. The proposed occurrence of abundant mirabilite in higher-elevation soils of the dry valley region agrees with geochemical models developed, but not tested, in the late 1970s. The geochemical data demonstrate that these seeps could be important in ‘rinsing’ the soils by dissolving and redistributing the long-term accumulation of salts, and perhaps improving habitat suitability for soil biota. The H4SiO4 concentration is 2–3 times greater in WHC than in the surrounding streams, indicating a large silicate-weathering component in the seep waters.
An rth-order extremal process Δ(r) = (Δ(r)t)t≥0 is a continuous-time analogue of the rth partial maximum sequence of a sequence of independent and identically distributed random variables. Studying maxima in continuous time gives rise to the notion of limiting properties of Δt(r) as t ↓ 0. Here we describe aspects of the small-time behaviour of Δ(r) by characterising its upper and lower classes relative to a nonstochastic nondecreasing function bt > 0 with limt↓bt = 0. We are then able to give an integral criterion for the almost sure relative stability of Δt(r) as t ↓ 0, r = 1, 2, . . ., or, equivalently, as it turns out, for the almost sure relative stability of Δt(1) as t ↓ 0.
In 1902 the University of Toronto joined American universities in celebrating the twenty-fifth anniversary of Johns Hopkins University. For the occasion, A. Bruce Macallum, Professor of Physiology and holder of the Johns Hopkins' Ph.D. (1888), wrote a short essay in commemoration of the American institution. He acknowledged the contemporary debt owed to Johns Hopkins and, by inference, the obligation of Toronto to its example:
But what the Johns Hopkins University lacked in age it made up in service to American scholarship and higher education. In those few years it completely reformed American university ideals, and it developed the higher university work on this continent to a degree that no other university succeeded in doing.
Physics forms the core of any Materials Science Programme at undergraduate level. Knowing the properties of materials is fundamental to developing and designing new materials and new applications for known materials.
“Physical Physics” is a physics education approach which is an innovative and promising instruction model that integrates physical activity with mechanics and material properties. It aims to significantly enhance the learning experience and to illustrate how physics works, while allowing students to be active participants and take ownership of the learning process. It has been successfully piloted with undergraduate students studying mechanics on a Games Development Programme. It is a structured guided learning approach which provides a scaffold for learners to develop their problem solving skills.
The objective of having applied physics on a programme is to introduce students to the mathematical world. Today students view the world through smart devices. By incorporating student recorded videos into the laboratory experience the student can visualise the mathematical world. Sitting in a classroom learning about material properties does not easily facilitate an understanding of mathematical equations as mapping to a physical reality. In order to get the students motivated and immersed in the real mathematical and physical world, an approach which makes them think about the cause and effect of actions is used. Incorporating physical action with physics enables students to assimilate knowledge and adopt an action problem solving approach to the physics concept. This is an integrated approach that requires synthesis of information from various sources in order to accomplish the task. As a transferable skill, this will ensure that the material scientists will be visionary in their approach to real life problems.
This book presents a wide range of new research on many aspects of naval strategy in the early modern and modern periods. Among the themes covered are the problems of naval manpower, the nature of naval leadership and naval officers, intelligence, naval training and education, and strategic thinking and planning. The book is notable for giving extensive consideration to navies other than those ofBritain, its empire and the United States. It explores a number of fascinating subjects including how financial difficulties frustrated the attempts by Louis XIV's ministers to build a strong navy; how the absence of centralised power in the Dutch Republic had important consequences for Dutch naval power; how Hitler's relationship with his admirals severely affected German naval strategy during the Second World War; and many more besides. The book is a Festschrift in honour of John B. Hattendorf, for more than thirty years Ernest J. King Professor of Maritime History at the US Naval War College and an influential figure in naval affairs worldwide.
N.A.M. Rodger is Senior Research Fellow at All Souls College, Oxford.
J. Ross Dancy is Assistant Professor of Military History at Sam Houston State University.
Benjamin Darnell is a D.Phil. candidate at New College, Oxford.
Evan Wilson is Caird Senior Research Fellow at the National Maritime Museum, Greenwich.
Contributors: Tim Benbow, Peter John Brobst, Jaap R. Bruijn, Olivier Chaline, J. Ross Dancy, Benjamin Darnell, James Goldrick, Agustín Guimerá, Paul Kennedy, Keizo Kitagawa, Roger Knight, Andrew D. Lambert, George C. Peden, Carla Rahn Phillips, Werner Rahn, Paul M. Ramsey, Duncan Redford, N.A.M. Rodger, Jakob Seerup, Matthew S. Seligmann, Geoffrey Till, Evan Wilson
The eastern bettong Bettongia gaimardi, a potoroid marsupial, has been extinct on the Australian mainland since the 1920s. Sixty adult bettongs were reintroduced from the island of Tasmania to two predator-free fenced reserves on mainland Australia. We examined baseline health parameters (body weight, haematology and biochemistry, parasites and infectious disease exposure) in a subset of 30 (13 male, 17 female) individuals at translocation and again at 12–24 months post-reintroduction. The mean body weight increased significantly post-reintroduction but there were no significant differences in body weight between the two reintroduction sites or between the sexes in response to reintroduction. Differences were evident in multiple haematological and biochemical variables post-reintroduction but there were few differences between the two reintroduced populations or between the sexes in response to reintroduction. Ectoparasite assemblages differed, with five of 13 species failing to persist, and an additional four species were identified post-reintroduction. None of the bettongs had detectable antibodies to the alphaherpesviruses Macropodid herpesvirus 1 and 2 post-reintroduction, including one individual that was seropositive at translocation. Similarly, the novel gammaherpesvirus potoroid herpesvirus 1 was not detected by polymerase chain reaction (PCR) in any of the bettongs post-reintroduction, including one individual that was PCR-positive at translocation. None of the bettongs had detectable antibodies to Toxoplasma gondii either at translocation or post-reintroduction. Our data demonstrate changing baseline health parameters in eastern bettongs following reintroduction to the Australian mainland are suggestive of improved health in the reintroduced populations, and provide additional metrics for assessing the response of macropodoids to reintroduction.