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The SPARC tokamak is a critical next step towards commercial fusion energy. SPARC is designed as a high-field ($B_0 = 12.2$ T), compact ($R_0 = 1.85$ m, $a = 0.57$ m), superconducting, D-T tokamak with the goal of producing fusion gain $Q>2$ from a magnetically confined fusion plasma for the first time. Currently under design, SPARC will continue the high-field path of the Alcator series of tokamaks, utilizing new magnets based on rare earth barium copper oxide high-temperature superconductors to achieve high performance in a compact device. The goal of $Q>2$ is achievable with conservative physics assumptions ($H_{98,y2} = 0.7$) and, with the nominal assumption of $H_{98,y2} = 1$, SPARC is projected to attain $Q \approx 11$ and $P_{\textrm {fusion}} \approx 140$ MW. SPARC will therefore constitute a unique platform for burning plasma physics research with high density ($\langle n_{e} \rangle \approx 3 \times 10^{20}\ \textrm {m}^{-3}$), high temperature ($\langle T_e \rangle \approx 7$ keV) and high power density ($P_{\textrm {fusion}}/V_{\textrm {plasma}} \approx 7\ \textrm {MW}\,\textrm {m}^{-3}$) relevant to fusion power plants. SPARC's place in the path to commercial fusion energy, its parameters and the current status of SPARC design work are presented. This work also describes the basis for global performance projections and summarizes some of the physics analysis that is presented in greater detail in the companion articles of this collection.
Animal experimental studies suggest that 5-HT4 receptor activation holds promise as a novel target for the treatment of depression and cognitive impairment. 5-HT4 receptors are post-synaptic receptors that are located in striatal and limbic areas known to be involved in cognition and mood. Consistent with this, 5-HT4 receptor agonists produce rapid antidepressant effects in a number of animal models of depression, and pro-cognitive effects in tasks of learning and memory. These effects are accompanied by molecular changes, such as the increased expression of neuroplasticity-related proteins that are typical of clinically useful antidepressant drugs. Intriguingly, these antidepressant-like effects have a fast onset of their action, raising the possibility that 5-HT4 receptor agonists may be a particularly useful augmentation strategy in the early stages of SSRI treatment. Until recently, the translation of these effects to humans has been challenging. Here, we review the evidence from animal studies that the 5-HT4 receptor is a promising target for the treatment of depression and cognitive disorders, and outline a potential pathway for the efficient and cost-effective translation of these effects into humans and, ultimately, to the clinic.
Locally acquired hepatitis A infection is re-emerging in Australia owing to person-to-person outbreaks among men who have sex with men and imported frozen produce. This paper describes a multi-state foodborne outbreak in the first half of 2018. Enhanced human epidemiological investigation including a case–control study, as well as microbial surveillance and trace-back investigations concluded that the outbreak was caused by consumption of imported frozen pomegranate arils. A total of 30 cases of hepatitis A infection, genotype IB with identical sequences met the outbreak case definition, including 27 primary cases and three secondary cases. Twenty-five (83%) of the cases were hospitalised for their illness and there was one death. Imported frozen pomegranate arils from Egypt were strongly implicated as the source of infection through case interviews (19 of 26 primary cases) as well as from a case–control study (adjusted odds ratio 43.4, 95% confidence interval 4.2–448.8, P = 0.002). Hepatitis A virus (HAV) was subsequently detected by polymerase chain reaction in two food samples of the frozen pomegranate aril product. This outbreak was detected and responded to promptly owing to routine genetic characterisation of HAVs from all hepatitis A infections in Australia as part of a national hepatitis A enhanced surveillance project. This is now the third outbreak of hepatitis A in Australia from imported frozen fruits. A re-assessment of the risk of these types of imported foods is strongly recommended.
Medicine-related research includes numerous studies on the hazards of mortality and what risk factors are associated with these hazards, such as diseases and treatments. These hazards are estimated in a sample of people and summarised over the observed period. From these observations, inferences can be made about the underlying population and consequently inform medical guidelines for intervention. New health interventions are usually based on these estimated hazards obtained from clinical trials. A lengthy lead time would be needed to observe their effect on population longevity. This paper shows how estimated mortality hazards can be translated to hypothetical changes in life expectancies at the individual and population levels. For an individual, the relative hazards are translated into the number of years gained or lost in “effective age”, which is the average chronological age with the same risk profile. This translation from hazard ratio to effective age could be used to explain to individuals the consequences of various diseases and lifestyle choices and as a result persuade clients in life and health insurance to pursue a healthier lifestyle. At the population level, a period life expectancy is a weighted average of component life expectancies associated with the particular risk profiles, with the weights defined by the prevalences of the risk factor of interest and the uptake of the relevant intervention. Splitting the overall life expectancy into these components allows us to estimate hypothetical changes in life expectancy at the population level at different morbidity and uptake scenarios. These calculations are illustrated by two examples of medical interventions and their impact on life expectancy, which are beta blockers in heart attack survivors and blood pressure treatment in hypertensive patients. The second example also illustrates the dangers of applying the results from clinical trials to much wider populations.
Recent cases of acute kidney injury due to Seoul hantavirus infection from exposure to wild or pet fancy rats suggest this infection is increasing in prevalence in the UK. We conducted a seroprevalence study in England to estimate cumulative exposure in at-risk groups with contact with domesticated and wild rats to assess risk and inform public health advice. From October 2013 to June 2014, 844 individual blood samples were collected. Hantavirus seroprevalence amongst the pet fancy rat owner group was 34.1% (95% CI 23·9–45·7%) compared with 3·3% (95% CI 1·6–6·0) in a baseline control group, 2·4% in those with occupational exposure to pet fancy rats (95% CI 0·6–5·9) and 1·7% with occupational exposure to wild rats (95% CI 0·2–5·9). Variation in seroprevalence across groups with different exposure suggests that occupational exposure to pet and wild rats carries a very low risk, if any. However incidence of hantavirus infection among pet fancy rat owners/breeders, whether asymptomatic, undiagnosed mild viral illness or more severe disease may be very common and public health advice needs to be targeted to this at-risk group.
Fronto-limbic structural brain abnormalities have been reported in patients with bipolar disorder (BD), but findings in individuals at increased genetic risk of developing BD have been inconsistent. We conducted a study in adolescents and young adults (12–30 years) comparing measures of fronto-limbic cortical and subcortical brain structure between individuals at increased familial risk of BD (at risk; AR), subjects with BD and controls (CON). We separately examined cortical volume, thickness and surface area as these have distinct neurodevelopmental origins and thus may reflect differential effects of genetic risk.
Method
We compared fronto-limbic measures of grey and white matter volume, cortical thickness and surface area in 72 unaffected-risk individuals with at least one first-degree relative with bipolar disorder (AR), 38 BD subjects and 72 participants with no family history of mental illness (CON).
Results
The AR group had significantly reduced cortical thickness in the left pars orbitalis of the inferior frontal gyrus (IFG) compared with the CON group, and significantly increased left parahippocampal gyral volume compared with those with BD.
Conclusions
The finding of reduced cortical thickness of the left pars orbitalis in AR subjects is consistent with other evidence supporting the IFG as a key region associated with genetic liability for BD. The greater volume of the left parahippocampal gyrus in those at high risk is in line with some prior reports of regional increases in grey matter volume in at-risk subjects. Assessing multiple complementary morphometric measures may assist in the better understanding of abnormal developmental processes in BD.
We carried out an extensive photometric and spectroscopic investigation of the SPB binary, HD 25558 (see Fig. 1 for the time and geographic distribution of the observations). The ~2000 spectra obtained at 13 observatories during 5 observing seasons, the ground-based multi-colour light curves and the photometric data from the MOST satellite revealed that this object is a double-lined spectroscopic binary with a very long orbital period of about 9 years. We determined the physical parameters of the components, and have found that both lie within the SPB instability strip. Accordingly, both components show line-profile variations consistent with stellar pulsations. Altogether, 11 independent frequencies and one harmonic frequency were identified in the data. The observational data do not allow the inference of a reliable orbital solution, thus, disentangling cannot be performed on the spectra. Since the lines of the two components are never completely separated, the analysis is very complicated. Nevertheless, pixel-by-pixel variability analysis of the cross-correlated line profiles was successful, and we were able to attribute all the frequencies to the primary or secondary component. Spectroscopic and photometric mode-identification was also performed for several of these frequencies of both binary components. The spectroscopic mode-identification results suggest that the inclination and rotation of the two components are rather different. While the primary is a slow rotator with ~6 d rotation period, seen at ~60° inclination, the secondary rotates fast with ~1.2 d rotation period, and is seen at ~20° inclination. Our spectropolarimetric measurements revealed that the secondary component has a magnetic field with at least a few hundred Gauss strength, while no magnetic field was detected in the primary.
The detailed analysis and results of this study will be published elsewhere.
We describe an investigation of 3 postoperative Gordonia bronchialis sternal infections. A nurse anesthetist was identified as the source of the outbreak, her scrubs likely becoming contaminated by her home washing machine. The outbreak ended after disposal of the implicated washing machine. Domestic laundering of surgical scrubs may need reevaluation.
Escherichia coli, like other gram-negative bacteria, is protected from the surrounding harsh environment by a cell wall consisting of the peptidoglycan and outer membrane. Whereas the cytoplasmic membrane is the selective barrier, the cell wall provides mechanical strength for the cell. As bacteria navigate various environments, osmotic pressure can change dramatically due to changes in local solute concentration. The peptidoglycan together with the cellular proteins mitigates the osmotic stress that would otherwise cause lysis. The mechanical properties of E. coli cells and its individual layers have been largely indeterminable until the recent development of probe-based measurement tools. Since their invention, scientists have reported significant data measuring elasticity, modulus, and stiffness using atomic force microscopy (AFM). Fundamentally, in order to determine these mechanical properties through probe-based techniques, the contact area and load should be well defined. The load can be precisely calculated through the AFM cantilever spring constant. However, the silicon tip contact area can only be estimated, potentially leading to compounding uncertainties. Therefore, we developed a methodology to determine nanomechanical properties of E. coli using a nanoindenter.
Genetic studies in adults indicate that genes influencing the personality trait of neuroticism account for substantial genetic variance in anxiety and depression and in somatic health. Here, we examine for the first time the factors underlying the relationship between neuroticism and anxiety/depressive and somatic symptoms during adolescence.
Method
The Somatic and Psychological Health Report (SPHERE) assessed symptoms of anxiety/depression (PSYCH-14) and somatic distress (SOMA-10) in 2459 adolescent and young adult twins [1168 complete pairs (35.4% monozygotic, 53% female)] aged 12–25 years (mean=15.5±2.9). Differences between boys and girls across adolescence were explored for neuroticism, SPHERE-34, and the subscales PSYCH-14 and SOMA-10. Trivariate analyses partitioned sources of covariance in neuroticism, PSYCH-14 and SOMA-10.
Results
Girls scored higher than boys on both neuroticism and SPHERE, with SPHERE scores for girls increasing slightly over time, whereas scores for boys decreased or were unchanged. Neuroticism and SPHERE scores were strongly influenced by genetic factors [heritability (h2)=40–52%]. A common genetic source influenced neuroticism, PSYCH-14 and SOMA-10 (impacting PSYCH-14 more than SOMA-10). A further genetic source, independent of neuroticism, accounted for covariation specific to PSYCH-14 and SOMA-10. Environmental influences were largely specific to each measure.
Conclusions
In adolescence, genetic risk factors indexed by neuroticism contribute substantially to anxiety/depression and, to a lesser extent, perceived somatic health. Additional genetic covariation between anxiety/depressive and somatic symptoms, independent of neuroticism, had greatest influence on somatic distress, where it was equal in influence to the factor shared with neuroticism.
The protozoan parasite Toxoplasma gondii is prevalent worldwide and can infect a remarkably wide range of hosts despite felids being the only definitive host. As cats play a major role in transmission to secondary mammalian hosts, the interaction between cats and these hosts should be a major factor determining final prevalence in the secondary host. This study investigates the prevalence of T. gondii in a natural population of Apodemus sylvaticus collected from an area with low cat density (<2·5 cats/km2). A surprisingly high prevalence of 40·78% (95% CI: 34·07%–47·79%) was observed despite this. A comparable level of prevalence was observed in a previously published study using the same approaches where a prevalence of 59% (95% CI: 50·13%–67·87%) was observed in a natural population of Mus domesticus from an area with high cat density (>500 cats/km2). Detection of infected foetuses from pregnant dams in both populations suggests that congenital transmission may enable persistence of infection in the absence of cats. The prevalences of the related parasite, Neospora caninum were found to be low in both populations (A. sylvaticus: 3·39% (95% CI: 0·12%–6·66%); M. domesticus: 3·08% (95% CI: 0·11%–6·05%)). These results suggest that cat density may have a lower than expected effect on final prevalence in these ecosystems.
When exposed to hot (22–35°C) and dry climatic conditions in the field during the final 4–6 weeks of pod filling, peanuts (Arachis hypogaea L.) can accumulate highly carcinogenic and immuno-suppressing aflatoxins. Forecasting of the risk posed by these conditions can assist in minimizing pre-harvest contamination. A model was therefore developed as part of the Agricultural Production Systems Simulator (APSIM) peanut module, which calculated an aflatoxin risk index (ARI) using four temperature response functions when fractional available soil water was <0·20 and the crop was in the last 0·40 of the pod-filling phase. ARI explained 0·95 (P⩽0·05) of the variation in aflatoxin contamination, which varied from 0 to c. 800 μg/kg in 17 large-scale sowings in tropical and four sowings in sub-tropical environments carried out in Australia between 13 November and 16 December 2007. ARI also explained 0·96 (P⩽0·01) of the variation in the proportion of aflatoxin-contaminated loads (>15 μg/kg) of peanuts in the Kingaroy region of Australia during the period between the 1998/99 and 2007/08 seasons. Simulation of ARI using historical climatic data from 1890 to 2007 indicated a three-fold increase in its value since 1980 compared to the entire previous period. The increase was associated with increases in ambient temperature and decreases in rainfall. To facilitate routine monitoring of aflatoxin risk by growers in near real time, a web interface of the model was also developed. The ARI predicted using this interface for eight growers correlated significantly with the level of contamination in crops (r=0·95, P⩽0·01). These results suggest that ARI simulated by the model is a reliable indicator of aflatoxin contamination that can be used in aflatoxin research as well as a decision-support tool to monitor pre-harvest aflatoxin risk in peanuts.
The Older Australian Twins Study (OATS) was recently initiated to investigate genetic and environmental factors and their associations and interactions in healthy brain ageing and ageing-related neurocognitive disorders. The study extends the classic MZ-DZ design to include one or two equivalently aged siblings for each twin pair and utilizes the rich resources of the Australian Twin Registry. The study has a number of distinguishing features including comprehensive psychiatric, neuropsychological, cardiovascular, metabolic, and neuroimaging assessments, a longitudinal design and links with a brain donor program. The study measures many behavioral and environmental factors, but in particular lifetime physical and mental activity, physical and psychological trauma, loss of parent early in life, later losses and life events, early-life socioeconomic environment, alcohol and drug use, occupational exposure, and nutrition. It also includes comprehensive cardiovascular assessment, blood biochemistry, genetics and proteomics. The socio-demographic and health data on the first 172 pairs of twins participating in this study are presented. Prevalence of mild cognitive impairment is 12.8% and of dementia 1.5% in the sample. The target sample size is 1000, with at least 400 pairs of twins aged 65–90 years. The cohort will be assessed every two years, with in-depth assessments being repeated. OATS offers an excellent opportunity for collaboration with other similar studies as well as researchers who share the same interests.
We present a photometric analysis of the properties of asymptotic giant branch stars identified in the INT Photometric H-alpha Survey (IPHAS) of the northern Galactic plane. Follow-up spectroscopy has revealed that the IPHAS (r - Ha) colour is a valuable diagnostic of the photospheric C/O ratio, and may be used to identify hundreds of carbon and S-type stars.
A Cambridge expedition was in Svalbard during late June, July and August 1977 and undertook geological field work concerning late Precambrian/Palaeozoic stratigraphy. One party of the expedition completed a small scale exploration drilling contract for a German industrial concern. Members of the expedition were: W. B. Harland (leader, geologist); C. A. G. Pickton (geologist/driller with Party D); N. J. R. Wright (Party D, geologist); K. Swett and D. Johnson (Party A, geologists from the University of Iowa); M. J. Hambrey and P. Waddams (Party C, geologists); S. R. Larter and B. Bowler (Party D, drillers/geoscientists from the University of Newcastle); J. Gammage, R. Hanks, D. Burkitt, P. Doughty, and G. Thwaites (Party B, boat captains and crews). The activities of the expedition were divided into two phases.
This article attempts to locate and briefly describe all the main mining operations that are currently active within the Arctic. In addition, many smaller mining operations, where grouped into recognizable mining districts, are included, as well as some mines which are no longer active. It is beyond the scope of this work to review the potential mineral resources of the Arctic, but where deposits are large, and figure prominently in the literature or have been investigated in detail with a view to future exploitation, they have been included and located on the various maps.