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Recent genetic findings suggest shared genetic risk between autism, epilepsy and schizophrenia. A sodium channel subunit gene, SCN2A, exhibits de novo stop-codon mutations in individuals with autism and a stop-codon mutation in an individual with a seizure disorder. Our recent exome-sequencing study of schizophrenia cases identified a de novo splicesite mutation at SCN2A and further mutations may exist.
To examine a role for rare, protein damaging mutations at SCN2A in the aetiology of schizophrenia.
We aim to show an excess of coding sequence mutations in schizophrenia cases when compared to controls.
Mutation screening of the coding sequence of SCN2A in 993 Caucasian individuals with DSM-IV schizophrenia. We employed High-Resolution Melt Analysis(LightScanner™), followed by dye- terminator sequencing to confirm allele carriers. We compared our results to an exome-sequencing dataset of 4300 Caucasian individuals (NHLBI Exome Sequencing Project).
34 variants were identified; 15 intronic, 13 synonymous and 7 non-synonymous. One of the non-synonymous variants introduces a stop codon at amino acid 169 (169 E>X). No stop-codon variants were identified in the control dataset. Burden analysis did not show an excess of protein damaging changes in the UK dataset when compared to controls.
A total of 4 stop-codon mutations have been identified at SCN2A; all in individuals with a neuropsychiatric disorder. Our data do not suggest a general role for protein coding mutations at SCN2A in the pathogenesis of schizophrenia; however there may be a role for very damaging alleles at SCN2A in several neuropsychiatric disorders.
A developing application of laser-driven currents is the generation of magnetic fields of picosecond–nanosecond duration with magnitudes exceeding
. Single-loop and helical coil targets can direct laser-driven discharge currents along wires to generate spatially uniform, quasi-static magnetic fields on the millimetre scale. Here, we present proton deflectometry across two axes of a single-loop coil ranging from 1 to 2 mm in diameter. Comparison with proton tracking simulations shows that measured magnetic fields are the result of kiloampere currents in the coil and electric charges distributed around the coil target. Using this dual-axis platform for proton deflectometry, robust measurements can be made of the evolution of magnetic fields in a capacitor coil target.
The Wisconsin Twin Project comprises multiple longitudinal studies that span infancy to early adulthood. We summarize recent papers that show how twin designs with deep phenotyping, including biological measures, can inform questions about phenotypic structure, etiology, comorbidity, heterogeneity, and gene–environment interplay of temperamental constructs and mental and physical health conditions of children and adolescents. The general framework for investigations begins with rich characterization of early temperament and follows with study of experiences and exposures across childhood and adolescence. Many studies incorporate neuroimaging and hormone assays.
Neighboring tidewater glaciers often exhibit asynchronous dynamic behavior, despite relatively uniform regional atmospheric and oceanic forcings. This variability may be controlled by a combination of local factors, including glacier and fjord geometry, fjord heat content and circulation, and glacier surface melt. In order to characterize and understand contrasts in adjacent tidewater glacier and fjord dynamics, we made coincident ice-ocean-atmosphere observations at high temporal resolution (minutes to weeks) within a 10 000 km2 area near Uummannaq, Greenland. Water column velocity, temperature and salinity measurements reveal systematic differences in neighboring fjords that imply contrasting circulation patterns. The observed ocean velocity and hydrography, combined with numerical modeling, suggest that subglacial discharge plays a major role in setting fjord conditions. In addition, satellite remote sensing of seasonal ice flow speed and terminus position reveal both speedup and slow-down in response to melt, as well as differences in calving style among the neighboring glaciers. Glacier force budgets and modeling also point toward subglacial discharge as a key factor in glacier behavior. For the studied region, individual glacier and fjord geometry modulate subglacial discharge, which leads to contrasts in both fjord and glacier dynamics.
Community-based conservation efforts are designed to foster local stewardship of important ecological resources. However, inequitable distribution of costs and benefits in communities surrounding protected areas can negatively impact livelihoods, increase wealth disparities and create conflict. To examine the potential for conflict between host communities involved in a community-based conservation program and neighbouring (non-host) communities, we explored local residents’ attitudes towards conservation at Tiwai Island Wildlife Sanctuary (TIWS) in Sierra Leone. Intercept surveys (n = 368) were conducted in 18 villages (eight host, ten non-host) within 8 km of TIWS during 2010. Results revealed significant differences between residents of the host and non-host villages with respect to attitudes towards resource use and overall support for site protection. The most substantial discrepancies centred on perceived benefits associated with TIWS, and these drastically different perspectives generated a high potential for conflict. To minimize conflict and foster broader community support for conservation, managers must carefully consider how benefits associated with protected areas are communicated and distributed across protected area-proximate landscapes.
Almost 100 years have passed since J.M. Swaine, the assistant entomologist in charge of Forest Insect Investigations, wrote, “Canadian bark-beetles: a preliminary classification, with an account of the habits and means of control”. The goal was to “put into the hands of practical foresters information of inestimable practical value… to prevent the continued loss of timber now being destroyed” by “the most insidious enemies of the forest”. In this paper, we celebrate Swaine’s pioneering work by summarising the foundational aspects of his early treatise of 1918: the “general habits” of bark beetles, classifications of their behaviour, causes of population increase, and mitigation tactics. In the founding text, Swaine identified all major Dendroctonus Erichson (Coleoptera: Curculionidae) bark beetles found in Canada, although details on life histories were scarce. We summarise current knowledge of the life histories and population dynamics of the spruce beetle, D. rufipennis Kirby; the Douglas-fir beetle, D. pseudotsugae Hopkins; the eastern larch beetle, D. simplex; and address the current range expansion of mountain pine beetle, D. ponderosae Hopkins. We review how aspects of global change, such as invasive species, have altered the population dynamics of certain bark beetles. Finally, we conclude with lessons from two of the many past contributors to bark beetle ecology in Canada, J.M. Swaine and H.A. Richmond.
This study aims to compare conventional simultaneous integrated boost (SIB) planning technique with a hybrid SIB intensity-modulated radiation therapy (IMRT) technique with varying open tangent to IMRT field dose ratios. Furthermore, we investigated which of the dose ratios proves the most favourable as a class solution across a sample.
In total, 15 patients with conventional SIB treatment plans were re-planned with hybrid SIB IMRT technique using three differing open field:IMRT dose ratios, that is, 80:20, 70:30 and 60:40. Plans were compared using dosimetric comparison of organs at risk (OARs) and homogeneity and conformity indexes across target structures.
All hybrid plans reduced dose maximums and showed a reduction of high doses to both lungs but increased lower doses, that is, V5, with similar results discovered for the heart. Contralateral breast dose was shown to decrease V5 and V1 measures by hybrid arms, whereas increasing the V2. Left anterior descending artery dose and non-irradiated structures were reduced by all hybrid arms. The homogeneity and conformity increased across all hybrid arms. Qualitative assessment of all plans also favoured hybrid plans.
Hybrid plans produced superior dose conformity, homogeneity, reduced dose maximums and showed an improvement in most OAR parameters. The 70:30 hybrid technique exhibited greater benefits as a class solution to the sample than conventional plans due to superior dose conformity and homogeneity to target volumes.
The Murchison Widefield Array is a new low-frequency interferometric radio telescope built in Western Australia at one of the locations of the future Square Kilometre Array. We describe the automated radio-frequency interference detection strategy implemented for the Murchison Widefield Array, which is based on the aoflagger platform, and present 72–231 MHz radio-frequency interference statistics from 10 observing nights. Radio-frequency interference detection removes 1.1% of the data. Radio-frequency interference from digital TV is observed 3% of the time due to occasional ionospheric or atmospheric propagation. After radio-frequency interference detection and excision, almost all data can be calibrated and imaged without further radio-frequency interference mitigation efforts, including observations within the FM and digital TV bands. The results are compared to a previously published Low-Frequency Array radio-frequency interference survey. The remote location of the Murchison Widefield Array results in a substantially cleaner radio-frequency interference environment compared to Low-Frequency Array’s radio environment, but adequate detection of radio-frequency interference is still required before data can be analysed. We include specific recommendations designed to make the Square Kilometre Array more robust to radio-frequency interference, including: the availability of sufficient computing power for radio-frequency interference detection; accounting for radio-frequency interference in the receiver design; a smooth band-pass response; and the capability of radio-frequency interference detection at high time and frequency resolution (second and kHz-scale respectively).
The B fields in OB stars (BOB) survey is an ESO large programme collecting spectropolarimetric observations for a large number of early-type stars in order to study the occurrence rate, properties, and ultimately the origin of magnetic fields in massive stars. As of July 2014, a total of 98 objects were observed over 20 nights with FORS2 and HARPSpol. Our preliminary results indicate that the fraction of magnetic OB stars with an organised, detectable field is low. This conclusion, now independently reached by two different surveys, has profound implications for any theoretical model attempting to explain the field formation in these objects. We discuss in this contribution some important issues addressed by our observations (e.g., the lower bound of the field strength) and the discovery of some remarkable objects.
In the summer of 2009, an outbreak of verocytotoxigenic Escherichia coli O157 (VTEC O157) was identified in visitors to a large petting farm in South East England. The peak attack rate was 6/1000 visitors, and highest in those aged <2 years (16/1000). We conducted a case-control study with associated microbiological investigations, on human, animal and environmental samples. We identified 93 cases; 65 primary, 13 secondary and 15 asymptomatic. Cases were more likely to have visited a specific barn, stayed for prolonged periods and be infrequent farm visitors. The causative organism was identified as VTEC O157 PT21/28 with the same VNTR profile as that isolated in faecal specimens from farm animals and the physical environment, mostly in the same barn. Contact with farm livestock, especially ruminants, should be urgently reviewed at the earliest suspicion of a farm-related VTEC O157 outbreak and appropriate risk management procedures implemented without delay.
We evaluated treatment decisions and antimicrobial use related to 2 testing algorithms for Clostridium difficile infection (CDI). findings suggest that a 2-step testing algorithm using rapid polymerase chain reaction confirmatory testing leads to decreased unnecessary anti-CDI antimicrobial use. In addition, a significant proportion of patients with confirmed CDI were not treated accordingto recommended guidelines.
A 2 × 2 factorial experiment was conducted to determine the effects of rearing environment (indoor (In) v. outdoor (Out)) and dietary zinc oxide (ZnO) supplementation (0 (−Zn) v. 3100 (+Zn) mg/kg feed) on the response of weaned pigs to a challenge infection with enterotoxigenic Escherichia coli (ETEC). Pigs from the two rearing environments were weaned onto trial diets at 4 weeks of age, moved into conventional accommodation and infected 3 days later with 109 CFU ETEC per os. Faecal ETEC shedding was determined before and after challenge. After 7 days of ETEC infection, all pigs were euthanized for gut lactic acid bacteria (LAB)-to-coliform ratio, pH and small intestine morphological measurements. Both ZnO and outdoor rearing reduced ETEC excretion, and these effects were additive. Outdoor rearing increased small intestine and colon tissue weight. ZnO increased villus height and goblet cell number in the upper small intestine, LAB-to-coliform ratio (through reduced coliforms) in the lower small intestine and proximal colon, and improved growth performance. There were interactive effects of rearing environment and ZnO supplementation on upper small intestine villus height and daily gain, as outdoor rearing conferred advantages on these variables only with ZnO dietary supplementation. Daily gains were 233, 174, 277 and 347 (s.e.m. 27.2) g/day for the In − Zn, Out − Zn, In + Zn and Out + Zn, respectively. These results suggest different, but complementary mechanisms of intestinal health and performance in outdoor-reared pigs and those offered ZnO supplemented diets. The results indicate that the benefits of ZnO to the weaned pig extend beyond suppression of ETEC and appear mediated through altered development of the small intestine mucosa.