Hybrid architecture for shallow accumulation mode AlGaAs/GaAs heterostructures with epitaxial gates

Accumulation mode devices with epitaxially grown gates have excellent electrical stability due to the absence of dopant impurities and surface states. We overcome typical fabrication issues associated with epitaxially gated structures (e.g., gate leakage and high contact resistance) by using separate gates to control the electron densities in the Ohmic and Hall bar regions. This hybrid gate architecture opens up a way to make ultrastable nanoscale devices where the separation between the surface gates and the 2D electron gas is small. In this work, we demonstrate that the hybrid devices made from the same wafer have reproducible electrical characteristics, with identical mobility and density traces over a large range of 2D densities. In addition, thermal cycling does not influence the measured electrical characteristics. As a demonstration of concept, we have fabricated a hybrid single-electron transistor on a shallow (50 nm) AlGaAs/GaAs heterostructure that shows clear Coulomb blockade oscillations in the low temperature conductance.This project was supported by the Australian Government under the Australia-India Strategic Research Fund and by the Australian Research Council (ARC) DP scheme. A.R.H. acknowledges an ARC Outstanding Researcher Award. Devices were fabricated using the facilities at the NSW Node of the Australian National Fabrication Facility (ANFF). J.R., A.L., and A.D.W. acknowledge support from Mercur Pr-2013-0001, BMBF-Q.com-H 16KIS0109, and DFH/UFA CDFA-05-06.Copyright (2015) American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in MacLeod SJ, See AM, Hamilton AR, Farrer I, Ritchie DA, Ritzmann J, Ludwig A, Wieck AD, Applied Physics Letters 106, 012105 (2015) and may be found at http://dx.doi.org/10.1063/1.4905210

Discovery of mating in the major African livestock pathogen Trypanosoma congolense

The protozoan parasite, Trypanosoma congolense, is one of the most economically important pathogens of livestock in Africa and, through its impact on cattle health and productivity, has a significant effect on human health and well being. Despite the importance of this parasite our knowledge of some of the fundamental biological processes is limited. For example, it is unknown whether mating takes place. In this paper we have taken a population genetics based approach to address this question. The availability of genome sequence of the parasite allowed us to identify polymorphic microsatellite markers, which were used to genotype T. congolense isolates from livestock in a discrete geographical area of The Gambia. The data showed a high level of diversity with a large number of distinct genotypes, but a deficit in heterozygotes. Further analysis identified cryptic genetic subdivision into four sub-populations. In one of these, parasite genotypic diversity could only be explained by the occurrence of frequent mating in T. congolense. These data are completely inconsistent with previous suggestions that the parasite expands asexually in the absence of mating. The discovery of mating in this species of trypanosome has significant consequences for the spread of critical traits, such as drug resistance, as well as for fundamental aspects of the biology and epidemiology of this neglected but economically important pathogen

Connectivity in the Deep: Phylogeography of the Velvet Belly Lanternshark

PublishedThe velvet belly lanternshark, Etmopterus spinax, is a deep-sea bioluminescent squaloid shark, found predominantly in the northeast Atlantic and Mediterranean Sea. It has been exposed to relatively high levels of mortality associated with by-catch in some regions. Its late maturity and low fecundity potentially renders it vulnerable to over-exploitation, although little remains known about processes of connectivity between key habitats/regions. This study utilised DNA sequencing of partial regions of the mitochondrial control region and nuclear ribosomal internal transcribed spacer 2 to investigate population structure and phylogeography of this species across the northeast Atlantic and Mediterranean Basin. Despite the inclusion of samples from the range edges or remote locations, no evidence of significant population structure was detected. An important exception was identified using the control region sequence, with much greater (and statistically significant) levels of genetic differentiation between the Mediterranean and Atlantic. This suggests that the Strait of Gibraltar may represent an important bathymetric barrier, separating regions with very low levels of female dispersal. Bayesian estimation of divergence time also places the separation between the Mediterranean and Atlantic lineages within the last 100,000 years, presumably connected with perturbations during the last Glacial Period. These results demonstrate population subdivision at a much smaller geographic distance than has generally been identified in previous work on deep-sea sharks. This highlights a very significant role for shallow bathymetry in promoting genetic differentiation in deepwater taxa. It acts as an important exception to a general paradigm of marine species being connected by high levels of gene-flow, representing single stocks over large scales. It may also have significant implications for the fisheries management of this species.We would like to thank Trude Thangstad, Merete Kvalsund (Institute of Marine Research, Norway), Cecilia Pinto, Eleonora de Sabata and the scientists and crew of the RV Celtic Explorer for assistance in the collection of samples. Funding for this project was provided by the University of Salford and the University of Bristol. We are grateful to all those who helped with sample collection, including the MEDITS survey programme, the Department of Fisheries and Marine Research (DFMR) of Cyprus, the Annual Demersal and Deep Water Fish Monitoring Surveys financed by the Azores Government and the CONDOR project (supported by a grant from Iceland, Liechtenstein, Norway through the EEA Financial Mechanism (PT0040/2008)

Differences between <i>Trypanosoma brucei gambiense</i> groups 1 and 2 in their resistance to killing by Trypanolytic factor 1

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The three sub-species of &lt;i&gt;Trypanosoma brucei&lt;/i&gt; are important pathogens of sub-Saharan Africa. &lt;i&gt;T. b. brucei&lt;/i&gt; is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. &lt;i&gt;T. b. rhodesiense&lt;/i&gt; and &lt;i&gt;T. b. gambiense&lt;/i&gt; are able to resist lysis by TLF. There are two distinct sub-groups of &lt;i&gt;T. b. gambiense&lt;/i&gt; that differ genetically and by human serum resistance phenotypes. Group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (&lt;i&gt;HpHbR&lt;/i&gt;)) gene. Here we investigate if this is also true in group 2 parasites.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology:&lt;/b&gt; Isogenic resistant and sensitive group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the &lt;i&gt;HpHbR&lt;/i&gt; gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to &lt;i&gt;T. b. brucei&lt;/i&gt;. Both resistant and sensitive group 2, as well as group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt;, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data indicate that, despite group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of &lt;i&gt;HpHbR&lt;/i&gt;. Thus there are differences in the mechanism of human serum resistance between &lt;i&gt;T. b. gambiense&lt;/i&gt; groups 1 and 2.&lt;/p&gt

Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

Exploring the equity of GP practice prescribing rates for selected coronary heart disease drugs: a multiple regression analysis with proxies of healthcare need

Background There is a small, but growing body of literature highlighting inequities in GP practice prescribing rates for many drug therapies. The aim of this paper is to further explore the equity of prescribing for five major CHD drug groups and to explain the amount of variation in GP practice prescribing rates that can be explained by a range of healthcare needs indicators (HCNIs). Methods The study involved a cross-sectional secondary analysis in four primary care trusts (PCTs 1–4) in the North West of England, including 132 GP practices. Prescribing rates (average daily quantities per registered patient aged over 35 years) and HCNIs were developed for all GP practices. Analysis was undertaken using multiple linear regression. Results Between 22–25% of the variation in prescribing rates for statins, beta-blockers and bendrofluazide was explained in the multiple regression models. Slightly more variation was explained for ACE inhibitors (31.6%) and considerably more for aspirin (51.2%). Prescribing rates were positively associated with CHD hospital diagnoses and procedures for all drug groups other than ACE inhibitors. The proportion of patients aged 55–74 years was positively related to all prescribing rates other than aspirin, where they were positively related to the proportion of patients aged >75 years. However, prescribing rates for statins and ACE inhibitors were negatively associated with the proportion of patients aged >75 years in addition to the proportion of patients from minority ethnic groups. Prescribing rates for aspirin, bendrofluazide and all CHD drugs combined were negatively associated with deprivation. Conclusion Although around 25–50% of the variation in prescribing rates was explained by HCNIs, this varied markedly between PCTs and drug groups. Prescribing rates were generally characterised by both positive and negative associations with HCNIs, suggesting possible inequities in prescribing rates on the basis of ethnicity, deprivation and the proportion of patients aged over 75 years (for statins and ACE inhibitors, but not for aspirin)

Using molecular data for epidemiological inference: assessing the prevalence of Trypanosoma brucei rhodesiense in Tsetse in Serengeti, Tanzania

Background: Measuring the prevalence of transmissible Trypanosoma brucei rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessing human disease risk and monitoring spatio-temporal trends and the impact of control interventions. Although an important epidemiological variable, identifying flies which carry transmissible infections is difficult, with challenges including low prevalence, presence of other trypanosome species in the same fly, and concurrent detection of immature non-transmissible infections. Diagnostic tests to measure the prevalence of T. b. rhodesiense in tsetse are applied and interpreted inconsistently, and discrepancies between studies suggest this value is not consistently estimated even to within an order of magnitude. Methodology/Principal Findings: Three approaches were used to estimate the prevalence of transmissible Trypanosoma brucei s.l. and T. b. rhodesiense in Glossina swynnertoni and G. pallidipes in Serengeti National Park, Tanzania: (i) dissection/microscopy; (ii) PCR on infected tsetse midguts; and (iii) inference from a mathematical model. Using dissection/microscopy the prevalence of transmissible T. brucei s.l. was 0% (95% CI 0–0.085) for G. swynnertoni and 0% (0–0.18) G. pallidipes; using PCR the prevalence of transmissible T. b. rhodesiense was 0.010% (0–0.054) and 0.0089% (0–0.059) respectively, and by model inference 0.0064% and 0.00085% respectively. Conclusions/Significance: The zero prevalence result by dissection/microscopy (likely really greater than zero given the results of other approaches) is not unusual by this technique, often ascribed to poor sensitivity. The application of additional techniques confirmed the very low prevalence of T. brucei suggesting the zero prevalence result was attributable to insufficient sample size (despite examination of 6000 tsetse). Given the prohibitively high sample sizes required to obtain meaningful results by dissection/microscopy, PCR-based approaches offer the current best option for assessing trypanosome prevalence in tsetse but inconsistencies in relating PCR results to transmissibility highlight the need for a consensus approach to generate meaningful and comparable data

Weight management during teenage pregnancy: Issues to consider when developing appropriate support

Teenage pregnancy is more prevalent in areas of high obesity, compared to areas where obesity levels are low. Risks associated with maternal obesity in pregnant teenagers include pre-eclampsia and caesarean delivery. To reduce these risks, pregnant teenagers need to be supported to gain a healthy weight in pregnancy. This includes encouraging these women to eat healthily through providing appropriate information including online or smartphone apps in conjunction with face-to-face support. These young women also need encouragement to be physically active. This support must be tailored to the teenage population considering their specific barriers and facilitators to behaviour change. Midwives with the aid of a multidisciplinary team play a key role in encouraging these healthy behaviours

The potential for land sparing to offset greenhouse gas emissions from agriculture

Greenhouse gas emissions from global agriculture are increasing at around 1% per annum, yet substantial cuts in emissions are needed across all sectors. The challenge of reducing agricultural emissions is particularly acute, because the reductions achievable by changing farming practices are limited and are hampered by rapidly rising food demand. Here we assess the technical mitigation potential offered by land sparing-increasing agricultural yields, reducing farm land area and actively restoring natural habitats on the land spared. Restored habitats can sequester carbon and can offset emissions from agriculture. Using the United Kingdom as an example, we estimate net emissions in 2050 under a range of future agricultural scenarios. We find that a land-sparing strategy has the technical potential to achieve significant reductions in net emissions from agriculture and land-use change. Coupling land sparing with demand-side strategies to reduce meat consumption and food waste can further increase the technical mitigation potential, however economic and implementation considerations might limit the degree to which this technical potential could be realised in practice.This research was funded by the Cambridge Conservation Initiative Collaborative Fund for Conservation and we thank its major sponsor Arcadia. We thank J. Bruinsma for the provision of demand data, the CEH for the provision of soil data and J. Spencer for invaluable discussions. A.L. was supported by a Gates Cambridge Scholarship.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nclimate291

Interpretation and expectation in childhood anxiety disorders: age effects and social specificity

Theory and treatment for childhood anxiety disorders typically implicates children’s negative cognitions, yet little is known about the characteristics of thinking styles of clinically anxious children. In particular, it is unclear whether differences in thinking styles between children with anxiety disorders and non-anxious children vary as a function of child age, whether particular cognitive distortions are associated with childhood anxiety disorders at different child ages, and whether cognitive content is disorder-specific. The current study addressed these questions among 120 7 - 12 year old children (53% female) who met diagnostic criteria for social anxiety disorder, other anxiety disorder, or who were not currently anxious. Contrary to expectations, threat interpretation was not inflated amongst anxious compared to non-anxious children at any age, although older (10 - 12 year old) anxious children did differ from non-anxious children on measures of perceived coping. The notion of cognitive-content specificity was not supported across the age-range. The findings challenge current treatment models of childhood anxiety, and suggest that a focus on changing anxious children’s cognitions is not warranted in mid-childhood, and in late childhood cognitive approaches may be better focussed on promoting children’s perceptions of control rather than challenging threat interpretations