Vertical Field Effect Transistor based on Graphene-WS2 Heterostructures for flexible and transparent electronics

The celebrated electronic properties of graphene have opened way for materials just one-atom-thick to be used in the post-silicon electronic era. An important milestone was the creation of heterostructures based on graphene and other two-dimensional (2D) crystals, which can be assembled in 3D stacks with atomic layer precision. These layered structures have already led to a range of fascinating physical phenomena, and also have been used in demonstrating a prototype field effect tunnelling transistor - a candidate for post-CMOS technology. The range of possible materials which could be incorporated into such stacks is very large. Indeed, there are many other materials where layers are linked by weak van der Waals forces, which can be exfoliated and combined together to create novel highly-tailored heterostructures. Here we describe a new generation of field effect vertical tunnelling transistors where 2D tungsten disulphide serves as an atomically thin barrier between two layers of either mechanically exfoliated or CVD-grown graphene. Our devices have unprecedented current modulation exceeding one million at room temperature and can also operate on transparent and flexible substrates

Macrosystems ecology: Understanding ecological patterns and processes at continental scales

Macrosystems ecology is the study of diverse ecological phenomena at the scale of regions to continents and their interactions with phenomena at other scales. This emerging subdiscipline addresses ecological questions and environmental problems at these broad scales. Here, we describe this new field, show how it relates to modern ecological study, and highlight opportunities that stem from taking a macrosystems perspective. We present a hierarchical framework for investigating macrosystems at any level of ecological organization and in relation to broader and finer scales. Building on well-established theory and concepts from other subdisciplines of ecology, we identify feedbacks, linkages among distant regions, and interactions that cross scales of space and time as the most likely sources of unexpected and novel behaviors in macrosystems. We present three examples that highlight the importance of this multiscaled systems perspective for understanding the ecology of regions to continents

Tuning of Human Modulation Filters Is Carrier-Frequency Dependent

Licensed under the Creative Commons Attribution License

The Generation of Successive Unmarked Mutations and Chromosomal Insertion of Heterologous Genes in Actinobacillus pleuropneumoniae Using Natural Transformation

We have developed a simple method of generating scarless, unmarked mutations in Actinobacillus pleuropneumoniae by exploiting the ability of this bacterium to undergo natural transformation, and with no need to introduce plasmids encoding recombinases or resolvases. This method involves two successive rounds of natural transformation using linear DNA: the first introduces a cassette carrying cat (which allows selection by chloramphenicol) and sacB (which allows counter-selection using sucrose) flanked by sequences to either side of the target gene; the second transformation utilises the flanking sequences ligated directly to each other in order to remove the cat-sacB cassette. In order to ensure efficient uptake of the target DNA during transformation, A. pleuropneumoniae uptake sequences are added into the constructs used in both rounds of transformation. This method can be used to generate multiple successive deletions and can also be used to introduce targeted point mutations or insertions of heterologous genes into the A. pleuropneumoniae chromosome for development of live attenuated vaccine strains. So far, we have applied this method to highly transformable isolates of serovars 8 (MIDG2331), which is the most prevalent in the UK, and 15 (HS143). By screening clinical isolates of other serovars, it should be possible to identify other amenable strains

Barriers to living donor kidney transplantation in the United Kingdom: a national observational study.

BACKGROUND: Living donor kidney transplantation (LDKT) provides more timely access to transplantation and better clinical outcomes than deceased donor kidney transplantation (DDKT). This study investigated disparities in the utilization of LDKT in the UK. METHODS: A total of 2055 adults undergoing kidney transplantation between November 2011 and March 2013 were prospectively recruited from all 23 UK transplant centres as part of the Access to Transplantation and Transplant Outcome Measures (ATTOM) study. Recipient variables independently associated with receipt of LDKT versus DDKT were identified. RESULTS: Of the 2055 patients, 807 (39.3%) received LDKT and 1248 (60.7%) received DDKT. Multivariable modelling demonstrated a significant reduction in the likelihood of LDKT for older age {odds ratio [OR] 0.11 [95% confidence interval (CI) 0.08-0.17], P < 0.0001 for 65-75 years versus 18-34 years}; Asian ethnicity [OR 0.55 (95% CI 0.39-0.77), P = 0.0006 versus White]; Black ethnicity [OR 0.64 (95% CI 0.42-0.99), P = 0.047 versus White]; divorced, separated or widowed [OR 0.63 (95% CI 0.46-0.88), P = 0.030 versus married]; no qualifications [OR 0.55 (95% CI 0.42-0.74), P < 0.0001 versus higher education qualifications]; no car ownership [OR 0.51 (95% CI 0.37-0.72), P = 0.0001] and no home ownership [OR 0.65 (95% CI 0.85-0.79), P = 0.002]. The odds of LDKT varied significantly between countries in the UK. CONCLUSIONS: Among patients undergoing kidney transplantation in the UK, there are significant age, ethnic, socio-economic and geographic disparities in the utilization of LDKT. Further work is needed to explore the potential for targeted interventions to improve equity in living donor transplantation

Change in renal function associated with drug treatment in heart failure: national guidance.

Inhibitors of the renin-angiotensin-aldosterone (RAAS) system are cornerstones of the management of patients with heart failure with reduced left ventricular ejection fraction (HFrEF). However, RAAS inhibitors may cause decline in renal function and/or hyperkalaemia, particularly during initiation and titration, intercurrent illness and during worsening of heart failure. There is very little evidence from clinical trials to guide the management of renal dysfunction. The Renal Association and British Society for Heart Failure have collaborated to describe the interactions between heart failure, RAAS inhibitors and renal dysfunction and give clear guidance on the use of RAAS inhibitors in patients with HFrEF. During initiation and titration of RAAS inhibitors, testing renal function is mandatory; a decline in renal function of 30% or more can be acceptable. During intercurrent illness, there is no evidence that stopping RAAS inhibitor is beneficial, but if potassium rises above 6.0 mmol/L, or creatinine rises more than 30%, RAAS inhibitors should be temporarily withheld. In patients with fluid retention, high doses of diuretic are needed and a decline in renal function is not an indication to reduce diuretic dose: if the patient remains congested, more diuretics are required. If a patient is hypovolaemic, diuretics should be stopped or withheld temporarily. Towards end of life, consider stopping RAAS inhibitors. RAAS inhibition has no known prognostic benefit in heart failure with preserved ejection fraction. Efforts should be made to initiate, titrate and maintain patients with HFrEF on RAAS inhibitor treatment, whether during intercurrent illness or worsening heart failure

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

General practitioners' evaluation of community psychiatric services: responsiveness to change of the General Practitioner Experiences Questionnaire (GPEQ)

<p>Abstract</p> <p>Background</p> <p>Instruments have been developed to assess professional views of the quality of care but have rarely been tested for responsiveness to change. The objective of this study was to test the responsiveness of the General Practitioner Experiences Questionnaire (GPEQ) for the measurement of Community Mental Health Centres in Norway.</p> <p>Methods</p> <p>National surveys were conducted in Norway in 2006 (n = 2,415) and 2008 (n = 2,209) to measure general practitioners' evaluation of community mental health centres. GPs evaluated the centres by means of a postal questionnaire, consisting of questions focused on centre quality and cooperation with GPs. As part of the national surveys 75 GPs in 2006 and 66 GPs in 2008 evaluated Hamar community mental health centre. Between the surveys, several quality improvement initiatives were implemented which were directed at cooperation with and guidance for GPs in Stange municipality, one of eight municipalities in Hamar centre catchment area. The main outcome measures were changes in GPEQ scores from 2006 to 2008 for GPs evaluating Hamar community mental health centre from Stange municipality, and changes in scores for GPs in the other seven municipalities and nationally which were assessed for statistical significance.</p> <p>Results</p> <p>GPs in Stange municipality rated Hamar community mental health centre significantly better on the guidance scale in 2008 than in 2006; on a 0-100 scale where 100 represents the best possible experiences the score was 26.5 in 2006 and 58.3 in 2008 (p < 0.001). Apart from one item about workforce situation, none of the other scales and items showed significant changes. The control group from the other seven municipalities gave significantly poorer rating for the emergency situation scale, the workforce situation scale and seven items in 2008 than in 2006. The national results showed small differences between 2006 and 2008, even though several scales and items were significantly different. A question about changes in centre performance over the last 2-3 years showed that 82% of GPs from Stange municipality reported that Hamar community mental health centre had improved, compared to only 36% from the other seven municipalities and 40% nationally which was statistically significant.</p> <p>Conclusions</p> <p>Following the implementation of an initiative designed to enhance service quality, the GPEQ identified expected changes in the guidance scale for the intervention group, indicating that the instrument is responsive to change. The worsening of services for GPs in the control group evaluating Hamar centre warrants further study.</p

In situ functional dissection of RNA cis-regulatory elements by multiplex CRISPR-Cas9 genome engineering.

RNA regulatory elements (RREs) are an important yet relatively under-explored facet of gene regulation. Deciphering the prevalence and functional impact of this post-transcriptional control layer requires technologies for disrupting RREs without perturbing cellular homeostasis. Here we describe genome-engineering based evaluation of RNA regulatory element activity (GenERA), a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 platform for in situ high-content functional analysis of RREs. We use GenERA to survey the entire regulatory landscape of a 3'UTR, and apply it in a multiplex fashion to analyse combinatorial interactions between sets of miRNA response elements (MREs), providing strong evidence for cooperative activity. We also employ this technology to probe the functionality of an entire MRE network under cellular homeostasis, and show that high-resolution analysis of the GenERA dataset can be used to extract functional features of MREs. This study provides a genome editing-based multiplex strategy for direct functional interrogation of RNA cis-regulatory elements in a native cellular environment