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This is a copy of the slides presented at the meeting but not formally written up for the volume.
At heterojunctions between different oxide perovskite phases both lattice and electronic structure is modified by the junction. One interesting question that several groups have studied is just how far into the neighboring materials these perturbations extend. We have studied this for insulating phases as well as conducting phases. For insulating phases it appears that the lattice distortions are healed in a layer about one unit cell thick. By stacking different materials each of which is only a single unit cell thick we have obtained materials that exhibit new properties determined by the stacking architecture. For example, superlattices that lack inversion symmetry have a built-in polarization that is controlled by the direction of the strain asymmetry. For conducting phases, the electronic structure also seems to be modified mainly in a layer only a few unit cells thick. We have studied this in superlattices of SrTiO3 and LaMnO3 in which we vary the thickness of the layers. We use optical conductivity to probe the electronic structure in the near infrared to near ultraviolet spectral region. The conductivity is close to the average of the two constituents, but differs in certain spectral regions, especially for the films with the thinnest supercells.This work was supported by the Department of Energy Basic Energy Sciences program at the Fredrick Seitz Materials Research Laboratory at the University of Illinois, Urbana, IL.
Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.
To investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.
Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.
The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.
These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.
This article retrospectively examines the evolution of rapid assessments (RAs) produced by the Health Technology Assessment (HTA) Program at the Institute of Health Economics over its 25-year relationship with a single requester, the Alberta Health Ministry (AHM).
The number, types, and methodological attributes of RAs produced over the past 25 years were reviewed. The reasons for developmental changes in RA processes and products over time were charted to document the push–pull tension between AHM needs and the HTA Program's drive to meet those needs while responding to changing methodological benchmarks.
The review demonstrated the dynamic relationship required for HTA researchers to meet requester needs while adhering to good HTA practice. The longstanding symbiotic relationship between the HTA Program and the AHM initially led to increased diversity in RA types, followed by controlled extinction of the less fit (useful) “transition species.” Adaptations in RA methodology were mainly driven by changes in best practice standards, requester needs, the healthcare environment, and staff expertise and technology.
RAs are a useful component of HTA programs. To remain relevant and useful, RAs need to evolve according to need within the constraints of HTA best practice.
The Health Technology Assessment (HTA) Program at the Institute of Health Economics (IHE) has conducted rapid assessments (RAs) for 25 years. The presentation draws on this experience to chart the evolution of RAs over a 25-year relationship between a policy maker and an arms-length HTA agency to quantify the effects of this partnership on the RAs produced.
The number, types, and methodological attributes of RAs produced over a 25-year partnership with a single requestor were reviewed. The reasons for developmental changes in RA products over time were charted to document the push-pull tension between requestor needs and HTA best practice. The elements contributing to the relevance and impact, or not, of the RAs were also identified.
Results demonstrated the dynamic relationship required for HTA researchers to meet best practice and requestor needs. As literature search spans lengthened and data analyses became more complex, limitations were imposed on RAs to fulfill the requirements of timeliness, utility, and best practice. Adaptations were driven by requestor, researcher, and the external policy environment. Facilitators of RA utility for HTA requestors include: asking focused, well-articulated questions; specifying the request's purpose; providing detailed information about local context and other relevant issues; and understanding the risk of bias associated with RAs. Considerations for HTA doers include: assembling a team using a triage process; involving requestors throughout RA development; negotiating deliverables and timelines using a HTA product matrix; transparently reporting methods; narratively describing methodological issues; and internally reviewing the draft RAs.
RAs are a useful component of HTA programs. To keep these products relevant and useful, HTA agencies must allow RAs to evolve according to need, but with grounding in good practice. Negotiating the line between rigor and relevance is a key skill for HTA agencies. Having the right team is helpful.
Although individual patient data meta-analysis (IPD MA) is considered the gold standard of systematic reviews (SRs), a recent International Network of Agencies for Health Technology Assessment survey indicates that IPD MA is not frequently included in a health technology assessment (HTA), or conducted by HTA researchers. The objective of this presentation is to describe our first experience with including an IPD MA in a HTA report, discuss the added value for an evidence-based decision-making process, and advocate for expanding work in this field.
An overview of SRs on endovascular therapy for acute ischemic stroke included one IPD MA and six study-level SRs/MAs. Methodological quality was appraised by two reviewers independently using the tool recommended by the Cochrane IPD MA working group for the IPD MA, and the AMSTAR (A MeaSurement Tool to Assess systematic Reviews) for the study-level reviews. Pooled results from subgroup analyses based on access to primary patient data were compared to those reported in SRs that conducted subgroup analyses based on the published data to identify patients or clinical factors that would impact clinical outcomes.
The overall findings were similar between the IPD MA and other SRs/MAs. However, when compared to aggregated data used in study-level SRs/MAs, subgroup analyses based on patient data allowed for adjustment of confounders, multiple categories within a subgroup, standardization of outcomes across trials, and detailed data checking. Larger sample sizes of each pre-defined subgroup permitted for more precise estimates of treatment effects. A number of methodological issues in the IPD MA were identified; particularly, no assessment of risk of bias of included trials was conducted.
Access to original patient data is demanding and conducting IPD MA requires extensive resources. The advantages of having an improved quality analysis, an appropriate quantification of the effects in the analyzed subgroups, and precision of results may justify additional efforts, and may increase confidence in the decision-making process.
Population growth, epidemiological and demographic transition, and a shortage of healthcare workers are affecting health care systems in Australia, Canada, the United Kingdom (UK), and the United States (US). Community paramedicine (CP) programs provide a bridge between primary care and emergency care to address the needs of patients with low acuity but lack of access to primary care. However, how to capture the key characteristics of these programs and present them in a meaningful way is still a challenge. The objective of this presentation is to identify and describe the characteristics of currently existing CP programs in the four countries to inform policy-making on CP program development in Alberta.
Information was obtained from systematic reviews, health technology assessments, general reviews, and government documents identified through a comprehensive literature search. The characteristics of the CP programs are described using a framework originally developed in Australia with three categories: (i) the primary health care model, (ii) the health integration model (in Australia, called the substitution model), and (iii) the community coordination model.
In general, Australia emphasizes rural/remote paramedics, whereas Canada, the UK, and the US implement expanded paramedic practice within different environments including rural, remote, regional, and metropolitan settings. Extended care provider programs have been intensively investigated and widely implemented in the UK. While the identified CP programs vary in terms of program components, designation of providers, skill mix, target population, and funding model, the majority of these CP programs fall under the primary health care category of the Australian framework.
Transitioning from hospital-based to community-based health care requires careful consideration of all key factors that could contribute to future program success. Delineating key components of CP programs using the Australian framework will help Alberta decision-makers design, develop, and implement appropriate CP programs that adequately address local needs.
The cost-effectiveness of endovascular therapy (EVT) compared to tissue plasminogen activator (tPA) alone for acute ischemic stroke (AIS) has been established in the literature. However, decision-makers still face challenges of how to best deliver EVT in a timely manner to maximize patient outcomes while minimizing the burden to the healthcare system, given that AIS has time-dependent treatment outcomes. The objective of this presentation is to report an optimization approach for improving health system value and outcomes for patients with AIS who are eligible for EVT in Alberta.
An economic model was developed to compare combinations of “mothership” (transport directly to a comprehensive stroke center [CSC] to receive tPA and EVT) and “drip-and-ship” (transport to a primary stroke centre to receive tPA, followed by transport to a CSC to receive EVT) methods across Alberta. The model considered geographical variation and searched for the best delivery methods through a pairwise comparison of all possible strategies. The controlled variables including in the model were population densities, disease epidemiology, time/distance to hospitals, available medical services, treatment eligibility and efficacy, and costs. Patient outcomes were measured by functional independence. The model defined optimal strategies by identifying the transport methods that produced the highest probability of improved health outcomes at the lowest cost.
The analysis produced an optimization map showing optimal strategies for EVT delivery. The lifetime cost (standard deviation [SD]) per patient and likelihood (SD) of good outcomes was CAD 291,769 (CAD 11,576) [USD 226,207 (USD 8,975)] and 41.82 percent (0.013) when considering optimal clinical outcomes, and CAD 287,725 (CAD 4,141) [USD 223,097 (USD 3,211)] and 41.67 percent (0.016) when considering optimal economic efficiency.
Our model reduces the gap that exists between health technology implementation and cost-effectiveness analysis; namely, neither fully addresses relative efficiency driven by geographical variation, which may misrepresent system value in local settings. Implementation strategies generated in our model capture full values in terms of patient outcomes and costs.
A series of CoCrFeNiMox (x = 0.2, 0.4, 0.6, 0.8, 1.0, and 1.2) high-entropy alloys were designed to develop a eutectic high-entropy alloy system and to acquire a superfine eutectic structure. The results show that for the CoCrFeNiMox alloys, with the increase of Mo content from 0.2 to 1.2, the microstructures shift from a typical dendrite structure to a hypoeutectic microstructure (x = 0.6), and then to a fully eutectic microstructure (x = 0.8) with a lamellar spacing only 110 nm, and finally culminate in the hypereutectic structure (x = 1.0, x = 1.2). The XRD results show that CoCrFeNiMox alloys have a single FCC phase when x is 0.2 or 0.4. When Mo content is over 0.6, it begins to separate Cr9Mo21Ni20 intermetallic compounds. The hardness of the CoCrFeNiMox alloys is increasing significantly from 172.8 to 763.7 HV with the increase of Mo content. Meanwhile, the fracture strength increased but the ductility decreases. Among these alloys, the CoCrFeNiMo0.6 alloy shows excellent integrated mechanical properties of compressive fracture strength and strain, which are 2051 Mpa and 23%, respectively.
The characteristics and mechanism for unsteady shock train motions were experimentally studied in a constant-area rectangular duct. High-speed Schlieren techniques and high-frequency pressure measurements were utilized in this research. The results show that the shock train undergoes periodical motions in response to downstream periodical excitations. The mechanism for unsteady shock train motions is that the shock train keeps changing its moving speed to change the relative Mach number ahead of shock train to match the varying back-pressure condition. It can be found that the unsteady shock train motion can be predicted well with a theoretical model, which is based on this mechanism. A correlation between the amplitude of shock train motions and some flow parameters was illustrated using an analytical equation, which was confirmed by the experimental results.
The Health Technology Assessment (HTA) researchers at the Institute of Health Economics, in collaboration with researchers from two HTA agencies in Australia and Spain, developed, piloted, and validated a 20-criteria quality appraisal checklist specific for case series studies (before-after single arm studies with no control group) (1,2). Since its publication in 2012, the use of the checklist has spread globally through the HTA community and to researchers in other areas. This presentation will briefly introduce the tool, summarize user experiences, outline potential challenges, and provide practical solutions for using or adapting the checklist to various HTA topics.
Feedback from fifteen researchers was collected informally by email and/or formally by questionnaire. The questions included focused on the relevance, clarity, and usefulness of the checklist and its instructions, as well as potential revisions and/or addition of other criteria.
While some of the checklist's criteria apply to all studies of a particular type, others are specific to the research question and/or the technology under investigation; discussion on the modification and/or adaptation of the checklist and its instructions is therefore required before commencing appraisal. Some criteria are difficult to score owing to study reporting limitations. Quality assessment can be challenging when multiple types of studies are included; however, currently there is no single universally validated tool available for diverse study designs. There are frequent demands for a cut-off point in order to separate high- from low-quality studies. However, no scale or numeric scoring was developed for the checklist, due to the well-recognized risks associated with such a scoring system.
The increased use of the checklist and general positive feedback indicates the need for such a tool. User feedback helped improve our understanding of the checklist's applicability with various topics, as well as the potential refinements needed to increase its utility and robustness.
To outline the methodological issues associated with the assessment of newborn screening for severe combined immunodeficiency, which was conducted to address the policy question of whether this test should be added to an existing newborn screening panel.
We conducted a systematic review of published primary studies and critically appraised the methodological quality of selected studies (1).
Fifteen studies were included; six focused on screening test performance, and seven on treatment effectiveness, and two on the effectiveness of a newborn screening program. The methodological issues identified included: (i) Overall poor methodological quality ratings of included studies using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2). This tool was originally developed for assessing diagnostic accuracy studies where subjects usually receive both index test and reference standard so a 2×2 table can be constructed; however it is almost impossible to apply this cross-sectional approach to studies of a screening test for a rare disease like severe combined immunodeficiency. (ii) Case control design using healthy controls could inflate estimates of test accuracy compared to studies using a cohort of consecutive patients, possibly due to spectrum effects and limited-challenge bias. This type of study is useful in the early phase of test development, but estimates of test accuracy based on this type of study should be interpreted with caution. (iii) Some screening programs reported no false negatives, indicating a sensitivity of 100 percent. However, lack of a systematic search for “missed cases” created uncertainty in arriving at a true value for the sensitivity. (iv) Variations in inclusion of pre-term infants, races/ethnicities, and screening protocols made it difficult to compare screening test performance across different studies.
Although severe combined immunodeficiency screening was the first addition to the US Recommended Uniform Screening Panel following an evidence-based review process, caution needs to be exercised when interpreting research findings due to important methodological issues.
On August 12, 2015, a hazardous chemical explosion occurred in the Tianjin Port of China. The explosions resulted in 165 deaths, 8 missing people, injuries to thousands of people. We present the responses of emergency medical services and hospitals to the explosions and summarize the lessons that can be learned.
This study was a retrospective analysis of the responses of emergency medical services and hospitals to the Tianjin explosions. Data on injuries, outcomes, and patient flow were obtained from the government and the hospitals.
A total of 46 ambulances and 143 prehospital care professionals were dispatched to the scene, and 198 wounded were transferred to hospitals by ambulance. More than 4000 wounded casualties surged into hospitals, and 798 wounded were admitted. Both emergency medical services and hospitals were quick and successful in the early stage of the explosions. The strategy of 4 centralizations (4Cs) for medical services management in a mass casualty event was successfully applied.
The risk of accidental events has increased in recent years. We should take advantage of the lessons learned from the explosions and apply these in future disasters. (Disaster Med Public Health Preparedness. 2018; 12: 411–414)
Although many studies worldwide have focused on the relationship between vitamin D and insulin resistance, results remain controversial. Furthermore, concentrations of serum 25-hydroxyvitamin D (25(OH)D) in the Chinese population are unclear. We aimed to investigate vitamin D status and its correlation with insulin resistance among a Chinese adult population.
Serum 25(OH)D, fasting blood glucose, fasting insulin, glycated Hb (HbA1c) and other metabolic parameters were assessed. Neck circumference, waist circumference, hip circumference, weight and height were also measured. Lifestyle factors including smoking and drinking status were obtained. Diabetes mellitus was diagnosed by HbA1c according to the 2010 American Diabetes Association criteria.
Of 7200 residents included, 6597 individuals were ultimately analysed.
We enrolled 2813 males (mean age 52·7 (sd 13·5) years) and 3784 females (52·3 (sd 13·5) years); mean serum 25(OH)D concentration was 43·1 (sd 11·6) and 39·6 (sd 9·8) nmol/l, respectively. Additionally, 83·3 % of participants were 25(OH)D deficient. A significant difference in 25(OH)D was observed between males and females in winter and spring (P<0·001). Furthermore, 25(OH)D concentrations were inversely associated with the homeostasis model assessment of insulin resistance (HOMA-IR) in the overweight and pre-diabetic populations. After adjusting for several variables, 25(OH)D was significantly associated with HOMA-IR in winter. When 25(OH)D values were categorized into quartiles, HOMA-IR was significantly associated with decreasing 25(OH)D.
The majority of the Chinese population was vitamin D deficient and this deficiency was negatively associated with insulin resistance, particularly in the overweight and pre-diabetic populations. Moreover, these associations might be more evident in the winter.
The present study aimed to explore the associations between food away-from-home (FAFH) consumption and body weight outcomes among Chinese adults.
FAFH was defined as food prepared at restaurants and the percentage of energy from FAFH was calculated. Measured BMI and waist circumference (WC) were used as body weight outcomes. Quantile regression models for BMI and WC were performed separately by gender.
Information on demographic, socio-economic, diet and health parameters at individual, household and community levels was collected in twelve provinces of China.
A cross-sectional sample of 7738 non-pregnant individuals aged 18–60 years from the China Health and Nutrition Survey 2011 was analysed.
For males, quantile regression models showed that percentage of energy from FAFH was associated with an increase in BMI of 0·01, 0·01, 0·01, 0·02, 0·02 and 0·03 kg/m2 at the 5th, 25th, 50th, 75th, 90th and 95th quantile, and an increase in WC of 0·04, 0·06, 0·06, 0·04, 0·06, 0·05 and 0·07 cm at the 5th, 10th, 25th, 50th, 75th, 90th and 95th quantile. For females, percentage of energy from FAFH was associated with 0·01, 0·01, 0·01 and 0·02 kg/m2 increase in BMI at the 10th, 25th, 90th and 95th quantile, and with 0·05, 0·04, 0·03 and 0·03 cm increase in WC at the 5th, 10th, 25th and 75th quantile.
Our findings suggest that FAFH consumption is relatively more important for BMI and WC among males rather than females in China. Public health initiatives are needed to encourage Chinese adults to make healthy food choices when eating out.
To assess correlations between cruciferous vegetable intake and urinary isothiocyanate (ITC) level, in addition to glutathione S-transferase (GST) genotypes and other individual factors.
The study included cohort participants whose urinary ITC levels had been previously ascertained. Urinary ITC was assessed using HPLC. Usual dietary intake of cruciferous vegetables was assessed using a validated FFQ and total dietary ITC intake was calculated. Recent cruciferous vegetable intake was determined. GST genotypes were assessed using duplex real-time quantitative PCR assays. Spearman correlations were calculated between the covariates and urinary ITC levels and linear regression analyses were used to calculate the mean urinary ITC excretion according to GST genotype.
Urban city in China.
The study included 3589 women and 1015 men from the Shanghai Women’s and Men’s Health Studies.
Median urinary ITC level was 1·61 nmol/mg creatinine. Self-reported usual cruciferous vegetable intake was weakly correlated with urinary ITC level (rs=0·1149; P<0·0001), while self-reported recent intake was more strongly correlated with urinary ITC (rs=0·2591; P<0·0001). Overall, the GST genotypes were not associated with urinary ITC level, but significant differences according to genotype were observed among current smokers and participants who provided an afternoon urine sample. Other factors, including previous gastrectomy or gastritis, were also related to urinary ITC level.
The study suggests that urinary secretion of ITC may provide additional information on cruciferous vegetable intake and that GST genotypes are related to urinary ITC level only in some subgroups.
Error-prone repair of radiation-induced DNA double-strand breaks (DSBs) results in DNA mutation that is essential for mutation breeding. Non-homologous end joining might be the principal DSB repair mechanism in eukaryotes, which is mediated and activated by Ku protein, a heterodimer of 70 and 80 kDa subunits. In this study, on the basis of complementary DNA (cDNA), the genomic sequences of TaKu70 and TaKu80 genes in all the three genomes of wheat were characterized. Only single-nucleotide substitutions and no insertions or deletions were detected in the exons of TaKu70 and TaKu80 genes. The size of the introns exhibited a slight variation between the sequences. Yeast two-hybrid analysis demonstrated that TaKu70 and TaKu80 formed a heterodimer, and electrophoretic mobility shift assays revealed that this heterodimer bound to double-stranded DNA, but not to single-stranded DNA. The quantitative polymerase chain reaction analysis revealed that the expression of TaKu70 and TaKu80 genes was up-regulated under γ-ray irradiation in a dose-dependent manner in the seedlings of wheat. These results suggest that TaKu70 and TaKu80 form a functional heterodimer and are associated with the repair of the induced DSBs in wheat.
We positionally cross-matched the stellar observations between LAMOST pilot survey and SDSS/SEGUE database, picked out more than 4000 targets observed by both projects, mostly are late A and FGK type stars. For the two dataset, we adopted ULySS program (Koleva et al. 2009, Wu et al. 2011a) to determine the stellar atmospheric parameters (Teff, log g, [Fe/H], Radial Velocity) with the ELODIE library as a reference (Wu et al. 2011b). For the individual parameter, we made two kinds of comparison, first for the SDSS spectra, second for the LAMOST spectra, tested the differences between the SSPP (SDSS/SEGUE stellar parameter pipeline) measurements and the ULySS derived results. Since the LAMOST pilot survey observations SNR (Signal to Noise Ratio) are low, for the latter comparison we excluded those stars with g band SNR < 10, then the sample volumn reduced to around 1300. Fig.1 displays the details of the second kind comparison for each parameter. All the comparisons demonstrate acceptable and reasonable agreement between each other for medium-resolution survey spectra. Our preliminary examination on the precision of the stellar parameters that could be derived from the LAMOST pilot survey observations exhibits the equivalent capability of LAMOST to study our Milky Way as for the SDSS/SEGUE. The LAMOST telescope executed its formal survey from Sep. 28th 2012, it will yield more better quality stellar spectroscopic data spanning in deeper and broader sky coverage (this work was supported by the Natural Science Foundation of China under No. 11103031).
A new method of epitaxial growth of CoSi2 film on Si substrate by ternary solid state interaction is investigated. XRD, RBS and TEM show that single-crystalline CoSi2 can be formed on both Si (111) and (100) substrates by using Co/Ti/Si or TiN/Co/Ti/Si multilayer. The evolution of multilayer structure and its resistivity is studied and epitaxy mechanism is discussed. Experimental results indicate strong affinity between Co and Si. During the ternary interaction the epitaxial CoSi2 can be grown directly on Si and its growth may behave as a diffusion controlled process. The thickness of Ti layer and the annealing procedure have important effect on CoSi2 epitaxial growth.
A multilayer structure of Co/a-Si/Ti/Si(100) together with Co/Ti/Si(100) is applied to investigate the process and mechanism of CoSi2 epitaxial growth on a Si(100) substrate. The experimental results show that by adding an amorphous Si layer with a certain thickness, the epitaxial quality of CoSi2 is significantly improved. A multi-element amorphous layer is formed by a solid state amorphization reaction at the initial stage of the multilayer reaction. This layer acts as a diffusion barrier, which controls the atomic interdiffusion of Co and Si and limits the supply of Co atoms. It has a vital effect on the multilayer reaction kinetics, and the epitaxial growth of CoSi2 on Si. The kinetics of the CoSi2 growth process from multilayer reactions is investigated.
Ultra-thin epitaxial CoSi2 films formed by Co(3∼5nm)/Ti(1 nm)/Si(100) and Co(3∼5nm)/Si(lnm)/Ti(Inm)/Si are studied. The multilayers are deposited by ion-beam sputtering. Rapid thermal annealing (RTA) is used for silicidation. XRD, RBS, TEM, AFM, four-point probe, I-V and C-V measurements are carried out for characterization. The XRD spectra show the CoSi2 film formed by Co/Ti/Si or Co/Si/Ti/Si solid phase epitaxy has, epitaxial characteristic. XTEM shows that the film is continuous. RBS/Channeling shows that the formed CoSi2 has sharp interface with a minimum channeling yield of Co signal of 40%. AFM shows that the surface of ultra-thin CoSi2 film is smooth with a roughness of nearly 0.7 nm. The Rs∼T relationship shows that the CoSi2 films formed by Co/Si/Ti/Si reaction have the best thermal stability (stable up to 900°C). Those formed by Co/Ti/Si reaction are stable up to 850°C, while those formed by Co/Si reaction are only stable up to 750°C. By fitting the experimental I-V and C-V curves of the epitaxial CoSi2/Si Schottky diodes, barrier heights of around 0.6 eV and close to unity ideality factors are obtained.