The 'ins and outs' of colonoscopy at Wits Donald Gordon Medical Centre, South Africa: A practice audit of the outpatient endoscopy unit.

BACKGROUND: In South Africa, there are no national guidelines for the conduct or quality assessment of colonoscopy, the gold standard for investigation and diagnosis of bowel pathology. OBJECTIVES: To describe the clinical profile of patients and evaluate the practice of colonoscopy using procedural quality indicators at the Wits Donald Gordon Medical Centre (WDGMC) outpatient endoscopy unit (OEU). METHODS: We conducted a prospective, clinical practice audit of colonoscopies performed on adults (≥18 years of age). A total of 1 643 patients were included in the study and variables that were collected enabled the assessment of adequacy of bowel preparation, length of withdrawal time and calculation of caecal intubation rate (CIR), polyp detection rate (PDR) and adenoma detection rate (ADR). We stratified PDR and ADR by sex, age, population group, withdrawal time and bowel preparation. CIR, PDR and ADR estimates were compared between patient groups by the χ2 test; Fisher's exact test was used for 2 × 2 tables. A p-value <0.05 was used. Benchmark recommendations by the American Society for Gastrointestinal Endoscopy (ASGE)/American College of Gastroenterology (ACG) Task Force on Colorectal Cancer (CRC) were used in this audit to assess individual endoscopist performance and that of the endoscopy unit as a whole. RESULTS: The mean age of patients was 55.7 (standard deviation (SD) 14.4; range 18 - 91) years, ~60% were female, and the majority (75.5%) were white. Of the outpatients, 77.6% had adequate bowel preparation (ASGE/ACG benchmark ≥85%). The CIR was 97.0% overall, and screening colonoscopy was 96.3% (ASGE/ACG benchmark ≥90% overall and ≥95% for screening colonoscopies). The median withdrawal time for negative-result screening colonoscopies was 5.7 minutes (interquartile range (IQR) 4.2 - 9.3; range 1.1 - 20.6) (ASGE/ACG benchmark ≥ 6minutes), and PDR and ADR were 27.6% and 15.6%, respectively (ASGE/ACG benchmark ADR ≥25%). We demonstrated a 23.7% increase in PDR and 14.1% increase in ADR between scopes that had mean withdrawal times of ≥6 minutes and <6 minutes, respectively. Although the number of black Africans in the study was relatively small, our results showed that they have similar ADRs and PDRs to the white population group, contradicting popular belief. CONCLUSIONS: The WDGMC OEU performed reasonably well against the international guidelines, despite some inadequacy in bowel preparation and lower than recommended median withdrawal times on negative-result colonoscopy. Annual auditing of clinical practice and availability of these data in the public domain will become standard of care, making this audit a baseline for longitudinal observation, assessing the impact of interventions, and contributing to the development of local guidelines.

Influence of morphology on electrical and optical properties of graphene/Al-doped ZnO-nanorod composites.

The development of future 3D-printed electronics relies on the access to highly conductive inexpensive materials that are printable at low temperatures (<100 ◦C). The implementation of available materials for these applications are, however, still limited by issues related to cost and printing quality. Here, we report on the simple hydrothermal growth of novel nanocomposites that are well suited for conductive printing applications. The nanocomposites comprise highly Al-doped ZnO nanorods grown on graphene nanoplatelets (GNPs). The ZnO nanorods play the two major roles of (i) preventing GNPs from agglomerating and (ii) promoting electrical conduction paths between the graphene platelets. The effect of two different ZnO-nanorod morphologies with varying Al-doping concentration on the nanocomposite conductivity and the graphene dispersity are investigated. Time-dependent absorption, photoluminescence and photoconductivity measurements show that growth in high pH solutions promotes a better graphene dispersity, higher doping levels and enhanced bonding between the graphene and the ZnO nanorods. Growth in low pH solutions yields samples characterized by a higher conductivity and a reduced number of surface defects. These samples also exhibit a large persistent photoconductivity attributed to an effective charge separation and transfer from the nanorods to the graphene platelets. Our findings can be used to tailor the conductivity of novel printable composites, or for fabrication of large volumes of inexpensive porous conjugated graphene-semiconductor composites.

The 'ins and outs' of faecal microbiota transplant for recurrent Clostridium difficile diarrhoea at Wits Donald Gordon Medical Centre, Johannesburg, South Africa.

BACKGROUND: Clostridium difficile-associated diarrhoea (CDAD) is a potentially life-threatening condition that is becoming increasingly common. A persistent burden of this infectious illness has been demonstrated over the past 4 years at Wits Donald Gordon Medical Centre (WDGMC), Johannesburg, South Africa, through implementation of active surveillance of hospital-acquired infections as part of the infection prevention and control programme. Oral treatment with metronidazole or vancomycin is recommended, but there is a major problem with symptomatic recurrence after treatment. Replacement of normal flora by the administration of donor stool through colonoscopy or nasogastric/duodenal routes is becoming increasingly popular. OBJECTIVES: To identify risk factors for the development of CDAD in patients referred for faecal microbiota transplant (FMT) and evaluate the safety of administration of donor stool as an outpatient procedure, including via the nasogastric route. METHODS: A retrospective record review of patients with recurrent CDAD referred for FMT at WDGMC between 1 January 2012 and 31 December 2016 was conducted. RESULTS: Twenty-seven patients were identified, all of whom fulfilled the criteria for recurrent CDAD. One-third were aged >65 years, and the majority were female. The most common risk factors were prior exposure to antibiotics or proton-pump inhibitors and underlying inflammatory bowel disease. Three procedures were carried out as inpatients and 24 in the outpatient gastroenterology unit. At 4-week follow-up, all patients reported clinical resolution of their diarrhoea after a single treatment and there were no recurrences. The FMT procedure was associated with no morbidity (with particular reference to the risk of aspiration when administered via the nasogastric route) or mortality. CONCLUSIONS: This case series confirms that FMT is a safe and effective therapy for recurrent CDAD. In most cases it can be administered via the nasogastric route in the outpatient department. We propose that the recently published South African Gastroenterology Society guidelines be reviewed with regard to recommendations for the route of administration of FMT and hospital admission. Meticulous prescription practice by clinicians practising in hospitals and outpatient settings, with particular attention to antimicrobials and chronic medication, is urgently required to prevent this debilitating and potentially life-threatening condition.

Advanced Methods for Dose and Regimen Finding During Drug Development: Summary of the EMA/EFPIA Workshop on Dose Finding (London 4-5 December 2014).

Inadequate dose selection for confirmatory trials is currently still one of the most challenging issues in drug development, as illustrated by high rates of late-stage attritions in clinical development and postmarketing commitments required by regulatory institutions. In an effort to shift the current paradigm in dose and regimen selection and highlight the availability and usefulness of well-established and regulatory-acceptable methods, the European Medicines Agency (EMA) in collaboration with the European Federation of Pharmaceutical Industries Association (EFPIA) hosted a multistakeholder workshop on dose finding (London 4-5 December 2014). Some methodologies that could constitute a toolkit for drug developers and regulators were presented. These methods are described in the present report: they include five advanced methods for data analysis (empirical regression models, pharmacometrics models, quantitative systems pharmacology models, MCP-Mod, and model averaging) and three methods for study design optimization (Fisher information matrix (FIM)-based methods, clinical trial simulations, and adaptive studies). Pairwise comparisons were also discussed during the workshop; however, mostly for historical reasons. This paper discusses the added value and limitations of these methods as well as challenges for their implementation. Some applications in different therapeutic areas are also summarized, in line with the discussions at the workshop. There was agreement at the workshop on the fact that selection of dose for phase III is an estimation problem and should not be addressed via hypothesis testing. Dose selection for phase III trials should be informed by well-designed dose-finding studies; however, the specific choice of method(s) will depend on several aspects and it is not possible to recommend a generalized decision tree. There are many valuable methods available, the methods are not mutually exclusive, and they should be used in conjunction to ensure a scientifically rigorous understanding of the dosing rationale.

Transient knock-down of kcna2 reduces sleep in larval zebrafish.

In the current study we set out to determine the effects of morpholino oligonucleotide (MO) knock-down of kcna2 on sleep-wake cycles in zebrafish. The results were compared to a non-overlapping MO injection, Dec2, who's mutant is also linked with a short sleep phenotype. Four groups of fish were used in the experiment: naïve fish, and fish injected with either control, kcna2, or Dec2 MO. All groups underwent 24-h behavioral monitoring of sleep-wake cycles at four and seven days-post-fertilization (dpf). First, we established an immobility dependent, sleep related, increase in arousal thresholds at both 4 and 7 dpf. Secondly, we show that kcna2 MO injected fish exhibit significantly less sleep behavior than controls and naïve fish, whereas Dec2 MO injections had similar but less severe effects. Finally, using kcna2 MO injected fish only, we turn to local field recordings at the level of the telencephalon and tectum opticum and rule out that the knock-down resulted in a non-specific increase in neural excitability that would mask sleep behavior.

Supramolecular Hemicage Cobalt Mediators for Dye-Sensitized Solar Cells.

A new class of dye-sensitized solar cells (DSSCs) using the hemicage cobalt-based mediator [Co(ttb)]2+/3+ with the highly preorganized hexadentate ligand 5,5'',5''''-((2,4,6-triethyl benzene-1,3,5-triyl)tris(ethane-2,1-diyl))tri-2,2'-bipyridine (ttb) has been fully investigated. The performances of DSSCs sensitized with organic D-π-A dyes utilizing either [Co(ttb)]2+/3+ or the conventional [Co(bpy)3 ]2+/3+ (bpy=2,2'-bipyridine) redox mediator are comparable under 1000 W m-2 AM 1.5 G illumination. However, the hemicage complexes exhibit exceptional stability under thermal and light stress. In particular, a 120-hour continuous light illumination stability test for DSSCs using [Co(ttb)]2+/3+ resulted in a 10 % increase in the performance, whereas a 40 % decrease in performance was found for [Co(bpy)3 ]2+/3+ electrolyte-based DSSCs under the same conditions. These results demonstrate the great promise of [Co(ttb)]2+/3+ complexes as redox mediators for efficient, cost-effective, large-scale DSSC devices.

Edoxaban Exposure-Response Analysis and Clinical Utility Index Assessment in Patients With Symptomatic Deep-Vein Thrombosis or Pulmonary Embolism.

Edoxaban exposure-response relationships from the phase III study evaluating edoxaban for prevention and treatment of venous thromboembolism (VTE) in patients with acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE) were assessed by parametric time-to-event analysis. Statistical significant exposure-response relationships were recurrent VTE with hazard ratio (HR) based on average edoxaban concentration at steady state (Cav) (HRCav) = 0.98 (i.e., change in the HR with every 1 ng/mL increase of Cav); the composite of recurrent DVT and nonfatal PE with HRCav = 0.99; and the composite of recurrent DVT, nonfatal PE, and all-cause mortality HRCav = 0.98, and all death using maximal edoxaban concentration (Cmax) with HR (Cmax) = 0.99. No statistical significant exposure-response relationships were found for clinically relevant bleeding or major adverse cardiovascular event. Results support the recommendation of once-daily edoxaban 60 mg, and a reduced 30 mg dose in patients with moderate renal impairment, body weight ≤60 kg, or use of P-glycoprotein inhibitors verapamil or quinidine.

Determination of critical diameters for intrinsic carrier diffusion-length of GaN nanorods with cryo-scanning near-field optical microscopy.

Direct measurements of carrier diffusion in GaN nanorods with a designed InGaN/GaN layer-in-a-wire structure by scanning near-field optical microscopy (SNOM) were performed at liquid-helium temperatures of 10 K. Without an applied voltage, intrinsic diffusion lengths of photo-excited carriers were measured as the diameters of the nanorods differ from 50 to 800 nm. The critical diameter of nanorods for carrier diffusion is concluded as 170 nm with a statistical approach. Photoluminescence spectra were acquired for different positions of the SNOM tip on the nanorod, corresponding to the origins of the well-defined luminescence peaks, each being related to recombination-centers. The phenomenon originated from surface oxide by direct comparison of two nanorods with similar diameters in a single map has been observed and investigated.

Evidence-based or traditional treatment of cancer-related lymphedema.

The incidence of lymphedema (LE) related to treatment of women's cancer (breast and gynecologic) is as high as 40%. Treatment of LE varies around the world but was decades ago initially based on programs including manual lymph drainage (MLD), compression, skin care and easy exercise. With accumulating evidence and experience, it is time to consider if altering these treatment principles is needed. Based on accumulating evidence, we suggest less emphasis on manual lymph drainage and more on early diagnosis, compression, weight control and exercise for improvement of strength and circulation.

Absence of rapid eye movements during sleep in adult zebrafish.

Sleep is not a uniform phenomenon, but is organized in alternating, fundamentally different states, rapid eye movement sleep and non-rapid eye movement sleep. Zebrafish (Danio rerio) have recently emerged as an excellent model for sleep research. Zebrafish are well characterized in terms of development, neurobiology and genetics. Moreover, there are many experimental tools not easily applied in mammalian models that can be readily applied to zebrafish, making them a valuable additional animal model for sleep research. Sleep in zebrafish is defined behaviorally and exhibits the hallmarks of mammalian sleep (e.g. sleep homeostasis and pressure). To our knowledge no attempts have been made to discern if sleep in zebrafish entails alternations of REM-NREM sleep cycles which are critical for further development of the model. In the current experiment we quantify two key REM sleep components, rapid eye movements and respiratory rates, across sleep-wake cycles. We find no sleep-related rapid eye movements. During sleep respiratory rates, however, are reduced and become less regular, further establishing that the behavioral definition used truly captures a change in the fish's physiology. We thus fail to find evidence for REM-NREM sleep cycles in zebrafish but demonstrate a physiological change that occurs concomitantly with the previously defined behavioral state of sleep. We do not rule out that other phasic REM components (e.g. atonia, cardiac arrhythmias, myoclonic twitches or desynchronized EEG) are coherently expressed during sleep but we conclude that adult zebrafish do not have REM-sleep-related rapid eye movements.

Polarized single photon emission and photon bunching from an InGaN quantum dot on a GaN micropyramid.

We report on excitonic single photon emission and biexcitonic photon bunching from an InGaN quantum dot formed on the apex of a hexagonal GaN micropyramid. An approach to suppress uncorrelated emission from the pyramid base is proposed, a metal film is demonstrated to effectively screen background emission and thereby significantly enhance the signal-to-background ratio of the quantum dot emission. As a result, the second order coherence function at zero time delay g(2)(0) is significantly reduced (to g(2)(0) = 0.24, raw value) for the excitonic autocorrelation at a temperature of 12 K under continuous wave excitation, and a dominating single photon emission is demonstrated to survive up to 50 K. The deterioration of the g(2)(0)-value at elevated temperatures is well understood as the combined effect of reduced signal-to-background ratio and limited time resolution of the setup. This result underlines the great potential of site-controlled pyramidal dots as sources of fast polarized single photons.

Serum level of cartilage oligomeric matrix protein is lower in children with idiopathic scoliosis than in non-scoliotic controls.

PURPOSE: The etiology of idiopathic scoliosis remains unknown, but growth is a risk factor for progression. Growth pattern differs in children with and without scoliosis. Cartilage oligomeric matrix protein (COMP) may be associated with scoliosis and growth. We, therefore, studied COMP in children with and without idiopathic scoliosis. METHODS: We included 105 children, with mean age 14.4 years (range 10-16), under observation or treatment for idiopathic scoliosis, and 103 children from an age-matched population-based cohort. COMP was measured in serum at the time of inclusion. Growth velocity was estimated from repeated height measurements. T tests, analysis of covariance or linear regression were used for statistical comparisons. RESULTS: COMP was mean (SD) 11 (5) units/liter (U/L) in children with scoliosis and 13 (5) U/L in the control cohort (p = 0.005, adjusted for sex and sampling time of the day). When patients and controls were analyzed together, high COMP was correlated with high growth velocity (ß = 0.19, p = 0.003). When patients and controls were analyzed separately, COMP was correlated with growth velocity in children with scoliosis (ß = 0.27, p = 0.007), but not in children without scoliosis (ß = 0.02, p = 0.83) (all analyses adjusted for age, sex and sampling time). Low COMP was significantly correlated with large curve size in children with scoliosis (ß = -0.29, p = 0.003), but not after adjustment for age, sex and sampling time (ß = -0.16; p = 0.14). CONCLUSION: COMP was lower in children with idiopathic scoliosis than in a control cohort. In children with scoliosis, high COMP was modestly correlated with high growth velocity, but not with curve severity.

Excitons and biexcitons in InGaN quantum dot like localization centers.

Indium segregation in a narrow InGaN single quantum well creates quantum dot (QD) like exciton localization centers. Cross-section transmission electron microscopy reveals varying shapes and lateral sizes in the range ∼1-5 nm of the QD-like features, while scanning near field optical microscopy demonstrates a highly inhomogeneous spatial distribution of optically active individual localization centers. Microphotoluminescence spectroscopy confirms the spectrally inhomogeneous distribution of localization centers, in which the exciton and the biexciton related emissions from single centers of varying geometry could be identified by means of excitation power dependencies. Interestingly, the biexciton binding energy (E(b)xx) was found to vary from center to center, between 3 to -22 meV, in correlation with the exciton emission energy. Negative binding energies are only justified by a three-dimensional quantum confinement, which confirms QD-like properties of the localization centers. The observed energy correlation is proposed to be understood as variations of the lateral extension of the confinement potential, which would yield smaller values of E(b)xx for reduced lateral extension and higher exciton emission energy. The proposed relation between lateral extension and E(b)xx is further supported by the exciton and the biexciton recombination lifetimes of a single QD, which suggest a lateral extension of merely ∼3 nm for a QD with strongly negative E(b)xx = -15.5 meV.

Long-term efficacy of Internet-based cognitive behavior therapy for obsessive-compulsive disorder with or without booster: a randomized controlled trial.

BACKGROUND: As relapse after completed cognitive behavior therapy (CBT) for obsessive-compulsive disorder (OCD) is common, many treatment protocols include booster programs to improve the long-term effects. However, the effects of booster programs are not well studied. In this study, we investigated the long-term efficacy of Internet-based CBT (ICBT) with therapist support for OCD with or without an Internet-based booster program. METHOD: A total of 101 participants were included in the long-term follow-up analysis of ICBT. Of these, 93 were randomized to a booster program or no booster program. Outcome assessments were collected at 4, 7, 12 and 24 months after receiving ICBT. RESULTS: The entire sample had sustained long-term effects from pre-treatment to all follow-up assessments, with large within-group effect sizes (Cohen's d = 1.58-2.09). The booster group had a significant mean reduction in OCD symptoms compared to the control condition from booster baseline (4 months) to 7 months, but not at 12 or 24 months. Participants in the booster group improved significantly in terms of general functioning at 7, 12 and 24 months, and had fewer relapses. Kaplan-Meier analysis also indicated a significantly slower relapse rate in the booster group. CONCLUSIONS: The results suggest that ICBT has sustained long-term effects and that adding an Internet-based booster program can further improve long-term outcome and prevent relapse for some OCD patients.

Outcome after HSCT in Philadelphia chromosome positive acute lymphoblastic leukemia in Sweden: a population-based study.

Even in the tyrosine kinase inhibitor era, allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as standard care for adult Philadelphia (Ph) positive acute lymphoblastic leukemia (ALL). In this retrospective national study, we have reviewed the outcome after HSCT in Sweden for adult Ph-positive ALL between 2000 and 2009. In total, 51 patients with median age 42 (range 20-66) years underwent HSCT. Mainly allogeneic HSCT was performed (24 related donor, 24 unrelated donor and one cord blood), and only two patients were treated with an autologous HSCT. The 5-year OS was 51 (37-64) %. The probabilities of morphological relapse and non-relapse mortality (NRM) at 5 years were 36 (23-49) and 18 (9-29) %, respectively. For the allogeneic transplanted, the 5-year OS was for patients <40 years 70 (50-90) % and for patients ≥40 years 34 (16-52) %, p = 0.002. The 5-year probability of NRM was for patients <40 years 10 (2-28) % compared to 25 (11-42) % for patients ≥40 years (p = 0.04). Patients with chronic graft-versus-host disease (GVHD) had a 5-year morphological relapse probability of 20 (6-40) % compared to 59 (35-77) % for patients without chronic GVHD (p = 0.03). Age ≥40 years and the absence of chronic GVHD were confirmed as independent negative prognostic factors for relapse and non-relapse mortality in a multivariate analysis although the impact of chronic GVHD was significant only in the older age cohort.

Real-time in vivo uric acid biosensor system for biophysical monitoring of birds.

Research on birds has long played an important role in ecological investigations, as birds are relatively easily observed, and their high metabolic rates and diurnal habits make them quite evidently responsive to changes in their environments. A mechanistic understanding of such avian responses requires a better understanding of how variation in physiological state conditions avian behavior and integrates the effects of recent environmental changes. There is a great need for sensor systems that will allow free-flying birds to interact with their environment and make unconstrained decisions about their spatial location at the same time that their physiological state is being monitored in real time. We have developed a miniature needle-based enzymatic sensor system suitable for continuous real-time amperometric monitoring of uric acid levels in unconstrained live birds. The sensor system was constructed with Pt/Ir wire and Ag/AgCl paste. Uricase enzyme was immobilized on a 0.7 mm sensing cavity of Nafion/cellulose inner membrane to minimize the influences of background interferents. The sensor response was linear from 0.05 to 0.6 mM uric acid, which spans the normal physiological range for most avian species. We developed a two-electrode potentiostat system that drives the biosensor, reads the output current, and wirelessly transmits the data. In addition to extensive characterization of the sensor and system, we also demonstrate autonomous operation of the system by collecting in vivo extracellular uric acid measurements on a domestic chicken. The results confirm our needle-type sensor system's potential for real-time monitoring of birds' physiological state. Successful application of the sensor in migratory birds could open up a new era of studying both the physiological preparation for migration and the consequences of sustained avian flight.

Electron correlations in Mn(x)Ga(1-x)A(s)as seen by resonant electron spectroscopy and dynamical mean field theory.

After two decades since the discovery of ferromagnetism in manganese-doped gallium arsenide, its origin is still debated, and many doubts are related to the electronic structure. Here we report an experimental and theoretical study of the valence electron spectrum of manganese-doped gallium arsenide. The experimental data are obtained through the differences between off- and on-resonance photo emission data. The theoretical spectrum is calculated by means of a combination of density-functional theory in the local density approximation and dynamical mean field theory, using exact diagonalization as impurity solver. Theory is found to accurately reproduce measured data and illustrates the importance of correlation effects. Our results demonstrate that the manganese states extend over a broad range of energy, including the top of the valence band, and that no impurity band splits-off from the valence band edge, whereas the induced holes seem located primarily around the manganese impurity.

Comparisons of Analysis Methods for Proof-of-Concept Trials.

Drug development struggles with high costs and time consuming processes. Hence, a need for new strategies has been accentuated by many stakeholders in drug development. This study proposes the use of pharmacometric models to rationalize drug development. Two simulated examples, within the therapeutic areas of acute stroke and type 2 diabetes, are utilized to compare a pharmacometric model-based analysis to a t-test with respect to study power of proof-of-concept (POC) trials. In all investigated examples and scenarios, the conventional statistical analysis resulted in several fold larger study sizes to achieve 80% power. For a scenario with a parallel design of one placebo group and one active dose arm, the difference between the conventional and pharmacometric approach was 4.3- and 8.4-fold, for the stroke and diabetes example, respectively. Although the model-based power depend on the model assumptions, in these scenarios, the pharmacometric model-based approach was demonstrated to permit drastic streamlining of POC trials.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e23; doi:10.1038/psp.2012.24; advance online publication 16 January 2013.

Mn-induced modifications of Ga 3d photoemission from (Ga, Mn)As: evidence for long range effects.

Using synchrotron based photoemission, we have investigated the Mn-induced changes in Ga 3d core level spectra from as-grown Ga(1-x)Mn(x)As. Although Mn is located in Ga substitutional sites, and therefore does not have any Ga nearest neighbors, the impact of Mn on the Ga core level spectra is pronounced even at Mn concentrations in the region of 0.5%. The analysis shows that each Mn atom affects a volume corresponding to a sphere with around 1.4 nm diameter.

InGaN quantum dot formation mechanism on hexagonal GaN/InGaN/GaN pyramids.

Growing InGaN quantum dots (QDs) at the apex of hexagonal GaN pyramids is an elegant approach to achieve a deterministic positioning of QDs. Despite similar synthesis procedures by metal organic chemical vapor deposition, the optical properties of the QDs reported in the literature vary drastically. The QDs tend to exhibit either narrow or broad emission lines in the micro-photoluminescence spectra. By coupled microstructural and optical investigations, the QDs giving rise to narrow emission lines were concluded to nucleate in association with a (0001) facet at the apex of the GaN pyramid.