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Objective: People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown. Methods: We collected longitudinal diagnostic information (mean = 36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other) and PSY. We pre-specified NfL > 582 pg/mL as indicative of ND/MCI/other. Results: Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone. Conclusions: CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.

Objectives: Carer burden is common in younger-onset dementia (YOD), often due to the difficulty of navigating services often designed for older people with dementia. Compared to Alzheimer’s disease (AD), the burden is reported to be higher in behavioral variant frontotemporal dementia (bvFTD). However, there is little literature comparing carer burden specifically in YOD. This study hypothesized that carer burden in bvFTD would be higher than in AD. Design: Retrospective cross-sectional study. Setting: Tertiary neuropsychiatry service in Victoria, Australia. Participants: Patient-carer dyads with YOD. Measurements: We collected patient data, including behaviors using the Cambridge Behavioral Inventory-Revised (CBI-R). Carer burden was rated using the Zarit Burden Inventory-short version (ZBI-12). Descriptive statistics and Mann-Whitney U tests were used to analyze the data. Results: Carers reported high burden (ZBI-12 mean score = 17.2, SD = 10.5), with no significant difference in burden between younger-onset AD and bvFTD. CBI-R stereotypic and motor behaviors, CBI-R everyday skills, and total NUCOG scores differed between the two groups. There was no significant difference in the rest of the CBI-R subcategories, including the behavior-related domains. Conclusion: Carers of YOD face high burden and are managing significant challenging behaviors. We found no difference in carer burden between younger-onset AD and bvFTD. This could be due to similarities in the two subtypes in terms of abnormal behavior, motivation, and self-care as measured on CBI-R, contrary to previous literature. Clinicians should screen for carer burden and associated factors including behavioral symptoms in YOD syndromes, as they may contribute to carer burden regardless of the type.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Research Foundation of Korea Background Exosomes have gained attention as nanocarrier; however, the poor targeting ability after systemic administration restrict exosomes' clinical application. The targeting ability of exosomes can be improved by surface modifications. Recently, the popular method is the cell engineering technique, but cell engineering processes are complex, high-cost, time-consuming, and labor-intensive. To resolve this problem, several previous reports demonstrated exosomes are directly modified by chemical reactions (e.g., biochemical conjugation or hydrophobic insertion). However, few studies have modified exosomes with targeting ligands for atrial fibrillation. Purpose This study aimed to develop exosomes endowed with heart-targeting properties using a fast and easy chemical modification method to serve as a promising therapeutic tool for atrial fibrillation. Methods We firstly generated heart-targeted delivery system (CTP-Exo) by engineering the surface of exosomes with cardiac targeting peptide (CTP) using bio-orthogonal copper-free click chemistry. Next, we loaded NOX4 siRNA into CTP-Exo, and NOX4 siRNA-mediated cardioprotective effects were examined in angiotensin II (Ang II)-treated human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and mice. Results CTP-Exo had typical exosome properties, such as ~ 150 nm rounded or cup-shaped morphology, and the presence of marker proteins. Compared with unmodified-Exo, CTP-Exo specifically accumulated in the heart (P < 0.05). In addition, NOX4 siRNA-loaded CTP-Exo (siNOX4/CTP-Exo) exerted strong cardioprotective effects with excellent heart-targeting ability. In Ang II-treated iPSC-CMs, siNOX4/CTP-Exo exhibited the reduced the peak-to-peak interval variability, beating frequency, and Ca2+ transient amplitude. After intravenous injection of siNOX4/CTP-Exo in Ang II-treated mice, there was a significant improvement in cardiac function (P < 0.05) with reduced fibrosis and arrhythmia inducibility. Conclusion Taken together, our results suggest that CTP-Exo function as efficient vehicles for heart-targeted delivery of siRNA, which in turn may potentially be used for the treatment of atrial fibrillation.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIT), the Korean Fund for Regenerative Medicine (KFRM) grant funded by the Korea government Background Functional mutations in the PITX2 (Paired-like homeodomain transcription factor 2) gene cause genetically inherited atrial fibrillation (AF). PITX2 is known to plays a pivotal role in regulating the expression of distinct ion channels, beta-adrenergic stimulation, cell-cell coupling and resulting in AF due to abnormal calcium abnormalities and electrical remodeling. However, the pathophysiological mechanisms linking impaired PITX2 with AF are still to be explored. This study was performed to generate PITX2c knockout human iPSC atrial cardiomyocytes (hiPSC-atrial CM), which are useful tools for arrhythmia modeling, and evaluate the mechanism of PITX2 deficiency leading to AF. Methods We generated a PITX2 knock-out iPSC line using a CRISPR/Cas9-based genome editing system. hiPSCs were electroporated with Cas9/sgRNA ribonucleoprotein (RNP) complexes. PITX2c knock-out hiPSC-CMs differentiated into atrial cardiomyocytes based on the manipulation of retinoic acid signaling. For the three-dimensional (3D) culture model, cells were plated in the spherical plate 5D. Electrophysiological properties and oxidative stress were assessed in PITX2c-deficient cardiomyocytes. Proarrhythmic effects of the PITX2c knock-out were quantified with AP morphology, AP duration (APD) restitution, wavelength (WL) and conduction velocity (CV) restitution using microelectrode arrays (MEA). Results We demonstrated that atrial-specific differentiated hiPSC-CMs expressed atrial-specific genes and the properties of action potentials were like those of human atrial cardiomyocytes. In addition, both 2D and 3D PITX2c knock-out atrial hiPSC-CMs showed signs of APD shortening and reduced wavelength (WL) and increased conduction velocity (CV) restitution (P 99). Conclusions This study provides an understanding of electrical remodeling by PITX2c loss-of-function mutations and suggests the potential therapeutic candidates by miR-374a-5p and miR-374b-5p, thus helping to understand the mechanism of PITX2 deficiency leading to atrial fibrillation.

BACKGROUND Hospital wards are a complex and dynamic environment which rely on optimal staff performance. However, there is little research evaluating group interventions to improve staff attention and teamwork. AIMS To evaluate whether a regular, short and guided group mindfulness practice for staff in an acute general medicine team improves attention and teamwork. METHODS A 10-min program comprising mindfulness exercises and techniques was delivered daily to a multidisciplinary general medicine team based in a tertiary hospital for four weeks. This was undertaken immediately prior to the team's interdisciplinary ward round. We used a mixed-method design, with self-rated surveys to measure mindfulness and staff perception of hospital safety culture, and a focus group to understand participants' experiences. We estimated mean differences using Kruskal-Wallis tests across 10 time-points and thematically analysed recorded transcripts. RESULTS There was an increase in staff attention to the team meeting as measured by the decentering domain across time (p

Background Diabetic ketoacidosis (DKA) is a potentially life-threatening but often preventable acute complication of type 1 diabetes (T1D). Understanding clinical and psychosocial characteristics of people with DKA, particularly those with multiple presentations, may aid the development of prevention strategies. Aims To describe clinical, psychological and demographic factors in adults with diabetic ketoacidosis (DKA) and particularly those factors associated with recurrent admissions. Methods A retrospective analysis was performed of all admissions with DKA in people with T1D over a 4-year period from 1st November 2013 to 31st October 2017 at a metropolitan tertiary hospital in Australia. Potential cases were identified by ICD-10 coding data. Data were then manually extracted by clinicians from the electronic medical record. Results There were 154 clinician-adjudicated admissions for DKA among 128 people with T1D. Of these, 16 (13%) had multiple DKA admissions. Forty-one (32%) had a history of depression. The most common factors contributing to presentation included insulin omission (54%), infection (31%), alcohol excess (26%) and new diabetes diagnosis (16%). Compared to people with single admissions, those with recurrent DKA were more likely to smoke (69% vs 27%, p = 0.003), be unemployed (31% vs 11%, p = 0.04) and use illicit substances (44% vs 17%, p = 0.02). Conclusions There is a high prevalence of psychiatric illness, illicit substance use and social disadvantage among people admitted with DKA, particularly those with recurrent presentations. Insulin omission, often due to inappropriate sick day management, was the most common reason for DKA occurrence. Innovative multidisciplinary models of care are required to address these challenges. This article is protected by copyright. All rights reserved.

This article analyzes the transfer of tacit knowledge between countries and continents, based on a case from the shipbuilding industry. The South Korean shipbuilder Hyundai Heavy Industries (HHI) was established in the early 1970s and had by the late 1980s become the world’s leading shipbuilder. Aided by foreign loan capital, HHI acquired technology through foreign licenses and imported equipment. However, shipbuilding is about more than hardware. This article presents and analyzes another important means of knowledge transfer: the acquisition of tacit knowledge in the form of shipbuilding skills, including shipyard processes and operations. This transfer was mainly accomplished through the “import” of foreign managers and the dispatch abroad of South Korean employees. One important element, which we investigate in detail, was the Korean personnel that HHI sent in 1972 to the Scott Lithgow shipyards in Scotland to observe and learn. Based on archival sources and interviews, we detail the manner in which tacit knowledge could be transferred across language and cultural barriers.

Study question What is primary factor of bioenergetics product activity between microtubule instability and the functional activity of mitochondria in embryo? Summary answer The actin cytoskeleton instability is presumably the primary cause for the bioenergenesis of mitochondrial function to the preimplantation embryo development. What is known already Mitochondria are cellular organelles dynamically moving and morphological changes. It provides for homeostatic energy to the cell. The dynamic property of the mitochondria is associated with the microtubule network in the cell. However, the stability of the microtubule was clearly identified for preimplantation embryo development. Study design, size, duration This study is designed to assess the ATP productivity of the mitochondria, and specifically to observe what its primary factor is in terms of providing microtubule stability in mammalian cells. Additionally, we investigated the relationship between blastocyst formation and actin cytoskeleton stabilization by EpD with 2-cell mice. Participants/materials, setting, methods We prepared the microtubule stability regulation model with the HEK293 cell line by using the microtubule stabilizer as an Epothilone D (EpD). Then we analyzed the metabolic activity of the cells through oxidative phosphorylation (OXP) ratios analysis. Also, we performed confocal live imaging to observe mitochondria morphology depending on the cells’ microtubule. Next, we treated EpD to 2-cell culture media for the analysis of blastocyst development ratios. Main results and the role of chance EpD significantly increased fusion form. Also, EpD enhance bioenergy ratios like OXP in the mitochondria and functional activity related marker, like mTOR compared with the control. These results suggest that microtubule stabilization enhances mitochondrial metabolism by increasing oxygen consumption. Also, EpD in 2-cell culture media led to a significant increase in the speed of development and 50% higher hatched out blastocyst formation ratios compared to the control group. Limitations, reasons for caution This study had limited animal experiments. For the next study, we are planning with an aim to improve the quality and development ratios of human embryos by EpD. Wider implications of the findings: Microtubule stabilizer has a possibility to recover the mitochondria’s functional activity in the preimplantation embryo development. Mitochondrial functional activity along the actin cytoskeleton may play a pivotal role in determining the embryo quality and development ratios for archive pregnancy. Trial registration number non-clinical trials

Background and aim Surgery and other non-pharmacological treatments such as sacral nerve stimulation are used for the treatment of difficult-to-treat chronic constipation. Novel pharmacological therapeutic agents are also being introduced. To evaluate the efficacy of these treatments, it is imperative to have a consistent definition of pharmacologically refractory constipation. A systematic review of studies on refractory, difficult-to-treat or surgically treated constipation was carried out to determine the criteria that various authors used to define this group of patients. Methods A systematic review was performed for literature published from June 2005 to June 2015 using PubMed, Cochrane, and Scopus databases, as well as manual searches. Studies on patients with refractory or intractable constipation were extracted. Criteria used for defining refractory constipation, as well as pharmacological agents tried including dosage, frequency, and duration, were reviewed. Results Sixty-one studies were included in this review. Forty-eight involved surgical treatment of constipation, while 13 examined non-surgical therapies for refractory constipation. There is no generally accepted definition of refractory constipation. Authors consider constipation to be refractory when response to management is suboptimal, but there is no consensus on the choice of drug, order of usage, and dosage or treatment duration. Prior medical therapy was not mentioned at all in five studies. Conclusions There is need for a detailed definition of pharmacologically refractory constipation before submitting patients to invasive treatments and to evaluate new pharmacological agents.

A microstructure-based integrated crystal plasticity (CP) and continuum damage mechanics (CDM) model is proposed for simulating rolling contact fatigue (RCF). The damage process through the formation of the dark etching region (DER) under RCF is implemented, i.e., a DER-CPCDM approach. A hierarchical microstructure of lath martensite is virtually generated by the Voronoi tessellation technique and the theoretical Kurdjumov-Sachs orientation relationship between the prior austenite grains and substructures of lath martensite. Moreover, the micro-plasticity calculated from the polycrystal finite element is coupled with dislocation-assisted carbon migration theory, which enables accurate predictions of the deformation inhomogeneity and the DER/damage distribution at the subsurface. The RCF lifespan of AISI 52100 bearing steel can be predicted within reasonable accuracy, in terms of Weibull probability analysis, when the jump-in-cycles approach is implemented in the DER-CPCDM model. The predicted representative lifespan of the Weibull plot is within an error of 13% when compared with reported experimental data. Process factors, including contact pressure, rotational speed, temperature, carbon concentration, and grain size, are analyzed in a numerical sensitivity study, which can be utilized for potential optimization of the RCF process for improving the performance of materials and parts.

The aim of this article is to present the early history of Hyundai Heavy Industries, currently the world’s largest shipbuilder. The company was established by the prolific South Korean entrepreneur Chung Ju-Yung in the early 1970s. Due to limited experience in shipbuilding, the establishment relied heavily on foreign assistance. This article sheds new light on the crucial relationship between Chung and two British companies: the Newcastle-upon-Tyne-based consulting firm A&P Appledore International Limited, and the Lower Clyde shipbuilders Scott Lithgow Limited, during the beginnings of large-scale South Korean shipbuilding. The article is based on a combination of British and South Korean archival sources, as well as secondary literature and the oral and written testimony of consultants and workers involved in the project.

OBJECTIVES: The global prevalence of IBS is difficult to ascertain, particularly in light of the heterogeneity of published epidemiological studies. The aim was to conduct a literature review, by experts from around the world, of community-based studies on IBS prevalence. DESIGN: Searches were conducted using predetermined search terms and eligibility criteria, including papers in all languages. Pooled prevalence rates were calculated by combining separate population survey prevalence estimates to generate an overall combined meta-prevalence estimate. The heterogeneity of studies was assessed. RESULTS: 1451 papers were returned and 83, including 288 103 participants in 41 countries, met inclusion criteria. The mean prevalence among individual countries ranged from 1.1% in France and Iran to 35.5% in Mexico. There was significant variance in pooled regional prevalence rates ranging from 17.5% (95% CI 16.9% to 18.2%) in Latin America, 9.6% (9.5% to 9.8%) in Asia, 7.1% (8.0% to 8.3%) in North America/Europe/Australia/New Zealand, to 5.8% (5.6% to 6.0%) in the Middle East and Africa. There was a significant degree of heterogeneity with the percentage of residual variation due to heterogeneity at 99.9%. CONCLUSIONS: The main finding is the extent of methodological variance in the studies reviewed and the degree of heterogeneity among them. Based on this, we concluded that publication of a single pooled global prevalence rate, which is easily calculated, would not be appropriate or contributory. Furthermore, we believe that future studies should focus on regional and cross-cultural differences that are more likely to shed light on pathophysiology.

This article compares and contrasts Very Large Crude Carrier shipbuilding at Scott Lithgow's Glen shipyard, Port Glasgow, Scotland and Hyundai Heavy Industries shipyard, Ulsan, South Korea, initially to the same design, and VLCC shipbuilding in the United Kingdom, 1970–77 in general, at the two other United Kingdom shipyards capable of constructing VLCCs, Swan Hunter on Tyneside and Harland & Wolff in Belfast. It also discusses the collapse of the British shipbuilding industry's major customer for VLCCs, Maritime Fruit Carriers.

In the present work, commercial Al-6061 alloy tubes were processed via multi-pass parallel tubular channel angular pressing (PTCAP). The effects of the number of passes on grain refinement and mechanical properties were investigated. The microstructural evolution was characterized using electron back-scattered diffraction (EBSD) and scanning electron microscopy. The mechanical properties were evaluated using tensile tests and hardness measurements. The EBSD analyses presented that the elongated subgrains or grains with ~800 nm in size and a high fraction of low-angle grain boundaries were formed after two PTCAP passes. After four passes, the elongated subgrains have transformed to almost equiaxed grains with ~400 nm in size and high-angle grain boundaries. Microhardness of the processed tube increased from 38.9 to 63.4 HV (~63 pct) after three PTCAP passes. An increase in the number of PTCAP passes after three passes has no more effect on the microhardness. Yield and ultimate tensile strength were increased by 2.1 and 1.6 times, respectively, after four PTCAP passes (e ~6.4) compared to the annealed sample. Ductile fracture with an extensive necking zone and many big dimples occur in the annealed sample, while fine dimples and limited ductile fracture features were observed in the ultra-fine grained PTCAP-processed samples.

Summary Background Cross-cultural, multinational research can advance the field of functional gastrointestinal disorders (FGIDs). Cross-cultural comparative research can make a significant contribution in areas such as epidemiology, genetics, psychosocial modulators, symptom reporting and interpretation, extra-intestinal co-morbidity, diagnosis and treatment, determinants of disease severity, health care utilisation, and health-related quality of life, all issues that can be affected by geographical region, culture, ethnicity and race. Aims To identify methodological challenges for cross-cultural, multinational research, and suggest possible solutions. Methods This report, which summarises the full report of a working team established by the Rome Foundation that is available on the Internet, reflects an effort by an international committee of FGID clinicians and researchers. It is based on comprehensive literature reviews and expert opinion. Results Cross-cultural, multinational research is important and feasible, but has barriers to successful implementation. This report contains recommendations for future research relating to study design, subject recruitment, availability of appropriate study instruments, translation and validation of study instruments, documenting confounders, statistical analyses and reporting of results. Conclusions Advances in study design and methodology, as well as cross-cultural research competence, have not matched technological advancements. The development of multinational research networks and cross-cultural research collaboration is still in its early stages. This report is intended to be aspirational rather than prescriptive, so we present recommendations, not guidelines. We aim to raise awareness of these issues and to pose higher standards, but not to discourage investigators from doing what is feasible in any particular setting.

Summary Background Coeliac disease (CD), originally thought to be largely confined to Northern Europe and Australasia and uncommon in North America and the Middle East, is now recognised to be equally common in all these countries. It is still thought to be rare in the Orient and Sub-Saharan Africa. Aim To assess geographical differences and time trends in the frequency of CD. Methods Medline and Embase searches were conducted on 10 November 2012, from 1946 and 1980 respectively, using the key words: coeliac disease or celiac disease + prevalence or incidence or frequency. Results There were significant intra- and inter-country differences in the prevalence and incidence of CD. Only 24 ethnic Chinese and Japanese patients have been reported in the English literature. Of CD-associated HLA DQ antigens, DQ2 occurs in 5–10% of Chinese and sub-Saharan Africans, compared to 5–20% in Western Europe. DQ8 occurs in 5–10% of English, Tunisians and Iranians, but in

Eosinophilic oesophagitis (EoE) is a chronic immune-mediated esophageal disease, characterized by symptoms related to esophageal dysfunction and histologically by eosinophil predominant inflammation. Current evidence for an adverse impact on quality of life (QoL) is conflicting and there are no data from a UK population regarding QoL. We conducted a prospective cross-sectional observational study using the Short Form-36 Health Survey, Hospital Dysphagia/Odynophagia Questionnaire, and the EoE Adult Quality of Life Questionnaire to assess QoL and severity of dysphagia in EoE patients, compared to age and gender matched healthy control subjects. Data were also collected on comorbidity and medication use. Eighty-eight subjects were recruited (44 patients). Patients had higher rates of antihistamine and topical (swallowed) corticosteroid use. Physical QoL did not differ between patients and controls, although patients did report a statistically significant lower mental QoL, with small absolute magnitude of difference. Patients reported higher dysphagia scores and these were negatively correlated with both physical and mental QoL. Higher rates of dysphagia and medication use in patients may among other things account for lower mental QoL. However, a higher rate of dysphagia in patients is not associated with a reduced physical QoL. Our findings are of clinical value, particularly when a new diagnosis of EoE is made, as clinicians can reassure patients that their general physical health should not be greatly affected by the diagnosis. Moreover, it may also be useful for patients to be aware that EoE may have an impact on their mental health, but this effect is likely to be small. We therefore advocate education and reassurance in this respect for all patients at diagnosis.

Eosinophilic oesophagitis (EoE) is a chronic immune-mediated esophageal disease, characterized by symptoms related to esophageal dysfunction and histologically by eosinophil predominant inflammation. Current evidence for an adverse impact on quality of life (QoL) is conflicting and there are no data from a UK population regarding QoL. We conducted a prospective cross-sectional observational study using the Short Form-36 Health Survey, Hospital Dysphagia/Odynophagia Questionnaire, and the EoE Adult Quality of Life Questionnaire to assess QoL and severity of dysphagia in EoE patients, compared to age and gender matched healthy control subjects. Data were also collected on comorbidity and medication use. Eighty-eight subjects were recruited (44 patients). Patients had higher rates of antihistamine and topical (swallowed) corticosteroid use. Physical QoL did not differ between patients and controls, although patients did report a statistically significant lower mental QoL, with small absolute magnitude of difference. Patients reported higher dysphagia scores and these were negatively correlated with both physical and mental QoL. Higher rates of dysphagia and medication use in patients may among other things account for lower mental QoL. However, a higher rate of dysphagia in patients is not associated with a reduced physical QoL. Our findings are of clinical value, particularly when a new diagnosis of EoE is made, as clinicians can reassure patients that their general physical health should not be greatly affected by the diagnosis. Moreover, it may also be useful for patients to be aware that EoE may have an impact on their mental health, but this effect is likely to be small. We therefore advocate education and reassurance in this respect for all patients at diagnosis.

Upper gastrointestinal haemorrhage (UGIH) in cardiac patients receiving antiplatelets presents a difficult management problem. The aim of this study was to describe a series of cardiac inpatients receiving antiplatelets who underwent endoscopy for an acute UGIH. Cardiac inpatients receiving antiplatelets and requiring endoscopy for UGIH over an 18-month period were followed up. Forty-one patients were studied. Most patients (25 [61%]) presented with melaena. Antiplatelets were withheld in 34 (83%) patients; predominantly in those with higher pre-endoscopy Rockall scores (median, 4; interquartile range [IQR], 3–5 versus median, 3; IQR, 2–4; P < 0.05). Positive findings were identified at endoscopy in 80%. Duodenal ulcers were the most common lesion and adrenaline the most common method of haemostasis. Median time to first endoscopy was 0 (IQR, 0–1) days. Seven (17%) patients re-bled, median Rockall score was six (IQR, 4–8). Three (7%) patients experienced procedural complications, two patients became hypoxic and one patient died. Following endoscopy, antiplatelets were restarted after a median of three (IQR, 3–5) days. On discharge, 27/28 (96%) patients continued with antiplatelet and proton-pump inhibitor therapy. Thirty-day inpatient mortality was 7% (3 patients). One patient re-bled within six months of discharge. Endoscopy helped assess the risk of re-bleeding and timing of antiplatelet re-introduction in cardiac inpatients experiencing UGIH.

User ID: 4556669 merged with this user on 30-Jul-2006 by Edwards, Doris (Kang, Jin-Yong)

Conventional undoped gallium nitride (GaN) surface was treated with trimethylgallium (TMGa) flow for 100 s in the ambient of H2 and low ammonia at 500 °C and 500 Torr followed by thermal annealing at 1050 °C. On the Gallium droplets and GaN nanoislands patterned layer-structured surface, droplet homoepitaxy of thin GaN layers was realized by flowing the surface with TMGa and low ammonia at 1035 °C for 400 s in the ambient of H2. By such an in situ three-step surface modification, the surface stoichiometry (Ga/N) changed from nonstoichiometry (N-rich, 0.92) to close-to-stoichiometry (slightly Ga-rich, 1.04) with very thin nanoislands (20 nm in diameter and 1 nm in height) patterning on the smooth layer-structured surface. Photoluminescence studies show significant reduction of yellow/blue emissions, which suggests improvement of surface/interface qualities of GaN films.

The self-organization of large-scale uniform aligned three-dimensional GaN nanoislands with triangular (0001) and distinct sidewall faceting has been realized by metal organic vapor-phase epitaxy on in situ Si-rich SiNx nanoislands patterned c-sapphire substrates. We find that the GaN island shaping is closely related to the SiNx pretreatment chemistry. It is suggested that enhanced surface Ga surfactant effects and compressive strain relaxation caused by site exchanges between excess Si and subsurface Ga atoms are responsible for the distinct triangular island shaping with large lateral size, smooth sidewall facets, and sharp triangle corners. Photoluminescence studies also show Si-doping-induced compressive strain relaxation and improved crystalline qualities for triangular GaN islands grown with the Si-rich SiNx pretreatment.

Aims: To determine time trends in hospital admissions for chronic liver disease in England between 1989/1990 and 2002/2003, mortality rates in England and Wales between 1979 and 2005, and the influence of alcohol-related disease on these trends. Methods: Hospital episode statistics for admissions in England were obtained from the Information Center for Health and Social Care and mortality data for England and Wales from the Office for National Statistics. Results: Hospital admission rates for chronic liver disease increased by 71% in males and 43% in females over the study period. This increase was largely due to alcoholic liver disease, admission rates for which more than doubled between 1989/1990 and 2002/2003. While there was a smaller rise for chronic viral hepatitis B and C, admission rates declined for hepatitis A, autoimmune hepatitis, and primary biliary cirrhosis. Mortality rates for chronic liver disease more than doubled between 1979 and 2005. Two thirds of these deaths were attributable to alcohol-related liver disease in 2005. The highest rate of alcoholic liver disease mortality was in the 45-64 age group, and the largest percentage increase between 1979 and 2005 occurred in the 25-34 age group. Conclusions: Hospital admissions and mortality in England from chronic liver disease are increasing. The underlying reasons are complex, but alcohol-induced liver disease makes a major contribution. There are clear social and health implications if the trend continues and addressing alcohol-related liver disease should be a public health priority.

Strain-induced misorientation development was studied in an IF steel as a function of strain for two deformation modes, plane strain compression and simple shear. Using electron back-scattered diffraction, orientation maps of “large” areas were obtained, from which several individual grains associated with the principal texture components could be extracted so that only intragranular misorientations could be estimated for these orientations. It was observed that the increase of the misorientation angle was more prominent in simple shear than in plane strain compression and that the orientation influence was different for each mode. Considering texture evolution as a possible source of misorientation development, the lattice spin tensor was estimated with the Taylor model for the two deformation modes; both reorientation axis and angle were compared with misorientation angle and axis. The striking concordance of both quantities allows us to conclude that there is a direct contribution of texture evolution to misorientation accumulation with strain.

SUMMARY Background: Alpha-interferon has been found to inhibit hepatitis B virus (HBV) replication in Chinese patients with chronic HBV infection although a sustained effect was rarely achieved in those with normal pre-treatment serum alanine amino transferase (ALT) levels. Prednisolone priming has been found to be beneficial over treatment with interferon alone in these subjects. We studied the effect of steroid pre-treatment followed by recombinant interferon alpha-2a in the treatment of asymptomatic HBV carriers with positive hepatitis Be antigen (HBeAg), hepatitis B viral DNA (HBV-DNA) and minimal changes in liver histology. Methods: The treatment regimen included a 6-week prednisolone priming, a 2 week rest followed by 14 weeks of three times weekly 9 mega units of interferon alpha-2a injection and 52 weeks of follow-up. There were seven patients in the treatment group and seven controls. Results: The mean age, pre-treatment ALT (normal in all except for one in each of the treatment and control groups), HBV-DNA levels and histological scores were similar in the two groups. Serum HBV-DNA levels fell in six patients during treatment and became undetectable in two of them by the end. During follow-up, serum HBV-DNA returned to pre-treatment levels in all patients. None of the treated patients had HBeAg sero-conversion and none of the controls had spontaneous clearance of HBV-DNA or sero-conversion of HBeAg. No improvement of liver histology was observed in any of the treated patients. There were only mild flu-like side-effects noted and interferon alpha-2a was well tolerated at the doses given among treated patients. Conclusion: Prednisolone priming followed by interferon alpha-2a treatment has no beneficial effect on HBV carriers in the early stages of chronic hepatitis B infection.

Background and aims Omega-3 fatty acids in fish oil exert a protective effect on the development of colorectal cancer in animal models. Patients with colorectal adenomas have been shown to have increased crypt cell proliferation and decreased apoptosis in macroscopically normal appearing colonic mucosa. We investigated whether dietary supplementation with eicosapentaenoic acid (EPA) could alter crypt cell proliferation and apoptosis in such patients. Patients/methods Thirty subjects were randomised to either 3 months of highly purified EPA in free fatty acid form (2 g/day) or to no treatment. Colonic biopsies were taken at the initial colonoscopy and repeated 3 months later, and analysed for cell proliferation and apoptosis (immunohistochemistry) and mucosal fatty acid content. Results/findings Crypt cell proliferation was significantly reduced whilst apoptosis was significantly increased after EPA supplementation. Neither crypt cell proliferation nor apoptosis were altered in the control group. EPA in the mucosa increased significantly after EPA supplementation, whereas there was no significant change in controls. Conclusions Dietary supplementation with EPA significantly increases levels of this fatty acid in colonic mucosa, associated with significantly reduced proliferation and increased mucosal apoptosis. Further studies are needed to assess the potential efficacy of EPA supplementation in preventing polyps in the chemoprevention of colorectal cancer.

Background: Oesophago-gastric (OG) cancer has a poor five-year survival. Wandsworth Public Health Department undertook a direct mail-out to raise awareness of OG cancer, highlighting symptoms and risk factors with the aim of improving survival. Objectives: To ascertain the impact of the mail-out on respondents awareness of OG cancer and intention to make lifestyle changes and assess acceptability of the information. Method: 5,048 men aged over 55 years in Wandsworth, London, were sent a direct mail containing a leaflet explaining the signs and symptoms of OG cancer and a flyer about lifestyle factors associated with cancer. A postal survey was then sent to assess recall of key health promotion messages and self-reported changes in knowledge, attitude and behaviour in relation to OG Cancer. Results: A response rate of 10.5% was achieved. 68.8% respondents were interested in the information and only 11.2% were made to feel uncomfortable and 6.8% made to feel worried. Most respondents recognised the key messages (Spotting the signs and symptoms of cancer (75.8%); Finding cancer early can save lives (73.5%); See your GP if you have a symptom (69.1%)). Almost 9% of respondents reported consulting their General Practitioner after receiving the leaflet. The survey suggested the mail-out had raised awareness of OG cancer as 50% of respondents reported talking to friends and family and/or intended to make lifestyle changes. Conclusions: OG cancer awareness information by direct mail-out has shown acceptability with target recipients and a positive effect with respondents seeking advice from healthcare professionals and evidence of raised awareness of OG cancer.

The performance of multiplication is crucial for multimedia applications such as 3D graphics and signal processing systems, which depend on the execution of large numbers of multiplications. Previously reported algorithms mainly focused on rapidly reducing the partial products rows down to final sums and carries used for the final accumulation. These techniques mostly rely on circuit optimization and minimization of the critical paths. In this paper, an algorithm to achieve fast multiplication in two's complement representation is presented. Rather than focusing on reducing the partial products rows down to final sums and carries, our approach strives to generate fewer partial products rows. In turn, this influences the speed of the multiplication, even before applying partial products reduction techniques. Fewer partial products rows are produced, thereby lowering the overall operation time. In addition to the speed improvement, our algorithm results in a true diamond-shape for the partial product tree, which is more efficient in terms of implementation. The synthesis results of our multiplication algorithm using the Artisan TSMC 0.13mum 1.2-volt standard-cell library show 13 percent improvement in speed and 14 percent improvement in power savings for 8-bit times 8-bit multiplications (10 percent and 3 percent, respectively, for 16-bit times 16-bit multiplications) when compared to conventional multiplication algorithms

Summary Background While overall hospital admission rates for peptic ulcer declined in England in the 1990 s, they increased among the elderly, especially for complicated ulcer. However, peptic ulcer admissions fell for all age groups in the United States. Aim To examine time trends in the incidence of hospital admissions, mortality and operations because of peptic ulcer in Scotland from 1982 to 2002, and the use of various drugs relevant to the aetiology and treatment of peptic ulcer from 1992 to 2002. Results There was a general decrease in admission rates, especially for younger individuals. For individuals aged above 74 years, admission rates actually increased for gastric ulcer with haemorrhage among men, and for duodenal ulcer haemorrhage between both sexes. The number of operations fell dramatically, especially for younger patients. Mortality rates generally declined. Case fatality rates were greater for women than men, and declined over the study period for gastric ulcer, but increased for duodenal ulcer. The use of low-dose aspirin, oral anticoagulants, selective serotonin reuptake inhibitors and proton-pump inhibitors increased while those of non-steroidal anti-inflammatory drugs and histamine-2 antagonists declined. Conclusions Admission rates for peptic ulcer generally fell for younger individuals, but increased for older people with haemorrhage.