Search

PURPOSE: To describe data on epidemiology, microbiology, clinical characteristics and outcome of adult patients admitted in the intensive care unit (ICU) with secondary peritonitis, with special emphasis on antimicrobial therapy and source control. METHODS: Post hoc analysis of a multicenter observational study (Abdominal Sepsis Study, AbSeS) including 2621 adult ICU patients with intra-abdominal infection in 306 ICUs from 42 countries. Time-till-source control intervention was calculated as from time of diagnosis and classified into 'emergency' (< 2 h), 'urgent' (2-6 h), and 'delayed' (> 6 h). Relationships were assessed by logistic regression analysis and reported as odds ratios (OR) and 95% confidence interval (CI). RESULTS: The cohort included 1077 cases of microbiologically confirmed secondary peritonitis. Mortality was 29.7%. The rate of appropriate empiric therapy showed no difference between survivors and non-survivors (66.4% vs. 61.3%, p = 0.1). A stepwise increase in mortality was observed with increasing Sequential Organ Failure Assessment (SOFA) scores (19.6% for a value ≤ 4-55.4% for a value > 12, p < 0.001). The highest odds of death were associated with septic shock (OR 3.08 [1.42-7.00]), late-onset hospital-acquired peritonitis (OR 1.71 [1.16-2.52]) and failed source control evidenced by persistent inflammation at day 7 (OR 5.71 [3.99-8.18]). Compared with 'emergency' source control intervention (< 2 h of diagnosis), 'urgent' source control was the only modifiable covariate associated with lower odds of mortality (OR 0.50 [0.34-0.73]). CONCLUSION: 'Urgent' and successful source control was associated with improved odds of survival. Appropriateness of empirical antimicrobial treatment did not significantly affect survival suggesting that source control is more determinative for outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT03270345.

INTRODUCTION: In sickle cell disease (SCD), a single amino acid substitution at β6 of the hemoglobin (Hb) chain replaces glutamate with valine, forming HbS instead of the normal adult HbA. Loss of a negative charge, and the conformational change in deoxygenated HbS molecules, enables formation of HbS polymers. These not only distort red cell morphology but also have other profound effects so that this simple etiology belies a complex pathogenesis with multiple complications. Although SCD represents a common severe inherited disorder with life-long consequences, approved treatments remain inadequate. Hydroxyurea is currently the most effective, with a handful of newer treatments, but there remains a real need for novel, efficacious therapies. AREAS COVERED: This review summarizes important early events in pathogenesis to highlight key targets for novel treatments. EXPERT OPINION: A thorough understanding of early events in pathogenesis closely associated with the presence of HbS is the logical starting point for identification of new targets rather than concentrating on more downstream effects. We discuss ways of reducing HbS levels, reducing the impact of HbS polymers, and of membrane events perturbing cell function, and suggest using the unique permeability of sickle cells to target drugs specifically into those more severely compromised.

The British Society for Haematology (BSH) produces Good Practice Papers to recommend good practice in areas where there is a limited evidence base but for which a degree of consensus or uniformity is likely to be beneficial to patient care. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org. This Good Practice Paper was produced as a collaboration with the European Hematology Association (EHA) compiled according to the (BSH) process at http://scanmail.trustwave.com/?c=8248&d=68DV3b1jbPPsVn-8nm3kGS2D_-Hms9YWMWrrk5K8Eg&u=http%3a%2f%2fb-s-h%2eorg.uk. This guideline group included UK-based medical experts representing the BSH and members of the Red Cell and Iron Scientific Working Group (SWG) of EHA. Literature review details: MEDLINE, EMBASE and PubMED were searched systematically for publications in English from 2000 to 2019 using the following key words. ‘NGS’ and ‘next-generation sequencing’ or ‘high throughput sequencing’ AND ‘haemolytic anaemia’ or ‘DBA or ‘Diamond Blackfan anaemia’ or ‘CDA’ or ‘congenital dyserythropoietic anaemia’ or ‘sideroblastic anaemia’ or ‘HS' or ‘hereditary spherocytosis’ or ‘red cell membrane disorders’ or ‘red cell enzyme disorders’ or ‘PK deficiency’ or ‘PKD’. References from relevant publications were also searched. Conference abstracts were included if deemed to be of particular relevance. Review of the manuscript: Review of the manuscript was performed by the BSH Guidelines Committee General Haematology Task Force, the BSH Guidelines Committee and the General Haematology sounding board of the BSH. It was also on the members section of the BSH website for comment. It has also been reviewed by members of the EHA Red Cell and Iron SWG and the EHA Guidelines Executive Committee. info:eu-repo/semantics/publishedVersion

Funder: Stroke Association; Id: http://dx.doi.org/10.13039/501100000364, α-Thalassemia is one of the most important genetic modulators of sickle cell disease (SCD). Both beneficial and detrimental effects have been described previously. We use a 12-year data set on a large cohort of patients with HbSS (n = 411) and HbSC (n = 146) to examine a wide range of these clinical and laboratory associations. Our novel findings are that α-thalassemia strongly reduces erythrocyte potassium chloride co-transporter (KCC) activity in both HbSS and HbSC (p = .035 and p = .00045 respectively), suggesting a novel mechanism through which α-thalassemia induces a milder phenotype by reducing red cell cation loss. This may be particularly important in HbSC where reduction in mean cell hemoglobin concentration is not seen and where KCC activity has previously been found to correlate with disease severity. Additionally, we show that α-thalassemia not only increases hemoglobin in patients with HbSS (p = .0009) but also reduces erythropoietin values (p = .0005), demonstrating a measurable response to improved tissue oxygenation. We confirm the reno-protective effect of α-thalassemia in patients with HbSS, with reduced proteinuria (p = .003) and demonstrate a novel association with increased serum sodium (p = .0004) and reduced serum potassium values (p = 5.74 × 10-10 ). We found patients with α-thalassemia had a reduced annualized transfusion burden in both HbSS and HbSC, but α-thalassemia had no impact on annualized admission rates in either group. Finally, in a larger cohort, we report a median survival of 62 years in patients with HbSS (n = 899) and 80 years in those with HbSC (n = 240). α-thalassemia did not influence survival in HbSS, but a nonsignificant trend was seen in those with HbSC.

Supplemental material, sj-docx-1-aln-10.1177_11771801221119266 for Applying the complementary knowledge bases of System Dynamics and Indigenous knowledge in public health research in Aotearoa, New Zealand by Pippa McKelvie-Sebileau, Crystal Pekepo, David Rees, Boyd Swinburn, Sarah Gerritsen and David Tipene-Leach in AlterNative: An International Journal of Indigenous Peoples

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X211072391 for Venous cerebral blood flow quantification and cognition in patients with sickle cell anemia by Hanne Stotesbury, Patrick W Hales, Melanie Koelbel, Anna M Hood, Jamie M Kawadler, Dawn E Saunders, Sati Sahota, David C Rees, Olu Wilkey, Mark Layton, Maria Pelidis, Baba PD Inusa, Jo Howard, Subarna Chakravorty, Chris A Clark and Fenella J Kirkham in Journal of Cerebral Blood Flow & Metabolism

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X211072391 for Venous cerebral blood flow quantification and cognition in patients with sickle cell anemia by Hanne Stotesbury, Patrick W Hales, Melanie Koelbel, Anna M Hood, Jamie M Kawadler, Dawn E Saunders, Sati Sahota, David C Rees, Olu Wilkey, Mark Layton, Maria Pelidis, Baba PD Inusa, Jo Howard, Subarna Chakravorty, Chris A Clark and Fenella J Kirkham in Journal of Cerebral Blood Flow & Metabolism

We present case histories of three patients who had β-thalassemia (β-thal) trait with 'unusual severity' managed as β-thal intermedia (β-TI) where the basis of disease severity could not be explained with routine hematological and genetic investigations. The clinical diagnosis of 'thalassemia intermedia' was justifiable as they had a β-thal mutation and disease severity that did not fit in with either β-thal trait or with β-thal major (β-TM). As mutations of α, β, and γ genes could not explain the unusual severity of the disease, further analysis with next-generation sequencing (NGS) for red cell diseases was carried out, which led to the diagnosis of coexisting membranopathies. This case series highlights the inherent difficulty in the diagnosis of β-TI with certainty in some patients where the genetic basis is not clear-cut.

In the β-thalassemias, oxidative stress, resulting from chronic hemolysis, globin chain imbalance, iron overload and depleted antioxidant defences, likely contributes to cell death, organ damage, anemia, hypoxia and inflammation. We assessed variations in these parameters in β-thalassemia syndromes in Sri Lanka. Between November 2017 and June 2018, we assessed children and adults attending two thalassemia centres in Sri Lanka: 59 patients with HbE β-thalassemia, 50 β-thalassemia major, 40 β-thalassemia intermedia and 13 HbS β-thalassemia. Median age was 26.0 years (IQR 15.3-38.8), 101 (62.3%) were female and 152 (93.8%) of Sinhalese ethnicity. Methemoglobin, plasma hemoglobin, heme and ferritin were measured as sources of oxidants; plasma total antioxidant capacity, haptoglobin, hemopexin and vitamins C and E assessed antioxidant status; plasma thiobarbituric acid reactive substances and 8-hydroxy-2'-deoxyguanosine assessed oxidative damage; hemoglobin, plasma erythropoietin and transferrin receptor assessed anemia and hypoxia and plasma interleukin-6 and C-reactive protein assessed inflammation. Fruit and vegetable intake was determined by dietary recall. Physical fitness was investigated using the six-minute walk test and measurement of handgrip strength. Oxidant sources were frequently increased and antioxidants depleted, with consequent oxidative damage, anemia, hypoxia and inflammation. Biomarkers were generally most abnormal in HbE β-thalassemia and least abnormal in β-thalassemia intermedia but also varied markedly between individuals with the same thalassemia syndrome. Oxidative stress and damage were also more severe in splenectomized patients and/or those receiving iron chelation therapy. Less than 15% of patients ate fresh fruits or raw vegetables frequently, and plasma vitamins C and E were deficient in 132/160 (82.5%) and 140/160 (87.5%) patients respectively. Overall, physical fitness was poor in all syndromes and was likely due to anemic hypoxia. Studies of antioxidant supplements to improve outcomes in patients with thalassemia should consider individual patient variation in oxidative status both between and within the thalassemia syndromes.

We present both time-averaged and time-resolved transport measurements of a two-dimensional electron (Wigner) crystal on the surface of superfluid helium confined in a narrow microchannel. We find that the field-current characteristics of the driven crystal obtained by the time-averaged measurements exhibit oscillations and negative differential conductivity. This unusual transport behavior was observed previously by Glasson et al. [Phys. Rev. Lett. 87, 176802 (2001)] and was attributed to a nonequilibrium transition of the electron system to a novel dynamically ordered phase of current filaments aligned along the channels. Contrarily to this explanation, our time-resolved transport measurements reveal that oscillating field-current characteristics appear due to dynamical decoupling (slipping) and recoupling (sticking) of the uniform electron crystal to the liquid helium substrate. Our result demonstrates that this unusual non-linear transport effect is intrinsic, does not depend on the device geometry, and is associated with the dynamical interaction of Wigner crystal with the surface excitations of the liquid substrate., Comment: 7 pages, 4 figures

Severe intra-abdominal infection commonly requires intensive care. Mortality is high and is mainly determined by disease-specific characteristics, i.e. setting of infection onset, anatomical barrier disruption, and severity of disease expression. Recent observations revealed that antimicrobial resistance appears equally common in community-acquired and late-onset hospital-acquired infection. This challenges basic principles in anti-infective therapy guidelines, including the paradigm that pathogens involved in community-acquired infection are covered by standard empiric antimicrobial regimens, and second, the concept of nosocomial acquisition as the main driver for resistance involvement. In this study, we report on resistance profiles of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis and Enterococcus faecium in distinct European geographic regions based on an observational cohort study on intra-abdominal infections in intensive care unit (ICU) patients. Resistance against aminopenicillins, fluoroquinolones, and third-generation cephalosporins in E. coli, K. pneumoniae and P. aeruginosa is problematic, as is carbapenem-resistance in the latter pathogen. For E. coli and K. pneumoniae, resistance is mainly an issue in Central Europe, Eastern and South-East Europe, and Southern Europe, while resistance in P. aeruginosa is additionally problematic in Western Europe. Vancomycin-resistance in E. faecalis is of lesser concern but requires vigilance in E. faecium in Central and Eastern and South-East Europe. In the subcohort of patients with secondary peritonitis presenting with either sepsis or septic shock, the appropriateness of empiric antimicrobial therapy was not associated with mortality. In contrast, failure of source control was strongly associated with mortality. The relevance of these new insights for future recommendations regarding empiric antimicrobial therapy in intra-abdominal infections is discussed.

In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research(1) aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by one to two section editors who were leading international experts in the field. In the five years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including eleven sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally a more funded future for European hematology research. The eleven EHA Research Roadmap sections include Normal Hematopoiesis; Malignant Lymphoid Diseases; Malignant Myeloid Diseases; Anemias and Related Diseases; Platelet Disorders; Blood Coagulation and Hemostatic Disorders; Transfusion Medicine; Infections in Hematology; Hematopoietic Stem Cell Transplantation; CAR-T and Other Cell-based Immune Therapies; and Gene Therapy.

Additional file 1: Table S1. Search strings. Table S2. Newcastle-Ottawa quality assessment scales. Table S3. Exclusions on full article. Supplementary Note: Consideration of confounding and bias. Table S4. Potential confounders of the association between silica, silicosis and tuberculosis. Table S5. E-values for potential confounders of the association between silicosis and tuberculosis.

Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications. In light of the priorities identified by the European Hematology Association Roadmap we generated specific recommendations for each disorder, except thalassemia syndromes for which there are other, recent guidelines. Our recommendations are intended to enable clinicians to achieve better informed decisions on disease management by splenectomy, on the type of splenectomy and the possible consequences. As no randomized clinical trials, case control or cohort studies regarding splenectomy in these disorders were found in the literature, recommendations for each disease were based on expert opinion and were subsequently critically revised and modified by the Splenectomy in Rare Anemias Study Group, which includes hematologists caring for both adults and children., SCOPUS: ar.j, info:eu-repo/semantics/published

Oxidative stress contributes to haemolytic anaemia in many species including dogs and cats, as well as in humans. Red cells are exposed to a continual oxidant challenge, both endogenously from within the red cells themselves and also exogenously from other tissues, and from ingested or administered oxidants. When the oxidative challenge exceeds the antioxidant provisions of the red cell, damage occurs in the form of lipid and protein peroxidation, cytoskeletal crosslinking, oxidation of haemoglobin to methaemolglobin, and precipitation of denatured sulphhaemoglobin as Heinz bodies. These deleterious sequelae produce fragile red cells with reduced lifespan, and result in poorer oxygen delivery to tissues, intravascular haemolysis, anaemia, haemoglobinuria and jaundice. A number of features increase the risk of oxidant damage in dogs and cats. Thus dog red cells have low levels of the antioxidant enzyme catalase. Cat haemoglobin has at least four times as many readily oxidizable thiol residues compared to most species, whilst their hepatic capacity for glucuronidation is much reduced, which can result in greater accumulation of oxidants. Like humans, both species may also be exposed to excess oxidants from systemic diseases such as diabetes mellitus, hepatic lipidosis, hypophosphataemia and neoplasias. Iatrogenic oxidants include drugs such as acetaminophen and other non-steroidal anti-inflammatory compounds. Ingested toxins include heavy metals, particularly important in dogs with their increased propensity for scavenging. Ingestion of feeds containing products from Allium species of plants has also long been associated with red cell oxidative damage and Heinz body formation in both dogs and cats. Though less common than in humans, there are occasional congenital enzyme deficiencies which reduce the enzymatic oxidant defence of the red cells in these species. Treatment usually relies on removal of the oxidant challenge or support against the resulting anaemia. Specific antioxidants currently lack efficacy but analogy with human medicine suggests that a range possible antioxidants may be potentially beneficial., None

Phosphatidylserine (PS) exposure increases as red cells age, and is an important signal for the removal of senescent cells from the circulation. PS exposure is elevated in red cells from sickle cell anaemia (SCA) patients and is thought to enhance haemolysis and vaso-occlusion. Although precise conditions leading to its externalisation are unclear, high intracellular Ca2+ has been implicated. Red cells from SCA patients are also exposed to an increased oxidative challenge, and we postulated that this stimulates PS exposure, through increased Ca2+ levels. We tested four different ways of generating oxidative stress: hypoxanthine and xanthine oxidase, phenazine methosulphate, nitrite and tert-butyl hydroperoxide, together with thiol modification with N-ethylmaleimide (NEM), dithiothreitol and hypochlorous acid (HOCl), in red cells permeabilised to Ca2+ using bromo-A23187. Unexpectedly, our findings showed that the four oxidants significantly reduced Ca2+ -induced PS exposure (by 40-60%) with no appreciable effect on Ca2+ affinity. By contrast, NEM markedly increased PS exposure (by about 400%) and slightly but significantly increased the affinity for Ca2+ . Dithiothreitol modestly reduced PS exposure (by 25%) and HOCl had no effect. These findings emphasise the importance of thiol modification for PS exposure in sickle cells but suggest that increased oxidant stress alone is not important.

Graphical abstract, Highlights • Bile acids and adenocarcinoma of the pancreas. • Bile acids extracted directly from common bile duct of patients undergoing surgery. • LC–MS analysis of bile acids. • Significantly elevated levels of unconjugated cholic acid in patients with adenocarcinoma of the pancreas., Bile acids have been implicated in the development of gastrointestinal malignancies. Both the specific nature of individual bile acids and their concentration appear key factors in the carcinogenic potency of bile. Using liquid chromatography mass spectrometry (LC–MS) we performed quantitative profiling of bile extracted directly from the common bile duct in 30 patients (15 patients with pancreatic cancer and 15 patients with benign disease). Separation and detection of bile acids was performed using a 1.7 μm particle size reversed-phase C18 LC column at a flow rate of 200 μL/min with negative electrospray ionization MS. A significant difference (p = 0.018) was seen in the concentration of unconjugated cholic acid in the malignant group (0.643 mmol/L) compared to the benign group (0.022 mmol/L), with an overall significant difference (p = 0.04) seen in the level of total unconjugated bile acids in the malignant group (1.816 mmol/L) compared to the benign group (0.069 mmol/L). This finding may offer the possibility of both understanding the biology of cancer development in the pancreas, as well as offering a potential diagnostic avenue to explore. However, a larger study is necessary to confirm the alterations in bile acid profiles reported here and explore factors such as diet and microbial populations on the bile acid profiles of these patient groups.

Objective To assess the prevalence of high body mass index (BMI) in children with sickle cell disease and assess correlation between BMI and disease severity. Design Retrospective chart review followed by statistical analysis. Setting A single tertiary paediatric clinic in inner city London. Patients All patients with sickle cell disease, including homozygous haemoglobin (HbSS) and compound heterozygous Hb (HbSC), age 2–18 years receiving clinical care at the centre, were included in the study. Interventions Height and weight measurements, steady-state laboratory blood tests, hospital admission rates, adjunct therapy such as hydroxycarbamide or blood transfusions and obstructive sleep apnoea (OSA) data were obtained from the hospital electronic patient records. Main outcome measures To study the prevalence of high BMI and to identify any correlation between BMI and disease severity. Results 385 patients were included. 64 children (17%) were overweight or obese, of which a significantly higher number of children with HbSC were obese or overweight (23 out of 91, 25%) compared with those with HbSS (36 out of 273, 13%), p≤0.001. No correlation was found between high BMI and presence of OSA, and markers of disease severity such as admission rates, fetal haemoglobin or lactate dehydrogenase levels. Conclusions High BMI did not correlate with disease severity in this cohort of patients with sickle cell disease. Obesity was more prevalent in females and those with HbSC. Further prospective studies are needed to determine long-term effects of BMI in disease severity and outcome.

WOS: 000379156300012, PubMed ID: 26819058, The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients., Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) [BB/L023776/1, BB/I00050X/1, BB/K021168/1]; Cancer Research UKCancer Research UK [11831]; Medical Research CouncilMedical Research Council UK (MRC) [G1000801a]; Novo Nordisk FondenNovo Nordisk [NNF12OC1015986]; British Heart FoundationBritish Heart Foundation [FS/09/039/27788]; Cancer Research UKCancer Research UK [12765]; Medical Research CouncilMedical Research Council UK (MRC) [MR/L022982/1, MC_UU_12009/8, MC_U137981013, MC_PC_12009]

No Abstract.

Objectives: To prospectively assess longitudinal lung function in children with sickle cell disease (SCD). Working hypothesis: Lung function in SCD children deteriorates with increasing age and the decline is more marked in younger children who have recently suffered ACS episodes. Study design: Two prospective longitudinal studies. Patient-subject selection: Two cohorts of SCD children and age and ethnic matched controls were recruited. Cohort One (47 SCD and 26 controls) had a median age of 8.8 years and follow up of 2 years and Cohort Two (45 SCD and 26 controls) a median age of 10.2 years and follow up of 10 years. Methodology: Forced expiratory volume in one second (FEV1), vital capacity (VC), forced expiratory flow between 25% and 75% of VC (FEF 25-75), total lung capacity (TLC) and residual volume (RV) were measured on two occasions. Results: In both groups of SCD children, lung function declined significantly, but in neither control group. ACS episodes were more frequent during the follow up period in Cohort One than Cohort Two (P1 (P=0.008), VC (P=0.001), FEF25-75 (P=0.030), TLC (P=0.004), and RV (P=0.043). In Cohort Two restrictive abnormalities were more common at follow up (P=0.006). Conclusions: Lung function deteriorated with increasing age in SCD children and the rate of decline was greater in younger children in whom ACS episodes were more common. Pediatr Pulmonol.

Multilayered protein coats are crucial to the dormancy, robustness, and germination of bacterial spores. In Bacillus subtilis spores, the coat contains over 70 distinct proteins. Identifying which proteins reside in each layer may provide insight into their distinct functions. We present image analysis methods that determine the order and geometry of concentric protein layers by fitting a model description for a spheroidal fluorescent shell image to optical micrographs of spores incorporating fluorescent fusion proteins. The radius of a spherical protein shell can be determined with

Generalized lymphatic dysplasia (GLD) is a rare form of primary lymphoedema characterized by a uniform, widespread lymphoedema affecting all segments of the body, with systemic involvement such as intestinal and/or pulmonary lymphangiectasia, pleural effusions, chylothoraces and/or pericardial effusions. This may present prenatally as non-immune hydrops. Here we report homozygous and compound heterozygous mutations in PIEZO1, resulting in an autosomal recessive form of GLD with a high incidence of non-immune hydrops fetalis and childhood onset of facial and four limb lymphoedema. Mutations in PIEZO1, which encodes a mechanically activated ion channel, have been reported with autosomal dominant dehydrated hereditary stomatocytosis and non-immune hydrops of unknown aetiology. Besides its role in red blood cells, our findings indicate that PIEZO1 is also involved in the development of lymphatic structures., Primary lymphoedema can lead to the swelling of the extremities and facial dysmorphism. Here the authors present evidence that compound heterozygous and homozygous mutations in PIEZO1 result in an autosomal recessive form of generalised lymphatic dysplasia.

BACKGROUND: Sickle cell anaemia (SCA) is an inherited disorder of haemoglobin. Patients experience long-term health care problems, affecting quality of life (QOL) including frequent acute pain, which is difficult to document in trials except as hospital admissions. Pilot data suggests that overnight respiratory support, either supplementary oxygen or auto-adjusting continuous positive airways pressure (APAP), is safe and may have clinical benefit. This pilot trial aims to determine which intervention is more acceptable to participants and whether there are other advantages of one over the other, e.g. in respiratory function or haematological parameters, before conducting the Phase 2 trial of overnight respiratory support funded by the National Institutes of Health Research.METHODS/DESIGN: This is a pilot cross-over interventional trial with the order of interventions decided by simple randomization. Ten adults (age over 18 years) and 10 children (aged between 8 and 18 years) with homozygous sickle cell disease (haemoglobin SS, HbSS), recruited regardless of symptoms of sleep-disordered breathing, will undergo overnight pulse oximetry and will have two interventions, overnight oxygen and APAP, for a week each in randomised order with a washout week between interventions. Participants will complete online diaries via an iPad throughout the 29 days of the study and will complete QOL questionnaires and have measurement of haematology, biochemistry, spirometry and lung volumes (adults only) at 3 time points, at baseline and after each intervention, as well as in-depth semi-structured qualitative interviews after each intervention, carried out by an experienced psychologist. Both qualitative and statistical methods will be used to analyze the data. The primary outcome is qualitative data looking at participant experience from the transcribed interviews after each intervention. The participant's view on feasibility, acceptability and preference will specifically be explored. The QOL, laboratory and lung function data will be compared with baseline for each arm.DISCUSSION: Patient and public involvement is an integral part of this trial and the key outcome is the qualitative result, which is dependent on obtaining good quality data to advise on participant feasibility, acceptability and preference. This is being addressed by using a standard interview. The development of a pain endpoint is another important outcome and collecting daily measurements is likely to be challenging. Research results will be used to inform design of the Phase 2 trial.TRIAL REGISTRATION: ISRCTN46078697 18 July 2014.

Background Sickle cell anaemia (SCA) is an inherited disorder of haemoglobin. Patients experience long-term health care problems, affecting quality of life (QOL) including frequent acute pain, which is difficult to document in trials except as hospital admissions. Pilot data suggests that overnight respiratory support, either supplementary oxygen or auto-adjusting continuous positive airways pressure (APAP), is safe and may have clinical benefit. This pilot trial aims to determine which intervention is more acceptable to participants and whether there are other advantages of one over the other, e.g. in respiratory function or haematological parameters, before conducting the Phase 2 trial of overnight respiratory support funded by the National Institutes of Health Research. Methods/Design This is a pilot cross-over interventional trial with the order of interventions decided by simple randomization. Ten adults (age over 18 years) and 10 children (aged between 8 and 18 years) with homozygous sickle cell disease (haemoglobin SS, HbSS), recruited regardless of symptoms of sleep-disordered breathing, will undergo overnight pulse oximetry and will have two interventions, overnight oxygen and APAP, for a week each in randomised order with a washout week between interventions. Participants will complete online diaries via an iPad throughout the 29 days of the study and will complete QOL questionnaires and have measurement of haematology, biochemistry, spirometry and lung volumes (adults only) at 3 time points, at baseline and after each intervention, as well as in-depth semi-structured qualitative interviews after each intervention, carried out by an experienced psychologist. Both qualitative and statistical methods will be used to analyze the data. The primary outcome is qualitative data looking at participant experience from the transcribed interviews after each intervention. The participant’s view on feasibility, acceptability and preference will specifically be explored. The QOL, laboratory and lung function data will be compared with baseline for each arm. Discussion Patient and public involvement is an integral part of this trial and the key outcome is the qualitative result, which is dependent on obtaining good quality data to advise on participant feasibility, acceptability and preference. This is being addressed by using a standard interview. The development of a pain endpoint is another important outcome and collecting daily measurements is likely to be challenging. Research results will be used to inform design of the Phase 2 trial. Trial registration ISRCTN46078697 18 July 2014 Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-0883-y) contains supplementary material, which is available to authorized users.

Personal cover image 1: Study logo. (DOC 21 kb)

CONSORT checklist. (PDF 70 kb)

Bournemouth Digital Pier is the name of a feasibility study funded by ESRC and completed by Steve Brewer (University of Southampton) and David Rees (Henley Business School) looking into the feasibility of replicating the Brighton Fuse Project. Brighton Fuse developed the concept of a new business paradigm, that of the superfused organisation that harnessed the combined benefits of creative, digital and IT (CDIT) approaches in a tightly coupled organisational structure.The Bournemouth Digital Pier study presents an overview of the current situation in Bournemouth and the surrounding area achieved through interviews with key figures, other research and a preliminary literature search. The report also includes a comparison of the key business models for CDIT enterprise around the UK including: Tech City, Soho and Greenwich in London and MediaCity UK in Salford, Greater Manchester as well as Brighton.

Background Household contact with an index case of an infectious disease is a known risk factor for infection transmission. However, such contact may be underestimated due to the dynamic nature of households, particularly in longitudinal studies. Such studies generally begin with contact defined at a single point in time (‘snap-shot’), leading to contact misclassification for some individuals who actually experienced contact before and after the snapshot. Objective To quantify contact misclassification with index cases of disease in households. Methods Historical data of 112,026 individuals from 17,889 households from an epidemiological study on leprosy in northern Malawi were used. Individuals were interviewed in the early 1980s and followed up over 5 years. It was possible to trace whether individuals died, changed household within the area, or moved out of the area between the two surveys. Using a 10% sample of households as the starting population and parameters for demographic and household changes over 5 years, the extent of contact misclassification was estimated through a simulation model of household dynamics, which traced contact with index cases in households over time. The model thereafter compared initial contact status and ‘true’ contact status generated from simulations. Results The starting population had 11,401 individuals, 52% female, and 224 (2%) leprosy index cases. Eleven percent of the households had at least one index case resident and 10% (1, 177) of non-case individuals were initial contacts. Sensitivity of initial contact status ranged from 0.52 to 0.74 and varied by age and sex. Sensitivity was low in those aged 20–29 and under 5 years but high in 5- to 14-year-olds. By gender, there were no differences among those aged under 5; females had lower sensitivity among those aged under 20 and higher for those above 30, respectively. Sensitivity was also low in simulations of long incubation periods. Conclusion This work demonstrates the implications of changes in households on household contact-associated disease spread, particularly for long durations of follow-up and infections with long incubation periods where earlier unobserved contact is critical., Background Although there are significant numbers of people displaced by war in Africa, very little is known about long-term changes in the fertility of refugees. Refugees of the Mozambican civil war (1977–1992) settled in many neighbouring countries, including South Africa. A large number of Mozambican refugees settled within the Agincourt sub-district, underpinned by a Health and Socio-demographic Surveillance Site (AHDSS), established in 1992, and have remained there. The AHDSS data provide a unique opportunity to study changes in fertility over time and the role that the fertility of self-settled refugee populations plays in the overall fertility level of the host community, a highly relevant factor in many areas of sub-Saharan Africa. Objectives To examine the change in fertility of former Mozambican self-settled refugees over a period of 16 years and to compare the overall fertility and fertility patterns of Mozambicans to host South Africans. Methods Prospective data from the AHDSS on births from 1993 to 2009 were used to compare fertility trends and patterns and to examine socio-economic factors that may be associated with fertility change. Results There has been a sharp decline in fertility in the Mozambican population and convergence in fertility patterns of Mozambican and local South African women. The convergence of fertility patterns coincides with a convergence in other socio-economic factors. Conclusion The fertility of Mozambicans has decreased significantly and Mozambicans are adopting the childbearing patterns of South African women. The decline in Mozambican fertility has occurred alongside socio-economic gains. There remains, however, high unemployment and endemic poverty in the area and fertility is not likely to decrease further without increased delivery of family planning to adolescents and increased education and job opportunities for women., Background There is a lack of reliable data in developing countries to inform policy and optimise resource allocation. Health and socio-demographic surveillance sites (HDSS) have the potential to address this gap. Mortality levels and trends have previously been documented in rural South Africa. However, complex space–time clustering of mortality, determinants, and their impact has not been fully examined. Objectives To integrate advanced methods enhance the understanding of the dynamics of mortality in space–time, to identify mortality risk factors and population attributable impact, to relate disparities in risk factor distributions to spatial mortality risk, and thus, to improve policy planning and resource allocation. Methods Agincourt HDSS supplied data for the period 1992–2008. Advanced spatial techniques were used to identify significant age-specific mortality ‘hotspots’ in space–time. Multivariable Bayesian models were used to assess the effects of the most significant covariates on mortality. Disparities in risk factor profiles in identified hotspots were assessed. Results Increasing HIV-related mortality and a subsequent decrease possibly attributable to antiretroviral therapy introduction are evident in this rural population. Distinct space–time clustering and variation (even in a small geographic area) of mortality were observed. Several known and novel risk factors were identified, and population impact was quantified. Significant differences in the risk factor profiles of the identified ‘hotspots’ included ethnicity; maternal, partner, and household deaths; household head demographics; migrancy; education; and poverty. Conclusions A complex interaction of highly attributable multilevel factors continues to demonstrate differential space–time influences on mortality risk (especially for HIV). High-risk households and villages displayed differential risk factor profiles. This integrated approach could prove valuable to decision makers. Tailored interventions for specific child and adult high-risk mortality areas are needed, such as preventing vertical transmission, ensuring maternal survival, and improving water and sanitation infrastructure. This framework can be applied in other settings within the region., Background South Africa accounts for more than a sixth of the global population of people infected with HIV and TB, ranking her highest in HIV/TB co-infection worldwide. Remote areas often bear the greatest burden of morbidity and mortality, yet there are spatial differences within rural settings. Objectives The primary aim was to investigate HIV/TB mortality determinants and their spatial distribution in the rural Agincourt sub-district for children aged 1–5 years in 2004. Our secondary aim was to model how the associated factors were interrelated as either underlying or proximate factors of child mortality using pathway analysis based on a Mosley-Chen conceptual framework. Methods We conducted a secondary data analysis based on cross-sectional data collected in 2004 from the Agincourt sub-district in rural northeast South Africa. Child HIV/TB death was the outcome measure derived from physician assessed verbal autopsy. Modelling used multiple logit regression models with and without spatial household random effects. Structural equation models were used in modelling the complex relationships between multiple exposures and the outcome (child HIV/TB mortality) as relayed on a conceptual framework. Results Fifty-four of 6,692 children aged 1–5 years died of HIV/TB, from a total of 5,084 households. Maternal death had the greatest effect on child HIV/TB mortality (adjusted odds ratio=4.00; 95% confidence interval=1.01–15.80). A protective effect was found in households with better socio-economic status and when the child was older. Spatial models disclosed that the areas which experienced the greatest child HIV/TB mortality were those without any health facility. Conclusion Low socio-economic status and maternal deaths impacted indirectly and directly on child mortality, respectively. These factors are major concerns locally and should be used in formulating interventions to reduce child mortality. Spatial prediction maps can guide policy makers to target interventions where they are most needed., Background Disparities in health outcomes between the poor and the better off are increasingly attracting attention from researchers and policy makers. However, policies aimed at reducing inequity need to be based on evidence of their nature, magnitude, and determinants. Objectives The study aims to investigate the relationship between household socio-economic status (SES) and under-five mortality, and to measure health inequality by comparing poorest/least poor quintile mortality rate ratio and the use of a mortality concentration index. It also aims to describe the risk factors associated with under-five mortality at Rufiji Demographic Surveillance Site (RDSS), Tanzania. Methods This analytical cross sectional study included 11,189 children under-five residing in 7,298 households in RDSS in 2005. Principal component analysis was used to construct household SES. Kaplan–Meier survival incidence estimates were used for mortality rates. Health inequality was measured by calculating and comparing mortality rates between the poorest and least poor wealth quintile. We also computed a mortality concentration index. Risk factors of child mortality were assessed using Poisson regression taking into account potential confounders. Results Under-five mortality was 26.9 per 1,000 person-years [95% confidence interval (CI) (23.7–30.4)]. The poorest were 2.4 times more likely to die compared to the least poor. Our mortality concentration index [−0.16; 95% CI (−0.24, −0.08)] indicated considerable health inequality. Least poor households had a 52% reduced mortality risk [incidence rate ratio (IRR) = 0.48; 95% CI 0.30–0.80]. Furthermore, children with mothers who had attained secondary education had a 70% reduced risk of dying compared to mothers with no education [IRR = 0.30; 95% CI (0.22–0.88)]. Conclusion Household socio-economic inequality and maternal education were associated with under-five mortality in the RDSS. Targeted interventions to address these factors may contribute towards accelerating the reduction of child mortality in rural Tanzania., Background Alcohol is a risk factor for the leading causes of mortality and morbidity among young people globally. Youth drinking, initiated in early adolescence and continued into early adulthood, is influenced by maternal socio-demographic factors and maternal education. Limited prospective data exists in South Africa on the prevalence of alcohol use during adolescence and adolescent and maternal socio-demographic correlates. Objective To examine the prevalence of lifetime alcohol use during early (13 years) and late (18 years) adolescence in Soweto, South Africa, and its association with child and maternal socio-demographic factors. Methods Data on alcohol use in early adolescence (age 13 years) and late adolescence (age 18 years) were collected using self-completed pen and paper and self-completed computer-based questionnaires, respectively. Univariate analyses were conducted on child (gender and number of school years repeated by grade 7), maternal socio-demographic correlates (education, marital status, and age), and household socioeconomic status (SES). Bivariate logistic regression analyses examined associations between alcohol use and all child and maternal socio-demographic factors. Multivariate logistic regression analyses were conducted on all the variables found to be significantly (p, Globally, communication plays an integral role in public health strategies, from infectious diseases to diseases related to lifestyles. The evolution of the field of social and behaviour change communication (SBCC), combined with the need for evidence based practice and multi-level interventions to promote health, and human resource gaps in sub-Saharan Africa have led to the imperative to standardise and formalise the field. Moreover, current practitioners come from different disciplinary backgrounds underlining the need to define common core skills and competencies. This paper describes the partnership between the Wits School of Public Health and the Soul City Institute for Health and Development Communication and how the partners responded to this need. It highlights the factors influencing sustainable institutional capacity to provide quality assured, accredited training. We describe an unexpected positive response from a number of practitioner organisations that have chosen to send multiple staff members for training, specifically to build a critical mass within their organisations. Finally, we note the interest from (mostly) southern-based academic institutions in setting up similar programmes and postulate that south–south collaborations can contribute to building sustainable context specific and evidence-informed SBCC programmes in the global south., Introduction In light of global concerns about insufficient numbers of doctors, midwives, and nurses, the World Health Organization (WHO) has identified the scale-up of the production of medical professionals who are competent and responsive to community needs as urgent and necessary. Coincident with this imperative, South African medical schools have also had to consider redressing apartheid-era inequities in access to medical education and changing the racial and gender profile of medical graduates to be representative of the population. In this article, we explore progress and challenges with regard to transformation, defined as intentional and planned changes aimed at addressing historical disadvantages, in the Gauteng Province of South Africa. Methods A cross-sectional, descriptive analysis was conducted using data on medical school admissions and graduations from the Health and Education Departments for the period 1999–2011. Admission and graduation statistics of 1999, 2005, 2008, and 2011 were analysed according to race and gender. Results The results show that there has been progress in transforming the race and gender composition of medical students and graduates, in line with the transformation strategies of the South African government. In 1999, black African enrolments and graduates were conspicuously low in two of the three medical schools in the Gauteng province. By 2011, an almost six-fold increase in black African student enrolments was seen in one medical school that was previously designated as a white institution. In contrast, at the historically black medical school, whites only represented 0.40% of enrolments in 1999 and 7.4% in 2011. Since 1999, the number and proportion of female medical enrolments and graduates has also increased substantially. Conclusion While there has been progress with redressing historical disparities and inequities in terms of race and gender, further efforts are needed to ensure that student intakes and graduations are in line with the South African population profile., Background Environmentally acquired asbestos-related diseases (ARDs) are of concern globally. In South Africa, there is widespread contamination of the environment due to historical asbestos mining operations that were poorly regulated. Although the law makes provision for the compensation of occupationally acquired ARDs, compensation for environmentally acquired ARDs is only available through the Asbestos Relief Trust (ART) and Kgalagadi Relief Trust, both of which are administered by the ART. This study assessed ARDs and compensation outcomes of environmental claims submitted to the Trusts. Methods The personal details, medical diagnoses, and exposure information of all environmental claims considered by the Trusts from their inception in 2003 to April 2010 were used to calculate the numbers and proportions of ARDs and compensation awards. Results There were 146 environmental claimants of whom 35 (23.9%) had fibrotic pleural disease, 1 (0.7%) had lung cancer, and 77 (52.7%) had malignant mesothelioma. 53 (36.3%) claimants were compensated: 20 with fibrotic pleural disease and 33 with mesothelioma. Of the 93 (63.7%) claimants who were not compensated, 33 had no ARDs, 18 had fibrotic pleural disease, 1 had lung cancer, and 44 had mesothelioma. In addition to having ARDs, those that were compensated had qualifying domestic (33; 62.2%) or neighbourhood (20; 37.8%) exposures to asbestos. Most of the claimants who were not compensated had ARDs but their exposures did not meet the Trusts’ exposure criteria. Conclusions This study demonstrates the environmental impact of asbestos mining on the burden of ARDs. Mesothelioma was the most common disease diagnosed, but most cases were not compensated. This highlights that there is little redress for individuals with environmentally acquired ARDs in South Africa. To stop this ARD epidemic, there is a need for the rehabilitation of abandoned asbestos mines and the environment. These issues may not be unique to South Africa as many countries continue to mine and use asbestos., Background Crystalline silica and asbestos are common minerals that occur throughout South Africa, exposure to either causes respiratory disease. Most studies on silicosis in South Africa have been cross-sectional and long-term trends have not been reported. Although much research has been conducted on the health effects of silica dust and asbestos fibre in the gold-mining and asbestos-mining sectors, little is known about their health effects in other mining sectors. Objective The aims of this thesis were to describe silicosis trends in gold miners over three decades, and to explore the potential for diamond mine workers to develop asbestos-related diseases and platinum mine workers to develop silicosis. Methods Mine workers for the three sub-studies were identified from a mine worker autopsy database at the National Institute for Occupational Health. Results From 1975 to 2007, the proportions of white and black gold mine workers with silicosis increased from 18 to 22% and from 3 to 32% respectively. Cases of diamond and platinum mine workers with asbestos-related diseases and silicosis, respectively, were also identified. Conclusion The trends in silicosis in gold miners at autopsy clearly demonstrate the failure of the gold mines to adequately control dust and prevent occupational respiratory disease. The two case series of diamond and platinum mine workers contribute to the evidence for the risk of asbestos-related diseases in diamond mine workers and silicosis in platinum mine workers, respectively. The absence of reliable environmental dust measurements and incomplete work history records impedes occupational health research in South Africa because it is difficult to identify and/or validate sources of dust exposure that may be associated with occupational respiratory disease., Context In the South African mining sector, cardiorespiratory-specific autopsies are conducted under the Occupational Diseases in Mines and Works Act (ODMWA) on deceased mineworkers to determine eligibility for compensation. However, low levels of autopsy utilisation undermine the value of the service. Objective To explore enablers and barriers to consent that impact on ODMWA autopsy utilisation for posthumous monetary compensation. Methods In-depth interviews were conducted with mineworkers, widows and relatives of deceased mineworkers as well as traditional healers and mine occupational health practitioners. Results A range of socio-cultural barriers to consent for an autopsy was identified. These barriers were largely related to gendered power relations, traditional and religious beliefs, and communication and trust. Understanding these barriers presents opportunities to intervene so as to increase autopsy utilisation. Conclusions Effective interventions could include engagement with healthy mine-workers and their families and re-evaluating the permanent removal of organs. The study adds to our understanding of utilisation of the autopsy services., Background In 2005, the South African government introduced a voluntary, subsidised health insurance scheme for civil servants. In light of the global emphasis on universal coverage, empirical evidence is needed to understand the relationship between new health financing strategies and health care access thereby improving global understanding of these issues. Objectives This study analysed coverage of the South African government health insurance scheme, the population groups with low uptake, and the individual-level factors, as well as characteristics of the scheme, that influenced enrolment. Methods Multi-stage random sampling was used to select 1,329 civil servants from the health and education sectors in four of South Africa's nine provinces. They were interviewed to determine factors associated with enrolment in the scheme. The analysis included both descriptive statistics and multivariate logistic regression. Results Notwithstanding the availability of a non-contributory option within the insurance scheme and access to privately-provided primary care, a considerable portion of socio-economically vulnerable groups remained uninsured (57.7% of the lowest salary category). Non-insurance was highest among men, black African or coloured ethnic groups, less educated and lower-income employees, and those living in informal-housing. The relatively poor uptake of the contributory and non-contributory insurance options was mostly attributed to insufficient information, perceived administrative challenges of taking up membership, and payment costs. Conclusion Barriers to enrolment include insufficient information, unaffordability of payments and perceived administrative complexity. Achieving universal coverage requires good physical access to service providers and appropriate benefit options within pre-payment health financing mechanisms., Background South Africa is currently undergoing major health system restructuring in an attempt to improve health outcomes and reduce inequities in access. Such inequities exist between private and public health care and within the public health system itself. Experience shows that rural health care can be disadvantaged in policy formulation despite good intentions. The objective of this study was to identify the major challenges and priority interventions for rural health care provision in South Africa thereby contributing to pro-rural health policy dialogue. Methods The Delphi technique was used to develop consensus on a list of statements that was generated through interviews and literature review. A panel of rural health practitioners and other stakeholders was asked to indicate their level of agreement with these statements and to rank the top challenges in and interventions required for rural health care. Results Response rates ranged from 83% in the first round (n=44) to 64% in the final round (n=34). The top five priorities were aligned to three of the WHO health system building blocks: human resources for health (HRH), governance, and finance. Specifically, the panel identified a need to focus on recruitment and support of rural health professionals, the employment of managers with sufficient and appropriate skills, a rural-friendly national HRH plan, and equitable funding formulae. Conclusion Specific policies and strategies are required to address the greatest rural health care challenges and to ensure improved access to quality health care in rural South Africa. In addition, a change in organisational climate and a concerted effort to make a career in rural health appealing to health care workers and adequate funding for rural health care provision are essential., Background Job satisfaction is an important determinant of health worker motivation, retention, and performance, all of which are critical to improving the functioning of health systems in low- and middle-income countries. A number of small-scale surveys have measured the job satisfaction and intention to leave of individual health worker cadres in different settings, but there are few multi-country and multi-cadre comparative studies. Objective The objective of this study was to compare the job satisfaction and intention to leave of different categories of health workers in Tanzania, Malawi, and South Africa. Methods We undertook a cross-sectional survey of a stratified cluster sample of 2,220 health workers, 564 from Tanzania, 939 from Malawi, and 717 from South Africa. Participants completed a self-administered questionnaire, which included demographic information, a 10-item job satisfaction scale, and one question on intention to leave. Multiple regression was used to identify significant predictors of job satisfaction and intention to leave. Results There were statistically significant differences in job satisfaction and intention to leave between the three countries. Approximately 52.1% of health workers in South Africa were satisfied with their jobs compared to 71% from Malawi and 82.6% from Tanzania (χ2=140.3, p, Background In 2007, the South African government introduced the occupation-specific dispensation (OSD), a financial incentive strategy, to attract, motivate, and retain health professionals in the public sector. Implementation commenced with the nursing sector, but there have been unintended negative consequences. Objective First, to examine implementation of the OSD for nurses using Hogwood and Gunn's framework that outlines ‘perfect implementation’ pre-conditions. Second, to highlight the conditions for the successful implementation of financial incentives. Methods A qualitative case study design using a combination of a document review and in-depth interviews with 42 key informants. Results The study found that there were several implementation weaknesses. Only a few of the pre-conditions were met for OSD policy implementation. The information systems required for successful policy implementation, such as the public sector human resource data base and the South African Nursing Council register of specialised nurses were incomplete and inaccurate, thus undermining the process. Insufficient attention was paid to time and resources, dependency relationships, task specification, and communication and coordination. Conclusion The implementation of financial incentives requires careful planning and management in order to avoid loss of morale and staff grievances., Background Mid-level medical workers play an important role in health systems and hold great potential for addressing the human resource shortage, especially in low- and middle-income countries. South Africa began the production of its first mid-level medical workers – known as clinical associates – in small numbers in 2008. Objective We describe the way in which scopes of practice and course design were negotiated and assess progress during the early years. We derive lessons for other countries wishing to introduce new types of mid-level worker. Methods We conducted a rapid assessment in 2010 consisting of a review of 19 documents and 11 semi-structured interviews with a variety of stakeholders. A thematic analysis was performed. Results Central to the success of the clinical associate training programme was a clear definition and understanding of the interests of various stakeholders. Stakeholder sensitivities were taken into account in the conceptualisation of the role and scope of practice of the clinical associate. This was achieved by dealing with quality of care concerns through service-based training and doctor supervision, and using a national curriculum framework to set uniform standards. Conclusions This new mid-level medical worker can contribute to the quality of district hospital care and address human resource shortages. However, a number of significant challenges lie ahead. To sustain and expand on early achievements, clinical associates must be produced in greater numbers and the required funding, training capacity, public sector posts, and supervision must be made available. Retaining the new cadre will depend on the public system becoming an employer of choice. Nonetheless, the South African experience yields positive lessons that could be of use to other countries contemplating similar initiatives., Background In light of an increasing global focus on health system strengthening and integration of vertical programmes within health systems, methods and tools are required to examine whether general health service managers exercise administrative authority over vertical programmes. Objective To measure the extent to which general health service (horizontal) managers, exercise authority over the HIV programme's monitoring and evaluation (M&E) function, and to explore factors that may influence this exercise of authority. Methods This cross-sectional survey involved interviews with 51 managers. We drew ideas from the concept of ‘exercised decision-space’ – traditionally used to measure local level managers’ exercise of authority over health system functions following decentralisation. Our main outcome measure was the degree of exercised authority – classified as ‘low’, ‘medium’ or ‘high’ – over four M&E domains (HIV data collection, collation, analysis, and use). We applied ordinal logistic regression to assess whether actor type (horizontal or vertical) was predictive of a higher degree of exercised authority, independent of management capacity (training and experience), and M&E knowledge. Results Relative to vertical managers, horizontal managers had lower HIV M&E knowledge, were more likely to exercise a higher degree of authority over HIV data collation (OR 7.26; CI: 1.9, 27.4), and less likely to do so over HIV data use (OR 0.19; CI: 0.05, 0.84). A higher HIV M&E knowledge score was predictive of a higher exercised authority over HIV data use (OR 1.22; CI: 0.99, 1.49). There was no association between management capacity and degree of authority. Conclusions This study demonstrates a HIV M&E model that is neither fully vertical nor integrated. The HIV M&E is characterised by horizontal managers producing HIV information while vertical managers use it. This may undermine policies to strengthen integrated health system planning and management under the leadership of horizontal managers., Background Ninety percent of the world's 2.1 million HIV-infected children live in sub-Saharan Africa, and 2.5% of South African children live with HIV. As HIV care and treatment programmes are scaled-up, a rise in loss to follow-up (LTFU) has been observed. Objective The aim of the study was to determine the rate of LTFU in children receiving antiretroviral treatment (ART) and to identify baseline characteristics associated with LTFU in the first year of treatment. We also explored the effect of patient characteristics at 12 months treatment on LTFU in the second year. Methods The study is an analysis of prospectively collected routine data of HIV-infected children at the Harriet Shezi Children's Clinic (HSCC) in Soweto, Johannesburg. Cox proportional hazards models were fitted to investigate associations between baseline characteristics and 12-month characteristics with LTFU in the first and second year on ART, respectively. Results The cumulative probability of LTFU at 12 months was 7.3% (95% CI 7.1–8.8). In the first 12 months on ART, independent predictors of LTFU were age, Background South Africa is experiencing a demographic and epidemiological transition with an increase in population aged 50 years and older and rising prevalence of non-communicable diseases. This, coupled with high HIV and tuberculosis prevalence, puts an already weak health service under greater strain. Objective To measure self-reported chronic health conditions and chronic disease risk factors, including smoking and alcohol use, and to establish their association with health care use in a rural South African population aged 50 years or older. Methods The Study on Global Ageing and Adult Health (SAGE), in collaboration with the INDEPTH Network and the World Health Organization, was implemented in the Agincourt sub-district in rural northeast South Africa where there is a long-standing health and socio-demographic surveillance system. Household-based interviews were conducted in a random sample of people aged 50 years and older. The interview included questions on self-reported health and health care use, and some physical measurements, including blood pressure and anthropometry. Results Four hundred and twenty-five individuals aged 50 years or older participated in the study. Musculoskeletal pain was the most prevalent self-reported condition (41.7%; 95% Confidence Interval [CI] 37.0–46.6) followed by hypertension (31.2%; 95% CI 26.8–35.9) and diabetes (6.1%; 95% CI 4.1–8.9). All self-reported conditions were significantly associated with low self-reported functionality and quality of life, 57% of participants had hypertension, including 44% of those who reported normal blood pressure. A large waist circumference and current alcohol consumption were associated with high risk of hypertension in men, whereas in women, old age, high waist–hip ratio, and less than 6 years of formal education were associated with high risk of hypertension. Only 45% of all participants reported accessing health care in the last 12 months. Those who reported higher use of the health facilities also reported lower levels of functioning and quality of life. Conclusion Self-reported chronic health conditions, especially hypertension, had a high prevalence in this population and were strongly associated with higher levels of health care use. The primary health care system in South Africa will need to provide care for people with non-communicable diseases., Background This article is a review of the PhD thesis by Elizabeth Kimani-Murage that explores the double burden of malnutrition in rural South Africa. This is in the context of a worryingly rapid increase in obesity and obesity-related diseases in low- and middle-income countries (LMICs) including South Africa, and in the wake of on-going nutrition transition and lifestyle changes in these countries. Objective To understand the profiles of malnutrition among children and adolescents in a poor, high HIV prevalent, transitional society in a middle-income country. Methods A cross-sectional growth survey was conducted in 2007 targeting 4,000 children and adolescents aged 1–20 years. In addition, HIV testing was carried out on children aged 1–5 years and Tanner pubertal assessment among adolescents aged 9–20 years. Results The study shows stunting at an early age and adolescent obesity, particularly among girls, that co-exists in the same socio-geographic population. The study also shows that HIV is an independent modifiable risk factor for poor nutritional outcomes in children and makes a significant contribution to nutritional outcomes at the individual level. Significant predictors of undernutrition at an early age, documented at individual, household, and community levels, include child's HIV status, age and birth weight, maternal age, age of household head, and area of residence. Significant predictors of overweight/obesity and risk for metabolic disease during adolescence, documented at individual and household levels include child's age, sex, and pubertal development, household-level food security, socio-economic status, and household head's highest education level. Conclusions The combination of early stunting and adolescent obesity raises critical concerns in the wake of the rising public health importance of metabolic diseases in LMICs. This is because, both paediatric obesity and adult short stature are risk factors for metabolic syndrome and metabolic diseases in adulthood. Clearly, policies and interventions to address malnutrition in this and other transitional societies need to be double-pronged and gender-sensitive., Background Increasing urbanisation and rising unhealthy lifestyle risk factors are contributing to a growing diabetes epidemic in South Africa. In 2000, a study estimated diabetes prevalence to be 5.5% in those aged over 30. Accurate, up-to-date information on the epidemiology and burden of disease due to diabetes and its sequelae is essential in the planning of health services for diabetes management. Objective To calculate the non-fatal burden of disease in Years Lost due to Disability (YLD) due to diabetes and selected sequelae in South Africa in 2009. YLD measures the equivalent loss of life due to ill-health. Methods A series of systematic literature reviews identified data on the epidemiology of diabetes and its sequelae in South Africa. The data identified were then applied to Global Burden of Disease (GBD) methodology to calculate the burden attributable to diabetes. Results Prevalence of type 2 diabetes in South Africa in 2009 is estimated at 9.0% in people aged 30 and older, representing approximately 2 million cases of diabetes. We modelled 8,000 new cases of blindness and 2,000 new amputations annually caused by diabetes. There are 78,900 YLD attributed to diabetes, with 64% coming from diabetes alone, 24% from retinopathy, 6% from amputations, 9% from attributable stroke disability, and 7% from attributable ischemic heart disease disability. Conclusion We estimate that the prevalence of diabetes is increasing in South Africa. Significant disability associated with diabetes is demonstrated. Some of the attributed burden can be prevented through early detection and treatment., Background Non-communicable diseases (NCD) and infectious chronic illnesses are recognised as significant contributing factors to the burden of disease globally, specifically in South Africa, yet clinical management is often poor. The involvement of community health workers (CHWs) in TB and HIV care in South Africa, and other low- and middle-income settings, suggests that they could make an important contribution in the management of NCDs. Objectives Using a rapid assessment, this study examines the outcomes of a pilot CHW programme to improve the management of hypertension and diabetes in Gauteng province, South Africa. Methods A record review compared outcomes of patients receiving home visits (n56) with a control group (n168) attending the clinic, matched, as far as possible, on age, gender, and condition. Focus group discussions and semi-structured interviews with CHWs, patients, district, clinic, and NGO staff were used to obtain descriptions of the functioning of the programme and patient experiences. Results Despite the greater age and co-morbidity among those in the pilot programme, the findings suggest that control of hypertension was improved by CHW home visits in comparison to usual clinic care. However, too few doctor visits, insufficient monitoring of patient outcomes by clinic staff, and a poor procurement process for supplies required by the CHWs hampered the programme's activities. Conclusion The role of CHWs in the management of hypertension should be given greater consideration, with larger studies being conducted to provide more robust evidence. Adequate training, supervision, and operational support will be required to ensure success of any CHW programme., Introduction In South Africa, there are renewed efforts to strengthen primary health care and community health worker (CHW) programmes. This article examines three South African CHW programmes, a small local non-governmental organisation (NGO), a local satellite of a national NGO, and a government-initiated service, that provide a range of services from home-based care, childcare, and health promotion to assist clients in overcoming poverty-related barriers to health care. Methods The comparative case studies, located in Eastern Cape and Gauteng, were investigated using qualitative methods. Thematic analysis was used to identify factors that constrain and enable outreach services to improve access to care. Results The local satellite (of a national NGO), successful in addressing multi-dimensional barriers to care, provided CHWs with continuous training focused on the social determinants of ill-health, regular context-related supervision, and resources such as travel and cell-phone allowances. These workers engaged with, and linked their clients to, agencies in a wide range of sectors. Relationships with participatory structures at community level stimulated coordinated responses from service providers. In contrast, an absence of these elements curtailed the ability of CHWs in the small NGO and government-initiated service to provide effective outreach services or to improve access to care. Conclusion Significant investment in resources, training, and support can enable CHWs to address barriers to care by negotiating with poorly functioning government services and community participation structures.

International audience; BACKGROUND: The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. METHODS: Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. RESULTS: Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). CONCLUSIONS: There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.

International audience; The HACEK organisms (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) are rare causes of infective endocarditis (IE). The objective of this study is to describe the clinical characteristics and outcomes of patients with HACEK endocarditis (HE) in a large multi-national cohort. Patients hospitalized with definite or possible infective endocarditis by the International Collaboration on Endocarditis Prospective Cohort Study in 64 hospitals from 28 countries were included and characteristics of HE patients compared with IE due to other pathogens. Of 5591 patients enrolled, 77 (1.4%) had HE. HE was associated with a younger age (47 vs. 61 years; p < 0.001), a higher prevalence of immunologic/vascular manifestations (32% vs. 20%; p < 0.008) and stroke (25% vs. 17% p = 0.05) but a lower prevalence of congestive heart failure (15% vs. 30%; p = 0.004), death in-hospital (4% vs. 18%; p = 0.001) or after 1 year follow-up (6% vs. 20%; p = 0.01) than IE due to other pathogens (n = 5514). On multivariable analysis, stroke was associated with mitral valve vegetations (OR 3.60; CI 1.34-9.65; p < 0.01) and younger age (OR 0.62; CI 0.49-0.90; p < 0.01). The overall outcome of HE was excellent with the in-hospital mortality (4%) significantly better than for non-HE (18%; p < 0.001). Prosthetic valve endocarditis was more common in HE (35%) than non-HE (24%). The outcome of prosthetic valve and native valve HE was excellent whether treated medically or with surgery. Current treatment is very successful for the management of both native valve prosthetic valve HE but further studies are needed to determine why HE has a predilection for younger people and to cause stroke. The small number of patients and observational design limit inferences on treatment strategies. Self selection of study sites limits epidemiological inferences.

Sickle cell disease (SCD) is characterized by vasculopathy, which has been causally linked to intravascular haemolysis and high levels of free plasma haemoglobin. Soluble CD163 (sCD163) is implicated in the clearance of free plasma haemoglobin and high plasma concentrations have been linked to arterial disease. We therefore investigated the value of sCD163 as a biomarker in children with SCD, and also measured haptoglobin levels in this population. We measured sCD163 in 25 control children with no haemoglobinopathy, 41 with sickle cell anaemia (HbSS) in the steady state, 27 with HbSS taking hydroxycarbamide, and 7 with HbSC disease. There was no significant difference between sCD163 levels in steady-state HbSS (1·78 mg/l) and controls (1·81 mg/l) (P = 0·86). However, sCD163 levels were significantly lower in those HbSS children taking hydroxycarbamide (1·35 mg/l) compared to both steady state HbSS (P = 0·004) and controls (P = 0·036). In children on hydroxycarbamide, sCD163 correlated negatively and highly significantly with percentage HbF (R = -0·76, P

We retrospectively audited children with sickle cell disease (SCD) admitted to paediatric intensive care (PICU) at King's College Hospital between January 2000 and December 2008. Forty-six children with SCD were admitted, on 49 separate occasions. Ages ranged from 4 months to 15 years (median 7 6 years). Three children died in PICU, however two presented to hospital in cardiorespiratory arrest; overall mortality was 6%. The most common reason for admission was acute chest syndrome (43%). 88% of admissions required blood transfusion, of which 74% had exchange blood transfusions. The mortality among children with SCD admitted to PICU is low.

The purpose of this study was to assess changes in psychophysiological fitness following reconstructive knee surgery and early phase (2.5 months) physical rehabilitation. Nine patients (7 male, 2 female; mean age, 29.9 years) electing to undergo anterior cruciate ligament reconstructive surgery (central third, bone-patella tendon-bone graft) were assessed on four separate assessment occasions post-surgery. Repeated measures ANOVAs showed significant condition (injured/non-injured leg) by test occasion (2 weeks pre-surgery and 6, 8 and 10 weeks post-surgery) interactions for knee ligamentous compliance (anterior tibiofemoral displacement), peak force and electromechanical delay associated with the knee flexors of the injured and noninjured legs (F3,24 = 4.7 to 6.6; p < 0.01), together with individualized emotional profile disturbance scores that were significantly less at 10 weeks post-surgery compared to pre-surgery, 6 weeks and 8 weeks post-surgery (F3,24 = 7.6; p < 0.01). Spearman rank correlation coefficients identified significant relationships between musculoskeletal fitness and emotional profile scores at pre-surgery (r = 0.69–0.72; p < 0.05) and at 8 weeks post-surgery (r = 0.70–0.73; p < 0.05). The 6 Bi-POMS subscales and the 12 ERAIQ responses found inconsistent patterns of response and relationships across the assessment occasions. Overall, the patterning of changes and associations amongst emotional performance profile discrepancy scores in conjunction with those scores from indices of musculoskeletal fitness performance capability offered important support for the efficacy of an approach which integrates self-perceptive and objective measurements of fitness capability during rehabilitation following surgery to a synovial joint.

Münchner Beiträge zur jüdischen Geschichte und Kultur, Nr. 2 (2007): Zur Historischen Gestalt Gershom Scholems

Münchner Beiträge zur jüdischen Geschichte und Kultur, Nr. 2 (2007): Zur Historischen Gestalt Gershom Scholems

The quality of higher education programs has been, historically, evaluated using criteria framed by a traditional worldview of higher education, which is centred on faculty expertise and in-class instruction as the mode of delivery. As the result of significant changes in the past decade higher education institutions are responding with new program delivery models that challenge the established concept and traditional measures of quality. “Blended” programs represent a relatively new delivery model, combining both on-campus and online delivery methods. Whereas traditional universities have long-standing, and well-tested, methods for evaluating the quality of programs, blended programs must be assessed using different criteria. The purpose of this research project was, first, to identify indicators that could be used to assess the quality of blended, graduate programs and, second, to determine which of these were the strongest indicators of program quality. Using a logic model approach as the theoretical framework, which views programs as systems with inputs, processes, outputs and outcomes, measures were developed and assessed by graduate students, faculty, and program administrators. Of the 75 indicators developed, process-related measures were rated most highly overall and outcome-related measures lowest. 33 of the 75 indicators were rated most highly and, of these, graduate students, faculty and program administrators all agreed on ten as the strongest indicators of program quality. These included three groups of indicators: (a) faculty/instructors’ enthusiasm, communication skills, availability and responsiveness; (b) learners’ mastery of the competencies, their ability to integrate theory and practice, and apply learning outcomes to work /life, and (c) the extent to which program goals are defined, program and course materials are well organized, and the extent to which feedback is use to improve the program.

This thesis reports the results of a prospective multicentred case-control study of mesothelioma carried out in South Africa. The objectives of the study were: 1) to examine asbestos exposure of cases in detail with respect to source, risk occupations, fibre type and duration; 2) to determine relative risks for level (certainty) of exposure (definite, probable, possible, unlikely), for category of exposure (occupational, environmental), and for fibre type and skin colour; 3) to determine whether cases without recall of exposure were exposed to other non-asbestos putative agents; 4) to investigate the possible protective effect of certain dietary components. Previous studies of mesothelioma in South Africa had, with the exception of one incidence study, focused on particular occupational or case material, exposure data had been gathered in a non-systematic way, often indirectly from surrogates, and non-asbestos agents had not been investigated. In this case-control study these issues are all addressed. In addition, special efforts were made to minimise potential sources of bias (e.g. interviewer bias) and so to furnish reliable effect estimates. The study incorporated the following methodological features: 1) a prospective approach to gather exposure and dietary information directly from the cases and controls in life and so avoid the use of surrogates for this information; 2) the study was multicentred with study teams established in six cities, each with a major referral hospital, to maximise nation-wide coverage; 3) information was gathered with interviewers blind (at least at the beginning of the study) to study objectives and case control status at the time of the interview; 4) rigorous pathologic review was used to establish the diagnosis of mesothelioma; 5) two controls were selected for each case, a cancer and a non-cancer patient matched for hospital, sex, age and skin colour; 6) in analysis the case control datasets were treated separately (i.e cases and cancer controls, and cases and non-cancer controls were treated as two separate datasets). One hundred and twenty three cases were accepted into the study. No case was documented with purely chrysotile exposure nor exposure to a putative non-asbestos cause of the tumour without some evidence of asbestos exposure. A minimum of 22 cases (18%) had exclusively environmental exposure, 20 were from the NW Cape (a crocidolite mining region). Fifty eight percent had occupational exposure, three of whom had mined amosite. The relative risks associated environmental exposure in the NW Cape were larger than for environmental exposure in the NE Transvaal: 21.9 versus 7.1 for the cancer control dataset and 50.9 versus 12.0 for the medical control dataset. Increasing consumption of carotene rich fruit was found to be protective for mesothelioma when adjusted for asbestos exposure. The results confirm the high disease burden due to occupational exposure, the importance of environmental exposure in the crocidolite mining area of the NW Cape, the relative paucity of cases linked to amosite, the rarity of chrysotile cases, and are consistent with the view that there is a fibre gradient in mesotheliomagenic potential for South African asbestos with crocidolite > amosite > chrysotile. The evidence for a protective effect of carotene rich fruit is new in the South African context.

The Stokes Profile Synthesis Routine (SPSR) calculates the Stokes vector emerging from a model atmosphere using the Diagonal Element Lambda Operator (DELO) method described in Rees, Murphy, and Durrant (1989). The DELO technique combines speed, accuracy, and robustness making it well suited to the problem of radiative transfer in the presence of magnetic fields. This report describes the data required by the SPSR and also the format of its results.

Hemispheric differences in the structure and dynamics of the polar regions of the thermosphere and ionosphere are caused by seasonal/latitudinal asymmetries of solar insolation acting in addition to the effects of the distinctive asymmetries of the main geomagnetic field. Viewing the earth from a satellite, the longitudinal and universal time variations of the thermosphere and ionosphere are far more spectacular in the southern polar thermosphere and ionosphere than in the northern polar regions. This is simply caused by the greater offset of the geomagnetic pole from the geographic pole in the southern hemisphere, and the associated geomagnetic forcing of the polar thermosphere and ionosphere. The southern polar cusp is a localised region of intense forcing with a diurnal migration in geographic latitude from 55° to the southern geographic pole. At times of major geomagnetic disturbances, the combination of the equatorward expansion of the auroral oval and the greater offset of the southern geomagnetic pole from the rotational pole causes dramatic effects in southern mid-latitude and near-equatorial regions. The northern auroral oval rarely expands within 40° of the equator (at mid-American longitudes). In the Australian sector, equivalent major geomagnetic disturbances may extend to a southern latitude of 30°. Wind, gravity wave and ionospheric perturbations originating in the auroral ovals decrease rapidly in amplitude with increasing distance from the source region. The greater frequency and amplitude of auroral-related disturbances reaching a particular mid- or low-latitude region in the southern hemisphere, particularly in the Australian sector is thus explained. A survey of recent satellite data will be presented, highlighted by simulations using a global theoretical model, to demonstrate the causes of these hemispheric asymmetries. Future complementary ground-based and space measurements can exploit the hemispheric asymmetries to clearly identify geomagnetic forcing mechanisms. The greater UT and latitudinal modulation in the southern hemisphere may be used to identify sub-auroral excitation of the thermosphere and ionosphere during major storms. The cause of the related negative F-region storm-time response is still not certain, even after 30 years of study.

1. Field work was first carried out on the Upper River as the geological materials in the bed-sediment are more easily identified than in the Lower River. However, the Debris Proportions for the confluences in the middle section could not be found due to the width of the active flood plain there and the relatively small size of the tributaires which results in poor mixing of the debris below the confluence. The most important results here are the Sampling Accuracy Tests carried out at Kamikochi. Samples were taken from along a 〓/4 Km stretch of the river which is free from addition of debris for some kilometers upstream. Sampling was conducted on three size ranges, referred to as 10mm. (9.52-15.8mm), 5mm. (4.6-9.52mm.), and 2.5mm. (2.5-4.6mm.) size ranges respectively. At this Station a few samples were taken above and below these sizes, but above this size samples become too bulky to handle by a small field party, and below this size the individual particles become partly mineral rather than rock fragments and it is difficult or impossible to identify. It was established from these tests that a sample size of 2,250 particles gave the required accuracy, and was used as a standard throughout this project. Using this sample size it was concluded that: i. The geological composition can be measured from relatively small samples and that the composition is independant of the grain size distribution. The accuracy of measurement depends upon: (a) ease of identification and skill of operators, (b) random variations in the composition of the bed material which depend upon the river's characteristics (eg. wide flood plains show greater variations than rivers confined between narrow banks), and (c) sample size. How-ever increasing the latter will not overcome errors due to (a) and (b), but too small a sample introduces unacceptably large variations. ii. The grain size distribution varies widely, and a reliable average can-not be found even from large samples. The surface layer of the bed is almost always found to contain a large proportion of larger particles, which form an "insulating layer" against removal of material from below them. These pebbles are too large to be moved by the existing flow and so remain covering the bed, the smaller sizes have for the most part been moved away. This phenomena occurs during floods and prevents the river from carrying its capacity load. iii. A practical difficulty is to allow a long enough stretch of river below confluences to allow for complete mixing of the bed-sediment, without having extra material added to the river below the confluence. Large scale aerial photographs are indispensable in this connection in the field. At Kamikochi the standard deviation of the measured geological compositions of five samples was less than 2.2% in all cases (expressed as% of the whole sample) for the three main geological components, and of this it is estimated that less than 1% was due to errors in identification, the rest being due to random variations in the composition Geological grain size distribution curves are shown on Fig. 4, where the heading inferred refers to sizes below 2.5mm: larger sizes were measured directly. "Ss" corresponds to symbol "P" on Fig. 2; other symbols correspond directly." One other result for the Upper River must be mentioned: Between Station "M" and Kamikochi, no Paleozoic Rocks enter the river, but the concentration of Paleozoic Rocks at Kamikochi is nearly 6% higher, which is greater than the known variations in measurement. This trend has been also found on the Lower River, and is thought to be due to non-uniform transport mechanism during floods owing to the differences in gradient and discharge between the main stream and the tributaries at different stages of the flood and hence their transporting capacities. 2. In order to calculate the Debris Proportions for the Lower River, it was necessary to separate the sandstones, shales and cherts of the Paleozoic sediments; however, results were obtained for all the main confluences on the three size ranges (Step 1), and considerable differences exist between the movement on the different sizes. The accuracy with which this can be done depends upon the differences in geological composition of the bed-sediment between the tributaries in addition to the accuracy of sampling. If this difference is greater than 15%, the error in the results is less than 10%, and in practice better than this as several results can be averaged (for different geological materials). This accuracy is also affected by the relative volume of debris carried by the tributaries and their gradients, both of which should preferably be of the same order, but limits cannot be easily given. 3. The movement of debris along reaches of a river between confluences (Step 2) can be measured if: i. The Debris-delivery Ratio is 100% (i.e. no aggradation or degradation). ii. and one of the geological groups in the bed-sediment does not enter the river along the reach, the percentage reduction of which indicates the volume of material entering the river along the reach. The first requirement is almost never found in nature, in which case it is necessary to calculate or estimate the Debris-delivery Ratio indepen-dently (eg. from bed level surveys). Alternatively, one may assume a Debris delivery Ratio of 100%, and work out the results in terms of the downstream point on the system, in which case the results indicate the source of material arriving at that point. In order to obtain the results in volume per annum, the results in percentage must be correlated with measured Debris Yields somewhere on the river, usually in the form of measured accumulations behind debris control dams. However, such data gives the yield behind the dam but gives no indication of the yield below the dam, and cannot be used directly unless the river was also sampled before the construction of the dam, except in the case of a dam situated at the downstream end of the river system under consideration. There is also the difficulty that the data may not be for the same period as the river analysis, and there are large fluctuations in the yield from year to year. Practical results for the case of the reservoir to be formed behind Nagawa Dam are summarised in Fig. 3. The author has suggested a long-term study of a small catchment area chosen with suitable geological and other conditions in order to clarify some of the problems encountered during a study of this nature.