Process evaluation results of a cluster randomised controlled childhood obesity prevention trial: the WAVES study.

BACKGROUND: Increasing prevalence of childhood obesity and its related consequences emphasises the importance of developing and evaluating interventions aimed at prevention. The importance of process evaluation in health intervention research is increasingly recognised, assessing implementation and participant response, and how these may relate to intervention success or failure. A comprehensive process evaluation was designed and undertaken for the West Midlands ActiVe lifestyle and healthy Eating in School children (WAVES) study that tested the effectiveness of an obesity prevention programme for children aged 6-7 years, delivered in 24 UK schools. The four intervention components were: additional daily school-time physical activity (PA); cooking workshops for children and parents; Villa Vitality (VV), a 6-week healthy lifestyle promotion programme run by a local football club; and signposting to local PA opportunities. METHODS: Data relating to six dimensions (Fidelity, Reach, Recruitment, Quality, Participant Responsiveness, Context) were collected via questionnaires, logbooks, direct observations, focus groups and interviews. Multiple data collection methods allowed for data triangulation and validation of methods, comparing research observations with teacher records. The 6-stage WAVES study model ((i) Data collection, (ii) Collation, (iii) Tabulation, (iv) Score allocation and discussion, (v) Consultation, (vi) Final score allocation) was developed to guide the collection, assimilation and analysis of process evaluation data. Two researchers independently allocated school scores on a 5-point Likert scale for each process evaluation dimension. Researchers then discussed school score allocations and reached a consensus. Schools were ranked by total score, and grouped to reflect low, medium or high intervention implementation. RESULTS: The intervention was predominantly well-implemented and well-received by teachers, parents and children. The PA component was identified as the most challenging, VV the least. Median implementation score across schools was 56/75 (IQR, 51.0 - 60.8). Agreement between teacher logbooks and researcher observations was generally high, the main discrepancies occurred in session duration reporting where in some cases teachers' estimations tended to be higher than researchers'. CONCLUSIONS: The WAVES study model provides a rigorous and replicable approach to undertaking and analysing a multi-component process evaluation. Challenges to implementing school-based obesity prevention interventions have been identified which can be used to inform future trials. TRIAL REGISTRATION: ISRCTN97000586 . 19 May 2010.

Obesity prevention in English primary schools: headteacher perspectives.

Schools are seen as important contributors to obesity prevention, yet face barriers in fulfilling this function. This qualitative study investigates headteacher views on the primary school role in preventing obesity. Semi-structured interviews were held with 22 headteachers from ethnically and socio-economically diverse schools in the West Midlands, UK. Data analysis was conducted using the framework approach. Two over-arching categories were identified: 'School roles and responsibilities' and 'Influencing factors'. Participants agreed that although schools contribute towards obesity prevention in many ways, a moral responsibility to support children's holistic development was the principal motivator, rather than preventing obesity per se. The perceived impact on learning was a key driver for promoting health. Parents were believed to have the main responsibility for preventing obesity, but barriers were identified. Whilst headteachers recognized the advantageous position of schools in offering support to parents, opinion varied on the degree to which schools could and should take on this role. Headteachers serving more deprived areas reported adopting certain responsibilities that elsewhere were fulfilled by parents, and were more likely to view working with families on healthy lifestyles as an important school function. Several factors were perceived as barriers to schools doing more to prevent obesity, including academic pressure, access to expert support and space. In conclusion, school leaders need more support, through resources and government policy, to enable them to maximize their role in obesity prevention. Additionally, school-based obesity prevention should be an integral part of the education agenda rather than bolt-on initiatives.

Testicular Microlithiasis: Is Sonographic Surveillance Necessary? Single Centre 14 Year Experience in 442 Patients with Testicular Microlithiasis.

PURPOSE: Increased prevalence of germ cell tumour (GCT) is seen with testicular microlithiasis (TM) suggesting TM is a premalignant condition with US surveillance advocated. We present a cohort of patients with TM followed up in a single centre and deliberate on the value of US surveillance. MATERIALS AND METHODS: A retrospective analysis of subjects with underlying US diagnosis of TM between 1998 and 2012. One-yearly US follow-up was offered to all patients with TM and a database maintained. Any co-existing tumour at presentation with TM was recorded. TM was divided into limited (< 5 microliths/field), classical (≥ 5 microliths/field) and florid ('snowstorm' appearance). Patient demographics, follow-up details and the development of any scrotal abnormalities were recorded. The radiological and histological findings were documented when a testicular lesion occurred during the follow-up period. RESULTS: 20 224 patients were examined: 867/20 224 (4.3 %) had TM. 21/867 (2.4 %) patients had histology proven malignant tumours at presentation. All TM patients consented to follow-up with 442/867 (51.0 %) achieving this and entering into a follow-up program (mean duration 28 months, range 8 - 165 months). Two patients developed primary GCT during the follow up period. One patient (limited TM) had undergone a previous orchiectomy for contralateral GCT and developed a palpable mass at follow up month 21. The other (limited TM) had an atrophic testis; a tumour was found on US at follow up month 62. CONCLUSION: Two patients of 442 (0.5 %) followed up for all forms of TM in a single centre developed a GCT over a mean duration of 28 months, both had independent risk factors for the development of GCT. These findings suggest that US surveillance is not required when TM is the only abnormality in the absence of any clinical risk factors for the development of GCT.

Scrotal calcification in a symptomatic paediatric population: Prevalence, location, and appearance in a cohort of 516 patients.

AIM: To describe the prevalence of all forms of scrotal calcification within a symptomatic paediatric population and to compare this with previous reported data in paediatric and adult populations. MATERIALS AND METHODS: A retrospective analysis of testicular ultrasound examinations performed in a single institution over a 55 month period. All examinations were performed by experienced operators using high-frequency linear array transducers. Types of scrotal calcification and position were recorded with all available images analysed by experienced radiologists. RESULTS: A total 516 male patients under the age of 19 years (mean age 10.5 years) were included. The prevalence of testicular microlithiasis (TM) was 8.7% and the prevalence of non-TM macrocalcification was 0.4%. 2.3% of the patients had scrotal pearls and 0.2% had epididymal calcification recorded. No other form of calcification was identified. A single patient had a co-existing testicular tumour and TM at examination. CONCLUSION: The prevalence of TM in the symptomatic paediatric population is greater than that reported in the symptomatic adult population, whereas the prevalence of intra-testicular macrocalcification is lower. It is speculated that TM and macrocalcification represent different pathways for the possible risk of testicular tumour development.

Identification of an autoantibody to vascular endothelial cell-specific antigens in patients with systemic vasculitis.

PURPOSE: Although immunologic mechanisms have been postulated in the pathogenesis of vasculitis, an autoimmune process directed against specific autologous vascular wall antigens has not been previously documented. We examined the role of an immunologic response to vascular endothelial cell (VEC) antigens in patients with vasculitis, because of the observed immunogenicity of VECs in renal and cardiac allograft recipients. PATIENTS AND METHODS: The study patients included 21 with systemic vasculitis and four with hypersensitivity vasculitis. A healthy, normal control group consisted of 51 young subjects and 61 older subjects. Thirty-two patients with connective tissue diseases were also evaluated. The presence of autoantibody to autologous monocytes and other cell types was determined with previously described standard crossmatch techniques. Patient sera exhibiting autoantibody to autologous monocytes were screened against a panel of allogeneic cells. The cell panel consisted of concordant T and B lymphocytes, monocytes, and VECs from 16 umbilical cord donors. Sera from four patients were analyzed for specificity to the vascular endothelium of frozen sections of vessels. RESULTS: An autoantibody to VEC antigens was detected in 18 of the 21 patients (86%) with confirmed systemic vasculitis, not of the hypersensitivity type. This autoantibody was highly cytotoxic, complement-fixing, and specific for antigens on the surface of the VEC. Findings on allogeneic VEC panel analysis support the existence of multiple allotypes in the VEC antigen system. In three patients, fluctuations in the titer of the autoantibody generally correlated with clinical symptoms. In the four patients screened for the specificity of the autoantibody to anatomically different cadaveric blood vessels, specific anatomic patterns of reactivity were observed. Autoantibody to VEC antigens was not found in young controls and was documented in low frequency in older controls and in patients with connective tissue diseases. The autoantibody was seen in one of four patients (25%) with hypersensitivity vasculitis. CONCLUSION: Our results indicate that an autoantibody to VEC antigens may be involved in the pathogenesis of systemic vasculitis or may be a diagnostic marker for the disease process.

Scrotal calcification: ultrasound appearances, distribution and aetiology.

This pictorial review illustrates the ultrasound appearances of scrotal calcification, distinguishing between intratesticular and extratesticular calcification. Intratesticular calcification may be due to phleboliths, spermatic granulomas or vascular calcification, or it may occur in association with tumours. Extratesticular calcification is more frequently encountered and is usually related to previous inflammatory disease of the epididymis. Testicular microlithiasis, a rare condition characterized by multiple scattered echogenic foci within the testis, is produced by the formation of microliths from degenerating cells in the seminiferous tubules. Testicular microlithiasis has been demonstrated as an incidental finding as well as in association with both benign and malignant tumours of the testis.

The genetic regulation of fucosylated and sialylated antigens on developing myeloid cells.

The first part of this article reviews the stages of normal development of haemopoietic cells committed to the myeloid lineage, properties of leukaemic cell lines that are arrested at specific maturation stages along the granulocytic pathway, the structures of carbohydrate antigenic markers that appear on myeloid cell surfaces, with especial reference to sialyl-Le(x) (NeuAcalpha2-3Galbeta1-4[Fucalpha1-3]GlcNAc), and the role of this antigen on mature granulocytes as a ligand for selectin molecules. The families of fucosyl- and sialyltransferase genes encoding enzymes responsible for the biosynthesis of sialyl-Le(x), and the pathways leading to the formation of this antigen, and more complex related structures, are described. The second part of the article outlines the work carried out in the authors' laboratory with leukaemic cell lines in an attempt to ascertain the biochemical and genetic basis of the lowering of sialyl-Le(x) expression that occurs at intermediate stages of normal haemopoietic development. Analysis of enzyme levels and mRNA expression of the fucosyl- and sialyltransferase genes has led to the conclusion that depletion of substrate resulting from high levels of enzyme activity from co-expressed genes FUT4 and ST6Gal1 probably accounts for the dip in expression of sialyl-Le(x), rather than a change in the level of expression of FUT7, the gene in myeloid cells encoding the enzyme ultimately responsible for the synthesis of sialyl-Le(x). The possible significance of this change in relation to normal cell maturation is discussed.

Leptomeningeal metastases in the MRI era.

BACKGROUND: Diagnosis of leptomeningeal metastasis (LM) has become increasingly frequent. The diagnostic gold standard has been CSF cytology, but MRI is now used routinely for diagnosis. Diagnosis and prognosis of LM has not been studied in the MRI era. METHODS: Patients with LM from 2002 through 2004 were identified through a neurology database, as well as by reviewing all abnormal CSF cytologies from a pathology database. Diagnosis was made by malignant cytology or imaging; suspicious cases treated as LM were also included. RESULTS: A total of 187 patients with LM were analyzed in this retrospective review. Of these, 150 had solid and 37 had hematopoietic malignancies. Median age was 56.4 years, and median Karnofsky performance status (KPS) was 70. The most common types of solid tumor were breast (65 patients), lung (47), gastrointestinal (11), and melanoma (9). Of the hematopoietic tumors, 21 were lymphoma and 15 were leukemia. Fifty-three percent of patients were diagnosed by imaging, 23% by cytology, and 24% by both. Treatment included radiation therapy in 55%, intrathecal chemotherapy in 29%, and systemic chemotherapy in 18%; 21% received supportive care alone. Median overall survival was 2.4 (95% confidence interval 1.9-3.1) months. Median survival for patients with hematopoietic tumors was 4.7 months and for solid tumors was 2.3 months (p = 0.0006). In multivariate analysis, initial KPS and tumor type (solid vs hematopoietic) were significant predictors of survival. CONCLUSIONS: Despite enhanced diagnosis with MRI, prognosis remains poor in leptomeningeal metastasis. Those with hematopoietic tumors continue to fare better than those with solid tumors.

Intratesticular haematoma: differentiation from tumour on clinical history and ultrasound appearances in two cases.

Intratesticular haematoma is not well described in the ultrasound literature and may be mistaken for a primary testicular malignancy if a detailed clinical history and careful ultrasound examination are not performed. We report two cases of intratesticular haematoma (one complicated by the presence of microlithiasis), describe the ultrasound appearances and document the natural history of the haematomas. A clinical history coupled with Doppler ultrasound features is crucial for conservative management.

Immunoselection techniques for cloning DNA-encoding parasite-specific antigens.

New techniques sometimes generate a 'band- waggon' effect, with research workers keen to jump on and apply the technique in their own favourite field without always pausing to consider why. Michael Miles and Louise Clarke describe a new technique which they are applying to a well-defined and valuable end - improvement in the differential diagnosis of parasitic infections.

Use of larvivorous fish for vector control in the Malvides Republic.

The paper reports on the use of three larvivorous fishes in the Maldives Republic: Poecilia reticulata (Poeciliidae), Mollienesia sphenops (Cyprinodontidae) and for the first time Kuhlia taeniurus (Kuhliidae), a sea fish adapted to life in wells, which are the only sources of water supply (with the exception of a few rain-water cisterns). The approximately 20 000 wells are the main and all-year-round breeding places for both Anophelines and Culicines. Due to this type of breeding places, Maldives are in a unique situation, that the fish can theoretically be used as the main control measure for filariasis. This requires an absolute minimum of work and no cost at all. There has been a reduction of the filariasis overall endemicity rates over the last 10 years although no specific measures have been carried out (except in the capital city of Male) nor have any ecological changes taken place, which could explain this decrease. With this decrease however there has been lately a marked reduction in the percentage of wells with fish in some atolls.

Three different endogenous alpha-L-fucosyltransferases expressed in COS cells.

The monkey kidney COS cell line is frequently used for the transient expression of cloned human fucosyltransferase cDNAs in the belief that negligible endogenous expression of fucosyltransferase genes occurs in these cells. In the course of transfection experiments we observed weak cell surface expression of sialyl-Lex and weak fucosyltransferase activity in extracts of control untransfected cells. Since these activities could complicate interpretation of the results with the transfected genes, a more detailed examination was undertaken that has now revealed expression of three different fucosyltransferases in the cells. One enzyme, which utilises N-acetyllactosamine as substrate, has a pH optimum of 7.0, is resistant to heat inactivation, and has been tentatively identified as an alpha1,3-fucosyltransferase. A second enzyme which acts on asialo-fetuin has a pH optimum of 5.5 and is rapidly inactivated by heat; the acceptor sugar and positional linkage of the transferred fucose are not yet established. A third enzyme that utilises asialo-agalacto-fetuin as acceptor is provisionally identified as an alpha1,6-fucosyltransferase.

Alpha1,3-L-fucosyltransferase expression in developing human myeloid cells. Antigenic, enzymatic, and mRNA analyses.

In an attempt to correlate the cell surface expression of Lex and sialyl-Lex structures in immature and mature myeloid cells with the genes expressing alpha1,3-fucosyltransferase(s) we have examined: 1) the properties of the cellular alpha1,3-fucosyltransferases and the mRNA transcripts corresponding to the five cloned genes, Fuc-TIII, Fuc-TIV, Fuc-TV, Fuc-TVI, and Fuc-TVII, in mature granulocytes and in the myeloid cell line HL-60, before and after dimethyl sulfoxide-induced differentiation and 2) the properties of the alpha1,3-fucosyltransferases expressed in COS-7 cells transfected with plasmids containing Fuc-TIV and Fuc-TVII cDNAs. The previously shown increase in cell surface expression of sialyl-Lex on differentiation of HL-60 cells (Skacel P. O., Edwards A. J., Harrison C. T., and Watkins W. M. (1991) Blood 78, 1452-1460) is accompanied by a sharp fall in expression of Fuc-TIV mRNA and a persistence of expression of Fuc-TVII mRNA. The properties of the alpha1,3-fucosyltransferase expressed in COS-7 cells transfected with Fuc-TIV are consistent with this being the major gene responsible for the expression of Lex in the immature myeloid cells. In Northern blot analyses, no transcripts of Fuc-TIII, Fuc-TV, or Fuc-TVI were detected in total RNA from mature granulocytes or mRNA from HL-60 cells before or after differentiation. In total RNA from mature granulocytes, Fuc-TIV transcripts were only faintly visible, whereas Fuc-TVII transcripts were quite definitely expressed. The specificity properties of Fuc-TVII expressed in COS-7 cells are consistent with this gene being the major candidate alpha1, 3-fucosyltransferase controlling the expression of sialyl-Lex on mature cells. However, Lex continues to be expressed on the surface of mature granulocytes and cell extracts retain the capacity to transfer fucose to non-sialylated acceptor substrates. The question therefore remains as to whether these properties result from the weakly expressed Fuc-TIV gene or whether another alpha1, 3-fucosyltransferase gene remains to be identified.

Independent regulation of Fuc-TIV and Fuc-TVII genes leading to modulation of cell surface antigen expression in developing myeloid cells.

Fucosylated antigen expression, fucosyltransferase activities and expression of Fuc-TIV and Fuc-TVII genes have been measured in the human leukemic cell lines KG1a, arrested at the undifferentiated myeloblast stage of maturation and KG1, arrested at the myeloblast and early promyelocytic stage. The results are compared with those we earlier found for the later promyelocytic cell line HL-60 and the myelocyte form into which HL-60 cells can be induced to differentiate. These leukemic cell lines, and the differentiated HL-60 cells, are believed to correspond to four successive stages of myeloid maturation in the bone marrow. Fuc-TVII mRNA was strongly expressed in the myeloblastic KG1a cells but expression was less in KG1 and HL-60 cells. In contrast to the sharp fall in Fuc-TIV expression observed on differentiation of HL-60 cells, the expression of Fuc-TIV mRNA showed a progressive increase from KG1a to HL-60 cells; thus the peak of expression of this gene was at the HL-60 promyelocyte stage. This peak correlated with an increase in fucosyltransferase activity with nonsialylated acceptors and the transitory downregulation of cell surface sialyl-Le(x) expression and upregulation of Le(x), VIM-2 and Le(y) expression. The variations in levels of expression of the fucosylated antigens on the surface of the developing myeloid cells therefore correlate with variations in mRNA expression arising from the independent regulation of Fuc-TIV and Fuc-TVII genes.