Progress Towards Using Linked Population-Based Data For Geohealth Research: Comparisons Of Aotearoa New Zealand And The United Kingdom.

Globally, geospatial concepts are becoming increasingly important in epidemiological and public health research. Individual level linked population-based data afford researchers with opportunities to undertake complex analyses unrivalled by other sources. However, there are significant challenges associated with using such data for impactful geohealth research. Issues range from extracting, linking and anonymising data, to the translation of findings into policy whilst working to often conflicting agendas of government and academia. Innovative organisational partnerships are therefore central to effective data use. To extend and develop existing collaborations between the institutions, in June 2019, authors from the Leeds Institute for Data Analytics and the Alan Turing Institute, London, visited the Geohealth Laboratory based at the University of Canterbury, New Zealand. This paper provides an overview of insight shared during a two-day workshop considering aspects of linked population-based data for impactful geohealth research. Specifically, we discuss both the collaborative partnership between New Zealand's Ministry of Health (MoH) and the University of Canterbury's GeoHealth Lab and novel infrastructure, and commercial partnerships enabled through the Leeds Institute for Data Analytics and the Alan Turing Institute in the UK. We consider the New Zealand Integrated Data Infrastructure as a case study approach to population-based linked health data and compare similar approaches taken by the UK towards integrated data infrastructures, including the ESRC Big Data Network centres, the UK Biobank, and longitudinal cohorts. We reflect on and compare the geohealth landscapes in New Zealand and the UK to set out recommendations and considerations for this rapidly evolving discipline.

Assessing diet in a university student population: a longitudinal food card transaction data approach.

Starting university is an important time with respect to dietary changes. This study reports a novel approach to assessing student diet by utilising student-level food transaction data to explore dietary patterns. First-year students living in catered accommodation at the University of Leeds (UK) received pre-credited food cards for use in university catering facilities. Food card transaction data were obtained for semester 1, 2016 and linked with student age and sex. k-Means cluster analysis was applied to the transaction data to identify clusters of food purchasing behaviours. Differences in demographic and behavioural characteristics across clusters were examined using χ2 tests. The semester was divided into three time periods to explore longitudinal changes in purchasing patterns. Seven dietary clusters were identified: 'Vegetarian', 'Omnivores', 'Dieters', 'Dish of the Day', 'Grab-and-Go', 'Carb Lovers' and 'Snackers'. There were statistically significant differences in sex (P < 0·001), with women dominating the Vegetarian and Dieters, age (P = 0·003), with over 20s representing a high proportion of the Omnivores and time of day of transactions (P < 0·001), with Dieters and Snackers purchasing least at breakfast. Many students (n 474, 60·4 %) changed dietary cluster across the semester. This study demonstrates that transactional data present a feasible method for dietary assessment, collecting detailed dietary information over time and at scale, while eliminating participant burden and possible bias from self-selection, observation and attrition. It revealed that student diets are complex and that simplistic measures of diet, focusing on narrow food groups in isolation, are unlikely to adequately capture dietary behaviours.

Surgical decision-making in infants with suspected UPJ obstruction: stakeholder perspectives.

INTRODUCTION: Although there are significant demographic and clinical variations in treatment decisions for infants with high-grade hydronephrosis concerning for ureteropelvic junction obstruction (UPJO), there has been little research on the roles of parents and surgeons in the surgical decision-making (DM) process. OBJECTIVE: The purpose of this study was to understand parents' and surgeons' perceived roles in the surgical DM process for infants with high-grade hydronephrosis. STUDY DESIGN: Semistructured interviews were conducted with pediatric urologists from three regionally diverse tertiary referral sites and parents of infants diagnosed and treated for unilateral Society for Fetal Urology grade 3 or 4 hydronephrosis at one tertiary pediatric urology practice. Purposive sampling was used to ensure adequate representation of parents based on treatment choice, patient gender, race/ethnicity, and distance from the practice. Survey domains included (1) discussions about diagnosis and treatment options, (2) factors guiding treatment choice, and (3) participants' role in the DM process. Transcribed data and field notes were analyzed using a team-based, inductive grounded theory qualitative approach. RESULTS: Thirteen physicians and 32 parents were interviewed between November 2016 and November 2017. Parents and surgeons agreed that the surgeon was best equipped to guide treatment decisions because of their clinical knowledge and experience. Parents reported that their trust in the surgeon was the primary factor in their decisions. Surgeons reported tailoring discussions with parents to not only educate them about treatment options but also to develop an ongoing relationship with parents. Both parents and surgeons reported being satisfied with their roles in the DM process. DISCUSSION: This study suggests that parental trust in the surgeon and surgeon recommendations drive DM. This may be due to a lack of explicit discussion of options or of parental values and preferences for care. Limited discussions may also impact parental understanding of risks and potential complications. These findings are similar to those of prior studies in adults and children considering elective surgery. CONCLUSIONS: In this study, parents and surgeons reported that surgeon recommendations, rather than parent preferences, guide treatment choices for infants with suspected UPJO. Both parents and surgeons are satisfied with a physician-driven approach to DM, suggesting that, in situations where the perceived risk is low and parental knowledge is limited, parents may find a physician-led approach beneficial. Data gleaned from this study will be used to inform future quantitative studies evaluating factors guiding surgeon recommendations for treatment and their associations with underlying treatment variation.

Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications.

12-lipoxygenase (12-LOX) is one of several enzyme isoforms responsible for the metabolism of arachidonic acid and other poly-unsaturated fatty acids to both pro- and anti-inflammatory lipid mediators. Mounting evidence has shown that 12-LOX plays a critical role in the modulation of inflammation at multiple checkpoints during diabetes development. Due to this, interventions to limit pro-inflammatory 12-LOX metabolites either by isoform-specific 12-LOX inhibition, or by providing specific fatty acid substrates via dietary intervention, has the potential to significantly and positively impact health outcomes of patients living with both type 1 and type 2 diabetes. To date, the development of truly specific and efficacious inhibitors has been hampered by homology of LOX family members; however, improvements in high throughput screening have improved the inhibitor landscape. Here, we describe the function and role of human 12-LOX, and mouse 12-LOX and 12/15-LOX, in the development of diabetes and diabetes-related complications, and describe promise in the development of strategies to limit pro-inflammatory metabolites, primarily via new small molecule 12-LOX inhibitors.

Feature analysis of ultrasound elastography image for quantitative assessment of cutaneous carcinoma.

BACKGROUND: To evaluate the feasibility of using quantitative texture features computed from high frequency ultrasound and ultrasound elastography (USE) images in the discrimination of benign from malignant skin lesions. METHODS: A commercial ultrasound system with a 14 MHz transducer was used to visualize skin lesions requiring biopsy on clinical evaluation. Patients were enrolled over a 6-month period and imaged prospectively by operators blind to the histopathologic diagnosis. Anatomic ultrasound and USE imaging of the skin lesions was performed using a 2-4 mm gel standoff pad before biopsy and histopathologic evaluation. The ElastoAnalysis software developed for the texture analysis of USE images was provided by Hitachi. The software computes thirteen texture features within a region of interest (ROI), which have demonstrated promise in diagnostic characterization of liver fibrosis staging and in quantitative elastography of breast cancer. This approach has not yet been studied in the quantitative assessment of skin cancer. Results were retrospectively compared to the histopathologic diagnosis and a diagnostic criteria with the goal of maximizing sensitivity was evaluated for each textural feature. RESULTS: Of the 37 lesions included, among 30 patients who participated, 12 lesions were malignant and 25 were benign. Eleven out of thirteen textural metrics computed by the software were useful in differentiating benign from malignant lesions with 100% sensitivity and specificities ranging from 28% to 85%. CONCLUSIONS: This feasibility study demonstrated that feature analysis of USE may be useful in quantitatively differentiating cancerous from benign primary solitary skin lesions prior to biopsy.

Mechanical properties and biocompatibility of the sputtered Ti doped hydroxyapatite.

The hydroxyapatite enriched with Ti were prepared as possible candidates for biomedical applications especially for implantable devices that are in direct contact to the bone. The hydroxyapatites with different Ti content were prepared by RF magnetron sputtering on Ti-6Al-4V alloy using pure hydroxyapatite and TiO2 targets. The content of Ti was modified by changing the RF power fed on TiO2 target. The XPS and FTIR analyses revealed the presence of hydroxyapatite structure. The hardness and elastic modulus of the hydroxyapatite were increased by Ti addition. After 5 days of culture, the cell viability of the Ti-6Al-4V was enhanced by depositing with undoped or doped hydroxyapatite. The Ti additions led to an increase in cell viability of hydroxyapatite, after 5 days of culture. The electron microscopy showed the presence of more cells on the surface of Ti-enriched hydroxyapatite than those observed on the surface of the uncoated alloys or undoped hydroxyapatite.

Polymeric Based Therapeutic Delivery Systems Prepared Using Electrohydrodynamic Processes.

The development of therapeutic dosage (e.g. pharmaceutical) systems is an ongoing process which, in recent times has incorporated several emerging disciplines and themes at timely intervals. While the concepts surrounding dosage forms have developed and evolved, many polymeric excipients remain as the preferred choice of materials over existing counterparts, serving functions as matrix materials, coatings and providing other specific functional properties (e.g. adhesion, controlled release and mechanical properties). There have been, however, developments in the deployment of synthetic polymeric materials (e.g. polycaprolactone, poly lactic co-glycolic acid) when compared to naturally occurring materials (e.g. lactose, gelatin). Advances in pharmaceutical process technologies have also provided novel engineering platforms to develop a host of exciting structure based materials ranging from the nanometer to the macro scales. Some of these structure enabling technologies include spray drying, super critical processing, microfluidics and even wet chemical methods. More recently electrohydrodynamic (EHDA) engineering methods have emerged as robust technologies offering potential to fabricate a plethora of generic structures (e.g. particles, fibres, bubbles and pre-determined patterns) on a broad scale range. This review focuses on key developments using various EHDA technologies for the pharmaceutical and biomaterial remits when selecting synthetic and/or naturally occurring polymers as pharmaceutical (and therapeutic) excipients. In addition, the underlying EHDA process principles are discussed along with key parameters and variables (both materials and engineering). EHDA technologies are operational at ambient conditions and recent developments have also demonstrated their viability for large scale production. These are promising technologies which have potential in established (e.g. films, dressings and microparticles) and emerging scientific themes (e.g. nanomedicines and tissue engineering).

Interaction between cytokines and inflammatory cells in islet dysfunction, insulin resistance and vascular disease.

Inflammation is an established pathogenic player in insulin resistance, islet demise and atherosclerosis. The complex interactions between cytokines, immune cells and affected tissues result in sustained inflammation in diabetes and atherosclerosis. 12- and 15-lipoxygenase (LO), such as 12/15-LO, produces a variety of metabolites through peroxidation of fatty acids and potentially contributes to the complex molecular crosstalk at the site of inflammation. 12- and 15-LO pathways are frequently activated in tissues affected by diabetes and atherosclerosis including adipose tissue (AT), islets and the vasculature. Moreover, mice with whole body and tissue-specific knockout of 12/15-LO are protected against insulin resistance, hyperglycaemia and atherosclerosis supporting functional contribution of 12- and 15-LO pathways in diabetes and atherosclerosis. Recently, it has emerged that there is a temporal regulation of the particular isoforms of 12- and 15-LO in human AT and islets during the development of type 1 and type 2 diabetes and obesity. Analyses of tissues affected by diabetes and atherosclerosis also implied the roles of interleukin (IL)-12 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1 (NOX-1) in islets and IL-17A in atherosclerosis. Future studies should aim to test the efficacy of inhibitions of these mediators for treatment of diabetes and atherosclerosis.

Comparability of methods assigning monetary costs to diets: derivation from household till receipts versus cost database estimation using 4-day food diaries.

BACKGROUND/OBJECTIVES: Diet cost could influence dietary patterns, with potential health consequences. Assigning a monetary cost to diet is challenging, and there are contrasting methods in the literature. This study compares two methods-a food cost database linked to 4-day diet diaries and an individual cost calculated from household till receipts. SUBJECTS/METHODS: The Diet and Nutrition Tool for Evaluation (DANTE) had supermarket prices (cost per 100 g) added to its food composition table. Agreement between diet costs calculated using DANTE from food diaries and expenditure recorded using food purchase till receipts for 325 individuals was assessed using correlation and Bland Altman (BA) plots. RESULTS: The mean difference between the methods' estimates was £0.10. The BA showed 95% limits of agreement of £2.88 and -£3.08. Excluding the highest 5% of diet cost values from each collection method reduced the mean difference to £0.02, with limits of agreement ranging from £2.31 to -£2.35. Agreement between the methods was stronger for males and for adults. CONCLUSIONS: Diet cost estimates using a food price database with 4-day food diaries are comparable to recorded expenditure from household till receipts at the population or group level. At the individual level, however, estimates differed by as much as £3.00 per day. The methods agreed less when estimating diet costs of children, females or those with more expensive diets.

Lifestyle and metabolic approaches to maximizing erectile and vascular health.

Oxidative stress and inflammation, which disrupt nitric oxide (NO) production directly or by causing resistance to insulin, are central determinants of vascular diseases including ED. Decreased vascular NO has been linked to abdominal obesity, smoking and high intakes of fat and sugar, which all cause oxidative stress. Men with ED have decreased vascular NO and circulating and cellular antioxidants. Oxidative stress and inflammatory markers are increased in men with ED, and all increase with age. Exercise increases vascular NO, and more frequent erections are correlated with decreased ED, both in part due to stimulation of endothelial NO production by shear stress. Exercise and weight loss increase insulin sensitivity and endothelial NO production. Potent antioxidants or high doses of weaker antioxidants increase vascular NO and improve vascular and erectile function. Antioxidants may be particularly important in men with ED who smoke, are obese or have diabetes. Omega-3 fatty acids reduce inflammatory markers, decrease cardiac death and increase endothelial NO production, and are therefore critical for men with ED who are under age 60 years, and/or have diabetes, hypertension or coronary artery disease, who are at increased risk of serious or even fatal cardiac events. Phosphodiesterase inhibitors have recently been shown to improve antioxidant status and NO production and allow more frequent and sustained penile exercise. Some angiotensin II receptor blockers decrease oxidative stress and improve vascular and erectile function and are therefore preferred choices for lowering blood pressure in men with ED. Lifestyle modifications, including physical and penile-specific exercise, weight loss, omega-3 and folic acid supplements, reduced intakes of fat and sugar, and improved antioxidant status through diet and/or supplements should be integrated into any comprehensive approach to maximizing erectile function, resulting in greater overall success and patient satisfaction, as well as improved vascular health and longevity.

De novo duplication of MECP2 in a girl with mental retardation and no obvious dysmorphic features.

Loss-of-function mutations of MECP2 are responsible for Rett syndrome (RTT), an X-linked neurodevelopmental disorder affecting mainly girls. The availability of MECP2 testing has led to the identification of such mutations in girls with atypical RTT features and the recognition of milder forms. Furthermore, duplication of the entire gene has recently been described in boys with mental retardation and recurrent infections. We describe a girl with a heterozygous de novo MECP2 duplication. The patient, at the age of 19, has mental retardation with no autistic features. She is friendly but gets frequently anxious. She has neither dysmorphic features nor malformations. Her motor development was delayed with walking at 20 months. Speech is fluid with good pronunciation but is simple and repetitive. Diagnosis was made after single-strand conformation analysis (SSCA) and multiplex ligation-dependent probe amplification (MLPA) analysis of MECP2. Array comparative genomic hybridization (aCGH) analysis showed a duplication of 29 kb including MECP2 and part of IRAK1. Fluorescent in situ hybridization (FISH) has revealed that the duplicated region is inserted near the telomere of the short arm of chromosome 10. X-chromosome inactivation in leukocyte DNA was not skewed. We conclude that it is likely that this MECP2 duplication is responsible for the mental retardation in this patient. This case broadens the phenotypic spectrum of MECP2 abnormalities with consequent implication in diagnosis and genetic counselling of girls with non-syndromic mental retardation.

Accreditation of the PGD laboratory.

Accreditation according to an internationally recognized standard is increasingly acknowledged as the single most effective route to comprehensive laboratory quality assurance, and many countries are progressively moving towards compulsory accreditation of medical testing laboratories. The ESHRE PGD Consortium and some regulatory bodies recommend that all PGD laboratories should be accredited or working actively towards accreditation, according to the internationally recognized standard ISO 15189, 'Medical laboratories-Particular requirements for quality and competence'. ISO 15189 requires comprehensive quality assurance. Detailed management and technical requirements are defined in the two major chapters. The management requirements address quality management including the quality policy and manual, document control, non-conformities and corrective actions, continual improvement, auditing, management review, contracts, referrals and resolution of complaints. Technical requirements include personnel competence (both technical and medical), equipment, accommodation and environment, and pre-analytical, analytical and post-analytical processes. Emphasis is placed on the particular requirements of patient care: notably sample identification and traceability, test validation and interpretation and reporting of results. Quality indicators must be developed to monitor contributions to patient care and continual improvement. We discuss the implementation of ISO 15189 with a specific emphasis on the PGD laboratory, highlight elements of particular importance or difficulty and provide suggestions of effective and efficient ways to obtain accreditation. The focus is on the European environment although the principles are globally applicable.

The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening.

BACKGROUND: Cystic fibrosis (CF) is caused by compound heterozygosity or homozygosity of CF transmembrane conductance regulator gene (CFTR) mutations. Phenotypic variability associated with certain mutations makes genetic counselling difficult, notably for R117H, whose disease phenotype varies from asymptomatic to classical CF. The high frequency of R117H observed in CF newborn screening has also introduced diagnostic dilemmas. The aim of this study was to evaluate the disease penetrance for R117H in order to improve clinical practice. METHODS: The phenotypes in all individuals identified in France as compound heterozygous for R117H and F508del, the most frequent CF mutation, were described. The allelic prevalences of R117H (p(R117H)), on either intron 8 T5 or T7 background, and F508del (p(F508del)) were determined in the French population, to permit an evaluation of the penetrance of CF for the [R117H]+[F508del] genotype. RESULTS: Clinical details were documented for 184 [R117H]+[F508del] individuals, including 72 newborns. The disease phenotype was predominantly mild; one child had classical CF, and three adults' severe pulmonary symptoms. In 5245 healthy adults, p(F508del) was 1.06%, p(R117H;T7) 0.27% and p(R117H;T5)<0.01%. The theoretical number of [R117H;T7]+[F508del] individuals in the French population was estimated at 3650, whereas only 112 were known with CF related symptoms (3.1%). The penetrance of classical CF for [R117H;T7]+[F508del] was estimated at 0.03% and that of severe CF in adulthood at 0.06%. CONCLUSIONS: These results suggest that R117H should be withdrawn from CF mutation panels used for screening programmes. The real impact of so-called disease mutations should be assessed before including them in newborn or preconceptional carrier screening programmes.

Characterization of aluminium-based water treatment residual for potential phosphorus removal in engineered wetlands.

Aluminium-based water treatment residual (Al-WTR) is the most widely generated residual from water treatment facilities worldwide. It is regarded as a by-product of no reuse potential and landfilled. This study assessed Al-WTR as potential phosphate-removing substrate in engineered wetlands. Results indicate specific surface area ranged from 28.0 m(2) g(-1) to 41.4 m(2) g(-1). X-ray Diffraction, Fourier transform infrared and energy-dispersive X-ray spectroscopes all indicate Al-WTR is mainly composed of amorphous aluminium which influences its phosphorus (P) adsorption capacity. The pH and electrical conductivity ranged from 5.9 to 6.0 and 0.104 dS m(-1) to 0.140 dS m(-1) respectively, showing that it should support plant growth. Batch tests showed adsorption maxima of 31.9 mg P g(-1) and significant P removal was achieved in column tests. Overall, results showed that Al-WTR can be used for P removal in engineered wetlands and it carries the benefits of reuse of a by-product that promotes sustainability.

Elicited repetitive daily blindness: a new phenotype associated with hemiplegic migraine and SCN1A mutations.

OBJECTIVE: Familial hemiplegic migraine (FHM) is a genetically heterogeneous disorder in which three genes, CACNA1A, ATP1A2, and SCN1A, are currently known to be involved. FHM is occasionally associated with other neurologic symptoms such as cerebellar ataxia or epileptic seizures. A unique eye phenotype of elicited repetitive daily blindness (ERDB) has also been reported to be cosegregating with FHM in a single Swiss family. METHODS: We report an additional family in whom the proband had, in addition to FHM, typical ERDB. In this family and the previously reported Swiss family, the whole coding region of the SCN1A gene was screened after exclusion of mutation in CACNA1A and ATP1A2 genes. RESULTS: We identified two novel SCN1A mutations (c.4495T>C/p.Phe1499Leu and c.4467G>C/p.Gln1489His missense substitutions) in exons 24 and 23, respectively, segregating with the disease in all living affected members. Both mutations were absent from 180 healthy Caucasian controls and were located in an intracellular loop highly conserved throughout evolution. CONCLUSION: We report new clinical data supporting cosegregation of familial hemiplegic migraine and the new eye phenotype of elicited repetitive daily blindness and two novel SCN1A mutations as the underlying genetic defect in two unrelated families. SCN1A encodes the voltage-gated sodium channel Nav1.1 that is highly expressed in the CNS including the retina. This remarkably stereotyped new eye phenotype has clinical characteristics of abnormal propagation of the retinal electrical signal that may be a retinal spreading depression. These results suggest that SCN1A mutations, which alter neuronal brain excitability, may occasionally alter retinal cell excitability.

In situ cell culture monitoring on a Ti-6Al-4V surface by electrochemical techniques.

In this work, the in situ interaction between Ti-6Al-4V alloy and osteoblastic cells has been studied by electrochemical techniques as a function of time. The interaction has been monitored for cell adhesion and growth of human osteoblastic Saos-2 cells on Ti-6Al-4V samples. The study has been carried out by electrochemical techniques, e.g., studying the evolution of corrosion potential with exposure time and by electrochemical impedance spectroscopy. The impedance results have been analyzed by using different equivalent circuit models that simulate the interface state at each testing time. The adhesion of the osteoblastic cells on the Ti-6Al-4V alloy leads to surface areas with different cell coverage rates, thus showing the different responses in the impedance diagrams with time. The effect of the cells on the electrochemical response of Ti-6Al-4V alloy is clearly seen after 4 days of testing, in which two isolated and well-differentiated time constants are clearly observed. One of these is associated with the presence of the cells and the other with a passive film on the Ti-6Al-4V alloy. After 7 days of culture, the system is governed by a resistive component over a wide frequency range which is associated with an increase in the cell coverage rate on the surface due to the extracellular matrix.