Time in range: A best practice guide for UK diabetes healthcare professionals in the context of the COVID-19 global pandemic.

The emergence of continuous glucose monitoring has driven improvements in glycaemic control and quality of life for people with diabetes. Recent changes in access to continuous glucose monitoring systems within UK health services have increased the number of people able to benefit from these technologies. The COVID-19 pandemic has created an opportunity for diabetes healthcare professionals to use continuous glucose monitoring technology to remotely deliver diabetes services to support people with diabetes. This opportunity can be maximized with improved application and interpretation of continuous glucose monitoring-generated data. Amongst the diverse measures of glycaemic control, time in range is considered to be of high value in routine clinical care because it is actionable and is visibly responsive to changes in diabetes management. Importantly, it is also been linked to the risk of developing complications associated with diabetes and can be understood by people with diabetes and healthcare professionals alike. The 2019 International Consensus on Time in Range has established a series of target glucose ranges and recommendations for time spent within these ranges that is consistent with optimal glycaemic control. The recommendations cover people with type 1 or type 2 diabetes, with separate targets indicated for elderly people or those at higher risk from hypoglycaemia, as well as for women with type 1 diabetes during pregnancy. The aim of this best practice guide was to clarify the intent and purpose of these international consensus recommendations and to provide practical insights into their implementation in UK diabetes care.

The effect of a multi-target protocol on cetacean detection and abundance estimation in aerial surveys.

A double-platform protocol was implemented in the Bay of Biscay and English Channel during the SCANS-III survey (2016). Two observation platforms using different protocols were operating on board a single aircraft: the reference platform (Scans), targeting cetaceans, and the 'Megafauna' platform, recording all the marine fauna visible at the sea surface (jellyfish to seabirds). We tested for a potential bias in small cetacean detection and density estimation when recording all marine fauna. At a small temporal scale (30 s, roughly 1.5 km), our results provided overall similar perception probabilities for both platforms. Small cetacean perception was higher following the detection of another cetacean within the previous 30 s in both platforms. The only prior target that decreased small cetacean perception during the subsequent 30 s was seabirds, in the Megafauna platform. However, at a larger scale (study area), this small-scale perception bias had no effect on the density estimates, which were similar for the two protocols. As a result, there was no evidence of lower performance regarding small cetacean population monitoring for the multi-target protocol in our study area. Because our study area was characterized by moderate cetacean densities and small spatial overlap of cetaceans and seabirds, any extrapolation to other areas or time requires caution. Nonetheless, by permitting the collection of cost-effective quantitative data for marine fauna, anthropogenic activities and marine litter at the sea surface, the multi-target protocol is valuable for optimizing logistical and financial resources to efficiently monitor biodiversity and study community ecology.

Working with Insulin, Carbohydrates, Ketones and Exercise to Manage Diabetes (WICKED): evaluation of a self-management course for young people with Type 1 diabetes.

AIMS: To evaluate a 5-day self-management education course for young people with Type 1 diabetes and assess its effects on knowledge, self-efficacy, beliefs, distress, self-management behaviours and HbA1c . METHODS: This is an evaluation of a structured education course. Young people (aged 16-24 years) with Type 1 diabetes were recruited from three diabetes centres. In the first centre, participants completed self-report measures of knowledge, self-efficacy, positive and negative outcome expectancies, and hypoglycaemic worries at baseline (n=47) and the end of the course (n=42). In two additional centres, participants completed these and other measures assessing self-management behaviours, cognitive adaptation to diabetes and diabetes distress at baseline (n=32), the end of the course (n=27) and 3-month follow-up (n = 27). HbA1c levels were recorded at baseline (n=79), 6 months (n=77) and 12 months (n=65). RESULTS: There were statistically significant increases in self-report knowledge, self-efficacy, positive outcome expectancies and self-management behaviours, and a statistically significant decrease in negative outcome expectances, between baseline and the end of the course. There were also statistically significant increases in self-report knowledge, self-efficacy, self-management behaviours and cognitive adaptation to diabetes between baseline and 3-month follow-up. Compared with baseline, HbA1c levels decreased by a mean (sd) of 5.44 (19.93) mmol/mol (0.48%) at 6 months (P=0.019), and by 5.98 (23.32) mmol/mol (0.54%) at 12 months (P =0.043). DISCUSSION: The results indicate the potential benefits of a self-management course designed to address the developmental needs and challenges faced by young people with Type 1 diabetes. Further studies with larger numbers and appropriate controls are required to confirm these initial findings.

Expanding the Menu of HIV Prevention Options: A Qualitative Study of Experiences with Long-Acting Injectable Cabotegravir as PrEP in the Context of a Phase II Trial in the United States.

Adherence challenges with oral pre-exposure prophylaxis have stimulated interest in alternate modes of administration including long-acting injections. We conducted 30 in-depth interviews with 26 male trial participants and 4 clinical providers in a Phase IIa study (ÉCLAIR) evaluating the use of long-acting cabotegravir (CAB-LA) injections in New York and San Francisco. Interviews exploring attitudes and experiences with CAB-LA were audiotaped, transcribed, and analyzed using thematic content analysis. Despite a high frequency of some level of side effects, almost all participants reported being interested in continuing with CAB-LA, versus a daily oral, due to its convenience and the perceived advantage of not worrying about adhering to pills. Providers reinforced the importance of CAB-LA as a prevention option and the need for guidelines to assist patient decision-making. Further research is needed on the acceptability of CAB-LA among men and women at higher risk for HIV in different settings.

The enduring impact of neurulation stage alcohol exposure: A combined behavioral and structural neuroimaging study in adult male and female C57BL/6J mice.

Prenatal alcohol exposure (PAE) can cause behavioral and brain alterations over the lifespan. In animal models, these effects can occur following PAE confined to critical developmental periods, equivalent to the third and fourth weeks of human gestation, before pregnancy is usually recognized. The current study focuses on PAE during early neurulation and examines the behavioral and brain structural consequences that appear in adulthood. On gestational day 8 C57BL/6J dams received two alcohol (2.8g/kg, i.p), or vehicle, administrations, four hours apart. Male and female offspring were reared to adulthood and examined for performance on the elevated plus maze, rotarod, open field, Morris water maze, acoustic startle, social preference (i.e. three-chambered social approach test), and the hot plate. A subset of these mice was later evaluated using magnetic resonance imaging to detect changes in regional brain volumes and shapes. In males, PAE increased exploratory behaviors on the elevated plus maze and in the open field; these changes were associated with increased fractional anisotropy in the anterior commissure. In females, PAE reduced social preference and the startle response, and decreased cerebral cortex and brain stem volumes. Vehicle-treated females had larger pituitaries than did vehicle-treated males, but PAE attenuated this sex difference. In males, pituitary size correlated with open field activity, while in females, pituitary size correlated with social activity. These findings indicate that early neurulation PAE causes sex specific behavioral and brain changes in adulthood. Changes in the pituitary suggest that this structure is especially vulnerable to neurulation stage PAE.

The Gulf of Ambracia's Common Bottlenose Dolphins, Tursiops truncatus: A Highly Dense and yet Threatened Population.

The common bottlenose dolphin (Tursiops truncatus) is the only cetacean present in the semiclosed waters of the Gulf of Ambracia, Western Greece. This increasingly degraded coastal ecosystem hosts one of the highest observed densities in the Mediterranean Sea for this species. Photo-identification data and tissue samples collected through skin-swabbing and remote biopsy sampling techniques during boat-based surveys conducted between 2006 and 2015 in the Gulf, were used to examine bottlenose dolphin abundance, population trends, site fidelity, genetic differentiation and toxicological status. Bottlenose dolphins showed high levels of year-round site fidelity throughout the 10-year study period. Dolphin population estimates mostly fell between 130 and 170 with CVs averaging about 10%; a trend in population size over the 10 years was a decline of 1.6% per year (but this was not significant). Genetic differentiation between the bottlenose dolphins of the Gulf and their conspecifics from neighbouring populations was detected, and low genetic diversity was found among individuals sampled. In addition, pesticides where identified as factors posing a real toxicological problem for local bottlenose dolphins. Therefore, in the Gulf of Ambracia, high dolphin density does not seem to be indicative of favourable conservation status or pristine habitat.

Charge based intra-cartilage delivery of single dose dexamethasone using Avidin nano-carriers suppresses cytokine-induced catabolism long term.

OBJECTIVE: Avidin exhibits ideal characteristics for targeted intra-cartilage drug delivery: its small size and optimal positive charge enable rapid penetration through full-thickness cartilage and electrostatic binding interactions that give long half-lives in vivo. Here we conjugated Avidin with dexamethasone (DEX) and tested the hypothesis that single-dose Avidin-delivered DEX can ameliorate catabolic effects in cytokine-challenged cartilage relevant to post-traumatic OA. METHODS: Avidin was covalently conjugated with DEX using fast (ester) and slow, pH-sensitive release (hydrazone) linkers. DEX release kinetics from these conjugates was characterized using (3)H-DEX-Avidin (scintillation counting). Cartilage explants treated with IL-1α were cultured with or without Avidin-DEX conjugates and compared to soluble DEX. Sulfated-glycosaminoglycan (sGAG) loss and biosynthesis rates were measured using DMMB assay and (35)S-incorporation, respectively. Chondrocyte viability was measured using fluorescence staining. RESULTS: Ester linker released DEX from Avidin significantly faster than hydrazone under physiological buffer conditions. Single dose Avidin-DEX suppressed cytokine-induced sGAG loss over 3-weeks, rescued IL-1α-induced cell death, and restored sGAG synthesis levels without causing cytotoxicity. The two Avidin-DEX conjugates in 1:1 combination (fast:slow) had the most prominent bioactivity compared to single dose soluble-DEX, which had a shorter-lived effect and thus needed continuous replenishment throughout the culture period to ameliorate catabolic effects. CONCLUSION: Intra-cartilage drug delivery remains inadequate as drugs rapidly clear from the joint, requiring multiple injections or sustained release of high doses in synovial fluid. A single dose of Avidin-conjugated drug enables rapid uptake and sustained delivery inside cartilage at low intratissue doses, and potentially can minimize unwanted drug exposure to other joint tissues.

Industrial-scale spray layer-by-layer assembly for production of biomimetic photonic systems.

Layer-by-layer assembly is a powerful and flexible thin film process that has successfully reproduced biomimetic photonic systems such as structural colour. While most of the seminal work has been carried out using slow and ultimately unscalable immersion assembly, recent developments using spray layer-by-layer assembly provide a platform for addressing challenges to scale-up and manufacturability. A series of manufacturing systems has been developed to increase production throughput by orders of magnitude, making commercialized structural colour possible. Inspired by biomimetic photonic structures we developed and demonstrated a heat management system that relies on constructive reflection of near infrared radiation to bring about dramatic reductions in heat content.

Modelling the extraction of soil contaminants with supercritical carbon dioxide.

Extractions of volatile organic compounds (VOC's) in contaminated soil from petroleum site were performed with supercritical carbon dioxide at different temperatures, pressures, extraction times, solvent flow rates, soil moisture contents and soil acidity. Three soil systems were investigated in order to compare the best parameters for extraction. A central composite rotatable design has been used to evaluate the influence of operation conditions on the extraction efficiency to generate model equations representing the types of soil. The results indicate that at least 70-80% of the initial amount of VOC's can be removed at moderate temperatures even at very high moisture content. Supercritical extraction is best suited to silt type soils which have a low adsorption capacity. VOC's recoveries from the artificial contaminated soil samples were higher in comparison with real contaminated soils. At moderate temperatures, the extraction efficiency for real soils is low because pollutants bind strongly to the soil.

The outcome of expectant management of congenital cystic adenomatoid malformations (CCAM) of the lung.

INTRODUCTION: The appropriate management of asymptomatic congenital cystic adenomatoid malformations of the lung (CCAM) remains controversial. The aim of this study is to determine the outcome of expectant management of these lesions and the sensitivity of antenatal ultrasound diagnosis. MATERIAL AND METHODS: A retrospective review was undertaken of all cases identified from prospectively collected databases with an antenatal or postnatal diagnosis of CCAM in the Northern region of England between 1985 and 2006 where such lesions underwent resection only when symptomatic. RESULTS: Thirty-seven cases of confirmed CCAM were identified antenatally or postnatally. Twenty-six (70%) were identified by antenatal ultrasound scans (during a period of near-universal antenatal scanning), of whom 21 (81%) were liveborn. In total, 16 of 29 (55%) liveborn infants with CCAM were symptomatic, and either died within the first postnatal week or underwent resection. Thirteen (45% of livebirths) were managed expectantly and remained asymptomatic. The sensitivity of antenatal ultrasound screening for CCAM increased over the period to 90% in the latter half of the study (p=0.035), although the positive predictive value (66%) did not improve. CONCLUSIONS: Expectant management was a reasonable option for almost half of the babies, but over one third required surgery for CCAM, most becoming symptomatic in infancy. In view of the uncertainty that surrounds decisions regarding expectant or pre-emptive resection in asymptomatic infants, the authors advocate having an open and honest discussion when counselling parents (particularly antenatally) regarding surveillance or expectant management as a reasonable strategy.

Collagen type III alpha I is a gastro-oesophageal reflux disease susceptibility gene and a male risk factor for hiatus hernia.

BACKGROUND AND OBJECTIVES: Gastro-oesophageal reflux disease (GORD) is a common gastrointestinal disorder with a genetic component. Our aim was to identify genetic factors associated with GORD. PATIENTS AND METHODS: Four separate patient cohorts were analysed using a step-wise approach. (1) Whole genome linkage analysis was performed in 36 families. (2) Candidate genes were tested for GORD association in a trio cohort. (3) Genetic association was replicated in a case-control cohort. We also investigated genetic association to hiatus hernia (HH). (4) Protein expression was analysed in oesophageal biopsies. RESULTS: A region on chromosome 2, containing collagen type III alpha 1 (COL3A1), was identified (LOD = 3.3) in families with dominant transmission of GORD, stratified for hiatus hernia (HH). COL3A1 showed significant association with GORD in an independent paediatric trio cohort (p(corr) = 0.003). The association was male specific (p(corr) = 0.018). The COL3A1 association was replicated in an independent adult case control cohort (p(corr) = 0.022). Moreover, male specific association to HH (p(corr) = 0.019) was found for a SNP not associated to GORD. Collagen type III protein was more abundant in oesophageal biopsies from male patients with GORD (p = 0.03). CONCLUSION: COL3A1 is a disease-associated gene in both paediatric and adult GORD. Furthermore, we show that COL3A1 is genetically associated with HH in adult males. The GORD- and HH-associated alleles are different, indicating two separate mechanisms leading to disease. Our data provides new insight into GORD aetiology, identifying a connective tissue component and indicating a tissue remodelling mechanism in GORD. Our results implicate gender differences in the genetic risk for both for GORD and HH.

Development and evaluation of an improved diagnostic PCR for Mycoplasma synoviae using primers located in the haemagglutinin encoding gene vlhA and its value for strain typing.

Using published primers, detection of Mycoplasma synoviae and strain identification using the vlhA gene sequence was attempted. However, of 21 M. synoviae strains examined, three could not be amplified, so a new reverse primer was designed with a target in the conserved region of the vlhA gene. This allowed all 21 M. synoviae strains, a further nine strains and also material from 11 swab samples from M. synoviae-positive birds, to produce a PCR product, suggesting that the method could also be suitable for clinical specimens. The protocol was then tested on the type strains of M. synoviae and the other 22 recognised avian Mycoplasma species, with amplification of M. synoviae only. Further testing demonstrated that this PCR was equally or more sensitive than other PCR tests used to detect M. synoviae. Subsequent DNA sequence analysis of the PCR product based on percent similarity and evolutionary relationship appeared to be a useful tool for strain differentiation.

Negative per capita effects of two invasive plants, Lythrum salicaria and Phalaris arundinacea, on the moth diversity of wetland communities.

Invasive plants have been shown to negatively affect the diversity of plant communities. However, little is known about the effect of invasive plants on the diversity at other trophic levels. In this study, we examine the per capita effects of two invasive plants, purple loosestrife (Lythrum salicaria) and reed canary grass (Phalaris arundinacea), on moth diversity in wetland communities at 20 sites in the Pacific Northwest, USA. Prior studies document that increasing abundance of these two plant species decreases the diversity of plant communities. We predicted that this reduction in plant diversity would result in reduced herbivore diversity. Four measurements were used to quantify diversity: species richness (S), community evenness (J), Brillouin's index (H) and Simpson's index (D). We identified 162 plant species and 156 moth species across the 20 wetland sites. The number of moth species was positively correlated with the number of plant species. In addition, invasive plant abundance was negatively correlated with species richness of the moth community (linear relationship), and the effect was similar for both invasive plant species. However, no relationship was found between invasive plant abundance and the three other measures of moth diversity (J, H, D) which included moth abundance in their calculation. We conclude that species richness within, and among, trophic levels is adversely affected by these two invasive wetland plant species.

Fulminant necrotising enterocolitis immediately following change to low birth weight formula feeds.

INTRODUCTION: The aim of this study was to investigate how low birth weight formula (LBWF) feeds may be implicated in the pathogenesis of a particularly fulminant form of necrotising enterocolitis (NEC). MATERIALS AND METHODS: A retrospective case note review was undertaken of cases of fulminant NEC between 1997 and 2003 with particular regard to the feeding history. RESULTS: Nine preterm infants were stable and already tolerating full enteral feeds for a median of seven days prior to developing fulminant NEC within a median of 24 hours following the introduction of LBWF. CONCLUSIONS: Although fortification of feeds undoubtedly benefits many premature neonates, there may be a tendency for LBWF feeds to preempt the development of fulminant NEC. This possible temporal association between LBWF and fulminant NEC requires further investigation.

Face-brain asymmetry in autism spectrum disorders.

The heterogeneity of autism spectrum disorders (ASDs) confounds attempts to identify causes and pathogenesis. Identifiable endophenotypes and reliable biomarkers within ASDs would help to focus molecular research and uncover genetic causes and developmental mechanisms. We used dense surface-modelling techniques to compare the facial morphology of 72 boys with ASD and 128 first-degree relatives to that of 254 unrelated controls. Pattern-matching algorithms were able to discriminate between the faces of ASD boys and those of matched controls (AUC=0.82) and also discriminate between the faces of unaffected mothers of ASD children and matched female controls (AUC=0.76). We detected significant facial asymmetry in boys with ASD (P<0.01), notably depth-wise in the supra- and periorbital regions anterior to the frontal pole of the right hemisphere of the brain. Unaffected mothers of children with ASD display similar significant facial asymmetry, more exaggerated than that in matched controls (P<0.03) and, in particular, show vertical asymmetry of the periorbital region. Unaffected fathers of children with ASD did not show facial asymmetry to a significant degree compared to controls. Two thirds of unaffected male siblings tested were classified unseen as more facially similar to unrelated boys with ASD than to unrelated controls. These unaffected male siblings and two small groups of girls with ASD and female siblings, all show overall directional asymmetry, but without achieving statistical significance in two-tailed t-tests of individual asymmetry of ASD family and matched control groups. We conclude that previously identified right dominant asymmetry of the frontal poles of boys with ASD could explain their facial asymmetry through the direct effect of brain growth. The atypical facial asymmetry of unaffected mothers of children with ASD requires further brain studies before the same explanation can be proposed. An alternative explanation, not mutually exclusive, is a simultaneous and parallel action on face and brain growth by genetic factors. Both possibilities suggest the need for coordinated face and brain studies on ASD probands and their first-degree relatives, especially on unaffected mothers, given that their unusual facial asymmetry suggests an ASD susceptibility arising from maternal genes.

Automated process for improved uniformity and versatility of layer-by-layer deposition.

The recently developed practice of spraying polyelectrolyte solutions onto a substrate in order to construct thin films via the layer-by-layer technique has been further investigated and extended. Here we describe a fully automated system capable of depositing thin polymer films from atomized mists of solutions containing species of complementary functionality. Film growth is shown to be similar to that in conventional "dipped" LbL assembly, whereas the reported technology allows us to realize 25-fold decreases in process times. Furthermore, complete automation removes human interaction and the possibility of operator-induced nonuniformities. We extend the versatility of the spray LbL technology by depositing both weak and strong polyelectrolyte films, hydrogen-bonded films, and dendritic compounds and nanoparticles, broadening its range of future applications. Finally, the technology is used to uniformly coat an otherwise hydrophobic substrate from aqueous solutions. ESEM images indicate that the atomization process produces a conformal coating of individual nanofibers within the substrate, dramatically changing the hydrophilicity of the macroscopic surface. Such an automated system is easily converted to an array of nozzle banks and could find application in the rapid, uniform coating of large areas of textile materials.

International survey of insulin pump users: Impact of continuous subcutaneous insulin infusion therapy on glucose control and quality of life.

AIMS: To record the characteristics and attitude of patients treated with continuous subcutaneous insulin infusion (CSII), and the impact on glycaemic control in a large number of CSII patients in routine daily life. METHODS: A structured questionnaire was distributed to 36,450 CSII patients from Europe and North America to determine patient characteristics, therapy characteristics, medical results, complications and treatment satisfaction. RESULTS: A 38% response rate was achieved, 92% from patients with Type 1 diabetes. The responses indicated that CSII users achieved good glycaemic control with a mean HbA(1c) level of 7.0+/-1.1%. A significant correlation was observed between HbA(1c) and the number of blood glucose measurements per day. Four to five blood glucose measurements are needed in a majority of patients to reach optimal glucose control in intensely treated diabetic patients. The clinical benefits of CSII therapy were matched by patient experience and improvements in quality of life. There were 5.74 episodes per patient year of hypoglycaemia needing assistance, although the number of serious adverse effects recorded was dependent on patient's self-reporting. CONCLUSIONS: These data suggest patients using CSII therapy achieve good metabolic control, are highly satisfied, and experience an acceptably small number of complications.