Big brands impact small islands: Sources of plastic pollution in a remote and protected archipelago.

Remote islands are disproportionately affected by plastic pollution, often originating from elsewhere, so it is important to understand its origins, to stop debris entering the ocean at their source. We investigated the origins of beached plastic drink bottles in the Chagos Archipelago, a large remote Marine Protected Area (MPA) in the Indian Ocean. We recorded the brands, countries of manufacture, types of drink, and ages of plastic bottles and their lids. The prevalent type of drink was water, with items mostly manufactured in Indonesia, China, and the Maldives. The main brands were Danone and the Coca-Cola Company. We deduced that 10 % of the items originated from ships passing the archipelago, including all the items manufactured in China. The identification of the brands creating plastic pollution in remote MPAs with high biodiversity supports extended producer responsibility, one of the proposed policy development areas of the Global Plastics Treaty.

A control-based observer approach for estimating energy intake during pregnancy.

Gestational weight gain outside of Institute of Medicine guidelines poses a risk to both the mother and her unborn child. Behavioral interventions such as Healthy Mom Zone (HMZ) that aim to regulate gestational weight gain require self-monitoring of energy intake, which is often significantly under-reported by participants. This paper describes the use of a control systems approach for energy intake estimation during pregnancy. It relies on an energy balance model that predicts gestational weight based on physical activity and energy intake, the latter treated as an unmeasured disturbance. Two control-based observer formulations relying on Internal Model Control and Model Predictive Control, respectively, are presented in this paper, first for a hypothetical participant, then on data collected from four HMZ participants. Results demonstrate the effectiveness of the method, with generally best results obtained when estimating energy intake over a weekly time period.

Clinical trial management: a profession in crisis?

Clinical trial managers play a vital role in the design and conduct of clinical trials in the UK. There is a current recruitment and retention crisis for this specialist role due to a complex set of factors, most likely to have come to a head due to the COVID-19 pandemic. Academic clinical trial units and departments are struggling to recruit trial managers to vacant positions, and multiple influences are affecting the retention of this highly skilled workforce. Without tackling this issue, we face major challenges in the delivery on the Department of Health and Social Care's Future of UK Clinical Research Delivery implementation plan. This article, led by a leading network of and for UK Trial Managers, presents some of the issues and ways in which national stakeholders may be able to address this.

Measuring particle size distribution and mass concentration of nanoplastics and microplastics: addressing some analytical challenges in the sub-micron size range.

HYPOTHESIS: The implementation of the proposal from the European Chemical Agency (ECHA) to restrict the use of nanoplastics (NP) and microplastics (MP) in consumer products will require reliable methods to perform size and mass-based concentration measurements. Analytical challenges arise at the nanometre to micrometre interface, e.g., 800 nm-10 µm, where techniques applicable at the nanometre scale reach their upper limit of applicability and approaches applicable at the micrometre scale must be pushed to their lower limits of detection. EXPERIMENTS: Herein, we compared the performances of nine analytical techniques by measuring the particle size distribution and mass-based concentration of polystyrene mixtures containing both nano and microparticles, with the educational aim to underline applicability and limitations of each technique. FINDINGS: Light scattering-based measurements do not have the resolution to distinguish multiple populations in polydisperse samples. Nanoparticle tracking analysis (NTA), nano-flowcytometry (nFCM) and asymmetric flow field flow fractionation hyphenated with multiangle light scattering (AF4-MALS) cannot measure particles in the micrometre range. Static light scattering (SLS) is not able to accurately detect particles below 200 nm, and similarly to transmission electron microscopy (TEM) and flow cytometry (FCM), is not suitable for accurate mass-based concentration measurements. Alternatives for high-resolution sizing and concentration measurements in the size range between 60 nm and 5 µm are tunable resistive pulse sensing (TRPS) and centrifugal liquid sedimentation (CLS), that can bridge the gap between the nanometre and micrometre range.

Teaching families to manage intake of candy in the home: Results from a feasibility study using multiphase optimization strategy (MOST).

BACKGROUND: Excess intake of desserts/sweets high in added sugars, such as candy, is linked with greater obesity risk. Parents often limit their childrens' intake of these sweet foods using controlling feeding practices, such as restriction; yet, restrictive feeding practices are counterproductive for childrens' self-regulation of energy intake. OBJECTIVE: This study developed a family-based behavioural intervention that taught parents alternatives to restrictive feeding practices and encouraged children to consume candy in moderation. METHODS: Using the multiphase optimization strategy (MOST), parent-child dyads (N = 37) were randomized into one of eight conditions that included a combination of intervention components delivered over 4 weeks: home supply, parent shared decision making, child mindfulness and child attention control strategies. RESULTS: Retention rate at follow-up was high (95%). Among parents who received parent shared decision making, 86.4% reported the structured-based candy routine they set with their child was easy to follow. Most children reported child mindfulness (95%) and attention control (89.5%) strategies were easy to play. Children recalled 4.1 ± 1.8 of the six mindfulness strategies and 2.7 ± 1.6 of the five attention control strategies at follow-up. Eating in the absence of hunger tended to be lower for children who received parent shared decision making and child mindfulness components. CONCLUSION: This intervention was feasible and well-implemented in the home environment. Findings will inform future, larger interventions designed to test similar strategies on childrens; eating behaviours and self-regulation.

Feasibility of enhancing well-child visits with family nutrition and physical activity risk assessment on body mass index.

OBJECTIVE: Integration of behavioural risk assessment into well-child visits is recommended by clinical guidelines, but its feasibility and impact is unknown. METHODS: A quasi-experimental study evaluated the feasibility and effectiveness of risk assessment on body mass index (BMI) at 1-year follow-up. Children with assessments (intervention) were compared with those who did not complete assessments (non-respondent) and those who received standard care (non-exposed). RESULTS: Analyses included 10,647 children aged 2-9 years (2,724 intervention, 3,324 non-respondent and 4,599 non-exposed). Forty-five per cent of parents completed the assessments. Intervention and non-respondent groups differed in change in BMI z-score at 1 year by -0.05 (confidence interval [CI]: -0.08, -0.02; P = 0.0013); no difference was observed with non-exposed children. The intervention group had a smaller increase in BMI z-score (0.07 ± 0.63) than non-respondent group (0.13 ± 0.63). For children with normal weight at baseline, intervention versus non-respondent groups differed in BMI z-score change by -0.06 (CI: -0.10, -0.02; P = 0.0025). However, children with overweight at baseline in the intervention versus the non-exposed group differed in BMI z-score change (0.07 [CI: 0.02, 0.14]; P = 0.016). When analysed by age, results were similar for 2- to 5-year-olds, but no differences were found for 6- to 9-year-olds. CONCLUSION: Automating risk assessment in paediatric care is feasible and effective in promoting healthy weight among preschool but not older children.

Microbiological investigation of the mandibular condyle in patients with advanced osteoarthritis of the temporomandibular joint.

PURPOSE: The aim of this study was to investigate the presence of bacteria in samples of the temporomandibular joint taken from patients suffering from advanced osteoarthritis of the temporomandibular joint (TMJ). MATERIALS AND METHODS: 25 fresh mandibular condyle samples were taken from 17 consecutive patients undergoing mandibular condylectomy (8 bilateral) for advanced TMJ osteoarthritis (Dimitroulis Category 5 joints). The joint samples were stained and cultured for the presence of microorganisms following a standardised joint culture protocol. RESULTS: No evidence of bacteria was found on staining or solid culture mediums. Late growth (day 12) of commensal skin organisms (P. Acnes, S. Epidermitis, S. Capitis) were identified in enriched broth samples in 5 joint samples. No statistically significant associations were noted between positive broth samples and age or previous joint intervention (p > 0.05) CONCLUSIONS: Within the limitations of this study, we have failed to identify meaningful bacterial growth in tissues (i.e. condylar head) of the TMJ that would suggest a contributory bacterial pathogenesis for arthritis of the TMJ.

Assessing an oral surgery specific protocol for patients on direct oral anticoagulants: a retrospective controlled cohort study.

Chronic therapy with the new direct oral anticoagulants (DOACs) poses new challenges for dental practitioners assessing the risk versus benefit of cessation versus non-cessation of anticoagulant therapy for dentoalveolar procedures. A retrospective controlled cohort study was designed to evaluate a non-cessation protocol for patients taking DOACs in the setting of dental extractions. A records review covering the period 1 January 2016 to 31 December 2016 identified 43 patients on DOAC therapy; 53 dentoalveolar procedures were performed under local anaesthesia, of which 15 included varying degrees of peri-procedural cessation. A control group of 50 patients on uninterrupted warfarin therapy undergoing 59 dentoalveolar procedures was identified. The incidence, severity, and timing of bleeding events were recorded for each group. Four (10.5%) minor bleeding events were recorded in the non-cessation DOAC group and nine (15.3%) minor bleeding events in the warfarin group. No bleeding events were recorded in the DOAC cessation group. Comparison of the incidence of bleeding events between the non-cessation DOAC group and the warfarin group showed no statistically significant difference (odds ratio 0.65, P=0.56). Within the limitations of this study, dental extractions in the context of continuing DOAC therapy can be performed safely provided extra local haemostatic measures are applied.

Evaluating the submission of digital images as a method of surveillance for Ixodes scapularis ticks.

Widespread access to the internet is offering new possibilities for data collection in surveillance. We explore, in this study, the possibility of using an electronic tool to monitor occurrence of the tick vector of Lyme disease, Ixodes scapularis. The study aimed to compare the capacity for ticks to be identified in web-based submissions of digital images/photographs, to the traditional specimen-based identification method used by the provincial public health laboratory in Quebec, Canada. Forty-one veterinary clinics participated in the study by submitting digital images of ticks collected from pets via a website for image-based identification by an entomologist. The tick specimens were then sent to the provincial public health laboratory to be identified by the 'gold standard' method using a microscope. Of the images submitted online, 74·3% (284/382) were considered of high-enough quality to allow identification. The laboratory identified 382 tick specimens from seven different species, with I. scapularis representing 76% of the total submissions. Of the 284 ticks suitable for image-based species identification, 276 (97·2%) were correctly identified (Kappa statistic of 0·92, Z = 15·46, P < 0·001). This study demonstrates that image-based tick identification may be an accurate and useful method of detecting ticks for surveillance when images are of suitable quality.

Dietary patterns in infancy are associated with child diet and weight outcomes at 6 years.

OBJECTIVE: To assess whether patterns of dietary exposures at 9 months are associated with child diet and weight at 6 years. METHODS: Data for this study were from the Infant Feeding Practices Study II and Year 6 Follow-Up Studies. All data were self-reported monthly. Results of a previous latent class analysis revealed five dietary patterns varying in milk and solid food intake. These five infant dietary patterns were used in the current study to predict child diet and weight outcomes at 6 years, while controlling for confounding variables. RESULTS: Infants with dietary patterns higher in fruit and vegetable intake at 9 months had higher fruit and vegetable intake at 6 years. Similarly, infants with the dietary pattern characterized by foods high in energy density (that is, French Fries and sweet desserts) continued to have higher consumption of these foods at 6 years, and had a higher prevalence of overweight at 6 years (43%) compared with the other classes. Formula-fed infants had higher sugar-sweetened beverage intake and fewer met the dietary guidelines for fruit and vegetable intake at 6 years than breastfed infants, controlling for factors such as income. CONCLUSIONS: Early decisions about milk-feeding, and the types of solid foods offered in infancy can foreshadow dietary patterns and obesity risk later in childhood. Infants who were offered energy-dense foods had higher intake of these foods at 6 years of age.

Brain regions implicated in inhibitory control and appetite regulation are activated in response to food portion size and energy density in children.

OBJECTIVE: Large portions of energy-dense foods drive energy intake but the brain mechanisms underlying this effect are not clear. Our main objective was to investigate brain function in response to food images varied by portion size (PS) and energy density (ED) in children using functional magnetic resonance imaging (fMRI). METHODS AND DESIGN: Blood-oxygen-level-dependent (BOLD) fMRI was completed in 36 children (ages 7-10 years) after a 2-h fast while viewing food images at two levels of PS (Large PS, Small PS) and two levels of ED (High ED, Low ED). Children rated perceived fullness pre- and post-fMRI, as well as liking of images on visual analog scales post-fMRI. Anthropometrics were completed 4 weeks before the fMRI. Large PS vs Small PS and High ED vs Low ED were compared with region-of-interest analyses using Brain Voyager v 2.8. RESULTS: Region-of-interest analyses revealed that activation in the right inferior frontal gyrus (P=0.03) was greater for Large PS vs Small PS. Activation was reduced for High ED vs Low ED in the left hypothalamus (P=0.03). Main effects were no longer significant after adjustment for pre-fMRI fullness and liking ratings (PS, P=0.92; ED, P=0.58). CONCLUSION: This is the first fMRI study to report increased activation to large portions in a brain region that is involved in inhibitory control. These findings may contribute to understanding why some children overeat when presented with large portions of palatable food.

Alternatives to restrictive feeding practices to promote self-regulation in childhood: a developmental perspective.

Intake of energy-dense snack foods is high among US children. Although the use of restrictive feeding practices has been shown to be counterproductive, there is very limited evidence for effective alternatives to restriction that help children moderate their intake of these foods and that facilitate the development of self-regulation in childhood. The developmental literature on parenting and child outcomes may provide insights into alternatives to restrictive feeding practices. This review paper uses a model of parental control from the child development and parenting literatures to (i) operationally define restrictive feeding practices; (ii) summarize current evidence for antecedents and effects of parental restriction use on children's eating behaviours and weight status, and (iii) highlight alternative feeding practices that may facilitate the development of children's self-regulation and moderate children's intake of palatable snack foods. We also discuss recent empirical evidence highlighting the role of child temperament and food motivation related behaviours as factors that prompt parents to use restrictive feeding practices and, yet, may increase children's dysregulated intake of forbidden foods.

Identification of roles for the SNARE-associated protein, SNAP29, in mouse platelets.

Platelets are critical for maintaining vascular hemostasis, but also play a major role in the formation of occlusive cardiovascular and cerebrovascular thrombi under disease conditions. Secretion of platelet alpha and dense granules is a requirement for efficient thrombus formation. Understanding and targeting the mechanisms of secretion is important to aid the development of effective antithrombotics. SNAP29 is a tSNARE found in platelets, but whose role has not been defined. Using a platelet-specific SNAP29 knockout mouse model, we assessed the role of SNAP29 in platelet secretion and function under standardized conditions and also in in vitro and in vivo thrombosis. The data showed no major defects in SNAP29-null platelets, but revealed a minor defect in α-granule secretion and a significant increase in embolization rate of thrombi in vivo. These data suggest that SNAP29 contributes to the regulation of platelet α-granule secretion and thrombus stability, possibly partially masked by functional redundancy with other tSNAREs, such as SNAP23.

Disruption of vitellogenesis and spermatogenesis by triclabendazole (TCBZ) in a TCBZ-resistant isolate of Fasciola hepatica following incubation in vitro with a P-glycoprotein inhibitor.

A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of P-glycoprotein (Pgp)-linked drug efflux pumps. The Sligo TCBZ-resistant fluke isolate was used for these experiments and the Pgp inhibitor selected was R(+)-verapamil [R(+)-VPL]. In the first experiment, flukes were initially incubated for 2 h in R(+)-VPL (100 µ m), then incubated in R(+)-VPL+triclabendazole sulphoxide (TCBZ.SO) (50 µg mL-1, or 133·1 µ m) until flukes ceased movement (at 9 h post-treatment). In a second experiment, flukes were incubated in TCBZ.SO alone and removed from the incubation medium following cessation of motility (after 15 h). In the third experiment, flukes were incubated for 24 h in R(+)-VPL on its own. Changes to the testis tubules and vitelline follicles following drug treatment and following Pgp inhibition were assessed by means of light microscope histology and transmission electron microscopy. Incubation of the Sligo isolate in either R(+)-VPL or TCBZ.SO on their own had a limited impact on the morphology of the two tissues. Greater disruption was observed when the drugs were combined, in terms of the block in development of the spermatogenic and vitelline cells and the apoptotic breakdown of the remaining cells. Sperm formation was severely affected and abnormal. Large spaces appeared in the vitelline follicles and synthesis of shell protein was disrupted. The results of this study support the concept of altered drug efflux in TCBZ-resistant flukes and indicate that drug transporters may play a role in the development of drug resistance.

Whole exome sequencing and functional studies identify an intronic mutation in TRAPPC2 that causes SEDT.

Skeletal dysplasias are challenging to diagnose because of their phenotypic variability, genetic heterogeneity, and diverse inheritance patterns. We conducted whole exome sequencing of a Turkish male with a suspected X-linked skeletal dysplasia of unknown etiology as well as his unaffected mother and maternal uncle. Bioinformatic filtering of variants implicated in skeletal system development revealed a novel hemizygous mutation, c.341-(11_9)delAAT, in an intron of TRAPPC2, the causative locus of spondyloepiphyseal dysplasia tarda (SEDT). We show that this deletion leads to the loss of wild-type TRAPPC2 and the generation of two functionally impaired mRNAs in patient cells. These consequences are predicted to disrupt function of SEDLIN/TRAPPC2. The clinical and research data were returned, with appropriate caveats, to the patient and informed his disease status and reproductive choices. Our findings expand the allelic repertoire of SEDT and show how prior filtering of the morbid human genome informed by inheritance pattern and phenotype, when combined with appropriate functional tests in patient-derived cells, can expedite discovery, overcome issues of missing data and help interpret variants of unknown significance. Finally, this example shows how the return of a clinically confirmed mutational finding, supported by research allele pathogenicity data, can assist individuals with inherited disorders with life choices.

Increased action of triclabendazole (TCBZ) in vitro against a TCBZ-resistant isolate of Fasciola hepatica following its co-incubation with the P-glycoprotein inhibitor, R(+)-verapamil.

A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of P-glycoprotein (Pgp)-linked drug efflux pumps. The Sligo TCBZ-resistant fluke isolate was used for these experiments and the Pgp inhibitor selected was R(+)-verapamil [R(+)-VPL]. In the first experiment, flukes were initially incubated for 2h in R(+)-VPL (1×10(-4) M), then incubated in R(+)-VPL + triclabendazole sulphoxide (TCBZ.SO) (50µg/ml) until flukes ceased movement (at 9h post-treatment). In a second experiment, flukes were incubated in TCBZ.SO alone and removed from the incubation medium following cessation of motility (after 15h). In the third experiment, flukes were incubated for 24h in R(+)-VPL on its own. Changes to the tegumental system and gut following drug treatment and following Pgp inhibition were assessed by means of light microscope histology and transmission electron microscopy. Incubation of the Sligo isolate in either R(+)-VPL or TCBZ.SO on their own had a limited impact on the tegumental syncytium and tegumental cells; the changes were consistent with a stress response by the fluke to drug action. Greater disruption was observed when the drugs were combined, in terms of the vacuolation and sloughing of the syncytium, spine disruption and the cessation of secretory activity in, and degradation of, the tegumental cells. In the gut, treatment with R(+)-VPL on its own did not lead to any cellular changes. Some limited changes to the mitochondria and the granular endoplasmic reticulum were observed after incubation in TCBZ.SO alone, together with reduced secretory activity and evidence of autophagy. However, these changes were far more pronounced in combination-treated flukes. The results of this study support the concept of altered drug efflux in TCBZ-resistant flukes and indicate that drug transporters may play a role in the development of drug resistance.

Increased susceptibility of a triclabendazole (TCBZ)-resistant isolate of Fasciola hepatica to TCBZ following co-incubation in vitro with the P-glycoprotein inhibitor, R(+)-verapamil.

A study was carried out to investigate whether the action of triclabendazole sulphoxide (TCBZ.SO) against the liver fluke, Fasciola hepatica is altered by inhibition of P-glycoprotein (Pgp)-linked drug efflux pumps. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible fluke isolates were used for this in vitro study and the Pgp inhibitor selected was R(+)-verapamil [R(+)-VPL]. For experiments with the Oberon isolate, flukes were incubated for 24 h with either R(+)-VPL (1×10-4 m) on its own, TCBZ.SO (15 µg mL-1) alone, a combination of R(+)-VPL (1×10-4 m) plus TCBZ.SO (15 µg mL-1), TCBZ.SO (50 µg mL-1) on its own, or a combination of TCBZ.SO (50 µg mL-1) plus R(+)-VPL (1×10-4 m). They were also incubated in TCBZ.SO (50 µg mL-1) alone or in combination with R(+)-VPL (1×10-4 m) until they became inactive; and in TCBZ.SO (50 µg mL-1) alone for a time to match that of the combination inactivity time. Flukes from the Cullompton isolate were treated with either TCBZ.SO (50 µg mL-1) alone or in combination with R(+)-VPL (1×10-4 m) until they became inactive, or with TCBZ.SO (50 µg mL-1) alone time-matched to the combination inactivity time. Morphological changes resulting from drug treatment and following Pgp inhibition were assessed by means of scanning electron microscopy. Incubation in R(+)-VPL alone had a minimal effect on either isolate. TCBZ.SO treatment had a relatively greater impact on the TCBZ-susceptible Cullompton isolate. When R(+)-VPL was combined with TCBZ.SO in the incubation medium, however, the surface disruption to both isolates was more severe than that seen after TCBZ.SO treatment alone; also, the time taken to reach inactivity was shorter. More significantly, though, the potentiation of drug activity was greater in the Oberon isolate; also, it was more distinct at the higher concentration of TCBZ.SO. So, the Oberon isolate appears to be particularly sensitive to efflux pump inhibition. The results of this study suggest that enhanced drug efflux in the Oberon isolate may be involved in the mechanism of resistance to TCBZ.

Use of 3D photography in complex-wound assessment.

OBJECTIVE: To review the evidence to support three-dimensional (3D) photographic imaging in wound care and undertake a feasibility evaluation of one device in the clinical environment. METHOD: A literature review was undertaken of the role of stereophotogrammetry in wound care.Subsequently, a 3D imaging and data storage system was selected and evaluated in two representative case studies within the clinical environment of the Royal Centre for Defence Medicine. RESULTS: The review suggested that 3D imaging has the potential to provide more accurate data on which to base treatment decisions. In practice, the device was found to be relatively easy to operate and sufficiently robust to handle the demands of clinical practice. However, the high initial cost of the unit and the time taken to download images to the database meant that its benefits were limited to more complex wound types. CONCLUSION: Three-dimensional photography has the potential to play a role in management options;however, current technical issues limit its potential and the incorporation of a highly defined image (similar to that of a standard digital 2D photograph) within its 3D representation would make it more powerful.

Effect of the P-glycoprotein inhibitor, R(+)-verapamil on the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica.

A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by the inhibition of P-glycoprotein (Pgp)-linked drug efflux pumps. The Sligo TCBZ-resistant and Cullompton TCBZ-susceptible fluke isolates were used for these experiments and the Pgp inhibitor selected was R(+)-verapamil [R-VPL]. In the first experiment, flukes were initially incubated for 2 h in R-VPL (100 µM), then incubated for a further 22 h in R-VPL+triclabendazole sulphoxide (TCBZ.SO) (50 µg/ml, or 0.1327 µM). For controls, flukes were incubated for 24 h in R-VPL and TCBZ.SO on their own. In a second experiment, flukes were removed from the incubation media following cessation of movement. In the third experiment, Sligo flukes were incubated in lower concentrations of R-VPL (10 µM) and TCBZ.SO (15 µg/ml, or 0.0398 µM). Morphological changes resulting from drug treatment and following Pgp inhibition were assessed by means of scanning electron microscopy. Incubation in R-VPL alone had minimal effect on either isolate. After treatment with TCBZ.SO alone, there was greater surface disruption to the Cullompton than Sligo isolate. However, combined treatment of R-VPL+TCBZ.SO led to more severe surface changes to the Sligo isolate than with TCBZ.SO on its own; this potentiation of drug activity was not seen with the Cullompton isolate. The phenomenon was evident at both concentrations of TCBZ.SO. Inclusion of R-VPL in the incubation medium also reduced the time taken for the flukes to become inactive; again, this effect was more distinct with the Sligo isolate. The results of this study support the concept of altered drug efflux in TCBZ-resistant flukes and indicate that drug transporters may play a role in the development of drug resistance.