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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Potential mechanisms for the association between fall birth and food allergy.

BACKGROUND: Season of birth has been reported as a risk factor for food allergy, but the mechanisms by which it acts are unknown. METHODS: Two populations were studied: 5862 children from the National Health and Nutrition Examination Survey (NHANES) III and 1514 well-characterized food allergic children from the Johns Hopkins Pediatric Allergy Clinic (JHPAC). Food allergy was defined as self-report of an acute reaction to a food (NHANES), or as milk, egg, and peanut allergy. Logistic regression compared fall or nonfall birth between (i) food allergic and nonallergic subjects in NHANES, adjusted for ethnicity, age, income, and sex, and (ii) JHPAC subjects and the general Maryland population. For NHANES, stratification by ethnicity and for JHPAC, eczema were examined. RESULTS: Fall birth was more common among food allergic subjects in both NHANES (OR, 1.91; 95% CI, 1.31-2.77) and JHPAC/Maryland (OR, 1.31; 95% CI, 1.18-1.47). Ethnicity interacted with season (OR, 2.34; 95% CI, 1.43-3.82 for Caucasians; OR, 1.19; 95% CI, 0.77-1.86 for non-Caucasians; P = 0.04 for interaction), as did eczema (OR, 1.47; 95% CI, 1.29-1.67 with eczema; OR, 1.00; 95% CI, 0.80-1.23 without eczema; P = 0.002 for interaction). CONCLUSIONS: Fall birth is associated with increased risk of food allergy, and this risk is greatest among those most likely to have seasonal variation in vitamin D during infancy (Caucasians) and those at risk for skin barrier dysfunction (subjects with a history of eczema), suggesting that vitamin D and the skin barrier may be implicated in seasonal associations with food allergy.

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.

Strain measurements and the potential for a great subduction earthquake off the coast of washington.

Geodetic measurements of deformation in northwestern Washington indicate that strain is accumulating at a rate close to that predicted by a model of the Cascadia subduction zone in which the plate interface underlying the continental slope and outer continental shelf is currently locked but the remainder of the interface slips continuously. Presumably this locked segment will eventually rupture in a great thrust earthquake with a down-dip extent greater than 100 kilometers.

Strain accumulation in the shumagin and yakataga seismic gaps, alaska.

Strain accumulation during the 1980-85 interval has been measured by means of trilateration surveys in the Shumagin and Yakataga seismic gaps, which are the two regions identified as the most likely sites for the next great thrust earthquakes along the Alaska-Aleutian arc. No significant strain accumulation was detected in the Shumagin gap, but experience at similar subduction zones and simple models of the subduction process suggest that a measurable amount of strain should have accumulated. The most likely explanation of the observation is that subduction there is either aseismic or episodic. The strain accumulation measured in the Yakataga gap is consistent with that expected for the plate convergence rate, although the direction of maximum compression may suggest a somewhat more oblique convergence than expected.

Magmatic resurgence in long valley caldera, california: possible cause of the 1980 mammoth lakes earthquakes.

Changes in elevation between 1975 and October 1980 along a leveling line across the Long Valley caldera indicate a broad (half-width, 15 kilometers) uplift (maximum, 0.25 meter) centered on the old resurgent dome. This uplift is consistent with reinflation of a magma reservoir at a depth of about 10 kilometers. Stresses generated by this magmatic resurgence may have caused the sequence of four magnitude 6 earthquakes near Mammoth Lakes in May 1980.

Strain in southern california: measured uniaxial north-South regional contraction.

The plate tectonics model of the Pacific moving northwest relative to North America implies that the regional strain in California should be simple shear across a vertical plane striking N45 degrees W or equivalently equal parts of north-south contraction and east-west extension. Measurements of the strain accumulation at seven separate sites in southern California in the interval 1972 through 1978 indicate a remarkably consistent uniaxial north-south contraction of about 0.3 part per million per year; the expected east-west extension is absent. It is not clear whether the period from 1972 through 1978 is anomalous or whether the secular strain in southern California is indeed a uniaxial north-south contraction.

Strain on the san andreas fault near palmdale, california: rapid, aseismic change.

Frequently repeated strain measurements near Palmdale, California, during the period from 1971 through 1980 indicate that, in addition to a uniform accumulation of right-lateral shear strain (engineering shear, 0.35 microradian per year) across the San Andreas fault, a 1-microstrain contraction perpendicular to the fault that accumulated gradually during the interval 1974 through 1978 was aseismically released between February and November 1979. Subsequently (November 1979 to March 1980), about half of the contraction was recovered. This sequence of strain changes can be explained in terms of south-southwestward migration of a slip event consisting of the south-southwestward movement of the upper crust on a horizontal detachment surface at a depth of 10 to 30 kilometers. The large strain change in 1979 corresponds to the passage of the slip event beneath the San Andreas fault.