Effect of endoscopic sleeve gastroplasty on gastric emptying, motility and hormones: a comparative prospective study.

OBJECTIVE: Endoscopic sleeve gastroplasty (ESG) has gained global adoption but our understanding of its mechanism(s) of action and durability of efficacy is limited. We sought to determine changes in gastric emptying (GE), gastric motility (GM), hormones and eating behaviours after ESG. DESIGN: A priori-designed single-centre substudy of a large US randomised clinical trial, adults with obesity were randomised to ESG or lifestyle interventions (LS) alone. We measured GE, hormones and weight loss and assessed eating behaviours. In a subset of ESG patients, we assessed GM. The primary outcome was the change in T1/2 (min) at 3 months, and secondary outcomes were changes in weight, GE, GM, hormones and eating behaviours. We used t-test analyses and regression to determine the association between GE and weight loss. RESULTS: 36 (ESG=18; LS=18) participated in this substudy. Baseline characteristics were similar between the two groups. At 3 months, T1/2 was delayed in the ESG group (n=17) compared with the LS group (n=17) (152.3±47.3 vs 89.1±27.9; p<0.001). At 12 months, T1/2 remained delayed in the ESG group (n=16) vs control group (n=14) (137±37.4 vs 90.1±23.4; p<0.001). Greater delays in GE at 3 months were associated with greater weight loss. GM was preserved and fasting ghrelin, glucagon-like peptide 1 and polypeptide YY significantly increased 18 months after ESG. CONCLUSION: ESG promotes weight loss through several key mechanistic pathways involving GE and hormones while preserving GM. These findings further support clinical adoption of this technique for the management of obesity. TRIAL REGISTRATION NUMBER: NCT03406975.

CT or MR Enterography to Assess Response During Vedolizumab Therapy for Small Bowel Crohn's Disease.

Background: To describe response to therapy of small bowel (SB) Crohn's disease (CD) at CT or MR enterography (CTE/MRE) in patients on vedolizumab. Methods: Patients with SB CD who underwent CTE/MRE exams greater than 12 months apart on vedolizumab therapy were included. Length (in cm) and inflammation severity (EMBARK score) of inflamed SB segments were assessed. Changes in inflammation length of 3.4 cm or greater or inflammation severity of 2 EMBARK points or greater was categorized as response or progression, as appropriate, with development of newly inflamed segments, strictures, or penetrating complications also indicating progression. Patients not meeting the criteria for response or progression were categorized as having stable disease. Results: Of 36 SB CD patients, the large majority had prior surgery (86%; 31), anti-TNF use (92%; 33), and internal penetrating (78%; 28) disease. Thirty-two patients had paired baseline and follow-up CTE/MRE exams without interval surgery, with clinical response observed in 24/32 (75%). Based on imaging response criteria, 22% (7/32; 95% CI: 9%-40%) had response, 50% (16/32; 95% CI: 32%-68%) were stable, and 28% (9/32; 95% CI: 14%-47%) had disease progression. Fifty-six percent of (18/32; 95% CI: 38%-74%) patients had clinical improvement with response or stable disease by imaging. Patients with stable disease had shorter median baseline lengths of SB inflammation (P = .012). Proportion of patients with colonic inflammation, perianal disease, or penetrating complications did not change. Conclusions: Most patients on vedolizumab for over 12 months demonstrated response or stable SB disease when using objective cross-sectional radiologic imaging criteria using CTE/MRE.

Preparing education for the crises of tomorrow: A framework for adaptability.

The COVID-19 crisis has disrupted learning globally, exacerbating regional and global disparities that predated the pandemic. This rupture presents a unique opportunity to reimagine our educational system in times of both calm and crisis. Drawing on the work of political scientist Kathleen Thelen and economist and philosopher Amartya Sen, this article introduces a Framework for adaptability that outlines examples of flexible and equitable adaptation to change. The authors define adaptability as the ability of educational systems to respond to rapidly changing circumstances while maintaining stability, promoting equality, and expanding substantive freedoms and well-being. The key components of educational adaptability are: (1) cooperation, (2) inclusion, and (3) flexibility. This article describes how adaptability in education might be facilitated at individual, community, state and global levels. The authors call attention to a critical need to collectivise our approach to risk at the level of national governance. They suggest that this can be achieved by coordinating various professional, scientific, corporate, community and governmental stakeholders in order to ensure continuity in educational service provision, promoting lifelong learning and overall workforce participation.

Préparer l'éducation aux crises de demain : un cadre d'adaptabilité ­ La crise de la COVID-19 a perturbé l'apprentissage partout dans le monde, exacerbant les disparités régionales et mondiales antérieures à la pandémie. Cette rupture offre une occasion unique de réinventer notre système d'éducation tant en période de calme que de crise. S'inspirant des travaux de la politologue Kathleen Thelen et de l'économiste et philosophe Amartya Sen, cet article présente un cadre d'adaptabilité qui esquisse quelques exemples d'adaptation flexible et équitable au changement. Les auteurs définissent l'adaptabilité comme la capacité des systèmes d'éducation à répondre à des situations qui évoluent rapidement et en même temps à maintenir la stabilité, à promouvoir l'égalité et à accroître des libertés et un bien-être essentiels. Les éléments clés de l'adaptabilité éducative sont : (1) la coopération, (2) l'inclusion et (3) la flexibilité. Cet article décrit comment l'adaptabilité pourrait être facilitée dans l'éducation aux niveaux des individus, de la communauté, de l'État et du monde. Ses auteurs attirent l'attention sur le besoin crucial de collectiviser notre approche du risque à l'échelle de la gouvernance nationale. Ils indiquent que l'on peut y parvenir en coordonnant différents acteurs professionnels, scientifiques, entrepreneuriaux, communautaires et gouvernementaux afin d'assurer la continuité de l'offre des services éducatifs, de la promotion de l'apprentissage tout au long de la vie et de la participation générale de la main-d'œuvre.

Youth Gaming Addiction: Implications for School Nurses.

Technology is pervasive in society and reaches across all age-groups. The use of technology in youth has risen steadily in the past two decades through access to television, internet, computers, social media, and gaming in various formats. Due to this increased exposure and access, concerns have developed among mental health and healthcare providers regarding gaming addiction in youth. The American Psychiatric Association mentioned internet gaming disorder in the 2013 publication of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.). While not recognized as a specific diagnosis at the time of publication, there was a call for further research and evaluation of this phenomenon. Research indicates there are negative impacts on academic performance, social development, and self-concept in game-addicted youth. The purpose of this article is to provide the school nurse with information needed to recognize and care for youth at risk for and those experiencing gaming addiction. The school nurse is poised to provide nursing care in the school setting to educate, prevent, and help manage youth with gaming addiction risks and experiences, as part of an interdisciplinary team.

Use of Stable Isotopes in Benthic Organic Material as a Baseline for Estimating Fish Trophic Positions in Lakes.

Estimating the trophic position of predators in food webs using stable isotopes requires establishing a 'baseline'; typically served by bivalves or snails. However, the frequent absence of such organisms in lakes leaves researchers in a difficult situation. Here we test the hypothesis that trophic position (TP) of largemouth bass (LB) in lakes can be estimated from δ15N of benthic organic material (BOM) in littoral surficial sediment. δ15NLB as a function of δ15NBOM was significant across 51 lakes with an R2 of 0.84, supporting our hypothesis. In a subset of six lakes, the mean TPLB did not differ significantly when calculated using baselines of δ15N in BOM, mussels (UN), gastropods (SN), or from a stable isotope mixing model. In a subset of 26 lakes, mean TPLB calculated from δ15NBOM and δ15NUN baselines were not significantly different, but TPLB calculated using δ15NBOM was not significantly correlated with TPLB calculated using δ15NUN. Although δ15NBOM should not be used interchangeably with δ15NUN as a baseline for estimating TPLB, δ15NBOM can be useful as a separate baseline where estimates of fish TP are needed in all study lakes given that mussels are frequently absent and BOM is always available for collection.

Low-dose CT for the detection and classification of metastatic liver lesions: Results of the 2016 Low Dose CT Grand Challenge.

PURPOSE: Using common datasets, to estimate and compare the diagnostic performance of image-based denoising techniques or iterative reconstruction algorithms for the task of detecting hepatic metastases. METHODS: Datasets from contrast-enhanced CT scans of the liver were provided to participants in an NIH-, AAPM- and Mayo Clinic-sponsored Low Dose CT Grand Challenge. Training data included full-dose and quarter-dose scans of the ACR CT accreditation phantom and 10 patient examinations; both images and projections were provided in the training data. Projection data were supplied in a vendor-neutral standardized format (DICOM-CT-PD). Twenty quarter-dose patient datasets were provided to each participant for testing the performance of their technique. Images were provided to sites intending to perform denoising in the image domain. Fully preprocessed projection data and statistical noise maps were provided to sites intending to perform iterative reconstruction. Upon return of the denoised or iteratively reconstructed quarter-dose images, randomized, blinded evaluation of the cases was performed using a Latin Square study design by 11 senior radiology residents or fellows, who marked the locations of identified hepatic metastases. Markings were scored against reference locations of clinically or pathologically demonstrated metastases to determine a per-lesion normalized score and a per-case normalized score (a faculty abdominal radiologist established the reference location using clinical and pathological information). Scores increased for correct detections; scores decreased for missed or incorrect detections. The winner for the competition was the entry that produced the highest total score (mean of the per-lesion and per-case normalized score). Reader confidence was used to compute a Jackknife alternative free-response receiver operating characteristic (JAFROC) figure of merit, which was used for breaking ties. RESULTS: 103 participants from 90 sites and 26 countries registered to participate. Training data were shared with 77 sites that completed the data sharing agreements. Subsequently, 41 sites downloaded the 20 test cases, which included only the 25% dose data (CTDIvol = 3.0 ± 1.8 mGy, SSDE = 3.5 ± 1.3 mGy). 22 sites submitted results for evaluation. One site provided binary images and one site provided images with severe artifacts; cases from these sites were excluded from review and the participants removed from the challenge. The mean (range) per-lesion and per-case normalized scores were -24.2% (-75.8%, 3%) and 47% (10%, 70%), respectively. Compared to reader results for commercially reconstructed quarter-dose images with no noise reduction, 11 of the 20 sites showed a numeric improvement in the mean JAFROC figure of merit. Notably two sites performed comparably to the reader results for full-dose commercial images. The study was not designed for these comparisons, so wide confidence intervals surrounded these figures of merit and the results should be used only to motivate future testing. CONCLUSION: Infrastructure and methodology were developed to rapidly estimate observer performance for liver metastasis detection in low-dose CT examinations of the liver after either image-based denoising or iterative reconstruction. The results demonstrated large differences in detection and classification performance between noise reduction methods, although the majority of methods provided some improvement in performance relative to the commercial quarter-dose images with no noise reduction applied.

Activity Profile and Between-Match Variation in Elite Male Field Hockey.

Sunderland, CD and Edwards, PL. Activity profile and between-match variation in elite male field hockey. J Strength Cond Res 31(3): 758-764, 2017-This study aimed to (a) provide a position-specific activity profile for elite male hockey players, (b) determine if the activity profile was altered by the introduction of the "self-pass" rule, and (c) provide information relating to match-to-match variability in elite male field hockey. The activity of 28 elite male field hockey players was analyzed over 2 seasons totaling 395 player-match analyses using Global Positioning Satellite technology. Total distance, high-speed running (>15.5 km·h), sprinting (>20 km·h), and mean speed were recorded. Players were categorized into 4 positions: fullback (FB), halfback (HB), midfield (M), and forward (F). Data were analyzed using a 2-way analysis of variance (season, position) and between-match coefficients of variation (CV). The time played differs with position (FB: 65.5 ± 5.3, HB: 49.5 ± 11.5, M: 45.9 ± 7.1, F: 39.5 ± 5.4 minutes; p < 0.0005) and thus affected the activity profile. Total distance covered was greater for fullbacks (FB: 8,001 ± 447, HB: 6,435 ± 1,399, M: 6,415 ± 908, F: 5,844 ± 762 m, p < 0.001), and mean speed and percentage time spent high-speed running and sprinting were greater for forwards than all other positions (HSR: FB: 6.8 ± 1.0, HB: 8.8 ± 1.3, M: 10.7 ± 1.2, F: 13.5 ± 1.8%, p < 0.001). The activity profile did not differ with the introduction of the self-pass. Match-to-match variability (CV) ranged from 5.0% to 22.0% for total and sprint distance, respectively. This is the first study to present an activity profile of elite men's field hockey and its associated variability and demonstrates that each position is unique, and therefore, training and recovery should be position specific.

Myocardial Perfusion: Characteristics of Distal Intramyocardial Arteriolar Trees.

A combination of experimental, theoretical, and imaging methodologies is used to examine the hierarchical structure and function of intramyocardial arteriolar trees in porcine hearts to provide a window onto a region of myocardial microvasculature which has been difficult to fully explore so far. A total of 66 microvascular trees from 6 isolated myocardial specimens were analyzed, with a cumulative number of 2438 arteriolar branches greater than or equal to 40 µm lumen diameter. The distribution of flow rates within each tree was derived from an assumed power law relationship for that tree between the diameter of vessel segments and flow rates that are consistent with that power law and subject to conservation of mass along hierarchical structure of the tree. The results indicate that the power law index increases at levels of arteriolar vasculature closer to the capillary level, consistent with a concomitant decrease in shear stress acting on endothelial tissue. These results resolve a long standing predicament which could not be resolved previously because of lack of data about the 3D, interconnected, arterioles. In the context of myocardial perfusion, the results indicate that the coefficient of variation of flow rate in pre-capillary distal arterioles is high, suggesting that heterogeneity of flow rate in these arterioles is not entirely random but may be due at least in part to active control.

Discovery of spirofused piperazine and diazepane amides as selective histamine-3 antagonists with in vivo efficacy in a mouse model of cognition.

A new series of potent and selective histamine-3 receptor (H3R) antagonists was identified on the basis of an azaspiro[2.5]octane carboxamide scaffold. Many scaffold modifications were largely tolerated, resulting in nanomolar-potent compounds in the H3R functional assay. Exemplar compound 6s demonstrated a selective profile against a panel of 144 secondary pharmacological receptors, with activity at only σ2 (62% at 10 µM). Compound 6s demonstrated free-plasma exposures above the IC50 (∼50×) with a brain-to-plasma ratio of ∼3 following intravenous dosing in mice. At three doses tested in the mouse novel object recognition model (1, 3, and 10 mg/kg s.c.), 6s demonstrated a statistically significant response compared with the control group. This series represents a new scaffold of H3 receptor antagonists that demonstrates in vivo exposure and efficacy in an animal model of cognition.

Application of three-dimensional rendering in joint-related ganglion cysts.

The origin of para-articular cysts is poorly understood and controversial. The relatively common, simple (extraneural) cysts are presumed to be derived from joints, although joint connections are not always established. Rarer complex cysts are thought by many to form de novo within nerves (intraneural ganglion cysts) or within vessels (adventitial cysts) (degenerative theory). We believe that these simple and complex ganglion cysts are joint-related (articular theory). Joint connections are often not readily appreciated with routine imaging or at surgery. Not identifying and/or treating joint connections frequently leads to cyst recurrence. More sophisticated imaging may enhance visualization of these joint connections. We created a 3D rendering technique to assess potential joint connections of simple and complex cysts localized to the knee and superior tibiofibular joints in patients with fibular (peroneal) neuropathy. Two- and three-dimensional data sets from MRI examinations were segmented semiautomatically by signal intensity with further refinement based on interaction with the user to identify specific anatomic structures, such as small nerves and vessels on serial images. The bone, cysts, nerves, and vessels were each assigned different color representations, and 3D renderings were created in ANALYZE using the data sets closest to isotropic (voxel with equal length in all dimensions) resolution as the primary background rendering. We selected four cases to illustrate the spectrum of pathology. In all of these cases, we demonstrated joint connections and correlated imaging and operative findings. Surgery addressing the cyst and the joint connection resulted in excellent outcomes; postoperative MRIs done more than 6 months later confirmed that there was no recurrence. In addition to highlighting the important relationship of these cysts to neighboring anatomic structures, this 3D technique allows visualization of "occult" connections not readily appreciated with standard MR imaging. We believe that these joint-related cysts have a common pathogenesis; they dissect through a capsular rent and follow the path of least resistance; they may form simple cysts by dissecting out into the soft tissue, or more complex cysts by dissecting within the epineurium of nerves or adventitia of vessels (along an articular branch), or various combinations of all of these types of cysts. Understanding the pathogenesis for cyst formation will improve surgical management and outcomes. We have adapted this 3D technique to enhance the visualization of cysts occurring at other joints.

Cadaver validation of intensity-based ultrasound to CT registration.

A method is presented for the registration of tracked B-mode ultrasound images to a CT volume of a femur or pelvis. This registration can allow tracked surgical instruments to be aligned with the CT image or an associated preoperative plan. Our method requires no manual segmentation of either the ultrasound images or the CT volume. The CT and US images are processed to produce images where the image intensity represents the probability of the presence of a bone edge. These images are then registered together using normalised cross-correlation as a similarity measure. The parameter which represents the speed of sound through tissue has also been included in the registration optimisation process. Experiments have been carried out on six cadaveric femurs and three cadaveric pelves. Registration results were compared with a "gold standard" registration acquired using bone implanted fiducial markers. Results show the registration method to be accurate, on average, to 1.7 mm root-mean-square target registration error.

Novel mutations of the growth hormone 1 (GH1) gene disclosed by modulation of the clinical selection criteria for individuals with short stature.

Subtle mutations in the growth hormone 1 (GH1) gene have been regarded as a comparatively rare cause of short stature. Such lesions were sought in a group of 41 individuals selected for short stature, reduced height velocity, and bone age delay; a group of 11 individuals with short stature and idiopathic growth hormone deficiency (IGHD); and a group of 154 controls. Heterozygous mutations were identified in all three groups but disproportionately in the individuals with short stature, both with (odds ratio 25.2; 95% CI, 5.1-132.2) and without (odds ratio 3.6; 95% CI, 1.0-12.9) IGHD. Twenty-four novel GH1 gene lesions were found. Thirteen novel missense mutations were characterized by assaying the signal transduction activity of in vitro expressed variants; six (T27I, K41R, N47D, S71F, S108R, and T175A) exhibited a reduced ability to activate the JAK/STAT pathway. Molecular modeling suggested that both K41R and T175A might compromise GH receptor binding. Seven GH variants (R16C, K41R, S71F, E74K, Q91L, S108C, and a functional polymorphism, V110I) manifested reduced secretion in rat pituitary cells after allowance had been made for the level of expression attributable to the associated GH1 proximal promoter haplotype. A further leader peptide variant (L-11P) was not secreted. Eleven novel mutations in the GH1 gene promoter were assessed by reporter gene assay but only two, including a GH2 gene-templated gene conversion, were found to be associated with a significantly reduced level of expression. Finally, a novel intron 2 acceptor splice-site mutation, detected in a family with autosomal dominant type II IGHD, was shown to lead to the skipping of exon 3 from the GH1 transcript. A total of 15 novel GH1 gene mutations were thus considered to be of probable phenotypic significance. Such lesions are more prevalent than previously recognized and although most may be insufficient on their own to account for the observed clinical phenotype, they are nevertheless likely to play a contributory role in the etiology of short stature.

Evaluating the ecological significance of laboratory response data to predict population-level effects for the estruarine amphipod Ampelisca abdita.

Ten-day acute mortality of the benthic amphipod Ampelisca abdita is used in a number of regulatory, research, and monitoring programs to evaluate chemical contamination of marine sediments. Although this endpoint has proven to be valuable for characterizing the relative toxicities of sediments, the significance of acute mortality with respect to population viability has not yet been established. In this study, population modeling along with empirical extrapolation were used to describe a relationship between acute mortality and population-level response of A. abdita. The research involved the performance of a standard 10-d sediment toxicity bioassay and a 70-d full life-cycle chronic population (including reproduction) bioassay exposing A. abdita to sediments spiked with concentrations of the divalent metal cadmium (normalized to acid volatile sulfide) expected to produce a range of biological effects. These data provided age-specific schedules of survival and fecundity that were used to parameterize an age-classified projection matrix model for A. abdita. Measured exposure data and population growth rate estimates, obtained using the demographic information collected during the 70-d assay, were used to develop exposure-response models. These data were also used to develop an empirical relationship between population growth rate (lambda) and acute mortality. This relationship describes how acute data may be used to predict concentrations that produce population-level effects. Model manipulations permit extrapolation of early life-stage mortality (the acute endpoint) to changes in population growth rate. These relationships were used to evaluate a range of ecologically acceptable acute mortality for A. abdita.