The implementation of DP will revolutionize current practice by providing pathologists with additional tools and algorithms to improve workflow. Furthermore, DP will open up opportunities for ...development of AI-based tools for more precise and reproducible diagnosis through computational pathology. One of the key features of AI is its capability to generate perceptions and recognize patterns beyond the human senses. Thus, the incorporation of AI into DP can reveal additional morphological features and information. At the current rate of AI development and adoption of DP, the interest in computational pathology is expected to rise in tandem. There have already been promising developments related to AI-based solutions in prostate cancer detection; however, in the GI tract, development of more sophisticated algorithms is required to facilitate histological assessment of GI specimens for early and accurate diagnosis. In this review, we aim to provide an overview of the current histological practices in AP laboratories with respect to challenges faced in image preprocessing, present the existing AI-based algorithms, discuss their limitations and present clinical insight with respect to the application of AI in early detection and diagnosis of GI cancer.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Wireless sensor networks have enabled smart infrastructures and novel applications. With the recent roll-out of Narrowband IoT (NB-IoT) cellular radio technology, wireless sensors can be widely ...deployed for data collection in cities around the world. However, empirical evidence regarding the coverage and connectivity of NB-IoT in dense urban areas is limited. This article presents an empirical study that focuses on evaluating the coverage and connectivity of NB-IoT in a dense urban environment. We have designed an NB-IoT sensor node and deployed over 100 of them in high-rise apartment buildings in Hong Kong. These sensor nodes utilize a commercial NB-IoT network to collect high-resolution water flow data for machine learning model training and provide timely feedback to users. We collect and analyze the empirical NB-IoT signal measurements from the sensor nodes deployed in various challenging outdoor and indoor environments for over three months. These empirical measurements reveal correlations between NB-IoT connectivity and sensor installation environments. We also observe that inter-cell interference, as a result of coverage by multiple neighboring NB-IoT cells in a dense urban environment, is a source of connectivity degradation. We discuss potential issues that IoT application designers and system integrators might encounter in practical NB-IoT devices deployment, and we propose a transmission decision algorithm based on signal measurements for mitigating energy wasted due to transmission failures. Finally, we demonstrate the results and the benefits of using high-resolution water flow data collected by our purpose-built NB-IoT sensor nodes for studying the patterns of domestic water consumption in Hong Kong.
Second-generation antipsychotics (SGAs) are commonly used to treat children with mental health conditions (MHCs) but are associated with adverse effects including obesity, hypertension, dyslipidemia, ...and type 2 diabetes. The mechanisms underlying these complications are unknown, but it has been suggested that SGAs increase appetite leading to weight gain. The present objective was to perform a pilot study to investigate appetite and satiety hormones in SGA-treated (risperidone or quetiapine) and SGA-naive children with similar mental health conditions.
Oral glucose tolerance tests (OGTTs) were conducted in SGA-naive (n = 18), risperidone-treated (n = 20), and quetiapine-treated (n = 16) children recruited from the British Columbia Children's Hospital Psychiatry Department. Over 5 time-points during the OGTT, appetite questionnaires using a visual analogue scale were administered, and blood was collected to measure ghrelin, peptide YY, glucose-dependent insulinotropic polypeptide, glucagon-like protein 1, leptin, and adiponectin. Mixed model analyses were conducted to examine between-group differences.
The children were similar in age, psychiatric diagnosis, and global assessment of functioning scores. Body mass index z-scores were also similar between groups. Appetite was increased during the OGTT in the risperidone-treated compared with the SGA-naive group for 2 questions ("How strong is your desire to eat"; P = 0.003 and "How much food do you think you can eat"; P = 0.028). No differences in satiety hormones were observed between the 3 groups.
Risperidone treatment in youth is associated with elevated appetite during an OGTT, with no differences in gut peptides or adipocytokines to explain risperidone's effect on appetite. Further research is needed to explore other mediators of weight gain and metabolic dysfunction in SGA-treated youth.
To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer.
Patients received tumor doses of 63 to 73 Gy in ...30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined.
Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years.
IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.
Full text
Available for:
GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Second-generation antipsychotics (SGAs) are used to treat children for mental health disorders but in some children they cause cardiometabolic complications including weight gain and type 2 diabetes. ...Genetic variants can place a child at risk of developing these metabolic complications. The fat mass and obesity-associated (FTO) rs9939609 A allele has been associated with obesity and dietary energy intakes in healthy children but its relation to metabolic complications in SGA-treated children is not known.
This study investigated the association of the FTO rs9939609 variant and SGA treatment with cardiometabolic complications and dietary intakes in children with mental health disorders.
A cross-sectional population of children (≤18 y; n = 506) with mental health disorders that were SGA-treated (n = 197) and SGA-naïve (n = 309) were recruited through the Department of Psychiatry at BC Children’s Hospital. Dietary intakes were estimated using 3-d food records in a subset of children (n = 73).
Genotype frequencies were not different between SGA-treated (TT genotype 42.6%, TA genotype 38.6%, AA genotype 18.8%) and SGA-naïve (TT 41.1%, TA 39.5%, AA 19.4%) children. Children with the A allele had lower BMI z-sores compared with the TT genotype (0.84 ± 1.19 compared with 1.19 ± 1.36; P = 0.005, adjusted for ethnicity). We observed an interaction between FTO genotype and SGA status on fasting glucose (P = 0.036). SGA-naïve children with the A allele had higher fasting glucose than those with the TT genotype (4.96 ± 0.35 compared with 4.81 ± 0.35 mmol/L; P = 0.001), in adjusted models (age, sex, ethnicity, and BMI z-score). This was not observed in SGA-treated children. Children with the A allele had higher daily total energy intakes compared with the TT genotype (1994 ± 619 compared with 1814 ± 484 kcal/d; P = 0.048), in adjusted models (age, sex, ethnicity, and BMI z-score); no effect of SGA-treatment was observed.
Our findings suggest the A allele of the FTO rs9939609 variant is associated with higher BMI in children with mental health disorders, but only in those not treated with SGAs.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms ...mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE.
Over one million Canadian children are estimated to have a mental health condition, such as depression, anxiety, and attention deficit hyperactivity disorder. Many are treated with second-generation ...antipsychotics (SGA). In some children, SGA treatment is associated with excessive weight gain and metabolic complications including a 3-fold greater risk for type 2 diabetes. We currently have no way to identify SGA-treated children at risk for metabolic complications. The goal of our study is to determine if the fat mass and obesity-associated gene (FTO) rs9939609 variant is associated with metabolic complications in SGA-treated children. A cross-sectional population of SGA-treated (n=232) and SGA-naïve (n=378) children (≤18y) were recruited through Child and Adolescent Psychiatry at BC Children’s Hospital. Participants were genotyped, metabolic markers assessed; dietary intakes were estimated in a subset of children (n=79). The FTO rs9939609 variant genotype frequencies were not different between SGA-treated (TT 44%, TA 38%, AA 18%) and SGA-naïve (TT 42%, TA 39%, AA 19%) children. An interaction was found between SGA status and FTO genotype for fasting glucose (p=0.014). In SGA-naïve children, the A allele carriers compared to non-carriers had higher fasting glucose (4.95 vs. 4.78 mmol/L; p=0.001) in a model adjusted for age, sex, ethnicity, and zBMI. This difference was not observed in SGA-treated children. Daily energy intakes of A allele carriers were not significantly higher compared to non-carries in SGA-treated (1855 vs. 2087 kcal) and SGA-naïve (1606 vs. 1871 kcal) children. Our findings suggest that the A allele of the FTO rs9939609 variant is associated with higher fasting glucose in SGA-naïve children with mental health conditions.
Disclosure
A.M. Wiedeman: None. Y. Ngai: None. A.M. Henderson: None. C. Panagiotopoulos: Advisory Panel; Self; Dexcom, Inc. A.M. Devlin: None.
Funding
BC Mental Health & Substance Use Services
Second-generation antipsychotics (SGAs) are commonly prescribed to youth but are associated with metabolic effects including obesity and diabetes. The mechanisms underlying diabetes development are ...unclear. The purpose of this study was to compare glucose homeostasis, insulin sensitivity, insulin secretion, and overall β-cell function in risperidone-treated, quetiapine-treated, and SGA-naive youth with mental illness. We conducted a cross-sectional study in which youth aged 9 to 18 years underwent a 2-hour oral glucose tolerance test. Indices for insulin sensitivity (Matsuda index), insulin secretion (insulinogenic index), and β-cell function (insulin secretion-sensitivity index-2 ISSI-2) were calculated. A total of 18 SGA-naive, 20 risperidone-treated, and 16 quetiapine-treated youth participated. The 3 groups were similar in age, sex, ethnicity, body mass index standardized for age and sex, pubertal status, degree of psychiatric illness, psychiatric diagnoses, and other medications. The median treatment duration was 17 months (range, 3-91 months) for risperidone-treated youth and 10 months (range, 3-44 months) for quetiapine-treated youth. The quetiapine-treated group had lower insulinogenic index (P < 0.01) and lower ISSI-2 (P < 0.01) compared with that in the SGA-naive group. Only the body mass index standardized for age and sex was negatively associated with Matsuda index (β = -0.540, P < 0.001) in all youth. Quetiapine treatment was negatively associated with insulinogenic index (β = -0.426, P = 0.007) and ISSI-2 (β = -0.433, P = 0.008). Quetiapine reduced the insulin expression in isolated mouse islets suggesting a direct β-cell effect. Our results suggest that quetiapine treatment in youth is associated with impaired β-cell function, specifically lower insulin secretion. Prospective longitudinal studies are required to understand the progression of β-cell dysfunction after quetiapine initiation.
Purpose
The O-(2-
18
F-fluoroethyl)-
l
-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET ...imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation.
Methods
Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (
n
= 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBR
max
), dynamic analysis (time activity curve TAC type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBR
max
/TBR
mean
) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient DSC) and boundary agreement (Hausdorff distance HD, mean absolute surface distance MASD).
Results
Data was accrued from 21 NMPs (10 centres,
n
≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBR
max
, and TBR
mean
were 21.53% (12.00–30.10%), 5.89% (5.01–6.68%), and 5.01% (3.37–6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63–0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement.
Conclusion
The FIG study credentialing program has increased expertise across study sites. TBR
max
and TBR
mean
were robust, with considerable variability in BTV delineation and image interpretation observed.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PDF
