Trial of Training to Reduce Driver Inattention in Teens with ADHD.

BACKGROUND: Teens with attention deficit-hyperactivity disorder (ADHD) are at increased risk for motor vehicle collisions. A computerized skills-training program to reduce long glances away from the roadway, a contributor to collision risk, may ameliorate driving risks among teens with ADHD. METHODS: We evaluated a computerized skills-training program designed to reduce long glances (lasting ≥2 seconds) away from the roadway in drivers 16 to 19 years of age with ADHD. Participants were randomly assigned in a 1:1 ratio to undergo either enhanced Focused Concentration and Attention Learning, a program that targets reduction in the number of long glances (intervention) or enhanced conventional driver's education (control). The primary outcomes were the number of long glances away from the roadway and the standard deviation of lane position, a measure of lateral movements away from the center of the lane, during two 15-minute simulated drives at baseline and at 1 month and 6 months after training. Secondary outcomes were the rates of long glances and collisions or near-collisions involving abrupt changes in vehicle momentum (g-force event), as assessed with in-vehicle recordings over the 1-year period after training. RESULTS: During simulated driving after training, participants in the intervention group had a mean of 16.5 long glances per drive at 1 month and 15.7 long glances per drive at 6 months, as compared with 28.0 and 27.0 long glances, respectively, in the control group (incidence rate ratio at 1 month, 0.64; 95% confidence interval [CI], 0.52 to 0.76; P<0.001; incidence rate ratio at 6 months, 0.64; 95% CI, 0.52 to 0.76; P<0.001). The standard deviation of lane position (in feet) was 0.98 SD at 1 month and 0.98 SD at 6 months in the intervention group, as compared with 1.20 SD and 1.20 SD, respectively, in the control group (difference at 1 month, -0.21 SD; 95% CI, -0.29 to -0.13; difference at 6 months, -0.22 SD; 95% CI, -0.31 to -0.13; P<0.001 for interaction for both comparisons). During real-world driving over the year after training, the rate of long glances per g-force event was 18.3% in the intervention group and 23.9% in the control group (relative risk, 0.76; 95% CI, 0.61 to 0.92); the rate of collision or near-collision per g-force event was 3.4% and 5.6%, respectively (relative risk, 0.60, 95% CI, 0.41 to 0.89). CONCLUSIONS: In teens with ADHD, a specially designed computerized simulated-driving program with feedback to reduce long glances away from the roadway reduced the frequency of long glances and lessened variation in lane position as compared with a control program. During real-world driving in the year after training, the rate of collisions and near-collisions was lower in the intervention group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT02848092.).

External validation of an artificial intelligence model for Gleason grading of prostate cancer on prostatectomy specimens.

OBJECTIVES: To externally validate the performance of the DeepDx Prostate artificial intelligence (AI) algorithm (Deep Bio Inc., Seoul, South Korea) for Gleason grading on whole-mount prostate histopathology, considering potential variations observed when applying AI models trained on biopsy samples to radical prostatectomy (RP) specimens due to inherent differences in tissue representation and sample size. MATERIALS AND METHODS: The commercially available DeepDx Prostate AI algorithm is an automated Gleason grading system that was previously trained using 1133 prostate core biopsy images and validated on 700 biopsy images from two institutions. We assessed the AI algorithm's performance, which outputs Gleason patterns (3, 4, or 5), on 500 1-mm2 tiles created from 150 whole-mount RP specimens from a third institution. These patterns were then grouped into grade groups (GGs) for comparison with expert pathologist assessments. The reference standard was the International Society of Urological Pathology GG as established by two experienced uropathologists with a third expert to adjudicate discordant cases. We defined the main metric as the agreement with the reference standard, using Cohen's kappa. RESULTS: The agreement between the two experienced pathologists in determining GGs at the tile level had a quadratically weighted Cohen's kappa of 0.94. The agreement between the AI algorithm and the reference standard in differentiating cancerous vs non-cancerous tissue had an unweighted Cohen's kappa of 0.91. Additionally, the AI algorithm's agreement with the reference standard in classifying tiles into GGs had a quadratically weighted Cohen's kappa of 0.89. In distinguishing cancerous vs non-cancerous tissue, the AI algorithm achieved a sensitivity of 0.997 and specificity of 0.88; in classifying GG ≥2 vs GG 1 and non-cancerous tissue, it demonstrated a sensitivity of 0.98 and specificity of 0.85. CONCLUSION: The DeepDx Prostate AI algorithm had excellent agreement with expert uropathologists and performance in cancer identification and grading on RP specimens, despite being trained on biopsy specimens from an entirely different patient population.

Examining Patterns and Predictors of ADHD Teens' Skill-Learning Trajectories During Enhanced FOrward Concentration and Attention Learning (FOCAL+) Training.

OBJECTIVE: Examine patterns and predictors of skill learning during multisession Enhanced FOrward Concentration and Attention Learning (FOCAL+) training. BACKGROUND: FOCAL+ teaches teens to reduce the duration of off-road glances using real-time error learning. In a randomized controlled trial, teens with ADHD received five sessions of FOCAL+ training and demonstrated significant reductions in extended glances (>2-s) away from the roadway (i.e., long-glances) and a 40% reduced risk of a crash/near-crash event. Teens' improvement in limiting long-glances as assessed after each FOCAL+ training session has not been examined. METHOD: Licensed teen (ages 16-19) drivers with ADHD (n = 152) were randomly assigned to five sessions of either FOCAL+ or modified standard driver training. Teens completed driving simulation assessments at baseline, after each training session, and 1 month and 6 months posttraining. Naturalistic driving was monitored for one year. RESULTS: FOCAL+ training produced a 53% maximal reduction in long-glances during postsession simulated driving. The number of sessions needed to achieve maximum performance varied across participants. However, after five FOCAL+ training sessions, number of long-glances was comparable irrespective of when teens achieved their maximum performance. The magnitude of reduction in long-glances predicted levels of long-glances during simulated driving at 1 month and 6 months posttraining but not naturalistic driving outcomes. FOCAL+ training provided the most benefit during training to teens who were younger and had less driving experience. CONCLUSION: FOCAL+ training significantly reduces long-glances beginning at the 1st training session. APPLICATION: Providing five FOCAL+ training sessions early on during teen driving may maximize benefit.

Groundwater constituents and the incidence of kidney cancer.

BACKGROUND: Kidney cancer incidence demonstrates significant geographic variation suggesting a role for environmental risk factors. This study sought to evaluate associations between groundwater exposures and kidney cancer incidence. METHODS: The authors identified constituents from 18,506 public groundwater wells in all 58 California counties measured in 1996-2010, and obtained county-level kidney cancer incidence data from the California Cancer Registry for 2003-2017. The authors developed a water-wide association study (WWAS) platform using XWAS methodology. Three cohorts were created with 5 years of groundwater measurements and 5-year kidney cancer incidence data. The authors fit Poisson regression models in each cohort to estimate the association between county-level average constituent concentrations and kidney cancer, adjusting for known risk factors: sex, obesity, smoking prevalence, and socioeconomic status at the county level. RESULTS: Thirteen groundwater constituents met stringent WWAS criteria (a false discovery rate <0.10 in the first cohort, followed by p values <.05 in subsequent cohorts) and were associated with kidney cancer incidence. The seven constituents directly related to kidney cancer incidence (and corresponding standardized incidence ratios) were chlordane (1.06; 95% confidence interval [CI], 1.02-1.10), dieldrin (1.04; 95% CI, 1.01-1.07), 1,2-dichloropropane (1.04; 95% CI, 1.02-1.05), 2,4,5-TP (1.03; 95% CI, 1.01-1.05), glyphosate (1.02; 95% CI, 1.01-1.04), endothall (1.02; 95% CI, 1.01-1.03), and carbaryl (1.02; 95% CI, 1.01-1.03). Among the six constituents inversely related to kidney cancer incidence, the standardized incidence ratio furthest from the null was for bromide (0.97; 95% CI, 0.94-0.99). CONCLUSIONS: This study identified several groundwater constituents associated with kidney cancer. Public health efforts to reduce the burden of kidney cancer should consider groundwater constituents as environmental exposures that may be associated with the incidence of kidney cancer.

Examining reaction time variability on the stop-signal task in the ABCD study.

OBJECTIVE: Reaction time variability (RTV) has been estimated using Gaussian, ex-Gaussian, and diffusion model (DM) indices. Rarely have studies examined interrelationships among these performance indices in childhood, and the use of reaction time (RT) computational models has been slow to take hold in the developmental psychopathology literature. Here, we extend prior work in adults by examining the interrelationships among different model parameters in the ABCD sample and demonstrate how computational models of RT can clarify mechanisms of time-on-task effects and sex differences in RTs. METHOD: This study utilized trial-level data from the stop signal task from 8916 children (9-10 years old) to examine Gaussian, ex-Gaussian, and DM indicators of RTV. In addition to describing RTV patterns, we examined interrelations among these indicators, temporal patterns, and sex differences. RESULTS: There was no one-to-one correspondence between DM and ex-Gaussian parameters. Nonetheless, drift rate was most strongly associated with standard deviation of RT and tau, while nondecisional processes were most strongly associated with RT, mu, and sigma. Performance worsened across time with changes driven primarily by decreasing drift rate. Boys were faster and less variable than girls, likely attributable to girls' wide boundary separation. CONCLUSIONS: Intercorrelations among model parameters are similar in children as has been observed in adults. Computational approaches play a crucial role in understanding performance changes over time and can also clarify mechanisms of group differences. For example, standard RT models may incorrectly suggest slowed processing speed in girls that is actually attributable to other factors.

Deep Learning Improves Speed and Accuracy of Prostate Gland Segmentations on Magnetic Resonance Imaging for Targeted Biopsy.

PURPOSE: Targeted biopsy improves prostate cancer diagnosis. Accurate prostate segmentation on magnetic resonance imaging (MRI) is critical for accurate biopsy. Manual gland segmentation is tedious and time-consuming. We sought to develop a deep learning model to rapidly and accurately segment the prostate on MRI and to implement it as part of routine magnetic resonance-ultrasound fusion biopsy in the clinic. MATERIALS AND METHODS: A total of 905 subjects underwent multiparametric MRI at 29 institutions, followed by magnetic resonance-ultrasound fusion biopsy at 1 institution. A urologic oncology expert segmented the prostate on axial T2-weighted MRI scans. We trained a deep learning model, ProGNet, on 805 cases. We retrospectively tested ProGNet on 100 independent internal and 56 external cases. We prospectively implemented ProGNet as part of the fusion biopsy procedure for 11 patients. We compared ProGNet performance to 2 deep learning networks (U-Net and holistically-nested edge detector) and radiology technicians. The Dice similarity coefficient (DSC) was used to measure overlap with expert segmentations. DSCs were compared using paired t-tests. RESULTS: ProGNet (DSC=0.92) outperformed U-Net (DSC=0.85, p <0.0001), holistically-nested edge detector (DSC=0.80, p <0.0001), and radiology technicians (DSC=0.89, p <0.0001) in the retrospective internal test set. In the prospective cohort, ProGNet (DSC=0.93) outperformed radiology technicians (DSC=0.90, p <0.0001). ProGNet took just 35 seconds per case (vs 10 minutes for radiology technicians) to yield a clinically utilizable segmentation file. CONCLUSIONS: This is the first study to employ a deep learning model for prostate gland segmentation for targeted biopsy in routine urological clinical practice, while reporting results and releasing the code online. Prospective and retrospective evaluations revealed increased speed and accuracy.

Surgical Confusions in Ophthalmology: Description, Analysis, and Prevention of Errors from 2006 through 2017.

PURPOSE: To characterize surgical confusions in ophthalmology to determine their incidence, root causes, and impact on patients and physicians. DESIGN: Retrospective cohort study of errors in ophthalmic surgical procedures between January 1, 2006, and December 31, 2017. PARTICIPANTS: One hundred forty-three cases involving surgical confusions. METHODS: Cases were identified by the Ophthalmic Mutual Insurance Company from closed case files and by the New York State Health Department from the New York Patient Occurrence Reporting and Tracking program that identified the surgical confusions. MAIN OUTCOME MEASURES: Incidence and impact by intended surgery, error type, and root cause as well as preventability by the Universal Protocol. RESULTS: Of the 143 cases of surgical confusions identified, 92 cases (64.3%) were deemed preventable by the Universal Protocol. Approximately two thirds, 95 cases (66.4%), were cases of incorrect implants being used during cataract surgery (cataract extraction and intraocular lens implantation), of which 33 cases (34.7%) were not preventable by the Universal Protocol. Wrong eye blocks or anesthesia accounted for 20 cases (14.0%), incorrect eye procedures accounted for 10 cases (7.00%), incorrect refractive surgery measurements accounted for 6 cases (4.20%), incorrect patient or procedure accounted for 5 cases (3.50%), incorrect intraocular gas concentration accounted for 4 cases (2.80%), and incorrect medication in surgery accounted for 3 cases (2.10%). The most common root cause of confusion was an inadequately performed time out, which was responsible for nearly one third of all surgical confusions, 46 cases (32.2%). Incorrect lens orders or calculations before surgery (so-called upstream errors) were the second most common cause of surgical confusion, involving 31 cases (21.7%). The average legal indemnity for incorrect implant during cataract surgery was $57 514 (United States dollars). The average indemnity for incorrect refractive surgery measurement was $123 125, that for incorrect eye procedure was $50 000, and that for incorrect gas concentration was $220 844. CONCLUSIONS: Most surgical confusions could have been prevented by following the Universal Protocol properly. However, upstream errors, originating in the clinic or office before surgery, and ineffective communication during time outs suggest a need for modification of the Universal Protocol.

Mutagenic, genotoxic and cytotoxic studies of invasive corals Tubastraea coccinea and Tubastraea tagusensis.

The high diversity of species in the marine environment gives rise to compounds with unique structural patterns not found as natural products in other systems and with great potential for pharmacological, cosmetic and nutritional use. The genus Tubastraea (Class Anthozoa, Order Scleractinia, Family Dendrophylliidae) is characterized as a hard coral without the presence of zooxanthellae. In species of this genus alkaloids derived from the compound aplysinopsin with pharmacological activity are known. In Brazil T. coccinea and T. tagusensis are characterized as non-indigenous and invasive and are currently found along the Brazilian coast, from Santa Catarina to Bahia states. This study aims to analyze the mutagenic, cytotoxic and genotoxic potential of methanolic and ethanolic extracts from T. coccinea and T. tagusensis collected in Ilha Grande Bay, Rio de Janeiro state, Brazil. Bacterial reverse mutation assay on the standard strains TA97, TA98, TA100, TA102 and TA104, in vitro micronucleus formation test and colorimetric assays for cytotoxic signals on the cell lines HepG2 and RAW264.7 were used. We also synthesized an oxoaplysinopsin derivate alkaloid (APL01) for comparative purposes. No mutagenic (250; 312.5; 375; 437.5 and 500 µg/plate) or genotoxic (0.05; 0.5; 5.0; 50 and 500 µg/mL) effects were observed in any sample tested for all measured concentrations. Cytotoxic responses were observed for eukaryotic cells in all tested samples at 500 and 5000 µg/mL concentrations. Cytotoxicity found in the WST-1 assay was independent of the metabolism of substances present in samples compositions. The cytotoxicity observed in the LDH release assay depended on metabolism.

Bone morphogenetic protein and Notch signalling crosstalk in poor-prognosis, mesenchymal-subtype colorectal cancer.

The functional role of bone morphogenetic protein (BMP) signalling in colorectal cancer (CRC) is poorly defined, with contradictory results in cancer cell line models reflecting the inherent difficulties of assessing a signalling pathway that is context-dependent and subject to genetic constraints. By assessing the transcriptional response of a diploid human colonic epithelial cell line to BMP ligand stimulation, we generated a prognostic BMP signalling signature, which was applied to multiple CRC datasets to investigate BMP heterogeneity across CRC molecular subtypes. We linked BMP and Notch signalling pathway activity and function in human colonic epithelial cells, and normal and neoplastic tissue. BMP induced Notch through a γ-secretase-independent interaction, regulated by the SMAD proteins. In homeostasis, BMP/Notch co-localization was restricted to cells at the top of the intestinal crypt, with more widespread interaction in some human CRC samples. BMP signalling was downregulated in the majority of CRCs, but was conserved specifically in mesenchymal-subtype tumours, where it interacts with Notch to induce an epithelial-mesenchymal transition (EMT) phenotype. In intestinal homeostasis, BMP-Notch pathway crosstalk is restricted to differentiating cells through stringent pathway segregation. Conserved BMP activity and loss of signalling stringency in mesenchymal-subtype tumours promotes a synergistic BMP-Notch interaction, and this correlates with poor patient prognosis. BMP signalling heterogeneity across CRC subtypes and cell lines can account for previous experimental contradictions. Crosstalk between the BMP and Notch pathways will render mesenchymal-subtype CRC insensitive to γ-secretase inhibition unless BMP activation is concomitantly addressed. © 2017 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Restoration of density of interstitial cells of Cajal in the jejunum of diabetic rats after quercetin supplementation.

BACKGROUND: Interstitial cells of Cajal (ICC) are required for normal motility in the gastrointestinal tract. Depletion of ICC has been associated with diabetic gastroenteropathy. PURPOSE: To determine the effect of quercertin supplementation on anoctamin-1 (Ano1) immunoreactive ICC in the myenteric region (ICC-MY) and deep muscular plexus (ICC-DMP) in the jejunum of diabetic rats. METHODS: Thirty-two 90-day-old male Wistar rats were distributed into the following groups: normoglycemic (C), normoglycemic supplemented with quercetin (CQ; 40 mg daily), diabetic (D), and diabetic supplemented with quercetin (DQ; 40 mg daily). Diabetes was induced by streptozotocin injection. After 120 days, preparations of the jejunal muscular and submucosal layers were immunostained for Ano1 to visualize ICC. Evaluation of the immunofluorescence intensity as well as density of ICC was performed. RESULTS: The density of ICC-MY was 46% lower in group D compared to group C (p < 0.01); ICC-DMP were reduced by 37% (p > 0.05). After quercertin treatment, the densities of ICC-MY were significantly higher in the DQ group compared to group D (ICC-MY: 58%, p < 0.05). Supplementation with quercetin in normoglycemic animals (CQ) compared with group C did not significantly change the ICC density (p > 0.05). CONCLUSIONS: In STZ-treated diabetic rats, diabetes promoted a reduction in the density of jejunal ICC-MY with no significant effect on ICC-DMP. Supplementation with quercetin (DQ) appeared to protect ICC-MY from depletion in diabetes possibly due to its antioxidant action.

Direct chemical evidence for eumelanin pigment from the Jurassic period.

Melanin is a ubiquitous biological pigment found in bacteria, fungi, plants, and animals. It has a diverse range of ecological and biochemical functions, including display, evasion, photoprotection, detoxification, and metal scavenging. To date, evidence of melanin in fossil organisms has relied entirely on indirect morphological and chemical analyses. Here, we apply direct chemical techniques to categorically demonstrate the preservation of eumelanin in two > 160 Ma Jurassic cephalopod ink sacs and to confirm its chemical similarity to the ink of the modern cephalopod, Sepia officinalis. Identification and characterization of degradation-resistant melanin may provide insights into its diverse roles in ancient organisms.

ZnO nanodisk based UV detectors with printed electrodes.

The fabrication of highly functional materials for practical devices requires a deep understanding of the association between morphological and structural properties and applications. A controlled hydrothermal method to produce single crystal ZnO hexagonal nanodisks, nanorings, and nanoroses using a mixed solution of zinc sulfate (ZnSO4) and hexamethylenetetramine (HMTA) without the need of catalysts, substrates, or templates at low temperature (75 °C) is introduced. Metal-semiconductor-metal (MSM) ultraviolet (UV) detectors were fabricated based on individual and multiple single-crystal zinc oxide (ZnO) hexagonal nanodisks. High quality single crystal individual nanodisk devices were fabricated with inkjet-printed silver electrodes. The detectors fabricated show record photoresponsivity (3300 A/W) and external quantum efficiency (1.2 × 10(4)), which we attribute to the absence of grain boundaries in the single crystal ZnO nanodisk and the polarity of its exposed surface.

Near-infrared excited state dynamics of melanins: the effects of iron content, photo-damage, chemical oxidation, and aggregate size.

Ultrafast pump-probe measurements can discriminate the two forms of melanin found in biological tissue (eumelanin and pheomelanin), which may be useful for diagnosing and grading melanoma. However, recent work has shown that bound iron content changes eumelanin's pump-probe response, making it more similar to that of pheomelanin. Here we record the pump-probe response of these melanins at a wider range of wavelengths than previous work and show that with shorter pump wavelengths the response crosses over from being dominated by ground-state bleaching to being dominated by excited-state absorption. The crossover wavelength is different for each type of melanin. In our analysis, we found that the mechanism by which iron modifies eumelanin's pump-probe response cannot be attributed to Raman resonances or differences in melanin aggregation and is more likely caused by iron acting to broaden the unit spectra of individual chromophores in the heterogeneous melanin aggregate. We analyze the dependence on optical intensity, finding that iron-loaded eumelanin undergoes irreversible changes to the pump-probe response after intense laser exposure. Simultaneously acquired fluorescence data suggest that the previously reported "activation" of eumelanin fluorescence may be caused in part by the dissociation of metal ions or the selective degradation of iron-containing melanin.

A response to a single cadaver study assessing the efficacy of two commercially available devices for airway foreign body relief.

A review of the speculative conclusions and poor methodology in assessing the efficacy of the LifeVac airway clearance device.

Preliminary examination of ADHD inattentive and cognitive disengagement syndrome symptoms in relation to probe-caught mind-wandering during a sustained attention to response task.

OBJECTIVE: The role of mind-wandering- periods of internally-directed distractibility - among patients with attention-deficit/hyperactivity disorder (ADHD) has recently garnered attention, though few studies have assessed mind-wandering using thought probes during a sustained attention to response task (SART) or examined the possible role of cognitive disengagement syndrome (CDS) symptoms. We examined whether parent- and/or teacher-reported ADHD-inattentive (ADHD-IN) or CDS symptoms were independently associated with probe-caught mind-wandering. METHODS: Fifty-four children (ages 9-12; 35.2% female) completed a SART with thought probes inquiring about various on- and off-task thoughts, including mind-wandering and distraction. Questionnaires provided information on demographics, medication treatment, and parent- and teacher-reported ADHD-IN and CDS symptoms. Regression models were estimated separately by informant to examine whether ADHD-IN or CDS symptoms were uniquely associated with mind-wandering or distraction frequency during the SART. RESULTS: Higher teacher-reported CDS ratings, but not ADHD-IN ratings, were uniquely associated with more probe-caught mind-wandering. No significant findings related to parent-reported symptoms or probe-caught distraction were observed. CONCLUSIONS: These preliminary findings add to an emerging body of work pointing to CDS as more consistently or strongly associated than ADHD-IN with mind-wandering. Theoretical and clinical implications are discussed.

Late Recurrence of Anisometropic Amblyopia.

A 15-year-old boy whose anisometropic amblyopia was effectively treated with glasses was examined. Despite years of stability, his visual acuity decreased from 20/20 to 20/60 with poor glasses compliance. Although amblyopia recurrence is well recognized, this case emphasizes potential late recurrence after prolonged success. Fortunately, he improved to 20/20 after improved compliance. [J Pediatr Ophthalmol Strabismus. 2024;61(1):e11-e12.].