Range Of Exposures Research Articles

A Longitudinal Experience and Annual “Check-Ins” to Increase Resident EEG and EMG Milestone Attainment and Improve Milestone Rating Accuracy (P1-2.002)

<h3>Objective:</h3> To determine if a longitudinal approach to EEG and EMG education with annual individual formative “check-ins” resulted in meaningful changes in quality and quantity of resident Milestone assessments. <h3>Background:</h3> By graduation, neurology residents are expected to achieve Level 4 ACGME Milestone proficiency at EEG and EMG interpretation. Surveys on EEG/EMG education in neurology residency reveal a wide range of exposure to these topics, approaches to assessment, and discrepancies between programs’ assessments of competence versus residents’ confidence in these skills. <h3>Design/Methods:</h3> Starting in 2020, residents in our program underwent annual individual “check-ins” with faculty to review a standard set of EEG and EMG studies. Anonymized semi-annual Milestone scores from 2014 to 2022 were reviewed, and scores were compared before and after initiation of the “check-ins.” Outcomes included the number of assessment points submitted (an indicator of how often these Milestones were recorded earlier in residency) and the proportion of graduating residents attaining the Level 4 Milestone. <h3>Results:</h3> Before the initiation of “check-ins,” there were missing Milestone scores for 17% (49/290) and 21% (60/290) of assessment points in EEG and EMG, respectively, mainly from PGY2 reports. Post-intervention, this significantly decreased to 1% (1/150, p&lt;0.001) for EEG, but not for EMG (20% [30/150], p = 0.865). Pre-intervention, resident Milestone achievement of at least Level 4 by graduation was 63% (26/41) for EEG and 17% (7/41) for EMG; this increased to 81% (25/31) for EEG (p = 0.111), and 52% (16/31) for EMG (p = 0.002). <h3>Conclusions:</h3> A longitudinal curriculum with annual “check-ins” significantly improved ability to track EEG Milestone progress. The proportion of graduating residents achieving Milestone goals for EMG increased significantly, and there was a trend toward higher attainment levels for EEG. We propose that these “check-ins” provide residents and programs with more accurate individualized feedback to better target future learning and program improvement. <b>Disclosure:</b> Dr. Sutherland has received personal compensation in the range of $0-$499 for serving as a Consultant for McGraw-Hill. Dr. Bower has nothing to disclose. Dr. Zuchowski has nothing to disclose. Dr. Dewey has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for United States. Dr. Moeller has received publishing royalties from a publication relating to health care.

Trofinetide for the treatment of Rett syndrome: an open-label study in girls 2 to 4 years of age (P13-9.005)

Trofinetide for the treatment of Rett syndrome: an open-label study in girls 2 to 4 years of age (P13-9.005)

The study of heat exchange processes during induction heating of the casing string in relation to the determination of behind-the-casing flows

One of the promising methods of geophysical survey of existing wells is active thermometry. The technology for conducting research using this method includes induction heating of a section of a metal casing string, registration and analysis of temperature changes in the range of induction exposure. As a result of heat exchange with the heated section of the column, a thermal disturbance is created in the fluid flow moving inside the column or in the behind-the-casing flow channel. The analysis of non-stationary temperature in the process of induction action allows solving actual practical problems, for example, determining the presence of fluid overflows in the space behind the casing string. In this work, on the basis of numerical simulation, the features of the formation of a temperature field in the process of inductive heating of the casing string are studied in relation to the determination of behind-the-casing fluid flows. Numerical simulation was performed using the Ansys Fluent software package. Fluid movement in the well is described by the Navier–Stokes equation in the Boussinesq–Oberbeck approximation, and its temperature is calculated taking into account forced and free convection. To calculate the temperature in the inductor, casing string, rocks and cement sheath, a non-stationary heat equation is used. The application of induction heating in diagnosing behind-the-casing flows in the sump, localized below the working perforated formations, in the annular space between the casing string and the cement ring is considered. The distribution curves of the cross-sectional average temperature in the casing string body in the induction heating interval at different flow rates in the casing cross-flow channel are plotted. It is shown that with an increase in the volume flow in the overflow channel, the maximum heating of the column decreases due to more intense heat transfer to the flow in the overflow channel. It has been established that the temperature curves show a “pull” of temperature (temperature disturbances in the body of the casing string propagate in the direction of flow in the overflow channel), the value of which increases with the flow rate in the overflow channel. It is shown that the temperature “pull” (the distance over which the thermal disturbance propagates) during upward flow exceeds the “pull” during downward flow, which is due to the influence of natural thermal convection in the fluid inside the casing string. On the example of the modeling conditions adopted in the work, it was found that up and down flows of more than 0.5 m3/day can be reliably determined from temperature measurements during the induction effect.

Population pharmacokinetic modelling to characterize the effect of chronic kidney disease on tenofovir exposure after tenofovir alafenamide administration.

Tenofovir alafenamide is gradually replacing tenofovir disoproxil fumarate, both prodrugs of tenofovir, in HIV prevention and treatment. There is thus an interest in describing tenofovir pharmacokinetics (PK) and its variability in people living with HIV (PLWH) under tenofovir alafenamide in a real-life setting. To characterize the usual range of tenofovir exposure in PLWH receiving tenofovir alafenamide, while assessing the impact of chronic kidney disease (CKD). We conducted a population PK analysis (NONMEM®) on 877 tenofovir and 100 tenofovir alafenamide concentrations measured in 569 PLWH. Model-based simulations allowed prediction of tenofovir trough concentrations (Cmin) in patients having various levels of renal function. Tenofovir PK was best described using a one-compartment model with linear absorption and elimination. Creatinine clearance (CLCR, estimated according to Cockcroft and Gault), age, ethnicity and potent P-glycoprotein inhibitors were statistically significantly associated with tenofovir clearance. However, only CLCR appeared clinically relevant. Model-based simulations revealed 294% and 515% increases of median tenofovir Cmin in patients with CLCR of 15-29 mL/min (CKD stage 3), and less than 15 mL/min (stage 4), respectively, compared with normal renal function (CLCR = 90-149 mL/min). Conversely, patients with augmented renal function (CLCR > 149 mL/min) had a 36% decrease of median tenofovir Cmin. Kidney function markedly affects circulating tenofovir exposure after tenofovir alafenamide administration in PLWH. However, considering its rapid uptake into target cells, we suggest only a cautious increase of tenofovir alafenamide dosage intervals to 2 or 3 days only in case of moderate or severe CKD, respectively.

Maternal Psychosocial Stress Is Associated with Reduced Diversity in the Early Infant Gut Microbiome.

The developing infant gut microbiome is highly sensitive to environmental exposures, enabling its evolution into an organ that supports the immune system, confers protection from infection, and facilitates optimal gut and central nervous system function. In this study, we focus on the impact of maternal psychosocial stress on the infant gut microbiome. Forty-seven mother-infant dyads were recruited at the HEAL Africa Hospital in Goma, Democratic Republic of Congo. Extensive medical, demographic, and psychosocial stress data were collected at birth, and infant stool samples were collected at six weeks, three months, and six months. A composite maternal psychosocial stress score was created, based on eight questionnaires to capture a diverse range of stress exposures. Full-length 16S rRNA gene sequences were generated. Infants of mothers with high composite stress scores showed lower levels of gut microbiome beta diversity at six weeks and three months, as well as higher levels of alpha diversity at six months compared to infants of low stress mothers. Longitudinal analyses showed that infants of high stress mothers had lower levels of health-promoting Lactobacillus gasseri and Bifidobacterium pseudocatenulatum at six weeks compared to infants of low stress mothers, but the differences largely disappeared by three to six months. Previous research has shown that L. gasseri can be used as a probiotic to reduce inflammation, stress, and fatigue, as well as to improve mental state, while B. pseudocatenulatum is important in modulating the gut-brain axis in early development and in preventing mood disorders. Our finding of reduced levels of these health-promoting bacteria in infants of high stress mothers suggests that the infant gut microbiome may help mediate the effect of maternal stress on infant health and development.

406 Living Review of World Trade Center Health Effects

OBJECTIVES/GOALS: The goal of this project is to develop a strategy to collect and extract published evidence in real time and to house and model these data for efficient downstream application to Program activities such as targeted reviews, grant evaluation and partner engagement. METHODS/STUDY POPULATION: We created the World Trade Center Health Effects Library in 2016. Today, this living review is ongoing and is fueled by daily systematic searches of online publication databases. Each day we screen new references for health effects of 9/11. The publication must include measurements, reports, or discussion of 9/11 health effects. If a publication meets these criteria, it is categorized by outcome and funding category. Primary outcome category data, reference metadata, and funding data are then made immediately available for programmatic analysis. All reference data are entered into a data pipeline and modelled for targeted reviews. RESULTS/ANTICIPATED RESULTS: The WTC Health Effects Library curates 1932 references and adds an average of 60 new references each year on a wide range of study populations, exposures, and conditions. The completeness of the library has been verified by comprehensive literature searches for 9/11 health outcomes conducted externally and by CDC Library staff. As a result, the curated library is a proven alternative to a lengthy literature search and allows the Program and stakeholders to explore the data and engage immediately in targeted reviews on curated topics. The data that are collected in the screening and categorization process are merged with publication metadata and funding data to inform a data pipeline that supports outputs such as interactive visuals, charts, reports, and curated bibliographies for structured review. DISCUSSION/SIGNIFICANCE: This living review allows the Program to rapidly conduct focused reviews, to evaluate grants, and to communicate accurate data to partners. By using the curated data, we have reduced the time required to perform mandated evidence reviews by weeks, have conducted two structured reviews, and defined gaps in research maturity and health equity.

Exposure–response relation for vibration-induced white finger: inferences from a published meta-analysis of population groups

PurposeIt is questioned whether the exposure–response relation for the onset of vibration-induced white finger (VWF) in ISO 5349-1:2001 needs to be revised based on the epidemiologic studies identified by Nilsson et al. (PLoS One https://doi.org/10.1371/journal.pone.0180795, 2017), and whether the relation they derive improves the prediction of VWF in vibration-exposed populations.MethodsA pooled analysis has been performed using epidemiologic studies that complied with selection rules and reported a VWF prevalence of 10% or more, and exposure constructed according to the provisions of ISO 5349-1:2001. The lifetime exposures at 10% prevalence were calculated for various data sets using linear interpolation. They were then compared to both the model from the standard and that developed by Nilsson et al.ResultsRegression analyses reveal excluding extrapolation to adjust group prevalences to 10% produce models with 95-percentile confidence intervals that include the ISO exposure–response relation but not that in Nilsson et al. (2017). Different curve fits are obtained for studies involving daily exposure to single or multiple power tools and machines. Studies with similar exposure magnitudes and lifetime exposure durations but markedly different prevalences are observed to cluster.ConclusionsA range of exposures and A(8)-values is predicted within which the onset of VWF is most likely to occur. The exposure–response relation in ISO 5349-1:2001, but not that proposed by Nilsson et al., falls within this range and provides a conservative estimate for the development of VWF. In addition, the analyses suggest that the method for evaluating vibration exposure contained in ISO 5349-1:2001 needs revision.

The interaction of socioeconomic stress and race on telomere length in children: A systematic review and meta-analysis

RationaleProposed mechanisms relating early life exposures to poor health suggest that biologic indicators of risk are observable in childhood. Telomere length (TL) is a biomarker of aging, psychosocial stress, and a range of environmental exposures. In adults, exposure to early life adversity, including low socioeconomic status (SES), is predictive of shorter TL. However, results in pediatric populations have been mixed. Defining the true relation between TL and SES in childhood is expected to enhance the understanding of the biological pathways through which socioeconomic factors influence health across the life span. ObjectiveThe aim of this meta-analysis was to systematically review and quantitatively assess the published literature to better understand how SES, race, and TL are related in pediatric populations. MethodsStudies in the United States in any pediatric population with any measure of SES were included and identified through the following electronic databases: PubMed, EMBASE, Web of Science, Medline, Socindex, CINAHL, and Psychinfo. Analysis utilized a multi-level random-effects meta-analysis accounting for multiple effect sizes within a study. ResultsThirty-two studies were included with a total of 78 effect sizes that were categorized into income-based, education-based, and composite indicators. Only three studies directly tested the relation between SES and TL as the primary study aim. In the full model, there was a significant relation between SES and TL (r = 0.0220 p = 0.0286). Analysis by type of SES categorization identified a significant moderating effect of income on TL (r = 0.0480, 95% CI: 0.0155 to 0.0802, p = 0.0045) but no significant effect for education or composite SES. ConclusionsThere is an overall association between SES and TL that is predominately due to the association with income-based SES measures implicating income disparities as a key target for efforts to address health inequity across the life span. Identification of associations between family income and biological changes in children that predict life-span health risk provides key data to support public health policies addressing economic inequality in families and presents a unique opportunity to assess the effect of prevention efforts at the biologic level.

Medial Olivocochlear Reflex Strength in Ears With Low-to-Moderate Annual Noise Exposure.

Studies in lower mammals demonstrate enhancement of the medial olivocochlear reflex (MOCR) following noise exposure. A similar effect may occur in humans, and there is some evidence of an individual's acoustic history affecting the MOCR. The current work evaluates the relationship between an individual's annual noise exposure history and their MOCR strength. Given the potential role of the MOCR as a biological hearing protector, it is important to identify factors associated with MOCR strength. Data were collected from 98 normal-hearing young adults. Annual noise exposure history was estimated using the Noise Exposure Questionnaire. MOCR strength was assayed using click-evoked otoacoustic emissions (CEOAEs) measured with and without noise presented to the contralateral ear. MOCR metrics included the MOCR-induced otoacoustic emission (OAE) magnitude shift and phase shift. A CEOAE signal-to-noise ratio (SNR) of at least 12 dB was required for estimation of the MOCR metrics. Linear regression was applied to evaluate the relationship between MOCR metrics and annual noise exposure. Annual noise exposure was not a statistically significant predictor of the MOCR-induced CEOAE magnitude shift. However, annual noise exposure was a statistically significant predictor of the MOCR-induced CEOAE phase shift-the MOCR-induced phase shift decreased with increasing noise exposure. Additionally, annual noise exposure was a statistically significant predictor of OAE level. Findings contrast with recent work that suggests MOCR strength increases with annual noise exposure. Compared with previous work, data for this study were collected using more stringent SNR criteria, which is expected to increase the precision of the MOCR metrics. Additionally, data were collected for a larger subject population with a wider range of noise exposures. Whether findings generalize to other exposure durations and levels is unknown and requires future study.

Suicide and Transportation Noise: A Prospective Cohort Study from Switzerland.

Although plausible from a pathophysiological point of view, robust evidence for effects of transportation noise on mental health remains scarce. Meanwhile, psychiatric diseases are among the most prevalent noncommunicable diseases worldwide, and suicide as a mortality outcome highly connected to mental disorders presents a pressing public health issue. The aim of this study was to investigate the association between source-specific transportation noise, particulate matter (PM) air pollution, residential greenness, and suicide by means of a nationwide cohort study. Road traffic, railway and aircraft noise exposure as well as exposure to air pollution [PM with aerodynamic diameter ()] and greenness [normalized difference vegetation index (NDVI)] were linked to 5.1 million adults (age 15 y and older) in the Swiss National Cohort, accounting for their address history. Mean noise exposure in 5-y periods was calculated. Individuals were followed for up to 15 y (2001-2015). Time-varying Cox regression models were applied to deaths by suicide (excluding assisted suicide). Models included all three noise sources, , and NDVI plus individual and spatial covariates, including socioeconomic status. Effect modification by sex, age, socioeconomic indicators, and degree of urbanization was explored. During the follow-up, there were 11,265 suicide deaths (10.4% poisoning, 33.3% hanging, 28.7% firearms, 14.7% falls). Road traffic and railway noise were associated with total suicides [hazard ratios: 1.040; 95% confidence interval (CI): 1.015, 1.065; and 1.022 (95% CI: 1.004, 1.041) per 10 dB day-evening-night level (Lden)], whereas for aircraft noise, a risk increase starting from 50 dB was masked by an inverse association in the very low exposure range (30-40 dB). Associations were stronger for females than males. The results were robust to adjustment for residential greenness and air pollution. In this longitudinal, nationwide cohort study, we report a robust association between exposure to road traffic and railway noise and risk of death by suicide after adjusting for exposure to air pollution and greenness. These findings add to the growing body of evidence that mental health disorders may be related to chronic transportation noise exposure. https://doi.org/10.1289/EHP11587.

ROS production in response to high-power microwave pulses induces p53 activation and DNA damage in brain cells: Radiosensitivity and biological dosimetry evaluation.

Background: Pulsed high-power microwave (HPM) has many applications and is constantly being researched to expand its uses in the future. As the number of applications grows, the biological effects and safety level of pulsed HPM become a serious issue, requiring further research. Objective: The brain is regarded as the most vulnerable organ to radiation, raising concerns about determining an acceptable level of exposure. The effect of nanosecond pulses and the mechanisms underlying HPM on the brain has not been studied. For the first time, we observed the effect of pulsed 3.5GHz HPM on brain normal astrocytes and cancer U87 MG cells, as well as the likely mechanisms involved. Methods: To generate 3.5GHz HPM, an axial virtual cathode oscillator was constructed on pulsed power generator "Chundoong". The cells were directly exposed to HPM (10, 25, 40, and 60) pulses (1mJ/pulse), with each pulse delivered after 1min of charging time to evaluate the dose dependent effects. Results: A strong electric field (∼23kV/cm) of HPM irradiation primarily causes the production of reactive oxygen species (ROS), altering cell viability, mitochondrial activity, and cell death rates in U87 and astrocytes at certain dosages. The ROS generation in response to HPM exposure was primarily responsible for DNA damage and p53 activation. The hazardous dosage of 60 pulses is acknowledged as having damaging effects on brain normal cells. Interestingly, the particular 25 pulses exhibited therapeutic effects on U87 cells via p53, Bax, and Caspase-3 activation. Conclusion: HPM pulses induced apoptosis-related events such as ROS burst and increased oxidative DNA damage at higher dosages in normal cells and specific 25 pulses in cancer U87. These findings are useful to understand the physiological mechanisms driving HPM-induced cell death, as well as the safety threshold range for HPM exposure on normal cells and therapeutic effects on cancer U87. As HPM technology advances, we believe this study is timely and will benefit humanity and future research.

Model-based prediction of effective target exposure for MEN1611 in combination with trastuzumab in HER2-positive advanced or metastatic breast cancer patients.

MEN1611 is a novel orally bioavailable PI3K inhibitor currently in clinical development for patients with HER2-positive (HER2+) PI3KCA mutated advanced/metastatic breast cancer (BC) in combination with trastuzumab (TZB). In this work, a translational model-based approach to determine the minimum target exposure of MEN1611 in combination with TZB was applied. First, pharmacokinetic (PK) models for MEN1611 and TZB in mice were developed. Then, in vivo tumor growth inhibition (TGI) data from seven combination studies in mice xenograft models representative of the human HER2+ BC non-responsive to TZB (alterations of the PI3K/AkT/mTOR pathway) were analyzed using a PK-pharmacodynamic (PD) TGI model for co-administration of MEN1611 and TZB. The established PK-PD relationship was used to quantify the minimum effective MEN1611 concentration, as a function of TZB concentration, needed for tumor eradication in xenograft mice. Finally, a range of minimum effective exposures for MEN1611 were extrapolated to patients with BC, considering the typical steady-state TZB plasma levels in patients with BC following three alternative regimens (i.v. 4 mg/kg loading dose +2mg/kg q1w, i.v. 8 mg/kg loading dose +6mg/kg q3w or s.c. 600 mg q3w). A threshold of about 2000 ng·h/ml for MEN1611 exposure associated with a high likelihood of effective antitumor activity in a large majority of patients was identified for the 3-weekly and the weekly i.v. schedule for TZB. A slightly lower exposure (i.e., 25% lower) was found for the 3-weekly s.c. schedule. This important outcome confirmed the adequacy of the therapeutic dose administered in the ongoing phase 1b B-PRECISE-01 study in patients with HER2+ PI3KCA mutated advanced/metastatic BC.

Characterizing the exposure-response relationship of idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma.

Idecabtagene vicleucel (ide-cel; bb2121) is a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cell therapy approved for treatment of patients with heavily pretreated relapsed and refractory multiple myeloma. This analysis evaluated exposure-response (ER) relationships of ide-cel with key efficacy end points and safety events. Ide-cel exposure data were available from 127 patients treated at target doses of 150, 300, or 450 × 106 CAR+ T cells from the phase II KarMMa study (NCT03361748). Key exposure metrics, including area under the curve of the transgene level from 0 to 28 days and maximum transgene level, were calculated using noncompartmental methods. Logistic regression models, using both linear and maximum response function of exposure on the logit scale, were evaluated to quantify observed ER trends, and modified by including statistically significant individual covariates in a stepwise regression analysis. There was wide overlap of exposures across the target doses. ER relationships were observed for the overall and complete response rates, with higher response rates associated with higher exposures. Model-based evaluations identified female sex and baseline serum monoclonal protein less than or equal to 10g/L as predictive of a higher objective response rate and a higher complete response rate, respectively. ER relationships were observed for safety events of cytokine release syndrome requiring tocilizumab or corticosteroids. The established ER models were used to quantify the ide-cel dose-response, which showed a positive benefit-risk assessment for the range of ide-cel exposures associated with the target dose range of 150-450 × 106 CAR+ T cells.

Sequence dependent UV damage of complete pools of oligonucleotides

Understanding the sequence-dependent DNA damage formation requires probing a complete pool of sequences over a wide dose range of the damage-causing exposure. We used high throughput sequencing to simultaneously obtain the dose dependence and quantum yields for oligonucleotide damages for all possible 4096 DNA sequences with hexamer length. We exposed the DNA to ultraviolet radiation at 266 nm and doses of up to 500 absorbed photons per base. At the dimer level, our results confirm existing literature values of photodamage, whereas we now quantified the susceptibility of sequence motifs to UV irradiation up to previously inaccessible polymer lengths. This revealed the protective effect of the sequence context in preventing the formation of UV-lesions. For example, the rate to form dipyrimidine lesions is strongly reduced by nearby guanine bases. Our results provide a complete picture of the sensitivity of oligonucleotides to UV irradiation and allow us to predict their abundance in high-UV environments.

Specialist medical toxicologist consultations provided by the New Zealand National Poisons Centre, 2018-2020.

The National Poisons Centre (NPC) provides 24/7 specialist medical toxicologist consultations to healthcare professionals regarding the clinical management of poisoning cases. The use of toxicologist services was investigated to characterise the extent and content of consults to inform further development of this service. A retrospective analysis of 2018-2020 medical toxicologist consultations summarised contact numbers, professional backgrounds and district health boards (DHBs) of the people contacting the NPC, and the patient(s) and substance(s) involved. There were 3,451 medical toxicologist consultations with 2,400 (67%) provided directly to healthcare professionals. Crude rates of consults increased across all DHBs. Of all 2,603 therapeutic substances that were consulted about during the study period, 1,492 (57.3%) were drugs affecting the nervous system, and paracetamol was the most common individual drug (528; 20.3%). Of all 1,185 non-therapeutic substance exposures that were advised on, 66 (5.6%) were unidentified mushrooms, 51 (4.3%) unidentified substances, and 47 (4.0%) lead exposures. There was increasing utilisation of the NPC service by healthcare professionals from all 24 areas of the country, covering a wide range of substance exposures and scenarios. The growing utilisation suggests healthcare professionals derive value from this consultation service for the care of their patients.

P849 Exposure to metals and minerals in hair samples of patients with preclinical inflammatory bowel disease

Abstract Background Previous data have shown that the inflammatory process underlying ulcerative colitis (UC) and Crohn’s disease (CD) can start years before the diagnosis, but the role of triggering factors and environmental exposures is still unknown. Hair element analysis is a valuable and inexpensive screen for physiological excess or deficiency of certain elements. Our aim was to determine if patients with an incidental diagnosis of UC or CD demonstrate exposure of minerals or toxic metals in the years preceding the symptomatic onset of the disease. Methods We performed a prospective single-center study including all asymptomatic subjects with a diagnosis of UC or CD during the colorectal cancer screening program between January 2021 – June 2022 in Vizcaya (Basque Country, Spain). The diagnosis of IBD was established by a combination of clinical data, endoscopic findings suggestive of UC or CD, and after histologic confirmation. Cases were compared with a healthy non-IBD control population. An approximate hair sample of 0.25 g was obtained up to 3 months since diagnosis. We used a commercial kit that allows the investigation of 17 metals (Al, Sb, As, Ba, Be, Bi, Cd, Pb, Hg, Pt, Tl, Th, U, Ni, Ag, Sn, Ti) and 22 minerals (Ca, Mg, Na, K, Cu, Zn, Mn, Cr, V, Mo, B, I, Li, P, Se, Sr, S, Co, Fe, Ge, Rb, Zr). Descriptive statistics and non-parametric tests were used for comparisons between both groups. Results Three patients with preclinical IBD were included (median age 53 years; 67% male; all former smokers). Two of them had a diagnosis of UC (one left-sided colitis and one extensive colitis) and one with ileal CD. Extraintestinal manifestations were observed in one patient (33%). No family history of IBD was reported. Thirteen healthy controls with no relevant environmental exposures (median age 34 years; 69% female; 92% non-smokers). We found that cases demonstrated statistically significant higher concentrations of bismuth, sodium and boron compared to controls (Figure). In contrast, there was a lower exposure to uranium, zinc and germanium, with a trend towards lower copper levels among cases. Conclusion A range of environmental exposures can be identified during the preclinical phase of IBD. However, their relationship with the symptomatic onset and disease progression should be further explored.

Characterizing the adult exposome in men and women from the general population: Results from the EHES-LUX study

Throughout life individuals are exposed to a large array of diverse environmental exposures (exposome). Hair analyses can assess chronic exposure to a large number of chemicals with less intra-variability than urine and blood. This is essential for studies that aim to achieve a global vision of the exposome. We aimed at characterizing the adult exposome by describing 175 environmental exposures and correlation patterns between and within exposure groups. A subsample of participants of the European Health Examination Survey, covering information on exposure to chemical pollutants in hair samples, were included in the present analysis (N = 442). Concentrations of micronutrients, lifestyle, home environment and socioeconomic information completed the exposome description and were obtained through blood analyses and questionnaires. We detected 29 persistent and non-persistent chemical pollutants in more than 70% of hair samples. Compared to women, men had higher concentrations of pesticides, lower concentrations of micronutrients (with the exception of vitamin A), and presented higher alcohol consumption. Across all exposures, a low median absolute correlation was found, 0.05 (5th − 95th centiles = 0.10, 0.20). We observed higher correlations and median correlations within exposure groups than between groups of exposure. The highest median correlation was observed between plasticizers (bisphenol A and S) in both men (0.50) and women (0.31). A 70% and 95% of cumulative variance was explained by 37 and 73 principal components respectively. We found a wide range of chemical exposures in hair samples of men and women. The adult exposome was complex and multidimensional. Future exposome studies should include hair as a matrix for characterizing exposure to multiple environmental chemicals.

Tool-Wear-Estimation System in Milling Using Multi-View CNN Based on Reflected Infrared Images.

A novel method for tool wear estimation in milling using infrared (IR) laser vision and a deep-learning algorithm is proposed and demonstrated. The measurement device employs an IR line laser to irradiate the tool focal point at angles of -7.5°, 0.0°, and +7.5° to the vertical plane, and three cameras are placed at 45° intervals around the tool to collect the reflected IR light at different locations. For the processing materials and methods, a dry processing method was applied to a 100 mm × 100 mm × 40 mm SDK-11 workpiece through end milling and downward cutting using a TH308 insert. This device uses the diffused light reflected off the surface of a rotating tool roughened by flank wear, and a polarization filter is considered. As the measured tool wear images exhibit a low dynamic range of exposure, high dynamic range (HDR) images are obtained using an exposure fusion method. Finally, tool wear is estimated from the images using a multi-view convolutional neural network. As shown in the results of the estimated tool wear, a mean absolute error (MAE) of prediction error calculated was to be 9.5~35.21 μm. The proposed method can improve machining efficiency by reducing the downtime for tool wear measurement and by increasing tool life utilization.

Population Pharmacokinetic and Exposure-Response Analyses for Efficacy and Safety of Risankizumab in Patients With Active Crohn's Disease.

The population pharmacokinetics (PK) of risankizumab and exposure-response relationships for efficacy and safety in patients with Crohn's disease (CD) were characterized using data from phase II and III studies to support dosing regimen selection. A two-compartment model with first-order absorption and first-order elimination adequately described risankizumab PK. Covariates including sex, baseline fecal calprotectin, corticosteroid use, baseline creatinine clearance, body weight, and baseline albumin were statistically correlated with risankizumab clearance, but their impact on exposure was not clinically relevant for efficacy or safety. Exposure-response analyses showed that exposures associated with the 600 mg intravenous (i.v.) induction dose at Weeks 0, 4, and 8 achieved a near maximal response for all efficacy end points evaluated, with negligible added benefit from the 1,200 mg i.v. regimen. By Week 52 of the maintenance treatment, trends of higher responses were observed for the exposure range associated with the 360 mg subcutaneous (s.c.) every-8-weeks (Q8W) regimen for most of the evaluated efficacy end points, particularly for the more stringent end points, such as endoscopic remission and ulcer-free endoscopy. Exposure-response analyses for safety did not identify any apparent relationship between exposure and safety. These results supported the final dose recommendation of 600 mg i.v. at Weeks 0, 4, and 8, followed by 360 mg s.c. at Week 12 and Q8W thereafter in patients with CD.

Improved Hydrogen Gas Sensing Performance of Carbon Nanotube Synthesized Using Microwave Oven

Obtaining a high-performance hydrogen (H2) gas sensor based on carbon nanotube (CNT) remains challenging. In this view, two CNT samples such as untreated (R-CNT) and nitric acid (HNO3)-treated (called functionalized or F-CNT in short) were deposited on the SiO2/Si substrate using an electrophoretic deposition technique. The structure, morphology, and electrical characteristics of these samples were evaluated. Fourier transform infrared (FTIR) spectra confirmed the presence of OH groups at the walls of nanotubes after acid treatment. Moreover, it found the current increased from <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$35 \mu \text{A}$ </tex-math></inline-formula> for R-CNT to 11 mA for F-CNT. In addition, both R-CNT and F-CNT were used to fabricate H2 gas sensors. The sensing capacity of the obtained sensors was measured under the H2 gas exposure range of 20 to 300 ppm operated at room temperature (RT), 50 °C, and 75 °C. The H2 gas sensor made of F-CNT showed a much higher response (368%) and shorter response time (15 s) as well as recovery time (72 s) than the one made using R-CNT. It was asserted that the H2 gas sensing performance of the proposed sensor can significantly be improved via the acid treatment or functionalization of CNT.