Data-driven analyses to quantify information seeking behaviour for women with uterine fibroids.

Uterine fibroids (UF) are noncancerous growths of the uterus and impact the livelihood of over 26 million women in the United States. Although UF may not have accompanying symptoms, for some women their presence leads to surgical treatment, which can be a difficult decision-making process. Web-scraping of online media is used to identify information-seeking behavior of women searching for UF treatment options. We synthesize the data to describe trends in UF treatment, including the identification of gaps between the information individuals are seeking (demand) and information that is publicly available as a resource (supply), which contributes to this study's creation of the term "information desert." We perform statistical analysis to understand information-seeking behavior, determine the gap between information supply and information demand, and determine the correlation between a doctor's treatment recommendation and a patient's treatment decision as a function of age, symptoms, and knowledge obtained about specific types of treatment.

Monochrome Multiplex Quantitative PCR Telomere Length Measurement.

Telomeres are ribonucleoprotein structures at the end of all eukaryotic chromosomes that protect DNA from damage and preserve chromosome stability. Telomere length (TL) has been associated with various exposures, biological processes, and health outcomes. This article describes the monochrome multiplex quantitative polymerase chain reaction (MMqPCR) assay protocol routinely conducted in our laboratory for measuring relative mean TL from human DNA. There are several different PCR-based TL measurement methods, but the specific protocol for the MMqPCR method presented in this publication is repeatable, efficient, cost-effective, and suitable for population-based studies. This detailed protocol outlines all information necessary for investigators to establish this assay in their laboratory. In addition, this protocol provides specific steps to increase the reproducibility of TL measurement by this assay, defined by the intraclass correlation coefficient (ICC) across repeated measurements of the same sample. The ICC is a critical factor in evaluating expected power for a specific study population; as such, reporting cohort-specific ICCs for any TL assay is a necessary step to enhance the overall rigor of population-based studies of TL. Example results utilizing DNA samples extracted from peripheral blood mononuclear cells demonstrate the feasibility of generating highly repeatable TL data using this MMqPCR protocol.

Undisclosed financial conflicts of interest in DSM-5-TR: cross sectional analysis.

OBJECTIVE: To assess the extent and types of financial ties to industry of panel and task force members of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, fifth edition, text revision (DSM-5-TR), published in 2022. DESIGN: Cross sectional analysis. SETTING: Open Payments database, USA. PARTICIPANTS: 92 physicians based in the US who served as members of either a panel (n=86) or task force (n=6) on the DSM-5-TR with information recorded in the Centers for Medicare and Medicaid Services Open Payments database during 2016-19. This period was chosen to include the year that development of the DSM-5-TR began and the three years preceding, a time consistent with previous research on conflicts of interest and consistent with the American Psychiatric Association's disclosure requirements for the fifth revision (DSM-5) of the manual. MAIN OUTCOME MEASURES: Type and amount of compensation the panel and task force members of DSM-5-TR received during 2016-19. RESULTS: After duplicate names had been removed, 168 individuals were identified who served as either panel or task force members of the DSM-5-TR. 92 met the inclusion criteria of being a physician who was based in the US and therefore could be included in Open Payments. Of these 92 individuals, 55 (60%) received payments from industry. Collectively, these panel members received a total of $14.2m (£11.2m; €13m). One third (33.3%) of the task force members had payments reported in Open Payments. CONCLUSIONS: Conflicts of interest among panel members of DSM-5-TR were prevalent. Because of the enormous influence of diagnostic and treatment guidelines, the standards for participation on a guideline development panel should be high. A rebuttable presumption should exist for the Diagnostic and Statistical Manual of Mental Disorders to prohibit conflicts of interest among its panel and task force members. When no independent individuals with the requisite expertise are available, individuals with associations to industry could consult to the panels, but they should not have decision making authority on revisions or the inclusion of new disorders.

E-cigarette vapor renders neutrophils dysfunctional due to filamentous actin accumulation.

BACKGROUND: Electronic cigarette (e-cigarette) use continues to rise despite concerns of long-term effects, especially the risk of developing lung diseases such as chronic obstructive pulmonary disease. Neutrophils are central to the pathogenesis of chronic obstructive pulmonary disease, with changes in phenotype and function implicated in tissue damage. OBJECTIVE: We sought to measure the impact of direct exposure to nicotine-containing and nicotine-free e-cigarette vapor on human neutrophil function and phenotype. METHODS: Neutrophils were isolated from the whole blood of self-reported nonsmoking, nonvaping healthy volunteers. Neutrophils were exposed to 40 puffs of e-cigarette vapor generated from e-cigarette devices using flavorless e-cigarette liquids with and without nicotine before functions, deformability, and phenotype were assessed. RESULTS: Neutrophil surface marker expression was altered, with CD62L and CXCR2 expression significantly reduced in neutrophils treated with e-cigarette vapor containing nicotine. Neutrophil migration to IL-8, phagocytosis of Escherichia coli and Staphylococcus aureus pHrodo bioparticles, oxidative burst response, and phorbol 12-myristate 13-acetate-stimulated neutrophil extracellular trap formation were all significantly reduced by e-cigarette vapor treatments, independent of nicotine content. E-cigarette vapor induced increased levels of baseline polymerized filamentous actin levels in the cytoplasm, compared with untreated controls. CONCLUSIONS: The significant reduction in effector neutrophil functions after exposure to high-power e-cigarette devices, even in the absence of nicotine, is associated with excessive filamentous actin polymerization. This highlights the potentially damaging impact of vaping on respiratory health and reinforces the urgency of research to uncover the long-term health implications of e-cigarettes.

"Following the Breath:" A Trauma-Informed Intervention for Educator Wellness in Rural Montana.

Given the prevalence of mental health issues for both educators and adolescents in rural Montana, this project is designed to help mitigate the impact of stressors by providing coping strategies linked to improvements in overall mental health outcomes for teachers, which may ultimately lead to improved co-regulation of students and classroom climate. The immediate goal of this pilot study was to measure physical and mental health outcomes of educators resulting from a remotely-delivered trauma-informed yoga intervention. Findings suggest improvements in participants' depression and anxiety levels, trauma symptoms, sleep quality, and non-significant changes in heart rate variability and cortisol levels.

Uterine Rupture Secondary to Pyomyoma, Leading to Intra-Abdominal Abscesses following an Uncomplicated Vaginal Delivery.

Background: Pyomyomas are an infrequent complication of uterine fibroids and, in extremely rare cases, the cause of spontaneous uterine rupture. A few documented cases were managed conservatively with oral antibiotics and CT-guided drainage or myomectomy with fertility preserved. However, treatment more frequently involves IV antibiotics and a hysterectomy. Case Description. A 31-year-old G2P0111 PPD 7 presented with intra-abdominal abscesses of unknown source. She was treated with broad-spectrum antibiotics, image-guided percutaneous (IR) drainage of the largest abscess, and surgical exploration with debridement. During surgery, she was diagnosed with spontaneous uterine rupture. The uterine defect was successfully repaired, and she was able to be successfully managed with fertility-sparing treatment. The patient ultimately did not require a hysterectomy. The final pathology was consistent with pyomyoma. Conclusion: In a majority of cases, pyomyoma treatment requires a hysterectomy, and fertility is unable to be preserved. However, conservative management with IV antibiotics, IR drainage, and surgical debridement could be a fertility-preserving approach to the treatment of pyomyomas.

A review and meta-analysis: Cross-tissue telomere length correlations in healthy humans.

BACKGROUND AND AIM: Tissue source has been shown to exert a significant effect on the magnitude of associations between telomere length and various health outcomes and exposures. The purpose of the present qualitative review and meta-analysis is to describe and investigate the impact of study design and methodological features on the correlation between telomere lengths measured in different tissues from the same healthy individual. METHODS: This meta-analysis included studies published from 1988 to 2022. Databases searched included PubMed, Embase, and Web of Science and studies were identified using the keywords "telomere length" and "tissues" or "tissue." A total of 220 articles of 7856 initially identified studies met inclusion criteria for qualitative review, of which 55 met inclusion criteria for meta-analysis in R RESULTS: Studies meeting inclusion criteria for meta-analysis tended to have enhanced demographic and methodological reporting relative to studies only included in the qualitative review. A total of 463 pairwise correlations reported for 4324 unique individuals and 102 distinct tissues were extracted from the 55 studies and subject to meta-analysis, resulting in a significant effect size z = 0.66 (p < 0.0001) and meta-correlation coefficient of r = 0.58. Meta-correlations were significantly moderated by sample size and telomere length measurement methodology, with studies of smaller size and those using hybridization-based analyses exhibiting the largest meta-correlation. Tissue source also significantly moderated the meta-correlation, wherein correlations between samples of a different lineage (e.g., blood vs. non-blood) or collection method (e.g., peripheral vs. surgical) were lower than correlations between samples of the same lineage or collection method. CONCLUSION: These results suggest that telomere lengths measured within individuals are generally correlated, but future research should be intentional in selecting a tissue for telomere length measurement that is most biologically relevant to the exposure or outcome investigated and balance this with the feasibility of obtaining the sample in sufficient numbers of individuals.

Epidemiology of Anterior and Lateral Basilar Skull Fractures With CSF Leak: A National Trauma Data Bank Analysis.

OBJECTIVE: Cerebrospinal fluid (CSF) leaks are a complication from dural violations that can occur in the setting of skull base fractures. No prior study provides a nationwide epidemiological analysis of traumatic CSF leaks. The objective of this report is to characterize patient demographics, injury-related variables, and operative management. METHODS: The national trauma data bank was queried for both anterior and lateral skull base fracture cases between 2008 and 2016. Clinical data were extracted. RESULTS: A total of 242 skull base fractures with CSF leak were identified. Most patients were male (84.3%), and the median patient age was 39.7±17.6 years old. Glasgow Coma Scale was 14.0 [interquartile range (IQR): 6.5-10.6] for lateral fractures, 13.0 (IQR: 3.0-10.0) for anterior fractures, and severe range for combined fractures at 7.0 (IQR: 5.0-9.0) (analysis of variance, P =0.122). Common mechanisms of injury were motor vehicle accidents (107, 44.2%), followed by falls and firearms (65, 26.9% and 20, 8.3%, respectively). The median length of stay was 2 weeks, with a median of 14 days (IQR: 10-25) for the anterior fractures and 10 days (IQR 5-19) among the lateral fractures ( P =0.592). Patients were most commonly discharged home in both the anterior (43.8%) and lateral (49.2%) groups. CONCLUSIONS: The prototypical patient tends to be a young adult male presenting with moderate-to-severe range neurological dysfunction after a vehicular accident. The overall prognosis of skull base fractures with CSF leak remains encouraging, with nearly half of these patients being discharged home within 2 weeks.

Detecting pathological exercise in college men: An investigation using latent profile analysis.

OBJECTIVE: Pathological exercise is a dangerous behavior often observed in eating disorders. Data investigating associated characteristics of pathological exercise in men are lacking, despite college men and women being at equally elevated risk for developing eating disorders. PARTICIPANTS: Two hundred and twenty-four college men who exercise regularly completed a series of self-report questionnaires. METHODS: Latent profile analysis was used to identify empirically-derived homogenous subgroups of regular exercisers based on severity of other eating disorder attitudes and behaviors. Profiles were also compared on differences in exercise motivation and general psychopathology (i.e., depression, anxiety). RESULTS: Fit indices indicated a three-profile solution. Profiles described an eating psychopathology group, a low psychopathology group, and a high exercise frequency group without eating disorder features. CONCLUSIONS: Pathological exercise cannot be identified using exercise frequency alone. Other features like body dissatisfaction and exercise motivation style are relevant in identifying pathological exercise behavior in college men.

Wisconsin Healthcare Utilization Cost Among American Indians/Alaska Natives with and without Alzheimer's Disease and Related Dementias.

Individuals with Alzheimer's disease and related dementias (ADRD) accrue higher healthcare utilization costs than peers without ADRD, but incremental costs of ADRD among American Indians/Alaska Natives (AI/AN) is unknown. State-wide paid electronic health record data were retrospectively analyzed using percentile-based bootstrapped 95% confidence intervals of the weighted mean difference of total 5-year billed costs to compare total accrued for non-Tribal and Indian Health Service utilization costs among Medicaid and state program eligible AI/AN, ≥40 years, based on the presence/absence of ADRD (matching by demographic and medical factors). AI/AN individuals with ADRD accrued double the costs compared to those without ADRD, costing an additional $880.45 million to $1.91 billion/year.

Effects of maternal hypertension on cord blood Arginine vasopressin receptor expression.

Arginine vasopressin (AVP) signaling is altered in preeclampsia and physiologic stress. AVP is implicated in fluid homeostasis and cardiovascular (CV) function, which is disrupted in some progeny from preeclamptic pregnancies. However, whether altered fetal AVP signaling occurs in preeclampsia is unknown. Here, we measured CV-related transcripts (e.g., AVP receptors) in cord blood via quantitative PCR. Chronic hypertension decreased AVPR1b, AVPR2, OXTR, LNPEP, and CUL5. AVPR1a, AVPR1b, and AVPR2 were decreased while OXTR was increased in preeclamptic cord blood. In sum, we found prenatal exposure to hypertension in pregnancy alters fetal AVP signaling and may thereby prime offspring CV disease risk.

Mitigating Rural Adolescent Trauma: Remote Delivery of a Trauma-Informed Yoga Intervention During COVID-19.

Given the prevalence of childhood trauma in rural Montana, this project is intended to help mitigate stressors that may contribute to poor behavioral and mental health in high school-aged children, which may be exacerbated by the collective trauma of the COVID-19 pandemic. The immediate goal was to measure physical and mental health outcomes in adolescents resulting from a remotely delivered trauma-informed yoga intervention designed to foster positive youth development. Our study builds on the successes from an initial feasibility pilot study one year prior in order to evaluate a more robust intervention comparing experimental and control group outcomes. Students at a small, rural high school in Montana volunteered to participate in a 6-week, twice-weekly trauma-informed yoga intervention in their physical education class. Validated survey measures, including the PHQ-A, GAD-7, and ACE-Q instruments, were utilized to measure mental health outcomes pre- vs. post-intervention. Salivary cortisol levels were also measured pre-, mid-, and post-intervention. Statistically significant declines in cortisol levels and improvements in sleep duration were noted when comparing experimental vs. control groups. Noteworthy declines in depression and anxiety levels were also seen when comparing the treatment to control groups. Descriptive differences between the control and experimental groups illustrate the mental health benefits of reduced anxiety and depressive symptoms in rural adolescents resulting from a remotely delivered trauma-informed yoga intervention. Our study holds the potential for a long-term public health impact in reducing adolescent rates of anxiety and depression while mitigating trauma in geographically isolated settings. Trial Registration: ClinicalTrials.gov identifier: NCT04664855.

A Single-Centre Experience of Post-COVID-19 Vaccine-Related Immune-Mediated Complications.

The significant impact of the COVID-19 pandemic has resulted in a worldwide effort to develop effective vaccines. In the United Kingdom, the COVID-19 vaccine development and roll-out has been overwhelmingly successful in reducing infections and deaths. However, case reports have emerged of a rare syndrome of vaccine-induced immune thrombocytopenia and thrombosis (VITT), as well as cases of immune thrombocytopenia (ITP). This has necessitated a better understanding of these conditions. However, as both VITT and "vaccine-associated ITP" are emerging conditions, evidence on the clinical features, epidemiology, and management is still evolving. Subsequently, with the initiation of the COVID-19 vaccine booster program, it has become increasingly important to continue to collect accurate data on post-COVID-19 vaccine complications to aid with their prompt recognition and management. In this case series, we report on the presentations and management of seven cases of post-COVID-19 vaccine-related immune-mediated complications which occurred at our center between the months of March and July 2021.

e-Cigarette Vapour Condensate Reduces Viability and Impairs Function of Human Osteoblasts, in Part, via a Nicotine Dependent Mechanism.

Cigarette consumption negatively impacts bone quality and is a risk-factor for the development of multiple bone associated disorders, due to the highly vascularised structure of bone being exposed to systemic factors. However, the impact on bone to electronic cigarette (e-cigarette) use, which contains high doses of nicotine and other compounds including flavouring chemicals, metal particulates and carbonyls, is poorly understood. Here, we present the first evidence demonstrating the impact of e-cigarette vapour condensate (replicating changes in e-cigarette liquid chemical structure that occur upon device usage), on human primary osteoblast viability and function. 24 h exposure of osteoblasts to e-cigarette vapour condensate, generated from either second or third generation devices, significantly reduced osteoblast viability in a dose dependent manner, with condensate generated from the more powerful third generation device having greater toxicity. This effect was mediated in-part by nicotine, since exposure to nicotine-free condensate of an equal concentration had a less toxic effect. The detrimental effect of e-cigarette vapour condensate on osteoblast viability was rescued by co-treatment with the antioxidant N-Acetyl-L-cysteine (NAC), indicating toxicity may also be driven by reactive species generated upon device usage. Finally, non-toxic doses of either second or third generation condensate significantly blunted osteoblast osteoprotegerin secretion after 24 h, which was sustained for up to 7 days. In summary we demonstrate that e-cigarette vapour condensate, generated from commonly used second and third generation devices, can significantly reduce osteoblast viability and impair osteoblast function, at physiologically relevant doses. These data highlight the need for further investigation to inform users of the potential risks of e-cigarette use on bone health, including, accelerating bone associated disease progression, impacting skeletal development in younger users and to advise patients following orthopaedic surgery, dental surgery, or injury to maximise bone healing.

Early Course of Symptom Development in Anorexia Nervosa.

PURPOSE: Anorexia nervosa (AN) commonly begins in adolescence; however, detailed knowledge of symptom trajectories, including their temporal sequence, is less well elucidated. The purpose of the present study is to describe the onset and duration of disordered eating behaviors prior to a diagnosis of AN, examine concordance between child and parent report, and examine the relationships between timing of symptom onset and illness severity. METHODS: Seventy-one adolescents (ages 12-18 years) and their parents were interviewed about dieting, restriction, loss of control/binge eating, purging, excessive/compulsive exercise, weight history, and amenorrhea. Body mass index percentiles were calculated, and adolescents completed the Eating Disorder Examination-Questionnaire. RESULTS: Restriction, being underweight, dieting, and excessive exercise were reported by most of the sample; purging, loss-of-control eating, and having been overweight were reported by less than a third. Dieting typically emerged first, on average around age 14; the remainder of behaviors tended to emerge between ages 14 and 14½; and average age of formal diagnosis was slightly over 15 years. Dyads had good agreement regarding presence and timing of all behaviors except for dieting, for which children reported about 6 months earlier onset/longer duration, compared to parents. Although older age at interview was associated with lower body mass index percentile and higher EDE-Q score, neither age of onset nor duration was associated with severity when controlling for current age. DISCUSSION: Teens and parents describe a similar sequence of behavior changes leading up to a diagnosis of AN that typically begins with dieting and occurs over an approximate 1- to 1½-year period. Querying teens and parents about eating behavior changes may aid in identification and early intervention in AN; adolescents with normal weight who engage in persistent dieting or restrictive eating may warrant more frequent weight monitoring.

Pure tone audiometry as assessed by a commercially-available mobile phone application compared to formal audiometry.

PURPOSE: Comparison of audiometric measurements of commercially available smartphone audiogram application thresholds as compared to gold standard audiometric evaluation. MATERIALS AND METHODS: A single-institution, original contribution. Ninety consecutive adult patients presenting to a tertiary care auditory clinic with auditory complaints were evaluated using standard audiometric testing and an application-based hearing test. Correlation between app results and standard audiogram for air conduction pure tone thresholds was evaluated. RESULTS: Mimi™ (Berlin, Germany) results for audiometric thresholds were moderately correlated with standard audiogram (r = 0.51-0.68) depending on severity. The percentage of patients whose hearing loss severity on formal audiometry results were accurately reflected in the Mimi™ (app-based hearing test: ABHT)1 results ranged from 18.2 to 80 %. Among patients whose results were at the extremes of hearing performance, app and standard audiogram results were similar. ABHT yielded an overall sensitivity of 35.5 % and specificity of 97.1 % for normal hearing, and an overall sensitivity of 80 % and specificity of 96 % for severe hearing loss. CONCLUSIONS: Results from an audiometric smart phone application showed accurate categorization of hearing loss at the high and extremes as compared to standard audiometry. However, correlation of pure tone values was more variable and dependent on hearing level.

Strength in Numbers: The Promise of Community-Based Participatory Research in Rural Education.

Montana is a state that is ravaged by a suicide epidemic and mental health crisis, particularly among its youth. In an area in which harsh climates, geographic challenges, and distance to rural healthcare providers are significant barriers to mental healthcare accessibility, educators are faced with the acute social and emotional challenges of their students on a daily basis. This article documents the process and promise of utilizing novel and innovative community-based participatory research to support rural schools. By integrating a trauma-informed intervention in the school setting, while mobilizing local community resources, this interdisciplinary approach shows the ability to address the needs of adolescents while supporting rural educators.

Predicting the pulmonary effects of long-term e-cigarette use: are the clouds clearing?

Commercially available since 2007, e-cigarettes are a popular electronic delivery device of ever-growing complexity. Given their increasing use by ex-smokers, smokers and never-smokers, it is important to evaluate evidence of their potential pulmonary effects and predict effects of long-term use, since there has been insufficient time to study a chronic user cohort. It is crucial to evaluate indicators of harm seen in cigarette use, and those potentially unique to e-cigarette exposure. Evaluation must also account for the vast variation in e-cigarette devices (now including at least five generations of devices) and exposure methods used in vivo and in vitroThus far, short-term use cohort studies, combined with in vivo and in vitro models, have been used to probe for the effects of e-cigarette exposure. The effects and mechanisms identified, including dysregulated inflammation and decreased pathogen resistance, show concerning overlaps with the established effects of cigarette smoke exposure. Additionally, research has identified a signature of dysregulated lipid processing, which is unique to e-cigarette exposure.This review will evaluate the evidence of pulmonary effects of, and driving mechanisms behind, e-cigarette exposure, which have been highlighted in emerging literature, and highlight the gaps in current knowledge. Such a summary allows understanding of the ongoing debate into e-cigarette regulation, as well as prediction and potential mitigation of future problems surrounding e-cigarette use.

Restrictive eating across a spectrum from healthy to unhealthy: behavioral and neural mechanisms.

BACKGROUND: Restriction of food intake is a central feature of anorexia nervosa (AN) and other eating disorders, yet also occurs in the absence of psychopathology. The neural mechanisms of restrictive eating in health and disease are unclear. METHODS: This study examined behavioral and neural mechanisms associated with restrictive eating among individuals with and without eating disorders. Dietary restriction was examined in four groups of women (n = 110): healthy controls, dieting healthy controls, patients with subthreshold (non-low weight) AN, and patients with AN. A Food Choice Task was administered during fMRI scanning to examine neural activation associated with food choices, and a laboratory meal was conducted. RESULTS: Behavioral findings distinguished between healthy and ill participants. Healthy individuals, both dieting and non-dieting, chose significantly more high-fat foods than patients with AN or subthreshold AN. Among healthy individuals, choice was primarily influenced by tastiness, whereas, among both patient groups, healthiness played a larger role. Dorsal striatal activation associated with choice was most pronounced among individuals with AN and was significantly associated with selecting fewer high-fat choices in the task and lower caloric intake in the meal the following day. CONCLUSIONS: A continuous spectrum of behavior was suggested by the increasing amount of weight loss across groups. Yet, data from this Food Choice Task with fMRI suggest there is a behavioral distinction between illness and health, and that the neural mechanisms underlying food choice in AN are distinct. These behavioral and neural mechanisms of restrictive eating may be useful targets for treatment development.

Microaggression and the adult stuttering experience.

BACKGROUND: Microaggressions are subtle insults, invalidations, or slights that target people due to their association with a marginalized group. Microaggressive experiences have been shown to degrade quality of life and corroborate negative stereotypes towards persons with disabilities. To date, minimal research has been dedicated to exploring microaggressions within adults who stutter. METHODS: Seven adults who stutter participated in semi-structured focus group interviews similar to Keller and Galgay's (2010) qualitative investigation of microaggressions experienced by adults with a disability. Group interviews were transcribed and analyzed using QSR NVivo software to develop themes and subthemes. RESULTS: Eight major themes were identified within two supraordinate themes: Microaggressive Behavior (patronization, second-class status, perceived helplessness, workplace microaggression, clinical microaggression, denial of privacy) and Perception of Microaggressive Behavior (exoneration of listener, no or minimal microaggressive experience). Although patronization, second-class status, and helplessness were mentioned frequently by multiple participants, exoneration of the listener was the most frequently recurring theme. DISCUSSION: Based on these preliminary focus group interviews, stuttering-based microaggressions broadly resemble ableist microaggressions reported by Keller and Galgay (2010). Interviewees also expressed a reluctance to identify slights related to stuttering as microaggression and often characterized these incidents as unavoidable.