Olfactory Dysfunction and Sinonasal Symptomatology in COVID-19: Prevalence, Severity, Timing, and Associated Characteristics.

OBJECTIVE: Olfactory dysfunction (OD)-hyposmia or anosmia-is a symptom of coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to better determine prevalence, severity, and timing of OD in COVID-19 relative to other sinonasal and pulmonary symptoms. STUDY DESIGN: Prospective, cross-sectional. SETTING: Regional/cantonal hospital. SUBJECTS: In total, 103 patients diagnosed with COVID-19 with reverse transcription polymerase chain reaction (RT-PCR)-based testing. METHODS: All patients testing positive for COVID-19 at Kantonsspital Aarau over a 6-week period were approached. Timing and severity (at its worst, on scale of 0 [none], 1 [mild], 2 [moderate], and 3 [severe]) of OD, loss of taste, nasal obstruction, rhinorrhea/mucus production, fever, cough and shortness of breath (SOB) were assessed for each patient. RESULTS: Prevalence of OD was 61.2%, and severity of OD was strongly correlated with severity of loss of taste experienced (ρ = 0.87, P < .001). OD was experienced on the first day of COVID-19 by 8.7% and overall occurred at median infection day 3 (mean, 3.4; range, 0-12). Most experiencing OD reported anosmia, and mean severity of all with OD was moderate to severe (mean [SD], 2.7 [0.6]). Nasal obstruction (49.5%) and rhinorrhea (35.0%) were frequently reported but not correlated with OD. SOB was more severe in patients with OD. OD was associated negatively with older age (OR, 0.96; 95% CI, 0.93-0.99; P = .007) and positively with female sex (OR, 2.46; 95% CI, 0.98-6.19; P = .056). CONCLUSIONS: OD is highly prevalent during COVID-19, occurring early and severely, often in conjunction with loss of taste. OD is associated negatively with older age and positively with female sex. Patients with OD may also experience more severe SOB.

CORRELATIONS between Functional and Structural Tests Measured by Spectral Domain Optical Coherence Tomography in Severe Glaucoma.

Purpose: To evaluate the relationship between visual acuity, visual field and spectral domain optical coherence tomography (OCT) parameters, including retinal nerve fiber layer (RNFL), ganglion cell-internal plexiform layer (GC-IPL) thicknesses, and optic nerve head parameters in patients with severe glaucoma. Material and Methods: Patients with the diagnosis of severe glaucoma were recruited from the data gathered at our glaucoma department. A detailed ophthalmic examination was performed using the Standard Automated Perimetry (the 30-2 SITA standard program was used for VF testing). Cirrus EDI-OCT was used for peripapillary RNFL and GC-IPL thickness measurements. Optic nerve head parameters, including mean cup-to-disc (c/d) ratio, rim area, vertical c/d ratio, cup volume, were also measured by spectral domain OCT. Correlations between these structural parameters and functional parameters (visual acuity, VF parameters) were investigated. Results: Forty-one eyes of 34 patients with severe glaucoma were enrolled in this study. Correlations between BCVA and mean GC-IPL thickness (p = .03), superior GC-IPL thickness (p = .03), inferonasal GC-IPL thickness (p = .01), superonasal GC-IPL thickness (p = .01), superotemporal GC-IPL thickness (p = .04), and rim area (p = .00) were found to be positive statistically significant. There was also a positive statistically significant correlation between MD and inferotemporal GC-IPL thickness (p = .03). Negative statistically significant correlations were found between BCVA and mean c/d ratio (p = .00), vertical c/d ratio (p = .02) and cup volume (p = .00). Discussion: Mean, superior, inferonasal, superonasal, and superotemporal GC-IPL thicknesses and mean c/d ratio, vertical c/d ratio and cup volume were found to be correlated with BCVA in patients with severe glaucoma.

Prenatal dioxin exposure and neuropsychological functioning in the Seveso Second Generation Health Study.

BACKGROUND: Prenatal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure has been shown to alter sexual differentiation of the brain in animal models, impacting pubertal development, behavior, cortical dominance, and cognition. The effects of early life exposure to dioxin-like compounds on human neurodevelopment, however, are less clear and warrant further investigation. METHODS: The Seveso Women's Health Study (SWHS), initiated in 1996, is a well-characterized cohort of 981 Italian women who lived in proximity to an industrial accident in July 1976 that resulted in one of the highest residential TCDD exposures on record. In 2014-2016, we enrolled offspring born after the accident into the Seveso Second Generation Health Study. Children aged 7-17 years old (n = 161) completed a neuropsychological assessment spanning executive function and reverse learning (Wisconsin Card Sort), non-verbal intelligence (Raven's Progressive Matrices), attention and hyperactivity (Connor's Continuous Performance (CPT), and memory (Rey's Auditory Verbal Learning). We used multivariate regression with robust standard error estimates accounting for clustering of siblings to model the associations between these outcomes and prenatal exposure defined as TCDD measured in maternal serum collected soon after the explosion and estimated to pregnancy. RESULTS: The children (82 male, 79 female) averaged 13.1 (±2.9) years of age. Adjusting for covariates, a 10-fold increase in maternal serum TCDD was not adversely associated with reverse learning/set-shifting, memory, attention/impulsivity, or non-verbal intelligence. In sex-stratified models, prenatal TCDD was associated with more non-perseverative errors in boys but not in girls (pint = 0.04). TCDD was also associated with attention deficits on the CPT but only among children with the shortest breastfeeding histories. CONCLUSIONS: While overall, there were no significant associations, the observed differential neurotoxic sensitivities to TCDD by sex and lactation history may warrant confirmation in future studies.

The Seveso accident: A look at 40 years of health research and beyond.

A 1976 chemical factory explosion near Seveso, Italy exposed residents to high levels of 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD or dioxin). Dioxin is a known human carcinogen and potent endocrine disruptor. It is highly lipophilic and has a long half-life in humans. Much of what we know and can learn about the risks of dioxin exposure on human health arose from the tragic circumstances of Seveso. This review aims to describe the Seveso accident, summarize the results of 40 years of research on the health of the Seveso population since the accident, and discuss next-stage research on the health of Seveso residents, their children, and grandchildren.

Subclinical Hypothyroidism and the Risk of Cardiovascular Disease and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies.

OBJECTIVES: To determine the impact of subclinical hypothyroidism (SCH) on the risk of cardiovascular disease (CVD) and all-cause mortality, a comprehensive meta-analysis was performed according to the age or coexisting CVD risk status of the participants. METHODS: Studies regarding the association of SCH with all-cause mortality from PubMed and Embase databases were included. The pooled relative risk (RR) of CVD and all-cause mortality was calculated using the Mantel-Haenszel method. A subgroup analysis of participants with high CVD risk was conducted, including history of coronary, cerebral, or peripheral artery disease; dilated cardiomyopathy; heart failure; atrial fibrillation; venous thromboembolism; diabetes mellitus; or chronic kidney disease. RESULTS: In total, 35 eligible articles incorporating 555,530 participants were included. SCH was modestly associated with CVD and all-cause mortality (RR for CVD = 1.33 [confidence interval (CI) 1.14-1.54]; RR for all-cause mortality = 1.20 [CI 1.07-1.34]). However, the association was not observed in participants aged ≥65 years. Subgroup analysis showed that participants with SCH and high CVD risk showed a significantly higher risk of all-cause mortality (RR for CVD = 2.20 [CI 1.28-3.77]; RR for all-cause mortality = 1.66 [CI 1.41-1.94]), whereas those with SCH and low CVD risk did not. Additional subgroup analysis of six studies with a mean participant age of ≥65 years and high CVD risk showed a significant high risk of all-cause mortality in the SCH group (RR = 1.41 [CI 1.08-1.85]; I2 = 0%). CONCLUSIONS: SCH is associated with an increased CVD risk and all-cause mortality, particularly in participants with high CVD risk.

A comparative assessment of major international disasters: the need for exposure assessment, systematic emergency preparedness, and lifetime health care.

BACKGROUND: The disasters at Seveso, Three Mile Island, Bhopal, Chernobyl, the World Trade Center (WTC) and Fukushima had historic health and economic sequelae for large populations of workers, responders and community members. METHODS: Comparative data from these events were collected to derive indications for future preparedness. Information from the primary sources and a literature review addressed: i) exposure assessment; ii) exposed populations; iii) health surveillance; iv) follow-up and research outputs; v) observed physical and mental health effects; vi) treatment and benefits; and vii) outreach activities. RESULTS: Exposure assessment was conducted in Seveso, Chernobyl and Fukushima, although none benefited from a timely or systematic strategy, yielding immediate and sequential measurements after the disaster. Identification of exposed subjects was overall underestimated. Health surveillance, treatment and follow-up research were implemented in Seveso, Chernobyl, Fukushima, and at the WTC, mostly focusing on the workers and responders, and to a lesser extent on residents. Exposure-related physical and mental health consequences were identified, indicating the need for a long-term health care of the affected populations. Fukushima has generated the largest scientific output so far, followed by the WTCHP and Chernobyl. Benefits programs and active outreach figured prominently in only the WTC Health Program. The analysis of these programs yielded the following lessons: 1) Know who was there; 2) Have public health input to the disaster response; 3) Collect health and needs data rapidly; 4) Take care of the affected; 5) Emergency preparedness; 6) Data driven, needs assessment, advocacy. CONCLUSIONS: Given the long-lasting health consequences of natural and man-made disasters, health surveillance and treatment programs are critical for management of health conditions, and emergency preparedness plans are needed to prevent or minimize the impact of future threats.

Goniometric evaluation of the spinal sagittal curves in children and adolescents: A reliability study.

BACKGROUND: Gold standard for spine deformities assessment is X rays, but the procedure bears a risk of exposure. OBJECTIVE: To investigate intra-rater and inter-rater reliability of a pocket compass needle goniometer (IncliMed®, University of Padua) to non-invasively evaluate spine curves in children and adolescents. METHODS: Prospective reliability study in a paediatric population (mean age 12.5 years ± 2.5). Children with spine deformities (Scheuermann's or postural kyphosis, idiopathic scoliosis) and healthy controls were included. Two physician measured spinal curves with the surface goniometer IncliMed® within a temporal range of 10 minutes. Participants were re-tested after a mean of 28 days for the intra-rater study. Agreement limit and coefficient of repeatability were calculated according to the linear regression analysis; the Bland and Altman method was applied to obtain average of differences and standard error of the mean of the differences. RESULTS: One hundred and thirty-nine subjects participated to the inter-rater reliability assessment; 30 to the intra-rater reliability assessment. Inter-observer variability for IncliMed® measurements was ± 11° both for kyphosis and for lordosis. The intra-observer variability for kyphosis and lordosis measurements was ± 11° and ± 12°. CONCLUSIONS: IncliMed® is a reliable, non-invasive tool to screen and monitor spinal curves in paediatric populations.

Calcifications in the carotid siphon inversely associate with cognitive performance in stroke-free community dwellers living in rural Ecuador (The Atahualpa Project).

We aimed to assess whether carotid siphon calcifications (as seen on computed tomography) are associated with worse performance in the Montreal Cognitive Assessment in 584 stroke-free individuals living in rural Ecuador. Using mean Montreal Cognitive Assessment score of subjects with Grade 1 calcifications (23.1 ± 4.2) as the referent category, fully adjusted generalized linear models showed significant associations between severity of carotid siphon calcifications and cognitive performance (mean Montreal Cognitive Assessment scores: 20.2 ± 4.8 for Grade 2 (p = 0.004), 19.7 ± 5.3 for Grade 3 (p = 0.0001), and 18.8 ± 4.1 for Grade 4 (p = 0.02)). Predictive Montreal Cognitive Assessment score margins were higher in individuals with Grade 1 calcifications than in other groups. This study shows an inverse relationship between calcium content in the carotid siphon and cognitive performance in Amerindians.

Posttraumatic Stress Disorder Symptom Severity and Relationship Functioning Among Partnered Heterosexual and Lesbian Women Veterans.

PURPOSE: Few studies have examined associations of posttraumatic stress disorder (PTSD) and relationship satisfaction among women Veterans, and no research has explored these factors in lesbian women Veterans, a large subgroup that may have unique concerns. This study examined the link between PTSD and relationship satisfaction in partnered heterosexual and lesbian women Veterans and evaluated potential moderation by sexual orientation, partner support, and conflict. METHODS: Women Veterans (heterosexual n = 260; lesbian n = 128) were recruited nationally to complete a cross-sectional online survey. Multiple linear regression models were used to evaluate moderation, using two- and three-way interactions. RESULTS: Partner support moderated the association between PTSD symptoms and relationship satisfaction to a different degree for heterosexual and lesbian women Veterans, playing a more prominent role in this association for lesbian women. Specifically, for lesbians with low partner support, as PTSD symptoms worsened, relationship satisfaction decreased at a steeper rate than for heterosexual women with low partner support. On the other hand, for lesbians with high partner support, as PTSD symptoms worsened, relationship satisfaction decreased less sharply than for heterosexual women with high partner support. Degree of conflict was highly correlated with relationship satisfaction and also appeared to moderate these relations differently by sexual orientation. CONCLUSION: These findings suggest that women Veterans with PTSD experience impairments in their romantic relationships, which vary by sexual orientation, partner support, and conflict. Partner support and conflict may be important targets in assessment and therapy for women Veterans with PTSD, and especially so for sexual minorities.

Electrode Migration in Patients with Perimodiolar Cochlear Implant Electrodes.

Migration of a cochlear implant electrode is a hitherto uncommon complication. So far, array migration has only been observed in lateral wall electrodes. Between 1999 and 2014, a total of 27 patients received bilateral perimodiolar electrode arrays at our institution. The insertion depth angle was estimated on the initial postoperative scans and compared with the insertion depth angle of the postoperative scans performed after contralateral cochlear implantation. Seven (25.93%) patients were found to have an electrode array migration of more than 15°. Electrode migration in perimodiolar electrodes seems to be less frequent and to occur to a lower extent than in lateral wall electrodes. Electrode migration was clinically asymptomatic in all cases.

Deficiency of Factor VII activating protease alters the outcome of ischemic stroke in mice.

Factor VII activating protease (FSAP) is a circulating protease with a putative role in hemostasis, remodeling and inflammation. A polymorphism giving rise to low proteolytic activity has been associated with an increased risk of stroke and carotid stenosis. To date, no in vivo studies or mechanistic information is available to explain these results. Based on the polymorphism data we hypothesize that a lack of endogenous FSAP will increase the severity of stroke. Stroke was induced by applying thrombin in the middle cerebral artery in wild-type (WT) and FSAP(-/-) mice. Increased stroke volume and worsened neurological deficit were observed in FSAP(-/-) mice. Raised levels of FSAP protein were detected in the infarcted area of WT mice together with enhanced leukocyte infiltration and apoptosis in FSAP(-/-) mice. There was a concomitant increase in the activation of the NFκB pathway and decrease in expression of the PI3K/AKT pathway proteins. At a cellular level, FSAP increased cell survival and decreased apoptosis in primary cortical neurons and astrocytes exposed to tPA/NMDA excitotoxicity or oxygen glucose deprivation (OGD)/reoxygenation, respectively. This was mediated via the PI3K/AKT pathway with involvement of the protease activated receptor-1. To corroborate the human epidemiological data, which link FSAP with stroke, we now show that the lack of FSAP in mice worsens the outcome of stroke. In the absence of FSAP there was a stronger inflammatory response and lower cell survival due to insufficient activation of the PI3K/AKT pathway.

Serum dioxin concentrations and thyroid hormone levels in the Seveso Women's Health Study.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant. Although experimental evidence suggests that TCDD alters thyroid hormone levels in rodents, human data are inconsistent. In 1976, a trichlorophenol plant exploded in Seveso, Italy. Women living in highly exposed areas were followed through the Seveso Women's Health Study. TCDD concentrations were measured in 1976 (n = 981) and 1996 (n = 260), and levels of total thyroxine, free thyroxine, free triiodothyronine, and thyroid-stimulating hormone were measured in 1996 (n = 909) and 2008 (n = 724). We used conditional multiple linear regression and marginal structural models with inverse-probability-of-treatment weights to evaluate associations and causal effects. TCDD concentration in 1976 was inversely associated with total thyroxine level in 1996 but not in 2008. Associations were stronger among women who had been exposed before menarche. Among these women, associations between total thyroxine and concurrent 1996 TCDD were slightly weaker than those with 1976 TCDD. A model including both 1976 and 1996 measurements strengthened the relationship between 1976 TCDD and total thyroxine but drove the association with 1996 TCDD to the null. TCDD exposure was not associated with levels of other thyroid hormones. TCDD exposure, particularly exposure before menarche, may have enduring impacts on women's total thyroxine levels. Initial exposure appears to be more influential than remaining body burden.

The appropriate use of neuroimaging in the diagnostic work-up of dementia: an economic literature review and cost-effectiveness analysis.

BACKGROUND: Structural brain imaging is often performed to establish the underlying causes of dementia. However, recommendations differ as to who should receive neuroimaging and whether computed tomography (CT) or magnetic resonance imaging (MRI) should be used. OBJECTIVES: This study aimed to determine the cost-effectiveness in Ontario of offering structural imaging to all patients with mild to moderate dementia compared with offering it selectively according to guidelines from the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCC). We compared the cost-effectiveness of CT and MRI as first-line strategies. METHODS: We performed a systematic literature search (2000 to 2013) to identify cost-effectiveness studies of clinical prediction rules and structural imaging modalities. Studies were assessed for quality and applicability to Ontario. We also developed a model to evaluate the cost-effectiveness of clinical guidelines (image all versus according to CCC) and modalities (CT versus MRI). Transition probabilities, utilities, and costs were obtained from published literature or expert opinion. Results were expressed in terms of costs and quality adjusted life years (QALYs). RESULTS: No relevant cost-effectiveness analyses were identified in the published literature. According to the base-case results of our model, the most effective and cost-effective strategy is to image patients who meet CCC criteria with CT and to follow-up with MRI for suspected cases of space-occupying lesions (SOL). However, the results were sensitive to the specificity of MRI for detecting vascular causes of dementia. At a specificity of 64%, the most cost-effective strategy is CCC followed by MRI. LIMITATIONS: Studies used to estimate diagnostic accuracy were limited by a lack of a gold standard test for establishing the cause of dementia. The model does not include costs to patients and their families, nor does it account for patient preferences about diagnostic information. CONCLUSIONS: Given the relative prevalence of vascular dementia and SOLs, and the improvement in QALYs associated with treatment, the strategy with the greatest combined sensitivity (CCC with CT followed by MRI for patients with SOLs) results in the greatest number of QALYs and is the least costly. Due to limitations in the clinical data and challenges in the interpretation of this evidence, the model should be considered a framework for assessing uncertainty in the evidence base rather than providing definitive answers to the research questions.

Serum TCDD and TEQ concentrations among Seveso women, 20 years after the explosion.

The Seveso Women's Health Study (SWHS) is a historical cohort study of the female population residing near Seveso, Italy, on 10 July 1976, when a chemical explosion resulted in the highest known residential exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Individual TCDD concentration was measured in serum collected near the time of the explosion, and in 1996, we collected adequate blood for TCDD and total dioxin toxic equivalent (TEQ) measurement. Polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls were measured in 1996 serum for a sample (n=225, 23%) of the SWHS cohort and WHO 2005 TEQs were calculated. We examined characteristics that predict 1996 TCDD concentrations and estimated TCDD elimination half-life over the 20-year period since the explosion. Median lipid-adjusted TCDD and total TEQ concentrations in 1996 serum were 7.3 and 26.2 p.p.t., respectively. Initial 1976 TCDD and age at explosion were the strongest predictors of 1996 TCDD. The TCDD elimination half-life was 7.1 years for women older than 10 years in 1976, but was shorter in those who were younger. Twenty years after the explosion, TCDD concentrations in this SWHS sample, the majority of who were children in 1976, remain elevated relative to background. These data add to the limited data available on TCDD elimination half-life in children.

Comparison of choroidal thickness in patients with diabetes by spectral-domain optical coherence tomography.

PURPOSE: To evaluate choroidal thickness in diabetes patients using spectral-domain optical coherence tomography. METHODS: We examined 203 eyes of 203 diabetic participants and 48 eyes of 48 healthy controls. The choroidal thickness at the foveal lesion was measured by enhanced-depth imaging optical coherence tomography. The participants were grouped according to diabetic retinopathy grade: no diabetic change, mild-to-moderate or severe non-proliferative, or proliferative diabetic retinopathy. The study parameters included history, age, axial length, intraocular pressure, central retinal thickness, fasting glucose, and blood pressure. RESULTS: The subfoveal choroidal thickness was thinner in eyes with non-proliferative or proliferative diabetic retinopathy than in normal eyes (p < 0.01). However, there was no difference between eyes with non-proliferative and proliferative diabetic retinopathy or between eyes with no diabetic change and the controls. Eyes exhibiting macular edema showed no significant difference in choroidal thickness compared with eyes having normal macular contours. CONCLUSIONS: The central choroid is thinner when eyes show diabetic changes on the retina. However, the presence of diabetic macular edema or proliferative change is not associated with more pronounced choroidal thinning.

Methods and reproducibility of grading optimized digital color fundus photographs in the Age-Related Eye Disease Study 2 (AREDS2 Report Number 2).

PURPOSE: To establish continuity with the grading procedures and outcomes from the historical data of the Age-Related Eye Disease Study (AREDS), color photographic imaging and evaluation procedures for the assessment of age-related macular degeneration (AMD) were modified for digital imaging in the AREDS2. The reproducibility of the grading of index AMD lesion components and for the AREDS severity scale was tested at the AREDS2 reading center. METHODS: Digital color stereoscopic fundus photographs from 4203 AREDS2 subjects collected at baseline and annual follow-up visits were optimized for tonal balance and graded according to a standard protocol slightly modified from AREDS. The reproducibility of digital grading of AREDS2 images was assessed by reproducibility exercises, temporal drift (regrading a subset of baseline annually, n = 88), and contemporaneous masked regrading (ongoing, monthly regrade on 5% of submissions, n = 1335 eyes). RESULTS: In AREDS2, 91% and 96% of images received replicate grades within two steps of the baseline value on the AREDS severity scale for temporal drift and contemporaneous assessment, respectively (weighted Kappa of 0.73 and 0.76). Historical data for temporal drift in replicate gradings on the AREDS film-based images were 88% within two steps (weighted Kappa = 0.88). There was no difference in AREDS2-AREDS concordance for temporal drift (exact P = 0.57). CONCLUSIONS: Digital color grading has nearly the same reproducibility as historical film grading. There is substantial agreement for testing the predictive utility of the AREDS severity scale in AREDS2 as a clinical trial outcome. (ClinicalTrials.gov number, NCT00345176.)

Plasma levels of dioxins, furans, non-ortho-PCBs, and TEQs in the Seveso population 17 years after the accident.

BACKGROUND: The Seveso accident (Italy) in 1976 caused the contamination of a large population by 2,3,7,8-tetrachlorodibenzo-para-dioxin (2,3, 7,8-TCDD). The contaminated territory was divided into three zones: A (very high contamination), B (high contamination), and R (low contamination). We report here the plasma concentrations of seven polychlorinated dibenzo-para-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), four non-ortho-polychlorinated biphenyls PCBs (nPCBs), and Toxic Equivalencies (TEQs) in a sample of residents in the most polluted zones A and B and in a reference non-contaminated zone. METHODS: From December 1992 to March 1994, 62 individuals were randomly selected from the population living in zone A (No. =7) and B (No. =55). A sample of 59 subjects living in a surrounding non-contaminated area (non-ABR), frequency-matched by gender, age, and smoking history, was used as reference. All subjects were administered a questionnaire surveying demographic, lifestyle, medical history, and accident-related factors. We assayed plasma PCDD, PCDF, and nPCB concentrations by high-resolution gas chromatography/high resolution mass spectrometric (HRGC/HRMS) analysis, with results reported as pg/g of lipid, or parts per trillion (ppt). We calculated TEQs using the WHO 2005 Toxic Equivalency Factors (TEFs). RESULTS: We found elevated median levels of 2,3, 7,8-TCDD in plasma samples of subjects living in zone A (73.3 ppt) and zone B (12.4 ppt), compared with residents in the reference zone (5.5 ppt). In analyses adjusted for gender, age, smoking, and body mass index (BMI), none of the other congeners showed levels higher than reference in the contaminated zones. Compared with men, women showed higher levels (113%) of 2,3, 7,8-TCDD and a slight elevation (17%) of TEQ for the other congeners. Age was strongly positively associated with most congener levels; TEQs for PCDDs, PCDFs, and nPCBs showed respectively 12%, 24%, and 41% increases for every 10 years of age. Current smokers had lower (from -37% to -67%) TEQ levels than subjects who had never smoked. BMI was negatively associated with levels of a few congeners, but with no impact on TEQ values. CONCLUSIONS: The Seveso accident caused a severe exposure of the population to 2,3,7,8-TCDD only. None of the other congeners analyzed showed variation across zones. Age showed a strong positive association with TEQs for all classes of compounds (PCDDs, PCDFs, and nPCBs).

Whistleblowers: an essential resource for the sustainable prevention of risks in sociotechnical systems.

Our world of industry and technology has, over the years, has seen undeniable successes in terms of safety and reliability. But major catastrophes and dramatic accidents continue, even today, to cause major human and material losses and to threaten the environment with pollution on a massive scale. Could these disasters and these accidents have been foreseen and avoided? Would it have been possible to anticipate their occurrence by detecting signals of potential hazards? It is unsettling to notice, through retrospective analysis of such events, that warnings had been issued long before the catastrophe or accident took place. This raises several questions, which we will attempt to address in this paper. Why are whistleblowers often not listened to, threatened, or simply ignored? Why are their warnings viewed as "bad omens" instead of essential resources to ensure safety? Do whistleblowers stand idly by, or do they implement individual and collective strategies to make themselves heard? Which managerial and organizational conditions are conducive to developing empowerment in whistleblowers? Based on four case studies, we attempt to address these questions, and offer a first level of analysis and explanation by proposing and defining two new concepts: operative resilience and strategic resilience.