Temporal trends, 2000-2017, of perfluoroalkyl acid (PFAA) concentrations in serum of Swedish adolescents

Per- and polyfluoroalkyl substances (PFAS) have been extensively used as surfactants because of their high stability and good water/oil-repellent properties. PFASs, especially perfluoroalkyl acids (PFAAs), have long biological half-lives, and exposure may cause adverse health effects in humans. We assessed temporal trends of concentrations of eight PFAAs in serum of Swedish adolescents (age 16-21 years) from the general population, and estimated the stability of PFAAs and serum samples after 6 years of storage. Repeated cross-sectional sampling was performed on five occasions (covering in total 1213 individuals, 83% males) in southern Sweden between 2000 and 2017. We analyzed serum for perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) using liquid chromatography-tandem mass spectrometry. We assessed time trends using linear regression, long-term stability was assessed by reanalyzing samples collected 2013, and the comparison was done using Pearson correlation and Bland-Altman plots. PFHxS, PFOS, and PFOA decreased by 6.7% (CI: -7.0, -6.3%), 12.6% (CI: -12.9, -12.3%), and 6.5% (CI: -6.8, -6.1%) per year, respectively, and year of sampling explained 48-81% of the variation in concentrations. PFNA and PFDA seemed to increase up to 2009 and decrease thereafter. The trends were consistent after sensitivity analyses excluding women. Strong correlations of 94-97% were observed for concentrations of all compounds, except PFHxS, after storage. The observed trends closely followed the timing of manufacturers' voluntary phaseout initiatives, and of regulatory measures governing the compounds implemented in the EU and USA. This indicates that these actions mitigated the population's exposure to PFHxS, PFOS, and PFOA and, in recent years, to PFNA and PFDA, in southern Sweden. Furthermore, the results suggest that PFAAs remain stable in serum samples after long-term storage

Uneven distribution of ventilation in acute respiratory distress syndrome

INTRODUCTION: The aim of this study was to assess the volume of gas being poorly ventilated or non-ventilated within the lungs of patients treated with mechanical ventilation and suffering from acute respiratory distress syndrome (ARDS). METHODS: A prospective, descriptive study was performed of 25 sedated and paralysed ARDS patients, mechanically ventilated with a positive end-expiratory pressure (PEEP) of 5 cmH(2)O in a multidisciplinary intensive care unit of a tertiary university hospital. The volume of poorly ventilated or non-ventilated gas was assumed to correspond to a difference between the ventilated gas volume, determined as the end-expiratory lung volume by rebreathing of sulphur hexafluoride (EELV(SF6)), and the total gas volume, calculated from computed tomography images in the end-expiratory position (EELV(CT)). The methods used were validated by similar measurements in 20 healthy subjects in whom no poorly ventilated or non-ventilated gas is expected to be found. RESULTS: EELV(SF6 )was 66% of EELV(CT), corresponding to a mean difference of 0.71 litre. EELV(SF6 )and EELV(CT )were significantly correlated (r(2 )= 0.72; P < 0.001). In the healthy subjects, the two methods yielded almost identical results. CONCLUSION: About one-third of the total pulmonary gas volume seems poorly ventilated or non-ventilated in sedated and paralysed ARDS patients when mechanically ventilated with a PEEP of 5 cmH(2)O. Uneven distribution of ventilation due to airway closure and/or obstruction is likely to be involved

Determinants of maternal and fetal exposure and temporal trends of perfluorinated compounds.

In recent years, some perfluorinated compounds (PFCs) have been identified as potentially hazardous substances which are harmful to the environment and human health. According to limited data, PFC levels in humans could be influenced by several determinants. However, the findings are inconsistent. In the present study, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) were measured in paired maternal and cord serum samples (N = 237) collected between 1978 and 2001 in Southern Sweden to study the relationship between these and to investigate several potential determinants of maternal and fetal exposure to PFCs. Time trends of PFCs in Swedish women were also evaluated. The study is a part of the Fetal Environment and Neurodevelopment Disorders in Epidemiological Research project. PFOS, PFOA, and PFNA levels (median) were higher in maternal serum (15, 2.1, and 0.24 ng/ml, respectively) than in cord serum (6.5, 1.7, and 0.20 ng/ml, respectively). PFC levels were among the highest in women originating from the Nordic countries and the lowest in women from the Middle East, North Africa, and sub-Saharan Africa. Multiparous women had lower serum PFOA levels (1.7 ng/ml) than primiparous women (2.4 ng/ml). Maternal age, body mass index, cotinine levels, and whether women carried male or female fetuses did not affect serum PFC concentrations. Umbilical cord serum PFC concentrations showed roughly similar patterns as the maternal except for the gestational age where PFC levels increased with advancing gestational age. PFOS levels increased during the study period in native Swedish women. In summary, PFOS levels tend to increase while PFOA and PFNA levels were unchanged between 1978 and 2001 in our study population. Our results demonstrate that maternal country of origin, parity, and gestational age might be associated with PFC exposure

Intensive care diaries reduce new onset post traumatic stress disorder following critical illness: a randomised, controlled trial

INTRODUCTION: Patients recovering from critical illness have been shown to be at risk of developing Post Traumatic Stress disorder (PTSD). This study was to evaluate whether a prospectively collected diary of a patient's intensive care unit (ICU) stay when used during convalescence following critical illness will reduce the development of new onset PTSD. METHODS: Intensive care patients with an ICU stay of more than 72 hours were recruited to a randomised controlled trial examining the effect of a diary outlining the details of the patients ICU stay on the development of acute PTSD. The intervention patients received their ICU diary at 1 month following critical care discharge and the final assessment of the development of acute PTSD was made at 3 months. RESULTS: 352 patients were randomised to the study at 1 month. The incidence of new cases of PTSD was reduced in the intervention group compared to the control patients (5% versus 13%, P = 0.02). CONCLUSIONS: The provision of an ICU diary is effective in aiding psychological recovery and reducing the incidence of new PTSD.RACHEL GROUP in addition to the authors: Denmark, Christensen D, Bogø I, Hansen R, Kjerrumgård H, Mathiasen L, Hyldested C, Toft C, Nordsjaelland Hospital; Bagger C, Larsen MB, Frank de Jong L, Odense University Hospital; Ågård AS, Knudsen K, Hinzel T, Århus University Hospital, Skejby; Italy, Scaramuzza A &amp; Bertacchini S, Ferrara; Norway, Schou Landmark J, Salomonsen A, Tøien K, Walther S, Oslo University Hospital Ulleval; Muri AK, Haukeland University Hospital; Portugal, Neutel E, Gomes E, Cardoso T, Ferreira R, Machado C, Santos C, Pinto S, Hospital Santo António - Centro Hospitalar do Porto, Amaro A, Morujão E, Jerónimo A, Rodrigues T, Carvalho F, Silva A, Morais A Hospital Pedro Hispano; Sweden, Löwenmark U, Etemad W, Rosell E, Sahgrenska University Hospital; Carlson U, Wirbrand Holmquist A, Kungälv Hospital; Åkerman E, Ersson A, Malmö University Hospital; UK, Tobin C, Whiston.</p

Exposure to PCBs and p,p′-DDE and Human Sperm Chromatin Integrity

Persistent organochlorine pollutants (POPs) such as polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (p,p′-DDE), the major metabolite of dichlorodiphenyltrichloroethane (DDT), are stable lipophilic compounds widely found in the environment and in the general population. They can enter the food chain, and their negative impact on male reproduction is currently under active scrutiny. To explore the hypothesis that environmental exposure to these compounds is associated with altered sperm chromatin structure integrity in human sperm, we conducted a study of 176 Swedish fishermen (with low and high consumption of fatty fish, a very important exposure source of POPs). We determined serum levels of 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153) and p,p′-DDE, and we used the sperm chromatin structure assay (SCSA) to assess sperm DNA/chromatin integrity. When CB-153 serum levels (individual dose range, 39–1,460 ng/g lipid) were categorized into equally sized quintiles, we found an association with the DNA fragmentation index (%DFI). A significantly lower %DFI was found in the lowest CB-153 quintile (< 113 ng/g lipid) compared with the other quintiles; there was a similar tendency, although not statistically significant, between %DFI and p,p′-DDE. These results suggest that POP exposure may have a slight negative impact on human sperm chromatin integrity

System Identification and Tuning of Wireless Power Transfer Systems with Multiple Magnetically Coupled Resonators

We present a procedure for system identification and tuning of a wireless power transfer (WPT) system with four magnetically coupled resonators, where each resonator consists of a coil and a capacitor bank. The system-identification procedure involves three main steps: 1) individual measurement of the capacitor banks in the system; 2) measurement of the frequency-dependent two-port impedance matrix of the magnetically coupled resonators; and 3) determining the inductance of all coils and their corresponding coupling coefficients using a Bayesian approach. The Bayesian approach involves solving an optimization problem where we minimize the mismatch between the measured and simulated impedance matrix together with a penalization term that incorporates information from a direct measurement procedure of the inductance and losses of the coils. This identification procedure yields an accurate system model which we use to tune the four capacitance values to recover high system-performance and account for, e.g., manufacturing tolerances and coil displacement. For a prototype WPT system, we achieve 3.3 kW power transfer with 91 % system efficiency over an air-gap distance of approximately 20 cm

Comparison of four clinical risk scores in comatose patients after out-of-hospital cardiac arrest.

BACKGROUND AND AIMS Several different scoring systems for early risk stratification after out-of-hospital cardiac arrest have been developed, but few have been validated in large datasets. The aim of the present study was to compare the well-validated Out-of-hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP)-scores to the less complex MIRACLE2- and Target Temperature Management (TTM)-scores. METHODS This was a post-hoc analysis of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Missing data were handled by multiple imputation. The primary outcome was discriminatory performance assessed as the area under the receiver operating characteristics-curve (AUROC), with the outcome of interest being poor functional outcome or death (modified Rankin Scale 4-6) at 6 months after OHCA. RESULTS Data on functional outcome at 6 months were available for 1829 cases, which constituted the study population. The pooled AUROC for the MIRACLE2-score was 0.810 (95% CI 0.790 - 0.828), 0.835 (95% CI 0.816 - 0.852) for the TTM-score, 0.820 (95% CI 0.800 - 0.839) for the CAHP-score and 0.770 (95% CI 0.748 - 0.791) for the OHCA-score. At the cut-offs needed to achieve specificities >95%, sensitivities were <40 % for all four scoring systems. CONCLUSIONS The TTM-, MIRACLE2- and CAHP-scores are all capable of providing objective risk estimates accurate enough to be used as part of a holistic patient assessment after OHCA of a suspected cardiac origin. Due to its simplicity, the MIRACLE2-score could be a practical solution for both clinical application and risk stratification within trials

Pregnancy serum concentrations of perfluorinated alkyl substances and offspring behaviour and motor development at age 5-9 years--a prospective study

Background: In animal studies, perfluorinated alkyl substances affect growth and neuro-behavioural outcomes. Human epidemiological studies are sparse. The aim was to investigate the association between pregnancy serum concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) and offspring behaviour and motor development at 5-9 years of age. Methods: Maternal sera from the INUENDO cohort (2002-2004) comprising 1,106 mother-child pairs from Greenland, Kharkiv (Ukraine) and Warsaw (Poland) were analysed for PFOS and PFOA, using liquid-chromatography-tandem-mass-spectrometry. Exposures were grouped into country specific as well as pooled tertiles as well as being used as continuous variables for statistical analyses. Child motor development and behaviour at follow-up (2010-2012) were measured by the Developmental Coordination Disorder Questionnaire 2007 (DCDQ) and Strength and Difficulties Questionnaire (SDQ), respectively. Exposure-outcome associations were analysed by multiple logistic and linear regression analyses. Results: In the pooled analysis, odds ratio (OR) (95% confidence interval (CI)) for hyperactivity was 3.1 (1.3, 7.2) comparing children prenatally exposed to the highest PFOA tertile with those exposed to the lowest PFOA tertile. Comparing children in the highest PFOS tertile with those in the lowest PFOS tertile showed elevated but statistically non-significant OR of hyperactivity (OR (95% CI) 1.7 (0.9, 3.2)). In Greenland, elevated PFOS was associated with higher SDQ-total scores indicating more behavioural problems (beta (95% CI) = 1.0 (0.1, 2.0)) and elevated PFOA was associated with higher hyperactivity sub-scale scores indicating more hyperactive behaviour (beta (95% CI) = 0.5 (0.1, 0.9)). Prenatal PFOS and PFOA exposures were not associated with motor difficulties. Conclusions: Prenatal exposure to PFOS and PFOA may have a small to moderate effect on children's neuro-behavioural development, specifically in terms of hyperactive behaviour. The associations were strongest in Greenland where exposure contrast is largest

Reproductive Hormone Levels in Men Exposed to Persistent Organohalogen Pollutants: A Study of Inuit and Three European Cohorts

OBJECTIVE: Persistent organohalogen pollutant (POP) exposure may have a negative impact on reproductive function. The objective of this study was to assess the impact of POP exposure on the male hypothalamo–pituitary–gonadal axis. PARTICIPANTS: Participants included 184 Swedish fishermen and spouses of pregnant women from Greenland (n = 258), Warsaw, Poland (n = 113), and Kharkiv, Ukraine (n = 194). EVALUATIONS/MEASUREMENTS: Serum levels of 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p′-DDE) were determined in the four populations, showing different exposure patterns: Swedish fishermen, high CB-153/low p,p′-DDE; Greenland, high CB-153/high p,p′-DDE; Warsaw, low CB-153/moderate p,p′-DDE; Kharkiv, low CB-153/high p,p′-DDE. Serum was also analyzed for testosterone, estradiol, sex hormone-binding globulin (SHBG), inhibin B, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Free testosterone levels were calculated based on testosterone and SHBG. RESULTS: We found significant center-to-center variations in the associations between exposure and the outcomes. The most pronounced effects were observed in Kharkiv, where statistically significant positive associations were found between the levels of both CB-153 and p,p′-DDE and SHBG, as well as LH. In Greenland, there was a positive association between CB-153 exposure and LH. In the pooled data set from all four centers, there was positive association between p,p′-DDE and FSH levels [β = 1.1 IU/L; 95% confidence interval (CI), 1.0–1.1 IU/L]. The association between CB-153 levels and SHBG was of borderline statistical significance (β = 0.90 nmol/L; 95% CI, −0.04 to 1.9 nmol/L). CONCLUSIONS: Gonadotropin levels and SHBG seem to be affected by POP exposure, but the pattern of endocrine response is the subject of considerable geographic variation

Neuropsychological outcome after cardiac arrest: a prospective case control sub-study of the Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2)

Background: This study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA. Methods: This longitudinal multi-center clinical study is a sub-study of the TTM2-trial, in which a comprehensive neuropsychological examination is performed in addition to the main TTM2-trial neurocognitive screening. Approximately 7 and 24 months after OHCA, survivors at selected study sites are invited to a standardized assessment, including performance-based tests of cognition and questionnaires of emotional problems, fatigue, executive function and insomnia. At 1:1 ratio, a matched control group from a cohort of acute myocardial infarction (MI) patients is recruited to perform the same assessment. We aim to include 100 patients per group. Potential differences between the OHCA patients and the MI controls at 7 and 24 months will be analyzed with a linear regression, using composite z-scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions) as primary outcome measures. Results from OHCA survivors on the main TTM2-trial neurocognitive screening battery will be compared with neuropsychological test results at 7 months, using sensitivity and specificity analyses. Discussion: In this study we collect detailed information on cognitive impairment after OHCA and compare this to a control group of patients with acute MI. The validation of the TTM2 neurocognitive screening battery could justify its inclusion in routine follow-up. Our results may have a potential to impact on the design of future follow-up strategies and interventions after OHCA