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The EU chemicals strategy for sustainability (CSS) asserts that both human health and the environment are presently threatened and that further regulation is necessary. In a recent Guest Editorial, members of the German competent authority for risk assessment, the BfR, raised concerns about the scientific justification for this strategy. The complexity and interdependence of the networks of regulation of chemical substances have ensured that public health and wellbeing in the EU have continuously improved. A continuous process of improvement in consumer protection is clearly desirable but any initiative directed towards this objective must be based on scientific knowledge. It must not confound risk with other factors in determining policy. This conclusion is fully supported in the present Commentary including the request to improve both, data collection and the time-consuming and bureaucratic procedures that delay the publication of regulations.

This chapter focuses on the role of advanced practice providers (APPs) in the context of emergency telehealth by describing one of the first successful programs, started in 2003, at the University of Mississippi Medical Center (UMMC). Important issues germane to developing a program to provide telehealth supervision to APPs are covered. Specific concerns addressed by UMMC as the program was developed are described and generalized to the current health care environment. Major considerations regarding delivery models, contracts, technology, rationale for using APPs, regulatory concerns, and educational preparation are also discussed.

Sex workers, including female ones, have a higher risk of developing cancer and oral diseases due to the overlapping of risk factors. To characterize oral health status and healthcare practices and behaviors in female sex workers. Both quantitative and qualitative concomitant approaches were used. A closed-ended questionnaire, clinical examination, and semi-structured interview were administered, from July 2017 to August 2018, to 21 intentionally selected participants, in the city of Itajai, southern Brazil. Although the participants reported having good oral health and healthcare habits, some oral diseases and harmful habits were observed. Poor oral hygiene and habits such as smoking, alcohol, and illicit drug use were found. Most of the participants had undergone gynecological follow-up in the last 12 months. Qualitative analysis gave rise to six categories: Social aspects of working as a sex worker, Work routine, Sexual practices and behaviors and protection from sexually transmitted infections, Practices and behaviors (including unprotected sun exposure, smoking, and alcohol use at work), Use of illicit drugs at work, and General and oral health care and perceptions about their oral health. Oral health status of the participants was variable, and most of them smoked cigarettes, drank alcohol, and consumed illicit drugs at work. Preventive condom use was reported. Most of them underwent recent serological tests for sexual diseases and gynecological follow-up, incentivized by the community health workers that facilitate access to public services.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Summary Noninvasive investigations are increasingly being used in engineering projects. The application of these investigative techniques can assist in important steps, such as in the maintenance phase of the structure safety conditions. Ground penetrating radar (GPR) is an excellent non-destructive engineering research tool capable of assisting in the identification of various anomalies in a reinforced concrete structures or pavements. This work aims to evaluate the concrete reinforcement conditions of a large test tank with fitted windows on the front and right-side faces by conducting investigations using the GPR method. This tank has inner dimensions of 10.0m x 2.1m x 2.6m, which will be used to perform geotechnical tests. Through this technique it was possible to identify the positioning of the reinforcement inside the concrete walls of the tank, obtain the spacing, arrangement and depth of the embedded reinforcement, and map eventual void areas in the concrete without causing damage to the structure, helping the recovery and reinforcement works of the tank concrete structure. The interior of some structural elements, such as the floor slab around the tank and the reservoir concrete walls, were investigated. The data are presented in a 3D visualization model of the metal beams of the tank structure.

International audience; Although the need for non-animal alternatives has been well recognised for the human health hazard assessment of chemicals in general, it has become especially pressing for cosmetic ingredients due to the full implementation of testing and marketing bans on animal testing under the European Cosmetics Regulation. This means that for the safety assessment of cosmetics, the necessary safety data for both the ingredients and the finished product can be drawn from validated (or scientifically-valid), so-called "Replacement methods". In view of the challenges for safety assessment without recourse to animal test data, the Methodology Working Group of the Scientific Committee on Consumer Safety organised a workshop in February 2019 to discuss the key issues in regard to the use of animal-free alternative methods for the safety evaluation of cosmetic ingredients. This perspective article summarises the outcomes of this workshop and reflects on the state-of-the-art and possible way forward for the safety assessment of cosmetic ingredients for which no experimental animal data exist. The use and optimisation of "New Approach Methodology" that could be useful tools in the context of the "Next Generation Risk Assessment" and the strategic framework for safety assessment of cosmetics were discussed in depth.

In April 2015, a multistate outbreak of illness linked to synthetic cannabinoid (SC) use was unprecedented in magnitude and severity. We identified Mississippi cases in near-real time, collected information on cases to characterize the outbreak, and identified the causative SC.A case was defined as any patient of a Mississippi healthcare facility who was suspected of SC use and presenting with ≥2 of the following symptoms: sweating, severe agitation, or psychosis during April 2-May 3, 2015. Clinicians reported cases to the Mississippi Poison Control Center (MPCC). We used MPCC data to identify cases at the University of Mississippi Medical Center (UMMC) to characterize in further detail, including demographics and clinical findings. Biologic samples were tested for known and unknown SCs by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS).Clinicians reported 721 cases (11 deaths) statewide; 119 (17%) were UMMC patients with detailed data for further analysis. Twelve (10%) were admitted to an intensive care unit and 2 (2%) died. Aggression (32%), hypertension (33%), and tachycardia (42%) were common. SCs were identified in serum from 39/56 patients (70%); 33/39 patients (85%) tested positive for MAB-CHMINACA (N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide) or its metabolites. Compared to all patients tested for SCs, those positive for MAB-CHMINACA were more likely to have altered mental status on examination (OR = 3.3, p = .05).SC use can cause severe health effects. MAB-CHMINACA was the most commonly detected SC in this outbreak. As new SCs are created, new strategies to optimize surveillance and patient care are needed to address this evolving public health threat.

Copperhead (Agkistrodon contortrix) and cottonmouth or water moccasin (Agkistrodon piscivorus) snakes account for the majority of venomous snakebites in the southern United States. Cottonmouth snakes are generally considered to have more potent venom. Copperheads are considered less venomous and there is some controversy as to whether or not bites from copperhead snakes need to be treated with antivenom. Copperhead and juvenile cottonmouth snakes are both brown in color. The purpose of this study was to evaluate the accuracy of identification by the public and healthcare providers between these two species.Snakebite victims sometimes bring dead snakes to the hospital or have taken pictures of the snake. When this occurred, ED personnel were asked to take a picture of the snake, and forward the picture to the state poison control center. The identification of the snake by witnesses and/or hospital personnel was compared to the identification by the state herpetologist.During the study period, there were 286 cases of snakebites reported to the state poison control center. Pictures were obtained on 49 of the responsible snakes. All copperhead snakes were identified correctly by callers. However, only 21% of cottonmouth snakes were identified correctly, with 74% of cottonmouth snakes being identified as copperheads. Both public and medical personnel performed poorly on identification of cottonmouth snakes.Forty percent of the snakes identified as copperheads were actually cottonmouth snakes. Juvenile cottonmouth snakes were often identified as copperhead snakes.

Background We explored the combination of rilpivirine plus cobicistat-boosted darunavir [a two-drug regimen (2DR)] when switching from standard triple combined ART. Methods In this randomized, open-label, non-inferiority trial, participants had an HIV-RNA 6 months) three-drug regimen. The primary endpoint was proportion with HIV-RNA Results One hundred and sixty patients were allocated (1:1) to 2DR or to continue current ART (CAR). At Week 24, 72 (90.0%) of participants with 2DR and 75 (93.8%) with CAR maintained HIV-RNA 50 copies/mL (0% for 2DR; 3.7% for CAR; 95% CI = −0.4 to 7.9). Four patients reported adverse events not leading to treatment discontinuation (one patient in the 2DR group and three patients in the CAR group); eight subjects discontinued therapy in the 2DR group and three in the CAR group. With 2DR, lipid serum concentrations increased, but differences were statistically significant only for tenofovir disoproxil fumarate-containing CAR and in 2DR patients receiving a pre-switch regimen including tenofovir disoproxil fumarate. Median bone stiffness decreased in the CAR group from 86.1 g/cm2 (IQR = 74–98) to 83.2 g/cm2 (IQR = 74–97) and increased in the 2DR group from 84.9 g/cm2 (IQR = 74–103) to 85.5 g/cm2 (IQR = 74–101). The reduction within the CAR group was significant (P = 0.043). Conclusions Once-daily rilpivirine plus cobicistat-boosted darunavir is an effective 2DR that combines a high virological efficacy with a potential to avoid major NRTI toxicities.

Background: Polybactum (Effik International, Brussels, Belgium) is a vaginal mucoadhesive product (medical device) designed to form a film that acts as a mechanical barrier with the aim of inhibiting colonization by specific pathogens. It contains polycarbophil, a bioadhesive agent, and lauryl glucoside (LG), a nonionic surfactant that reinforces the barrier effect through its tensioactive properties. Objective: To assess the local safety profile, tolerability, and efficacy of Polybactum formulations. Methods: The following studies were performed on 3 Polybactum formulations: 2 ovules (Type 1: LG 0.04% and Type 2: LG 0.1%) and 1 gel formulation. Bacteriologic tests assessing the effects on normal vaginal flora and pathogens; in vitro and in vivo tests designed to assess cytotoxicity, as well as irritant and sensitizing potentials; biocompatibility, barrier, residence time, and absorption tests using reconstituted human vaginal epithelium were performed. Results: Polybactum is a selective bacteriostatic agent that is active against Streptococcus agalactiae and Gardnerella vaginalis while sparing normal vaginal flora; that is, Lactobacillus spp. It had no cytotoxic, irritant, and sensitizing effects nor did it impair barrier and fence functions of the vaginal epithelium. The Type 1 ovule showed film-forming properties in vitro. Finally, LG absorption through reconstituted human vaginal epithelium was negligible, ruling out the risk for possible systemic toxicity. Conclusions: This favorable preclinical profile is encouraging and supports clinical studies on Polybactum Type 1 ovules for the prevention and management of recurring bacterial vaginosis.

BACKGROUND: Many foods rich in antioxidant and anti-inflammatory compounds have been shown to increase health and reduce markers of aging. A number of berry fruits high in polyphenols are known to ameliorate age-related declines in cellular, cognitive and behavioral function in rats. OBJECTIVES: This study evaluated the effectiveness of a red raspberry-supplemented diet on age-sensitive measures of learning, memory and motor performance in aged (19 mo) F344 rats. METHODS: Red raspberry extract was prepared from fresh whole fruit and incorporated in standard rodent chow to create a 2% diet. Following ten weeks on a control or 2% raspberry diet, cognitive and motor performance was assessed using the Morris Water Maze (MWM) and a battery of five psychomotor tasks. RESULTS: The supplemented diet significantly improved performance on three of the five motor tasks, but did not affect MWM performance. Specifically, old rats fed the 2% raspberry diet had significantly better performance on the rod and plank walks, which measure psychomotor coordination and balance, and on the inclined screen, which measures muscle tone, strength, stamina and balance. CONCLUSIONS: Given that falls are the number one health hazard for otherwise healthy older adults, these results may have important implications for increasing healthy aging.

Based on the new information provided by the Applicant, the SCCS considers the use of Hydroxyethoxyphenyl Butanone (HEPB) as a cosmetic preservative in rinse-off, oral care and leave-on cosmetic products with a maximum concentration of 0.7% safe with regard to eye irritation.

This paper describes the development and characterization of a Δ E-TOF detector composed of a plastic scintillator bar coupled at both ends to silicon photomultipliers. This detector is a prototype of a larger version which will be used in the FOOT (FragmentatiOn Of Target) experiment to identify the fragments produced by ion beams accelerated onto a hydrogen-enriched target. The final Δ E-TOF detector will be composed of two layers of plastic scintillator bars with orthogonal orientation and will measure, for each crossing fragment, the energy deposited in the plastic scintillator ( Δ E), the time of flight (TOF), and the coordinates of the interaction position in the scintillator. To meet the FOOT experimental requirements, the detector should have energy resolution of a few percents and time resolution of 70 ps, and it should allow to discriminate multiple fragments belonging to the same event. To evaluate the achievable performances, the detector prototype was irradiated with protons of kinetic energy in the 70–230 MeV range and interacting at several positions along the bar. The measured energy resolution σ Δ E ∕ Δ E was 6–14%, after subtracting the fluctuations of the deposited energy. A time resolution σ between 120 and 180 ps was obtained with respect to a trigger detector. A spatial resolution σ of 1.9 cm was obtained for protons interacting at the center of the bar.

FOOT (FragmentatiOn On Target) is an applied nuclear physics experiment aimed at measuring the production cross sections of fragments for energies, beams and targets relevant in particle therapy and radioprotection in space. The Δ E-TOF detector will measure the energy deposited by the fragments in a wall of plastic scintillators and the time of flight with respect to a start detector. These two quantities allow to determine the charge Z of the fragment. In this work, we summarize the charge identification procedure of a detector prototype with two scintillator modules.

We present the design and experimental demonstration of a 16-channel frequency domain multiplexing (FDM) readout for transition-edge sensor (TES) bolometers. This readout system is going to be implemented on the LSPE/SWIPE balloon-borne experiment, whose goal is to detect the polarization of cosmic microwave background (CMB) at large angular scales and whose launch is scheduled for December 2019. We describe the fabrication process of the Niobium superconducting inductors and the qualification tests performed in our 300 mK cryogenic facility in INFN Pisa of the boomerang shaped PCBs hosting the LC chains and the gradiometric SQUIDs, which are going to be mounted on the back of the SWIPE focal planes. The development of the warm readout electronics is presented, together with the firmware for the generation and readout of the biasing frequency comb.

Evidence suggests that flavonoids, polyphenolic compounds found in many plant-derived foods, such as berries, may allay cognitive impairment. We review recent research exploring the protective effects of flavonoids on age-related cognitive decline and neurodegenerative disorders in humans and animals. We also address the mechanisms by which flavonoids may exert their effects and promising avenues of future research. Flavonoids have been found to decrease neuroinflammation, reduce oxidative stress, and mediate neuroplasticity in animal models of neurodegeneration and aging. Injecting flavonoids encased in metal nanoparticles may further enhance the efficacy of flavonoids. Animal studies also demonstrate that flavonoid supplementation may alleviate neurodegenerative cognitive and memory impairments. Limited human studies, however, demonstrate the need for further clinical research investigating flavonoids. Flavonoid supplementation, as well as dietary modification to include whole foods high in flavonoids, may provide therapeutic potential for aging individuals experiencing cognitive deficits resulting from neurodegeneration.

Background/Objectives:Fatty acids are hypothesized to influence cardiovascular disease risk because of their effect on inflammation. The aim of this study is to assess the relationship between whole-blood fatty acids (WBFAs) and high-sensitivity C-reactive protein (hs-CRP) in European children.Subjects/Methods:A total of 1401 subjects (697 boys and 704 girls) aged between 2 and 9 years from the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects in Children and infantS) study were measured in this cross-sectional analysis. The sample was divided into three categories of hs-CRP. Associations between WBFA and hs-CRP were assessed by logistic regression models adjusting for body mass index (BMI), country, age, breastfeeding, mother's education and hours of physical activity.Results:Linoleic acid (LA) (P=0.013, 95% confidence interval (CI): 0.822-0.977) and sum of n-6 WBFA (P=0.029, 95% CI: 0.866-0.992) concentrations were associated with lower concentrations of hs-CRP in boys. In girls, a high ratio of eicosapentaenoic acid (EPA)/arachidonic acid (AA) was associated (P=0.018, 95% CI: 0.892-0.989) with lower hs-CRP concentrations. In contrast, sum of blood n-6 highly unsaturated fatty acids (P=0.012, 95% CI: 1.031-1.284), AA (P=0.007, 95% CI: 1.053-1.395) and AA/LA ratio (P=0.005, 95% CI: 1.102-1.703) were associated (P

For the phase II of MEG, we are going to develop a combined trigger and DAQ system. Here we focus on the former side, which operates an on-line reconstruction of detector signals and event selection within 450 μs from event occurrence. Trigger concentrator boards (TCB) are under development to gather data from different crates, each connected to a set of detector channels, to accomplish higher-level algorithms to issue a trigger in the case of a candidate signal event. We describe the major features of the new system, in comparison with phase I, as well as its performances in terms of selection efficiency and background rejection.

The FOXFIRE project (Feasibility Of a Xenon detector with Front-end for Ionization Real-time Extraction) aims at the realization of a Liquid Xenon TPC optimized for high rate particle physics experiments, in particular in the field of rare event searches, with particles in the 10–100 MeV energy range. Liquid Xenon has several attractive properties to be exploited resulting in superior time and energy resolution, by using the scintillation light readout with suitable photo-detectors. A novel approach with a complementary TPC readout scheme can improve the space resolution to a level of a few hundred microns. We are studying both the feasibility of a light readout with higher granularity by means of Silicon PhotoMultipliers optimized for the Xenon emission spectrum as well as on an innovative micro-fabricated device capable of charge multiplication in liquid phase. The detector will be equipped with a readout electronics capable of online reconstruction of events, allowing the detector to sustain a high rate of interactions.

Some recent EU Regulations have focused on the potential risks posed by the presence of endocrine disrupters (ED) into the environment. However there are conflicting opinions on how to assess the risk from exposure to these molecules that can reversibly modulate hormonal activity, endocrine active substances (EAS) rather than causing irreversible damage (ED). The present paper attempts to discuss that perturbation of normal endocrine homeostasis in itself may not be an adverse effect, since the endocrine system is naturally dynamic and responsive to various stimuli as part of its normal function and it is modulated according to the characteristic trend of the dose-response curve. EDs should be evaluated using a weight-of-evidence (WoE) approach. If a chemical meets the criteria to be defined as an ED in experimental animals, the relevance of observed effects to the human then needs to be addressed. Hazard-based risk management is therefore not justified since does not meet the criteria for a sound scientifically based assessment.

BACKGROUND/OBJECTIVES: Blood polyunsaturated fatty acids (PUFA) are involved in allergy development, but the etiological role of n-6 and n-3 PUFA is still controversial. A European multicenter study of children (IDEFICS) provided the opportunity to explore the cross-sectional association between fatty acids (FA) and allergy. SUBJECTS/METHODS: Blood FA levels were measured in 2600 children aged 2-9 years and were recorded as the percentage of weight of all FA detected. Logistic regression of allergy status on FA components was adjusted for age, sex, country, body mass index, family history of allergic disease, breast-feeding, and number of siblings. The results were given as odds ratios (OR) for current vs no allergy ever and an increase in FA by 1 s.d. RESULTS: Overall, higher proportions of n-6 PUFA were associated with higher odds of allergy (OR = 1.21 (1.05, 1.40)). Monounsaturated FA (MUFA) were associated with reduced risk for allergy (OR = 0.75 (0.65, 0.87)), whereas saturated FA did not differ by allergy status. The strongest associations were observed in children o4 years old, with ORs of allergy given as 1.62 (1.15, 2.29) for n-3 PUFA and 0.63 (0.42, 0.95) for MUFA. With regard to individual FA, these associations were independently observed for docosapentaenoic acid (22:5 n-3) and oleic acid (18:1 n-9). CONCLUSIONS: Both PUFA subtypes were positively associated with allergy in an age-dependent manner, whereas MUFA was associated with less allergy. The observation of high proportions of n-3 PUFA in allergic children younger than 4 years might help to understand the nature of early onset of atopic disease.

Item does not contain fulltext Following its inception in 1994, the certification of European Registered Toxicologists (ERT) by EUROTOX has been recognized as ensuring professional competence as well as scientific integrity and credibility. Criteria and procedures for registration are contained in the ERT "Guidelines for Registration 2012". The register of ERT currently has over 1900 members. In order to continue the harmonisation of requirements and processes between national registering bodies as a prerequisite for official recognition of the ERT title as a standard, and to take account of recent developments in toxicology, an update of the ERT Guidelines has been prepared in a series of workshops by the EUROTOX subcommittees for education and registration, in consultation with representatives of national toxicology societies and registers. The update includes details of topics and learning outcomes for theoretical training, and how these can be assessed. The importance of continuing professional development as the cornerstone of re-registration is emphasised. To help with the process of harmonisation, it is necessary to collate and share best practices of registration conditions and procedures across Europe. Importantly, this information can also be used to audit compliance with the EUROTOX standards. As recognition of professionals in toxicology, including specialist qualifications, is becoming more important than ever, we believe that this can best be achieved based on the steps for harmonisation outlined here together with the proposed new Guidelines.

Introduction Timely, appropriate intervention is key to improving outcomes in many emergent conditions. In rural areas, it is particularly challenging to assure quality, timely emergency care. The TelEmergency (TE) program, which utilizes a dual nurse practitioner and emergency medicine-trained, board-certified physician model, has the potential to improve access to quality emergency care in rural areas. The objective of this study was to examine how the implementation of the TE program impacts rural hospital Emergency Department (ED) operations. Methods Methods included a before and after study of the effect of the TE program on participating rural hospitals between January 2007 and December 2008. Data on ED and hospital operations were collected one year prior to and one year following the implementation of TE. Data from participating hospitals were combined and compared for the two time periods. Results Nine hospitals met criteria for inclusion and participated in the study. Total ED volumes did not significantly change with TE implementation, but ED admissions to the same rural hospital significantly increased following TE implementation (6.7% to 8.1%, p-value = 0.02). Likewise, discharge rates from the ED declined post-initiation (87.1% to 80.0%, p-value = 0.003). ED deaths and transfer rates showed no significant change, while the rate of patient discharge against medical advice significantly increased with TE use. Discussion In this analysis, we found a significant increase in the rate of ED admissions to rural hospitals with TE use. These findings may have important implications for the quality of emergency care in rural areas and the sustainability of rural hospitals’ EDs.

Today, only a limited number of training courses specifically in human health risk assessment are available in Europe and although some basic training in health risk assessment is part of most toxicology university programmes, the preparation is often not enough. The purpose of this commentary is to present provision of training program in risk assessment based on common European criteria, easily adopted by institutions across Europe and focusing on risk assessment methodology and procedure. It is worth mentioning that the following paper does not deal with microbiological risk assessment and ecotoxicological risk assessment but mainly with chemical risk assessment. The project focuses on understanding the profile and training requirements of risk assessors in order to design a modular training program covering a range of disciplines in risk assessment and providing a model to establish guidelines for the training and recognition of risk assessors in accordance to a well-defined and properly acknowledged training standard.

When a disaster occurs, what you learned in drills may not actually be much help. Circumstances may be more complex than practiced, key designated officials may be missing, and everyone must assume new roles for which they may not be prepared. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.

This article describes results obtained by testing the European Food Safety Authority-tiered guidance approach for safety assessment of botanicals and botanical preparations intended for use in food supplements. Main conclusions emerging are as follows. (i) Botanical ingredients must be identified by their scientific (binomial) name, in most cases down to the subspecies level or lower. (ii) Adequate characterization and description of the botanical parts and preparation methodology used is needed. Safety of a botanical ingredient cannot be assumed only relying on the long-term safe use of other preparations of the same botanical. (iii) Because of possible adulterations, misclassifications, replacements or falsifications, and restorations, establishment of adequate quality control is necessary. (iv) The strength of the evidence underlying concerns over a botanical ingredient should be included in the safety assessment. (v) The matrix effect should be taken into account in the safety assessment on a case-by-case basis. (vi) Adequate data and methods for appropriate exposure assessment are often missing. (vii) Safety regulations concerning toxic contaminants have to be complied with. The application of the guidance approach can result in the conclusion that safety can be presumed, that the botanical ingredient is of safety concern, or that further data are needed to assess safety.

Objective: To study the effects of maternal smoking on the status of long-chain polyunsaturated fatty acids (LCPUFA) in infants’ whole-blood lipids. Design: A case-control matched study planned on the basis of preliminary observations. Setting: Maternity ward. Patients: A total of 159 healthy, term, breastfed infants with weight appropriate for gestational age, subdivided (53 per group) into those born to non-smokers (reference), smokers (⩾5 cigarettes per day) who either stopped within the first trimester of pregnancy (early smokers) or who continued througout pregnancy (late smokers). Interventions: The fatty acid profile of 4-day-old infants was determined on whole blood. Results: Higher levels of linoleic (LA) and alpha-linolenic acid (ALA) and lower levels of the metabolic products di-homo-gammalinolenic (DHGLA) and arachidonic (AA), of the n-6 series, and docosahexaenoic acid (DHA), of the n-3 series, were found in infants born to late smokers compared with the reference group. The DHGLA/LA and AA/DHGLA ratios in the n-6 series and DHA/ALA in the n-3 series, which are indices of the metabolic processes in LCPUFA synthesis, were lower in infants born to smokers compared with those born to non-smokers. Infants born to early smokers showed n-6 PUFA levels and ratios similar to references and n-3 parameters closer to those born to late smokers. No dietary differences were found among the three groups of mothers. All the independent associations with smoking persisted after adjustment for maternal covariates. Pre-pregnancy body weight, which is lower in late smokers compared with non-smokers, independently correlated with LCPUFA levels in both series. Conclusions: Maternal smoking is associated with a reduction in LCPUFA pools in infants, which might have structural and functional consequences.

Staphylococcus aureus is the main pathogen responsible for bone and joint infections worldwide and is also capable of causing pneumonia and other invasive severe diseases. Panton-Valentine leukocidin (PVL) and methicillin-resistant S. aureus (MRSA) have been studied as factors related with severity in these infections. The aims of this study were to describe invasive community-acquired S. aureus (CA-SA) infections and to analyse factors related to severity of disease. Paediatric patients (aged 0-16 years) who had a CA-SA invasive infection were prospectively recruited from 13 centres in 7 European countries. Demographic, clinical and microbiological data were collected. Severe infection was defined as invasive infection leading to death or admission to intensive care due to haemodynamic instability or respiratory failure. A total of 152 children (88 boys) were included. The median age was 7.2 years (interquartile range, 1.3-11.9). Twenty-six (17%) of the 152 patients had a severe infection, including 3 deaths (2%). Prevalence of PVL-positive CA-SA infections was 18.6%, and 7.8% of the isolates were MRSA. The multivariate analysis identified pneumonia (adjusted odds ratio (aOR) 13.39 (95% confidence interval (CI) 4.11-43.56); p 0.008), leukopenia at admission (

A public appeal has been advanced by a large group of scientists, concerned that science has been misused in attempting to quantify and regulate unmeasurable hazards and risks.1 The appeal recalls that science is unable to evaluate hazards that cannot be measured, and that science in such cases should not be invoked to justify risk assessments in health, safety and environmental regulations. The appeal also notes that most national and international statutes delineating the discretion of regulators are ambiguous about what rules of evidence ought to apply. Those statutes should be revised to ensure that the evidence for regulatory action is grounded on the standards of the scientific method, whenever feasible. When independent scientific evidence is not possible, policies and regulations should be informed by publicly debated trade-offs between socially desirable uses and social perceptions of affordable precaution. This article explores the premises, implications and actions supporting the appeal and its objectives.

Drift chambers operated with helium-based gas mixtures represent a common solution for tracking charged particles keeping the material budget in the sensitive volume to a minimum. The drawback of this solution is the worsening of the spatial resolution due to primary ionisation fluctuations, which is a limiting factor for high granularity drift chambers like the MEG II tracker. We report on the measurements performed on three different prototypes of the MEG II drift chamber aimed at determining the achievable single-hit resolution. The prototypes were operated with helium/isobutane gas mixtures and exposed to cosmic rays, electron beams and radioactive sources. Direct measurements of the single hit resolution performed with an external tracker returned a value of 110 $\mu$m, consistent with the values obtained with indirect measurements performed with the other prototypes., Comment: 18 pages, 18 figures

Background After the advent of ART, non-AIDS-related comorbidities are the main causes of death in HIV patients. Multiple biomarkers have been studied as markers of disease. We wanted to test soluble endothelial protein C receptor (sEPCR) in an HIV setting. Objectives The primary objective was to determine whether sEPCR decreases after 48 weeks of ART in naive HIV patients. Secondary objectives were to compare sEPCR levels between patients with chronic HIV infection (CHI) and primary HIV infection (PHI) and to analyse if there is a correlation between sEPCR and both immunovirological parameters and different markers of inflammation. Patients and methods We analysed sEPCR in 33 patients with CHI and 19 patients with PHI naive to ART. sEPCR was compared together with immunovirological parameters (HIV RNA and CD4 cell count) and IL-6 or D-dimer (DD). Results and conclusions After 48 weeks of ART, in CHI, the sEPCR decrease was significant (P = 0.0006) and sEPCR at baseline was correlated with both CD4 cell increase (r = +0.463, P = 0.007) and HIV RNA decrease (r = -0.363, P = 0.038). In PHI, sEPCR was stable (P = 0.35); there was a correlation between 48 week DD change and IL-6 change (r = +0.696, P = 0.0009) and also between 48 week DD change and sEPCR change (r = +0.553, P = 0.014). Despite the small sample size, we hypothesize that sEPCR levels reflect coagulant pathway activation caused by the endothelial damage during chronic infection more than a marker of the cytokine storm that occurs during PHI. Alternatively, in PHI, the link found between sEPCR and DD secondary to IL-6 suggests sEPCR is an indirect marker of inflammation.

Toxicology's evolution from a traditional science of poisons to an extensive discipline has introduced complications and ambiguity in the definition of a scientific area of qualification and training. The need to define toxicology and to identify and standardise the roles and the profiles of practising toxicologists in order to certify the professional credibility of toxicologists has been recognised by national registries and certifying boards across the USA, Europe and Asia. Established in 1994, the EUROTOX Model (www.eurotox.com) has promoted the harmonisation of educational differences, practical experiences and common visions and requirements for the accreditation of toxicologists in Europe. Such harmonisation should be seen as an indispensable step towards the mutual recognition of registered toxicologists at a global level and to promote the development of shared educational and training programmes on a regional basis. A description of typical professional roles for toxicologists with required educational background, training and experience are presented in this paper and serve as the basis for the ERT templates, a self-evaluation tool for individuals seeking ERT recognition.

We present 2 cases, one adult and one pediatric, of acute migraine headache promptly relieved by intravenous oxytocin. Both cases were typical flares of a chronic intermittent headache pattern with classic vascular symptoms. Pain relief in both cases was rapid and temporally related to oxytocin administration. Vascular headache pathophysiology and possible oxytocin mechanisms of action are discussed.

LaBr3(Ce) is a very attractive material due to its ultra high light output and its fast response, resulting in a good candidate as a crystal for a calorimeter able to provide simultaneously very high energy and timing performances. We report here a first test with a cylindrical 3 ″ × 3 ″ LaBr3(Ce) crystal coupled to PMT (Photonics XP53A2B), where we explore the detector performances at relative high energies, on the region of interest for future charged Lepton Flavor Violation (cLFV) experiments, using photons in the interval of 55 ÷ 83 MeV from π 0 decays up to 129 MeV from the radiative capture of negative pions on protons.

Industrialized countries are facing an increase of diseases attributable to an alteration of the immune system function, and concern is growing that this trend could be at least partially attributable to new and modified patterns of exposure to chemicals. Among chemicals matter of concern, pesticides can be included. The Authors have reviewed the existing evidence of pesticide immunotoxicity in humans, showing that existing data are inadequate to raise conclusions on the immunotoxic risk related to these compounds. The limits of existing studies are: poor knowledge on exposure levels, heterogeneity of the approach, and difficulty in giving a prognostic significance to the slight changes often observed. To overcome these limits, the Authors have proposed a tier approach, based on three steps: the first, addressed at pointing out a possible immunomodulation; the second, at refining the results and the third one, when needed, to finalize the study and to point out concordance with previous results. Studies should preferably be carried out through comparison of pre- and post-exposure findings in the same groups of subjects to be examined immediately after the end of the exposure. A simplification of the first step approach can be used by the occupational health physician and the occupational toxicologist. Conclusions on the prognostic significance of the slight changes often observed will be reached only by validating the hypothesis generated by field studies with an epidemiological approach. In this field, the most useful option is represented by longitudinal perspective studies.

Objectives: To estimate the prevalence of and identify risk factors for lipodystrophy syndrome (LS) and body fat abnormality in a population of HIV-infected children and adolescents. Design: Cross-sectional observational study. Methods: HIV-infected subjects aged 2-18 years were recruited from 15 HIV centers in Belgium Italy, and Poland between January 2007 and December 2008. Standardized assessments by the patient's long-term clinician were performed to establish the presence of abnormality. Risk factors were explored in logistic regression models for fat abnormality outcomes and LS (abnormality plus dyslipidemia). Results: Among 426 subjects (70% white), median age was 12.2 years (interquartile range: 9.0-15.0 years) and median duration of antiretroviral therapy was 5.2 years (interquartile range: 2.2-8.8 years). Prevalence was 57% (n = 235) for LS and 42% (n =176) for fat abnormality; 90 subjects with abnormality were affected in ≥3 locations. Lipoatrophy occurred in 28% (n =117) of subjects and lipohypertrophy in 27% (n = 115), most commonly in the face and trunk, respectively. In multivariable analysis, white ethnicity, body mass index, ritonavir/lopinavir, and nonnucleoside reverse transcriptase inhibitors were each associated with an increased risk of LS (P

Objective: To investigate the relation between maternal smoking habits, plasma lipids and milk fatty acid (FA) content and composition. Design: Breastfeeding mothers who gave birth to healthy, full-term infants were recruited. Mothers were interviewed on smoking habits, being defined smokers (S) when usually smoking at least five cigarettes per day before pregnancy. Setting: Department of Pediatrics, San Paolo Hospital, Milan, Italy. Subjects: In total, 92 mothers: 61 non-S (NS) and 31 S. Interventions: Pooled hindmilk was collected at the first raise of milk (colostrum stage), 1, 3 and 6 months, and total lipid (TL) content and fatty acid (FA) composition were evaluated. Maternal dietary habits were assessed by a food-frequency questionnaire. Two subsamples (16 NS, 6 S) were investigated after delivery and at 3 months for serum lipids and FA status. At 6 months after delivery, the number of mothers still breastfeeding decreased to 30. Variables were compared using nonparametric tests. Results: In smoking mothers serum levels of triglycerides, cholesterol and low-density lipoproteins were higher, while those of high-density lipoproteins were lower. TL content in breast milk was similar in the two groups just after delivery but higher in milk from NS at 1 month. TL content and FA absolute amounts of linoleic, arachidonic, α-linolenic and docosahexaenoic (DHA) acid in breast milk were lower in S vs NS 1 month after delivery. Also 3 months after delivery, the breast milk of smoking mothers contained less DHA than the breast milk of nonsmoking mothers. Conclusions: Maternal cigarette smoking in early pregnancy is associated with higher plasma lipid levels and lower milk TL and DHA content in the first months of lactation.

This paper is one of several prepared under the project "Food Safety In Europe: Risk Assessment of Chemicals in Food and Diet" (FOSIE), a European Commission Concerted Action Programme, organised by the International Life Sciences Institute, Europe (ILSI). The aim of the FOSIE project is to review the current state of the science of risk assessment of chemicals in food and diet, by consideration of the four stages of risk assessment, that is, hazard identification, hazard characterisation, exposure assessment and risk characterisation. The contribution of animal-based methods in toxicology to hazard identification of chemicals in food and diet is discussed. The importance of first applying existing technical and chemical knowledge to the design of safety testing programs for food chemicals is emphasised. There is consideration of the presently available and commonly used toxicity testing approaches and methodologies, including acute and repeated dose toxicity, reproductive and developmental toxicity, neurotoxicity, genotoxicity, carcinogenicity, immunotoxicity and food allergy. They are considered from the perspective of whether they are appropriate for assessing food chemicals and whether they are adequate to detect currently known or anticipated hazards from food. Gaps in knowledge and future research needs are identified; research on these could lead to improvements in the methods of hazard identification for food chemicals. The potential impact of some emerging techniques and toxicological issues on hazard identification for food chemicals, such as new measurement techniques, the use of transgenic animals, assessment of hormone balance and the possibilities for conducting studies in which common human diseases have been modelled, is also considered.

OBJECTIVES: To establish reference values for fatty acids (FA) especially for n-3 and n-6 long-chain polyunsaturated FAs (LC PUFA) in whole-blood samples from apparently healthy 3-8-year-old European children. The whole-blood FA composition was analysed and the age-and sex-specific distribution of FA was determined. DESIGN AND SUBJECTS: Blood samples for FA analysis were taken from 2661 children of the IDEFICS (identification and prevention of dietary-and lifestyle-induced health effects in children and infants) study cohort. Children with obesity (n = 454) and other diseases that are known to alter the FA composition (n = 450) were excluded leaving 1653 participants in the reference population. MEASUREMENTS: The FA composition of whole blood was analysed from blood drops by a rapid, validated gas chromatographic method. RESULTS: Pearson correlation coefficients showed an age-dependent increase of C18:2n-6 and a decrease of C18:1n-9 in a subsample of normal weight boys and girls. Other significant correlations with age were weak and only seen either in boys or in girls, whereas most of the FA did not show any age dependence. For age-dependent n-3 and n-6 PUFA as well as for other FA that are correlated with age (16:0, C18:0 and C18:1n-9) percentiles analysed with the general additive model for location scale and shape are presented. A higher median in boys than in girls was observed for C20:3n-6, C20:4n-6 and C22:4n-6. CONCLUSIONS: Given the reported associations between FA status and health-related outcome, the provision of FA reference ranges may be useful for the interpretation of the FA status of children in epidemiological and clinical studies.

Introduction: Air medical transport of high-risk obstetric (HROB) patients can be accomplished and advantageous for neonate survival and maternal morbidity. A survey of U.S. helicopter air medical programs was conducted to determine the frequency and current practices of HROB transport. Methods: Each program was contacted by telephone, and air medical personnel were asked to answer 12 questions based on personal experience and statistics compiled by their programs. Results: Of the 203 programs surveyed, 133 (66%) provided responses. The mean number of HROB transports was 45.6 per year (4.6% of the mean 995 total transports). Although 83% of the responding programs used the standard flight crew during the HROB transport, only 52% required crew members to maintain neonatal resuscitation certification. Only 56% of the aircraft allow pelvic access in the normal patient configuration. While only 22% of programs have specific HROB launch (dispatch) protocols, 50% reported having obstetricians involved in dispatching flights, and 84% carry tocolytic agents in their drug kit. The greatest concerns included in-flight delivery (60%), inadequate fetal monitoring (6%), and inexperience (5%). Conclusion: While HROBs account for 5% of air medical flights, many programs appear to be poorly prepared for these patients.

This study investigates the effect of chronic treatment with Fluvoxamine, a potent and specific serotonin reuptake sites inhibitor (SSRI), on 5HT(2) serotonin and D(2) dopamine receptors in the brain of drug naive unipolar depressed patients. Drug effect was evaluated in different cortical areas and in the basal ganglia by positron emission tomography (PET) and fluoroethyl-spiperone ([(18)F]FESP), an high affinity 5HT(2) serotonin and D(2) dopamine receptors antagonist. Patients underwent a PET study at recruitment and after clinical response to Fluvoxamine treatment. Nine of the 15 patients recruited completed the study. Fluvoxamine treatment significantly improved clinical symptoms and modified [(18)F]FESP binding in the frontal and occipital cortex of all of the nine patients who completed the study; in these regions a mean 31% increase in the in vivo [(18)F]FESP binding was found (P < 0.01). On the contrary, no significant changes in the in vivo [(18)F]FESP binding were found in the basal ganglia where [(18)F]FESP binds mainly to D(2) dopamine receptors. Chronic treatment with Fluvoxamine significantly increases the in vivo binding of [(18)F]FESP in the frontal and occipital cortex of drug naive unipolar depressed patients. The increase of the in vivo binding of [(18)F]FESP may reflect a modification in 5HT(2) binding capacity secondary to changes in cortical serotonin activity. (C) 2000 Academic Press.