Patch testing with the European baseline series fragrance markers: a 2016 update.

BACKGROUND: Fragrance contact allergy is common and is currently screened for using the following European baseline series fragrance markers: fragrance mix (FM)I, FMII, Myroxylon pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde. OBJECTIVES: To investigate the validity of patch testing using these fragrance markers in detecting fragrance allergy to 26 individual fragrance substances for which cosmetic ingredient labelling is mandatory within the European Union. METHODS: We conducted a retrospective review of the patch test records of all patients with eczema who underwent testing using the European baseline series, extended with the individual fragrance substances during the period from 2015 to 2016. RESULTS: Overall, 359 patients (17·2%) reacted to one or more allergens from the labelled fragrance substance series and/or a fragrance marker from the European baseline series. The allergens that were positive with the greatest frequencies were oxidized linalool [n = 154; 7·4%, 95% confidence interval (CI) 6·3-8·6], oxidized limonene (n = 89; 4·3%, 95% CI 3·4-5·2) and Evernia furfuracea (n = 44; 2·1%, 95% CI 1·5-2·8). Of the 319 patients who reacted to any of the labelled fragrance substances, only 130 (40·8%) also reacted to a baseline series fragrance marker. The sensitivity of our history-taking for detecting fragrance allergy was 25·7%. CONCLUSIONS: Given the evolving trends in fragrance allergy, patch testing with FMI, FMII, M. pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde is no longer sufficient for screening for fragrance allergy.

A Tenuous Lunar Ionosphere in the Geomagnetic Tail.

We utilize measurements of electron plasma frequency oscillations made by the two-probe Acceleration, Reconnection, Turbulence, and Electrodynamics of Moon's Interaction with the Sun mission to investigate the charged particle density in the lunar environment as the Moon passes through the Earth's geomagnetic tail. We find that the Moon possesses a tenuous ionosphere with an average density of ~0.1-0.3 cm-3, present at least 50% of the time in the geomagnetic tail, primarily confined to within a few thousand kilometers of the dayside of the Moon. The day-night asymmetry and dawn-dusk symmetry of the observed plasma suggests that photoionization of a neutral exosphere with dawn-dusk symmetry produces the majority of the lunar-derived plasma. The lunar plasma density commonly exceeds the ambient plasma density in the tail, allowing the presence of the lunar ionosphere to appreciably perturb the local plasma environment.

A dynamic landscape of allergen associations in delayed-type cutaneous hypersensitivity.

BACKGROUND: Delayed-type hypersensitivity represents a significant clinical and public health challenge. Patients undergoing patch testing may exhibit positive reactions to more than one allergen. It is recognized that reactions to specific pairs of allergens are associated, reflecting a combination of exposure patterns and structural similarity. OBJECTIVES: To explore the influence of time of testing, age, sex and atopy status on allergen pair associations in a series of 45 110 consecutive patients tested over 30 years. METHODS: Patch test records of all patients undergoing testing with a modified European baseline series between 1985 and 2014 were retrieved from a database at St John's Institute of Dermatology. Reactions were read on days 2 and 4. For each allergen it was recorded whether the allergen was tested and whether the result was positive or negative. RESULTS: This is the largest reported study of patch test allergen pair relationships. Our analysis shows a high degree of variability in allergen pair associations. Rigorous statistical analysis reveals a large number of differences between groups, including a significant increase in the association between formaldehyde and multiple formaldehyde-releasing preservatives over the study period, in addition to pair associations with cobalt and formaldehyde-releasing preservatives. These were present to a significantly greater extent in men than in women. CONCLUSIONS: These observations extend our understanding of cutaneous allergy, with implications for both clinical practice and mechanisms of cutaneous hypersensitivity.

Photoemission and electrostatic potentials on the dayside lunar surface in the terrestrial magnetotail lobes.

Despite the need to accurately predict and assess the lunar electrostatic environment in all ambient conditions that the Moon encounters, photoemission and electrostatic potentials on the dayside lunar surface in the terrestrial magnetotail lobes remain poorly characterized. We study characteristics and variabilities of lunar photoelectron energy spectra by utilizing Acceleration, Reconnection, Turbulence, and Electrodynamics of the Moon's Interaction with the Sun (ARTEMIS) and Apollo measurements in combination with the Flare Irradiance Spectral Model (FISM). We confirm that the photoelectron spectral shapes are consistent between ARTEMIS and Apollo and that the photoelectron flux is linearly correlated with the FISM solar photon flux. We develop an observation-based model of lunar photoelectron energy distributions, thereby deriving the current balance surface potential. The model predicts that dayside lunar surface potentials in the tail lobes (typically tens of volts) could increase by a factor of 2 - 3 during strong solar flares.

A Review on the Potential Role of Basement Membrane Laminin in the Pathogenesis of Psoriasis.

We have previously reviewed alterations to basement membrane laminin in psoriasis and how disruption of this layer could lead to at least some of the pathological changes observed. We here postulate that basement membrane laminin is the key antigen in driving psoriasis, inducing a T cell-mediated autoimmune response. For laminin to be considered as the key autoantigen in psoriasis, it would be reasonable to expect the following to be demonstrable: (1) that autoantigens are present in psoriatic inflammation; (2) that basement membrane laminin is perturbed in involved and uninvolved skin, and that some of the pathological changes associated with psoriasis could be predicted as a sequel to this; (3) that disruption of the basement membrane is among the earliest events in the evolution of psoriatic lesions; (4) that as streptococcal pharyngitis is the most clearly defined event to trigger or exacerbate psoriasis, then a T cell-mediated autoimmune response to laminin should be anticipated as a potential sequelae to streptococcal pharyngitis; (5) that T cells in psoriasis can be shown to react to peptides with homology to laminin; (6) that HLACw6, as the most closely related gene associated with psoriasis and which is involved in antigen expression, should be preferentially expressed within lesional psoriasis towards the basement membrane, together with other proximal associated immune activity; and (7) that there is some association between antilaminin pemphigoid, a humorally mediated autoimmune disease to skin basement membrane laminin, and psoriasis. We here review the data relevant to each of these requirements.

T helper cell 2 immune skewing in pregnancy/early life: chemical exposure and the development of atopic disease and allergy.

During the last 50 years there has been a significant increase in Western societies of atopic disease and associated allergy. The balance between functional subpopulations of T helper cells (Th) determines the quality of the immune response provoked by antigen. One such subpopulation - Th2 cells - is associated with the production of IgE antibody and atopic allergy, whereas, Th1 cells antagonize IgE responses and the development of allergic disease. In seeking to provide a mechanistic basis for this increased prevalence of allergic disease, one proposal has been the 'hygiene hypothesis', which argues that in Westernized societies reduced exposure during early childhood to pathogenic microorganisms favours the development of atopic allergy. Pregnancy is normally associated with Th2 skewing, which persists for some months in the neonate before Th1/Th2 realignment occurs. In this review, we consider the immunophysiology of Th2 immune skewing during pregnancy. In particular, we explore the possibility that altered and increased patterns of exposure to certain chemicals have served to accentuate this normal Th2 skewing and therefore further promote the persistence of a Th2 bias in neonates. Furthermore, we propose that the more marked Th2 skewing observed in first pregnancy may, at least in part, explain the higher prevalence of atopic disease and allergy in the first born.

Ion temperature anisotropy across a magnetotail reconnection jet.

A significant fraction of the energy released by magnetotail reconnection appears to go into ion heating, but this heating is generally anisotropic. We examine ARTEMIS dual-spacecraft observations of a long-duration magnetotail exhaust generated by antiparallel reconnection in conjunction with particle-in-cell simulations, showing spatial variations in the anisotropy across the outflow far (>100di ) downstream of the X line. A consistent pattern is found in both the spacecraft data and the simulations: While the total temperature across the exhaust is rather constant, near the boundaries Ti,|| dominates. The plasma is well above the firehose threshold within patchy spatial regions at |BX |∈[0.1,0.5]B0, suggesting that the drive for the instability is strong and the instability is too weak to relax the anisotropy. At the midplane ( |BX|≲0.1B0), Ti,⊥>Ti,|| and ions undergo Speiser-like motion despite the large distance from the X line.

The multiple factors affecting the association between atopic dermatitis and contact sensitization.

Atopic dermatitis and allergic contact dermatitis are both common skin diseases having an immune pathogenesis. There has been considerable interest about their inter-relationships with regard to altered susceptibility. Recent investigations have shed new light on this important question, and in this article, we explore whether there is evidence that atopic dermatitis affects the risk of contact sensitization and allergic contact dermatitis. The use of topical products to treat xerotic and inflamed skin in atopic dermatitis often results in a higher prevalence of sensitization to, for example, fragrances and other ingredients in emollients. Moreover, the prevalence of metal allergy seems to be increased, probably due to compromised chelation of the metals in the stratum corneum of patients with atopic dermatitis. However, conversely, the T-helper cell 2 bias that characterizes immune responses in atopic dermatitis appears to lower the risk of contact sensitization compared to healthy controls. Based on these observations, we conclude that multiple factors affect the association between atopic dermatitis and contact sensitization, and that these need to be appreciated in the clinical management of atopic dermatitis patients.

The hapten-atopy hypothesis III: the potential role of airborne chemicals.

One explanation for the large increase in the prevalence of atopic disease in developed countries during the last 50 years is the 'hygiene hypothesis'. This proposes that a reduced exposure to pathogenic microorganisms at a key period(s) during development results in the maintenance or acquisition of an atopic phenotype. Alternatively, or additionally, we have postulated that increased exposure to chemicals generally, and to irritant/haptenic chemicals in particular, during critical windows of maternal pregnancy/early life have also contributed to changes in the prevalence of atopic disease. Having previously reviewed the potential roles of oral and cutaneous exposure to chemicals on the subsequent diagnosis of atopic disease, we here consider possible evidence of a role for exposure to airborne chemicals as a contributory factor in acquired susceptibility to atopic allergy. After controlling for known confounders, five specific maternal occupations during pregnancy have been implicated as being associated with subsequent atopic disease in the offspring. Each of these occupations is characterized by high and persistent exposure to airborne chemicals. High-level exposure to volatile organic compounds in the domestic environment, either during pregnancy or in early life, is also associated with development of childhood atopic disease. Similarly, sustained exposure to airborne chlorinated chemicals from swimming pools during childhood has been associated with the development of atopic allergy. A possible immunological basis for these associations is that exposure to certain airborne chemicals, even at low levels, can result in the delivery of 'danger' signals that, in turn, bias the immune response towards the selective induction or maintenance of preferential T helper 2-type immune responses consistent with the acquisition of allergic sensitization.

Acne, quorum sensing and danger.

Propionibacterium acnes is a ubiquitous skin commensal bacterium, which is normally well tolerated by the immune system in healthy human skin. However, there is increasing evidence to suggest a pivotal role for P. acnes in the inflammatory process underlying the acne pathogenesis. With its features of inflammation and pustulation, acne vulgaris resembles the skin's normal reaction to bacterial pathogens. P. acnes flourishes when sebum production increases in the follicles. Bacteria may undergo behavioural changes based on the surrounding bacterial population, a process called quorum sensing (QS). Evidence from in vitro studies suggests that QS enables P. acnes to upregulate its hydrolysis of sebum triglycerides by its bacterial lipases, secreting free fatty acids (FFAs) such as oleic, palmitic and lauric acids. These FFAs act as danger-associated molecular patterns (DAMPs), and activate Toll-like receptor (TLR)2 and TLR4, leading to selective T-helper (Th)-driven immunity, with subsequent expression of Th1/Th17-associated inflammatory cytokines. To our knowledge, there is currently no explanation as to what determines the shift of recognition by the immune system of P. acnes from being symbiotic to pathogenic. We present a novel hypothesis based on the essence of QS and DAMPs. P. acnes sends no or only 'safety' signals when present in 'controlled' quantities under commensal conditions, but becomes pathogenic and sends 'danger' signals via QS in the form of excess FFA production, which stimulates TLR2 and TLR4 as the bacterial population flourishes.

Why does allergic contact dermatitis exist?

The skin immune system's propensity to produce allergic contact dermatitis (ACD) to harmless chemicals, while otherwise being an efficient defence system, represents a dermatological paradox. We postulate that a major role in signalling in ACD is played by Toll-like receptor (TLR)2 and TLR4, and arises from their activation by extracellular danger-associated molecular patterns (DAMPs). Ligand activation of TLR4/2 results in the expression of interleukins (ILs) IL-1ß, IL-6, IL-12, IL-18 and IL-23, tumour necrosis factor-α and interferon-α. These cytokines promote acquisition of sensitization, and facilitate elicitation of contact allergy via multiple mechanisms, including the recruitment of CD4+ Th1 and Th17 cells. As Th1 cells secrete large amounts of DAMPs, a DAMP immune circuit (positive-feedback loop) is created. This is an important driver of skin sensitization and skin inflammation. Pathogenic extracellular bacteria, but not commensal bacteria, produce pathogen-associated molecular pattern molecules, which stimulate the expression of Th1- and Th17-promoting cytokines via TLR2 and TLR4. This also induces an immune circuit. The ability of the skin immune system to activate host defence mechanisms and to distinguish between pathogenic bacteria and commensals provides an explanation for why skin sensitization and ACD develop, as they are processes that rely on the same biological pathways. These pathways may also shed light on the pathogenesis of chronic pustular inflammatory dermatoses (e.g. acne vulgaris). The existence of safety signals from commensal bacteria, which prevent initiation of these pathways, may provide opportunities for novel therapeutic approaches to the treatment of inflammatory skin diseases.

Carbon Ion Fluxes at Mars: First Results of Tailward Flows From MAVEN-STATIC.

Characterizing C+ ions in the Martian ionosphere is important for understanding the history of the Martian atmosphere and surface due to its place in understanding carbon escape. Measuring minor ions, like C+, which are close in mass to major atmospheric ions, in this case O+, is difficult, requiring fitting algorithms and accurate background subtraction. Accurate measurement of these species is essential for understanding chemistry and transport in the ionosphere. In this paper, we use data from the Mars Atmospheric and Volatile EvolutioN SupraThermal And Thermal Ion Composition (MAVEN-STATIC) sensor to report the first C+ fluxes measured in the Martian magnetotail. We will describe a multistep method of background subtraction as well as fitting routines that are used to extract C+ fluxes from a 40-orbit subset of STATIC data. Our results show tailward fluxes in both optical shadow and the adjacent sunlit magnetotail at high altitudes ( > 3,000 km) and Mars-ward at low altitudes ( < 2,000 km) in shadow. These local flux values are similar to estimates of neutral carbon fluxes from photochemical escape. However, total carbon loss comparisons will require a more comprehensive study of integrated C+ loss over a larger data set from the Martian magnetotail.

The Hapten-Atopy hypothesis II: the 'cutaneous hapten paradox'.

One explanation for the striking increase in atopic disease in developed countries over the last 50 years has been the 'Hygiene Hypothesis'; a reduced exposure to pathogenic microorganisms. We have postulated previously that oral and cutaneous exposure to chemicals generally and to haptens in particular, may have also contributed to the increased prevalence of atopic disease; the 'Hapten-Atopy Hypothesis'. The purpose here is to extend further that hypothesis by consideration of the impact interplay between the innate and adaptive immune systems may have on the development of atopic allergy. It is clear that experimental cutaneous exposure to hapten can generate immune responses of different types with regard to T-helper (Th) cell phenotype. Allergic contact dermatitis is frequently associated with a selective Th1 (and Tc1)-driven inflammation, whereas atopic dermatitis is characterized by preferential Th2 cell responses. We postulate here that initial innate immune responses to chemical haptens result in the promotion of Th1 cell responses secondary to stimulation of Toll-like receptor. However, we argue also that under conditions where there is prolonged skin exposure to hapten there will be a shift of Th cell phenotype to selective Th2-type responses. The significance of such interactions is the possibility that repeated low-level skin exposure to certain types of hapten may result in the creation of an immunological environment in which the development of Th2 immune responses to third party antigens is favoured. The hypothesis is advanced that the nature and conditions of skin exposure to common haptens may impact on the quality of cutaneous immune responses such that in some circumstances the development atopic disease is favoured.

Direct evidence for a three-dimensional magnetic flux rope flanked by two active magnetic reconnection X lines at Earth's magnetopause.

We report the direct detection by three THEMIS spacecraft of a magnetic flux rope flanked by two active X lines producing colliding plasma jets near the center of the flux rope. The observed density depletion and open magnetic field topology inside the flux rope reveal important three-dimensional effects. There was also evidence for nonthermal electron energization within the flux rope core where the fluxes of 1-4 keV superthermal electrons were higher than those in the converging reconnection jets. The observed ion and electron energizations differ from current theoretical predictions.

Carbon, nitrogen, and phosphorus fluxes in household ecosystems in the Minneapolis-Saint Paul, Minnesota, urban region.

Rapid worldwide urbanization calls for a better understanding of the biogeochemical cycling of those macroelements that have large environmental impacts in cities. This study, part of the Twin Cities Household Ecosystem Project, quantified fluxes of carbon (C), nitrogen (N), and phosphorus (P) at the scale of individual households in the Minneapolis-Saint Paul metropolitan area in Minnesota, USA. We estimated input and output fluxes associated with several components of household activities including air and motor vehicle travel, food consumption, home energy use, landscape, pets, and paper and plastic use for 360 owner-occupied, stand-alone households. A few component fluxes dominated total input fluxes of elements. For instance, air and motor vehicle transportation, together with home energy use, accounted for 85% of total C consumption and emissions. All total and component fluxes were skewed to varying degrees, suggesting that policies targeting disproportionately high fluxes could be an effective and efficient way to reduce pollution. For example, 20% of households contributed 75% of air travel emissions and 40% of motor vehicle emissions. Home energy use was more nearly normally distributed. Nitrogen fluxes were dominated by human diet and lawn fertilizer applications, which together accounted for 65% of total household N inputs. The majority of P inputs were associated with human diet, use of detergents, and pet food. A large portion of the variation among household fluxes of C, N, and P was related to a few biophysical variables. A better understanding of the biophysical, demographic, and behavioral drivers of household activities that contribute to C, N, and P fluxes is pivotal for developing accurate urban biogeochemical models and for informing policies aimed at reducing sources of pollution in urban ecosystems.

In Situ Measurements of Thermal Ion Temperature in the Martian Ionosphere.

In situ measurements of ionospheric and thermospheric temperatures are experimentally challenging because orbiting spacecraft typically travel supersonically with respect to the cold gas and plasma. We present O 2 + temperatures in Mars' ionosphere derived from data measured by the SupraThermal And Thermal Ion Composition instrument onboard the Mars Atmosphere and Volatile EvolutioN spacecraft. We focus on data obtained during nine special orbit maneuvers known as Deep Dips, during which MAVEN lowered its periapsis altitude from the nominal 150 to 120 km for 1 week in order to sample the ionospheric main peak and approach the homopause. We use two independent techniques to calculate ion temperatures from the measured energy and angular widths of the supersonic ram ion beam. After correcting for background and instrument response, we are able to measure ion temperatures as low as 100 K with associated uncertainties as low as 10%. It is theoretically expected that ion temperatures will converge to the neutral temperature at altitudes below the exobase region (∼180-200 km) due to strong collisional coupling; however, no evidence of the expected thermalization is observed. We have eliminated several possible explanations for the observed temperature difference between ions and neutrals, including Coulomb collisions with electrons, Joule heating, and heating caused by interactions with the spacecraft. The source of the energy maintaining the high ion temperatures remains unclear, suggesting that a fundamental piece of physics is missing from existing models of the Martian ionosphere.