Lagrangian coherent structure assisted path planning for transoceanic autonomous underwater vehicle missions.

Transoceanic Gliders are Autonomous Underwater Vehicles (AUVs) for which there is a developing and expanding range of applications in open-seas research, technology and underwater clean transport. Mature glider autonomy, operating depth (0-1000 meters) and low energy consumption without a CO2 footprint enable evolutionary access across ocean basins. Pursuant to the first successful transatlantic glider crossing in December 2009, the Challenger Mission has opened the door to long-term, long-distance routine transoceanic AUV missions. These vehicles, which glide through the water column between 0 and 1000 meters depth, are highly sensitive to the ocean current field. Consequently, it is essential to exploit the complex space-time structure of the ocean current field in order to plan a path that optimizes scientific payoff and navigation efficiency. This letter demonstrates the capability of dynamical system theory for achieving this goal by realizing the real-time navigation strategy for the transoceanic AUV named Silbo, which is a Slocum deep-glider (0-1000 m), that crossed the North Atlantic from April 2016 to March 2017. Path planning in real time based on this approach has facilitated an impressive speed up of the AUV to unprecedented velocities resulting in major battery savings on the mission, offering the potential for routine transoceanic long duration missions.

Stratified coastal ocean interactions with tropical cyclones.

Hurricane-intensity forecast improvements currently lag the progress achieved for hurricane tracks. Integrated ocean observations and simulations during hurricane Irene (2011) reveal that the wind-forced two-layer circulation of the stratified coastal ocean, and resultant shear-induced mixing, led to significant and rapid ahead-of-eye-centre cooling (at least 6 °C and up to 11 °C) over a wide swath of the continental shelf. Atmospheric simulations establish this cooling as the missing contribution required to reproduce Irene's accelerated intensity reduction. Historical buoys from 1985 to 2015 show that ahead-of-eye-centre cooling occurred beneath all 11 tropical cyclones that traversed the Mid-Atlantic Bight continental shelf during stratified summer conditions. A Yellow Sea buoy similarly revealed significant and rapid ahead-of-eye-centre cooling during Typhoon Muifa (2011). These findings establish that including realistic coastal baroclinic processes in forecasts of storm intensity and impacts will be increasingly critical to mid-latitude population centres as sea levels rise and tropical cyclone maximum intensities migrate poleward.

Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014.

In January to February 2014, 16 hand, foot and mouth disease (HFMD) cases were identified in Edinburgh, United Kingdom. All presented with atypical features, with most (n=13) resembling eczema herpeticum or chickenpox. Coxsackievirus A6 (CV-A6) was identified in all the typed cases (n=11). As atypical forms of HFMD associated with CV-A6 are likely to emerge throughout Europe, clinicians should be alert to unusual clinical presentations of HFMD and virologists aware of effective diagnostic testing and enterovirus typing methods.

The European TREatment of severe Atopic eczema in children Taskforce (TREAT) survey.

BACKGROUND: There is a paucity of evidence for the use of systemic agents in children with atopic eczema refractory to conventional therapy, resulting in considerable variation in patient management. OBJECTIVES: The European TREatment of severe Atopic eczema in children Taskforce (TREAT) survey was established to collect data on current prescribing practice, to identify factors influencing the use of specific systemic agents, and to inform the design of a clinically relevant intervention study. METHODS: Consultant physician members of the paediatric dermatology societies and interest groups of eight European countries were invited to participate in a web-based survey. The multiple-response format questionnaire collated data on clinical practice in general, as well as detailed information on the use of systemic agents in refractory paediatric atopic eczema. RESULTS: In total, 343/765 members (44·8%) responded to the invitational emails; 89·2% were dermatologists and 71% initiate systemic immunosuppression for children with severe atopic eczema. The first-line drugs of choice were ciclosporin (43·0%), oral corticosteroids (30·7%) and azathioprine (21·7%). Ciclosporin was also the most commonly used second-line medication (33·6%), with methotrexate ranked as most popular third choice (26·2%). Around half of the respondents (53·7%) replied that they routinely test and treat reservoirs of cutaneous infection prior to starting systemic treatment. Across the eight countries, penicillins were the first-line antibiotic of choice (78·3%). CONCLUSIONS: In the absence of a clear evidence base, the European TREAT survey confirms the wide variation in prescribing practice of systemic immunosuppression in refractory paediatric atopic eczema. The results will be used to inform the design of a randomized controlled trial relevant to patient management across Europe.

A universal driver of macroevolutionary change in the size of marine phytoplankton over the Cenozoic.

The size structure of phytoplankton assemblages strongly influences energy transfer through the food web and carbon cycling in the ocean. We determined the macroevolutionary trajectory in the median size of dinoflagellate cysts to compare with the macroevolutionary size change in other plankton groups. We found the median size of the dinoflagellate cysts generally decreases through the Cenozoic. Diatoms exhibit an extremely similar pattern in their median size over time, even though species diversity of the two groups has opposing trends, indicating that the macroevolutionary size change is an active response to selection pressure rather than a passive response to changes in diversity. The changes in the median size of dinoflagellate cysts are highly correlated with both deep ocean temperatures and the thermal gradient between the surface and deep waters, indicating the magnitude and frequency of nutrient availability may have acted as a selective factor in the macroevolution of cell size in the plankton. Our results suggest that climate, because it affects stratification in the ocean, is a universal abiotic driver that has been responsible for macroevolutionary changes in the size structure of marine planktonic communities over the past 65 million years of Earth's history.

Kawasaki disease: an update.

Kawasaki disease is one of the commonest vasculitides seen in children. It presents with prolonged fever and a polymorphic exanthem. It is a major cause of acquired heart disease in western society. Its exact cause is not known, but exposure to a superantigen has been suggested as a possible aetiological factor. Diagnosis of Kawasaki disease still relies on clinical criteria (Table 1) and investigations are done mainly to exclude other diseases and to detect early or established cardiac complications. Coronary complications can be reduced significantly by the use of intravenous immunoglobulin therapy combined with oral aspirin. The serious consequences of Kawasaki disease require a heightened awareness of this condition when dealing with childhood exanthems.

Monochromatic ultraviolet light induced damage to Photosystem II efficiency and carbon fixation in the marine diatom Thalassiosira pseudonana (3H).

Low light adapted cultures of the marine diatom Thalassiosira pseudonana (3H) were cultured and incubated for 30 min under different ultraviolet (UV) wavelengths of near monochromatic light with and without background photosynthetically active radiation (PAR, 380-700 nm). Maximum damage to the quantum yield for stable charge separations was found in the UVB (280-320 nm) wavelengths without background PAR light while the damage under PAR was 30% less. UV induced damage to carbon fixation in the cells was described by a function similar to non-linear functions of inhibiting irradiance previously published with the exception that damage was slightly higher in the UVA (320-380). Various measurements of fluorescent transients were measured and the results indicate localised damage most likely on the acceptor side of the Photosystem II reaction center. However, dark adapted measurements of fluorescence transients with and without DCMU do not result in similar functions. This is also true for the relationships between fluorescence transients and carbon fixation for this species of marine diatom. The correlation between the weightings varepsilon (H) from measurements of carbon fixation and the quantum yield for stable charge separation as calculated from induction curves with DCMU and without DCMU is R (2) 0.44 and R (2) 0.78, respectively. The slopes of the two measurements are 3.8 and 1.4, respectively. The strong correlation between the weightings of the induction curves without DCMU and carbon fixation are due to a loss of electron transport from the reaction center to plastoquinone. Under these experimental conditions of constant photon flux density (PFD) this is manifested as a strong linear relationship between the decrease in the operational quantum yield of Photosystem II and carbon fixation.

Pseudoporphyria and nonsteroidal antiinflammatory agents in children with juvenile idiopathic arthritis.

Pseudoporphyria is characterized by erythema, blistering, and scarring on sun-exposed skin. Nonsteroidal antiinflammatory drugs (NSAIDs) are implicated in the etiology of this condition. In a 1-year prospective study of children attending the pediatric rheumatology clinic in Edinburgh we found a prevalence of pseudoporphyria of 10.9% in children taking NSAIDs for juvenile idiopathic arthritis. Naproxen was the most commonly implicated NSAID, independent of dosage. Blue/gray eye color was an independent risk factor for the development of pseudoporphyria. We would advise caution in prescribing naproxen in these children to prevent disfiguring facial scarring.

Characterization of sulfate assimilation in marine algae focusing on the enzyme 5'-adenylylsulfate reductase.

5'-Adenylylsulfate (APS) reductase was characterized in diverse marine algae. A cDNA encoding APS reductase from Enteromorpha intestinalis (EAPR) was cloned by functional complementation of an Escherichia coli cysH mutant. The deduced amino acid sequence shows high homology with APS reductase (APR) from flowering plants. Based on the probable transit peptide cleavage site the mature protein is 45.7 kD. EAPR expressed as a His-tagged recombinant protein catalyzes reduced glutathione-dependent reduction of APS to sulfite, exhibiting a specific activity of approximately 40 micromol min(-1) mg protein(-1) and Michealis-Menten kinetic constants of approximately 1.4 mM for reduced glutathione and approximately 6.5 microM for APS. APR activity and expression were studied in relation to the production of 3-dimethylsulfoniopropionate (DMSP), a sulfonium compound produced by many marine algae. A diverse group of DMSP-producing species showed extremely high enzyme activity (up to 400 times that found in flowering plants). Antibodies raised against a conserved peptide of APR strongly cross-reacted with a protein of 45 kD in several chlorophytes but insignificantly with chromophytes. In the chlorophyte Tetraselmis sp., APR activity varies significantly during the culture cycle and does not follow the changes in cellular DMSP content. However, a positive correlation was found between cell-based APR activity and specific growth rate.

Abnormal expression of epiligrin and alpha 6 beta 4 integrin in basal cell carcinoma.

BACKGROUND: Basal cell carcinoma is characterized by local invasion, and only rarely metastasizes. The role of the containing basement membrane (BM) in this tumor is unclear. Several BM components have been shown to be absent or significantly reduced in BM surrounding infiltrating tumor. OBJECTIVE: The purpose of this study is to examine the expression of epiligrin, a BM-associated glycoprotein, and the integrin chains alpha 3, alpha 6, beta 1, and beta 4 in the basement membranes surrounding basal cell carcinoma. METHODS: Samples were obtained from 20 patients with basal cell carcinomas and subjected to a standard avidin biotin complex/alkaline phosphatase immunohistochemical technique using a panel of antibodies. RESULTS: There was a consistent abnormality of expression of epiligrin, alpha 6, and beta 4. CONCLUSION: We propose that reduced expression of epiligrin is involved in the pathogenesis of the local invasion by tumor and that an altered integrin ratio in basal cell carcinoma enhances tumor spread.

Nodular basal cell carcinoma in vivo vs in vitro. Establishment of pure cell cultures, cytomorphologic characteristics, ultrastructure, immunophenotype, biosynthetic activities, and generation of antisera.

BACKGROUND AND DESIGN: In this study we developed an in vitro model of nodular basal cell carcinoma (BCC). We obtained pure cultures of BCC cells and compared the morphologic characteristics, ultrastructure, immunophenotype, and behavior of cultured tumor cells with those of their in vivo counterparts. Tumors were excised from patients undergoing Mohs micrographic surgery. We established 69 primary cell cultures from 32 patients with nodular BCC. RESULTS: Three cell types grew in primary cultures: fibroblasts, normal-appearing keratinocytes, and cells with dual (spindle and epithelioid) morphologic characteristics. Contaminating fibroblasts were removed using 0.125% trypsin-0.02% edetic acid, and normal-appearing keratinocytes were cornified and eliminated by temporarily increasing the concentration of calcium in the growth medium. The cells with dual morphologic characteristics remained intact and exhibited relentless growth in pure cultures. That these seemingly immortal cell strains represent true nodular BCC was demonstrated by (1) their biphasic morphologic characteristics and very slow cell growth rate, (2) their capability for anchorage-independent growth in soft agar, (3) their ultrastructural similarities to freshly excised nodular BCC, (4) their ability to generate antibodies selectively labeling nodular BCC tumor nests in vivo, and (5) their immunophenotypic similarities to BCC in vivo on more than 20 different cell markers. CONCLUSIONS: This study provides a simple technique for establishing pure cell cultures of nodular BCC and describes extensively the in vitro parameters of tumor cell growth. The striking differences in behavior of cultured tumor cells in the presence or absence of normal-appearing keratinocytes suggest that normal human epidermal keratinocytes can suppress the growth of BCC cells.

Epidermolysis bullosa pruriginosa: dystrophic epidermolysis bullosa with distinctive clinicopathological features.

We report a study of eight unrelated adult patients with a highly distinctive phenotype of dystrophic epidermolysis bullosa. It is characterized clinically by pruritus, lichenified or nodular prurigo-like lesions, violaceous linear scarring, occasional trauma-induced blistering, excoriations, milia, nail dystrophy and, in some cases, albopapuloid lesions on the trunk. The scarring is most evident on the limbs, particularly on the shins, with relative sparing elsewhere. Intact blisters are rarely seen. Physical signs were present at birth in three patients, but in the others skin manifestations were first noticed between 6 months and 10 years of age. Five cases are sporadic, but three of the eight patients have a history of familial involvement, with autosomal dominant inheritance in two cases and recessive transmission in the other case. Studies of the dermal-epidermal junction showed alterations in the number and ultrastructure of anchoring fibrils in lesional, perilesional and non-lesional skin, consistent with a diagnosis of dominant or localized recessive dystrophic epidermolysis bullosa. These patients represent an unusual, poorly recognized form or expression of dystrophic epidermolysis bullosa which has features in common with a variety of acquired inflammatory dermatoses.

Nicein (BM-600) in junctional epidermolysis bullosa: polyclonal antibodies provide new clues for pathogenic role.

We have raised polyclonal antibodies against each of three subunits of the new basement membrane component nicein (formerly BM-600), the antigen recognized by the monoclonal antibody GB3 (Biochem Biophys Acta 942:45-56, 1988). Preparation of such antibodies was achieved from gel electrophoresis purification of nicein isolated by immuno-affinity chromatography. These antibodies were reactive with each transblotted denatured nicein subunit and recognized the native protein both in cultured keratinocytes and in all normal human basement membranes where the GB3 antigen is located. A reciprocal immuno-cross-reactivity was detected with the antibodies directed against the 100-kD and 150-kD (sometimes resolved as a 146-150-kD doublet) subunits of nicein, showing that they share some identical epitopes. In tissues and keratinocyte cultures from patients with the Herlitz form of junctional epidermolysis bullosa (H-JEB), GB3 is unable to recognize nicein, and the question arises whether this is due to an absence of synthesis or a structural abnormality of the protein. We report here that the polyclonal antibody directed against the 150-kD subunit of nicein binds its antigen in H-JEB patients (although usually less intensely than in control skin), whereas the other two antibodies either do not recognize or recognize only weakly their respective antigen subunits. These data suggest that nicein is present but structurally altered in basement membranes from H-JEB tissues. Furthermore, in non-Herlitz junctional and dystrophic types of epidermolysis bullosa, all three polyclonal antibodies recognize their antigens normally. Consequently, such antibodies should serve as potentially useful molecular tools for studying the expression of nicein in H-JEB.