Hazy Blue Worlds: A Holistic Aerosol Model for Uranus and Neptune, Including Dark Spots.

We present a reanalysis (using the Minnaert limb-darkening approximation) of visible/near-infrared (0.3-2.5 µm) observations of Uranus and Neptune made by several instruments. We find a common model of the vertical aerosol distribution i.e., consistent with the observed reflectivity spectra of both planets, consisting of: (a) a deep aerosol layer with a base pressure >5-7 bar, assumed to be composed of a mixture of H2S ice and photochemical haze; (b) a layer of photochemical haze/ice, coincident with a layer of high static stability at the methane condensation level at 1-2 bar; and (c) an extended layer of photochemical haze, likely mostly of the same composition as the 1-2-bar layer, extending from this level up through to the stratosphere, where the photochemical haze particles are thought to be produced. For Neptune, we find that we also need to add a thin layer of micron-sized methane ice particles at ∼0.2 bar to explain the enhanced reflection at longer methane-absorbing wavelengths. We suggest that methane condensing onto the haze particles at the base of the 1-2-bar aerosol layer forms ice/haze particles that grow very quickly to large size and immediately "snow out" (as predicted by Carlson et al. (1988), https://doi.org/10.1175/1520-0469(1988)045<2066:CMOTGP>2.0.CO;2), re-evaporating at deeper levels to release their core haze particles to act as condensation nuclei for H2S ice formation. In addition, we find that the spectral characteristics of "dark spots", such as the Voyager-2/ISS Great Dark Spot and the HST/WFC3 NDS-2018, are well modelled by a darkening or possibly clearing of the deep aerosol layer only.

Atmospheric chemistry on Uranus and Neptune.

Comparatively little is known about atmospheric chemistry on Uranus and Neptune, because remote spectral observations of these cold, distant 'Ice Giants' are challenging, and each planet has only been visited by a single spacecraft during brief flybys in the 1980s. Thermochemical equilibrium is expected to control the composition in the deeper, hotter regions of the atmosphere on both planets, but disequilibrium chemical processes such as transport-induced quenching and photochemistry alter the composition in the upper atmospheric regions that can be probed remotely. Surprising disparities in the abundance of disequilibrium chemical products between the two planets point to significant differences in atmospheric transport. The atmospheric composition of Uranus and Neptune can provide critical clues for unravelling details of planet formation and evolution, but only if it is fully understood how and why atmospheric constituents vary in a three-dimensional sense and how material coming in from outside the planet affects observed abundances. Future mission planning should take into account the key outstanding questions that remain unanswered about atmospheric chemistry on Uranus and Neptune, particularly those questions that pertain to planet formation and evolution, and those that address the complex, coupled atmospheric processes that operate on Ice Giants within our solar system and beyond. This article is part of a discussion meeting issue 'Future exploration of ice giant systems'.

Evaluation of EC50 of factor VIII as predictor of prophylaxis efficacy in patients with severe haemophilia A.

Trough factor (F) VIII level is a not reliable bleeding risk indicator to predict prophylaxis efficacy in severe haemophilia A (SHA), therefore, accurate biomarkers are much needed. Thrombelastography (TEG) monitors both thrombin and clot formation addressing the global haemostatic status but its usefulness to tailor prophylaxis in haemophilia has been poorly evaluated. In this study, correspondence between individual pharmacodynamic/pharmacokinetic profile of FVIII and joint condition, physical activity and bleeding phenotype of SHA patients under prophylactic treatment was assessed. Nineteen SHA patients < 18 years old on long-term prophylaxis treatment with FVIII were studied in an observational cross-sectional study. Whole blood was withdrawn before FVIII administration and at five time-points after infusion for a TEG-based pharmacodynamic- and pharmacokinetic-study. Type of prophylaxis and joint condition at inclusion and physical activity as well as onset of treated spontaneous bleeding events in the previous two years were retrospectively assessed. Six patients had suffered at least one treated spontaneous bleeding event and were named as "bleeders". The rest were named as "non-bleeders". Only the half maximal effective concentration of FVIII (FVIII-EC50) for TEG parameters R-time, K-time and α-angle correlated with the bleeding phenotype being significantly higher in bleeders suggestive of a poorer response to FVIII. Poorer joint condition, trough FVIII levels or type of prophylaxis were not definitive predicting variables of bleeding phenotype. In conclusion, this study reveals FVIII-EC50 for the first time as a valuable biomarker to anticipate individual efficacy of prophylaxis in SHA.

Head trauma in the haemophilic child and management in a paediatric emergency department: Descriptive study.

INTRODUCTION: Haemophilia is one of the most common inherited bleeding disorders in the Emergency Department (ED). The most dangerous site of bleeding is the central nervous system. AIMS: To describe the characteristics of haemophiliacs arrived to our ED following a head trauma and to analyse the incidence of intracranial haemorrhage (ICH). MATERIALS AND METHODS: Retrospective, analytical, observational study, conducted in a Paediatric ED. We included haemophilic patients aged from birth to 16 years who consulted after a head trauma over a 6-year period. Data collected included age, type of haemophilia and head trauma, symptoms, prophylaxis status, CT imaging, treatment and number of visits to the ED. RESULTS: About 46 males and 85 episodes were analysed. The median age was 2.38 years. Severe haemophilia A was the most frequent type of disease (50%). All head injuries were mild, and the most frequent mechanism was a collision with an object (38.8%). In 62 episodes (72.9%) the patients were asymptomatic. The rest 23 events had symptomatology, being the most common headache (26%), emesis (21.7%) and drowsiness (17.4%). Head CT was obtained in 31 episodes, founding altered results in 10 (6 of them corresponding to ICH). All the patients with ICH had symptomatology. About 37 episodes required admission. CONCLUSION: Intracranial haemorrhage is one of the most dangerous events in haemophiliacs and it may occur after a head trauma. Our study suggests that, in case of head trauma, CT must be obtained in symptomatic patients and in those with additional risk factors. Asymptomatic patients must have prolonged observation.

Extended half-life pegylated, full-length recombinant factor VIII for prophylaxis in children with severe haemophilia A.

INTRODUCTION: Primary factor VIII (FVIII) prophylaxis is the optimal treatment in children with severe haemophilia A. They are expected to benefit from extended half-life (T1/2 ) FVIII coverage by reduced infusion frequency while maintaining haemostatic efficacy. AIMS: To determine immunogenicity, pharmacokinetics (PK), efficacy, safety and quality of life of prophylaxis with a polyethylene glycol (peg)-ylated FVIII (BAX 855) based on full-length recombinant FVIII (ADVATE) in paediatric previously treated patients (PTPs) with severe haemophilia A. METHODS: PTPs <12 years without history of FVIII inhibitors received twice-weekly infusions of 50 ± 10 IU kg-1 BAX 855 for ≥50 exposure days. Prophylactic dose increases to ≤80 IU kg-1 were allowed under predefined conditions. PK was evaluated after single infusions of 60 ± 5 IU kg-1 . RESULTS: T1/2 and mean residence time were extended 1.3- to 1.5-fold compared to ADVATE (n = 31), depending on the analysis used. The point estimate for the mean annualized bleeding rate in 66 subjects receiving a median of 1.9 weekly infusions of 51.3 IU kg-1 of BAX 855 each was 3.04 (median 2.0); 1.10 (median 0) for joint and 1.16 (median 0) for spontaneous bleeds. Overall, 38% of subjects had zero bleeds. No bleeds were severe. Haemostatic efficacy was rated excellent or good for 90% of bleeds; 91% were treated with one or two infusions. In 8/14 subjects all target joints resolved. No subject developed FVIII inhibitors or persistent binding antibodies that affected safety or efficacy. No adverse reactions occurred. CONCLUSION: Twice-weekly prophylaxis with BAX 855 was safe and efficacious in paediatric PTPs with severe haemophilia A.

European retrospective study of real-life haemophilia treatment.

INTRODUCTION: Haemophilia treatment varies significantly between individuals, countries and regions and details of bleed rates, factor consumption and injection frequency are often not available. AIM: To provide an overview of the FVIII/FIX treatment practice and outcome for patients with haemophilia A (HA) or haemophilia B (HB) across Europe. METHODS: Non-interventional, 12-month retrospective study where anonymized data were retrieved from haemophilia centres/registers in Belgium, France, Germany, Italy, Spain, Sweden and the United Kingdom. Male patients (all ages) receiving coagulation factor treatment 24 months prior to the study, with basal FVIII/FIX levels ≤5 IU dL-1 , without inhibitors, were included. Data were summarized descriptively. RESULTS: In total, 1346 patients with HA and 312 with HB were included in the analysis; 75% and 57% had severe disease (FVIII/FIX < 1 IU dL-1 ) respectively. Prophylaxis was most common for severe haemophilia, especially for children, whereas on-demand treatment was more common for moderate haemophilia in most countries. The mean (SD) prescribed prophylactic treatment ranged from 67.9 (30.4) to 108.4 (78.1) (HA) and 32.3 (10.2) to 97.7 (32.1) (HB) IU kg-1 per week, across countries. Most patients on prophylaxis were treated ≥3 times/week (HA) or two times/week (HB). The median annual bleeding rate (ABR) for patients on prophylaxis ranged from 1.0 to 4.0 for severe HA, and from 1.0 to 6.0 for severe HB, while those with moderate haemophilia generally had slightly higher ABRs. Median ABRs for on-demand-treated severe HA ranged from 4.5 to 18.0, and for HB, 1.5 to 14.0. CONCLUSION: Treatment practice varied greatly between centres and countries and patients treated on-demand and prophylactically both experienced bleeds, emphasizing the need for further optimization of care.

Terrestrial atmospheric responses on Svalbard to the 20 March 2015 Arctic total solar eclipse under extreme conditions.

This article reports on the near-surface atmospheric response at the High Arctic site of Svalbard, latitude 78° N, as a result of abrupt changes in solar insolation during the 20 March 2015 equinox total solar eclipse and notifies the atmospheric science community of the availability of a rare dataset. Svalbard was central in the path of totality, and had completely clear skies. Measurements of shaded air temperature and atmospheric pressure show only weak, if any, responses to the reduced insolation. A minimum in the air temperature at 1.5 m above the ground occurred starting 2 min following the end of totality, though this drop was only slightly beyond the observed variability for the midday period. Eclipse-produced variations in surface pressure, if present, were less than 0.3 hPa.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'.

Cost analysis of prophylaxis with activated prothrombin complex concentrate vs. on-demand therapy with activated factor VII in severe haemophilia A patients with inhibitors, in Spain.

OBJECTIVE: A cost analysis model was developed to compare annual cost of prophylaxis with activated prothrombin complex concentrate (aPCC) vs. on-demand therapy with activated recombinant factor VII (rFVIIa) in severe haemophilia A patients with inhibitors for the Spanish National Health System (NHS). METHODS: Model inputs were drug cost for prophylaxis (aPCC) and for on-demand treatment (rFVIIa or aPCC); bleeding episodes management (excluding bypassing agent cost); surgical costs and disease management (excluding bleeding episodes). Annual bleeding episodes treated on-demand was assumed to be 25, whereas breakthrough bleeds on prophylaxis was 8. Dose for prophylaxis was 75.72 U kg(-1) , three times per week. The total on-demand dose/bleeding episode was 679.66 µg kg(-1) (rFVIIa) and 235.28 U kg(-1) (aPCC). The average bleeding cost (€2998) considered different bleeding sites (62.5% joints, 28.6% muscles and soft tissues, 3.6% mucocutaneous tissues and 5.4% other areas). A 7.5% deduction was applied to ex-factory drug prices. Unitary costs (€2013) derived from local databases. Sensitivity analyses (SA) were performed. RESULTS: Annual cost of aPCC prophylaxis (€524,358) was 16% lower than on-demand treatment with rFVIIa (€627,876). Yearly drug costs were €497,017 for aPCC (€73,166 for on-demand treatment and €423,850 for prophylaxis), and €548,870 for rFVIIa. Disease management cost (€2645 per year) and surgical procedures (€708 per year) were common for both strategies. In the SA prophylactic treatment led to savings between €26,225 and €-1,008,960. CONCLUSION: Prophylaxis with aPCC reduces number of bleeding episodes in severe haemophilia A patients with inhibitors. aPCC prophylaxis resulted in savings in excess of €100,000 per-patient per year, being 16% less costly than on-demand treatment with rFVIIa, for the Spanish NHS.

Effects of thrombopoietin receptor agonists on procoagulant state in patients with immune thrombocytopenia.

Thrombopoietin receptor agonists (TPO-RA) have recently been introduced for the treatment of immune thrombocytopenia (ITP), an anti-platelet-antibodies autoimmune disease. The observation of a low frequency of bleeding episodes despite their thrombocytopenia suggests the existence of a compensatory mechanism. This study aimed to evaluate the effect of TPO-RA treatment on platelet function and on the procoagulant state in ITP patients before (ITP-bR) and after responding (ITP-aR) to treatment. Plasma- and microparticle (MP)-associated procoagulant capacity from ITP patients was similar before and after responding to the TPO-RA regimen but higher than the healthy control values. High MP-associated procoagulant activity did not seem to be due to increased platelet activation, since platelet stimulation by agonists was reduced in ITP-bR and ITP-aR patients. It could be related to increased platelet apoptosis, evaluated in terms of surface phosphatidylserine (PS), observed in both ITP groups. In summary, TPO-RA treatment increased platelet count but did not ameliorate their function and did not change plasma- and MP-associated procoagulant state of ITP patient responders to this therapy.

[Cutaneous infection caused by Mycobacterium chelonae. Presentation of 3 cases with multiple lesions]. / Infección cutánea por Mycobacterium chelonae. Presentación de tres casos con lesiones múltiples.

OBJECTIVE: To review the clinical, diagnostic, therapeutic and prognostic characteristics of cutaneous diseases caused by atypical mycobacteria and more specifically those by Mycobacterium chelonae. To improve our knowledge of this disease and its differential diagnosis with other cutaneous infections associated with folliculitis. DESIGN: Retrospective descriptive study. SETTING: Primary care and Dermatology specialty in a Health Center in the Madrid metropolitan area. PATIENTS AND OTHER PARTICIPANTS: The clinical records of non immunosuppressed patients, with multiple cutaneous lesions caused by Mycobacterium chelonae and confirmed by culture were reviewed. The evolution time, treatment regimes before diagnosis and possible epidemiological factors were studied. MEASUREMENTS AND MAIN OUTCOMES: Culture confirmed three non immunosuppressed patients with multiple lesions in both legs. Lesions had been present for longer than two months and had been treated with topical and systemic antibiotics with no improvement. The only relevant epidemiological finding was wax depilation. CONCLUSIONS: It is important to know the existence of this type of infection, since diagnostic suspicion allows for an early and efficient therapy which will present the emergency of important scars.

[Management of patients with terminal cancer at a primary care center]. / Manejo de los pacientes con cáncer terminal en un centro de atención primaria.

OBJECTIVE: To determine the characteristics, family surrounding and place of death of terminal oncologic patients from 1991. DESIGN: Descriptive and retrospective study. We used Fisher's test. SITE. San Gregorio, Telde (Las Palmas province). PATIENTS: We worked with 27 patients in terminal disease (17 were men and 10 were women). MEASUREMENTS AND MAIN RESULTS: Average age was 66.7 +/- 17 years. The most frequent type was digestive (10), breast (5) and lung (3). Average time of survival was 17.5 +/- 26.5 months. Principal symptoms were: pain (23), anorexia (17), constipation (13) and depression (11). 23 received analgesia (11 with morphine), 17 laxatives and 13 benzodiazepines. The numbers of visit they received was 13.6 +/- 9.3 patients knew their diagnostic. 22 of the families were considered collaborators. 70% of patients in control by Primary Care Center died at home; whereas no one did so in control by hospital (p = 0.029). CONCLUSIONS: Half of the patients in terminal phase in our zone die in their home. Patients under control by Primary Care Center are significantly more likely to die in their own homes. We give special attention to the high percentage of patients who use opiates. Finally we consider that workers in Primary Care Centers are a vital element in handle these patients and their families.

[Digestive hemorrhage caused by aorto-duodenal fistula. Report of 5 cases]. / Hemorragia digestiva por fístula aorto-duodenal. A propósito de 5 casos.

The aortoduodeonal fistula is a rare condition and has high mortality. We report five retrospective cases of digestive hemorrhage due to an aortoduodenal fistula (4 secondary and 1 primary) between 1986 and 1990. Three of them died. Attention is called to the importance of clinical suspicion and the main diagnostic methods in early diagnosis such as oral endoscopy. We also enhance the importance of emergency surgery for survival.