European guideline (EuroGuiDerm) on atopic eczema - part II: non-systemic treatments and treatment recommendations for special AE patient populations.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for paediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

Systematic literature review assessing the overall costs and societal impacts of moderate-to-severe atopic dermatitis in Europe.

Atopic dermatitis (AD) is a chronic inflammatory disease, driven by type 2 inflammation. The condition manifests as moderate-to-severe disease in approximately 20% of adults with AD across Europe and is associated with a substantial burden on patients, society and healthcare systems. However, systematic assessments capturing the totality of disease burden associated with moderate-to-severe AD are limited; therefore, the overall impacts of the disease may be underestimated. A systematic literature review (SLR) was carried out to assess the overall costs of moderate-to-severe AD across Europe, including the financial, societal and humanistic impacts. PubMed, Embase and Cochrane databases were searched to identify relevant studies published between 1 January 2010 and 2 June 2020. Scientific conference proceedings, health technology assessment websites and patient association group websites were also searched for relevant information. Twenty-seven publications, corresponding to 22 unique studies, were included in the analysis. Total costs (direct and productivity losses) reached €20 695 per-person-per-year (PPPY) for adults with uncontrolled symptoms of moderate-to-severe AD. Direct medical costs ranged between €307 and €6993 PPPY; prescription medications and specialist dermatologist visits were the main contributors. Costs increased with disease severity or with uncontrolled disease. Patients with AD also incurred personal costs of €927 per year for healthcare items not reimbursed, which increased by 9% for those with moderate-to-severe forms. Annual work productivity losses comprised most of the total costs reported for adults with moderate-to-severe AD (up to 60.8% of the total burden) and were highest in those with uncontrolled disease (€13 702 PPPY). Patients with moderate-to-severe disease also experienced physical, emotional, and social impacts. The overall costs of moderate-to-severe AD greatly impact on healthcare systems, patients and society. Sustained control of moderate-to-severe AD, through effective treatment and care management, is essential to limit the burden caused by the disease.

European guideline (EuroGuiDerm) on atopic eczema: part I - systemic therapy.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients.

Unveiling the true costs and societal impacts of moderate-to-severe atopic dermatitis in Europe.

Atopic dermatitis (AD) is a chronic, auto-immune condition that imposes a high burden on individuals, society, and the healthcare system. Approximately 4.4% of adults and up to 18.6% of children/adolescents have AD in Europe, with 20% of all cases accounting for moderate-to-severe forms. This form of the condition in adults results in annual societal costs across Europe of an estimated €30 billion; €15.2 billion related to missed workdays or reduced work productivity, €10.1 billion related to direct medical costs and €4.7 billion related to personal expenditure of patients/families. AD can also substantially impact physical, emotional, and social quality-of-life. Several studies have shown the debilitating itch-scratch cycle is the main cause of the multifaceted burden, as it causes substantial sleep deprivation and stigmatisation due to the physical appearance of the skin, and confidence issues. These factors lead to psychosocial issues and can cumulate over time and prohibit patients reaching their 'full life potential'. Despite this, many patients with the condition are undertreated, resulting in uncontrolled symptoms and a further strain placed on patients, society, and the economy. The authors of this White Paper comprise the European Atopic Dermatitis Working Group, which is a network of international specialists with expertise in dermatology and healthcare policy decisions. Their programme of action is focused on harnessing their expertise to build consensus, advance research, share knowledge, and ultimately seek to improve AD care outcomes through achieving long-term symptom control. This White Paper presents a systematic evaluation of the overall financial and humanistic burden of moderate-to-severe AD and the current challenges that exist with AD care. It introduces recommendations for how, collaboratively, key stakeholders and policy makers can support improvements in AD management to achieve better disease control, thus reducing the costs and associated burden placed on individuals, society, and the economy.

Screening two biodegradable polymers in enhanced efficiency fertiliser formulations reveals the need to prioritise performance goals.

Enhanced efficiency fertilisers (EEF) may reduce nitrogen (N) losses and improve uptake efficiency through synchronising N release with in-season plant requirements. We hypothesised that EEF formed via matrix encapsulation in biodegradable polymers will improve N use efficiency when compared to conventional urea fertiliser. This hypothesis was investigated for two biodegradable polymer matrices: polyhydroxyalkanoate (PHA), containing 11.6% urea (by mass), and polybutylene-adipate-co-terephthalate (PBAT), containing either 19.4 or 32.7% urea; and two contrasting soil types: sand and clay. Nitrogen availability and form was investigated under leaching conditions (water) with a growth accelerator pot experiment involving a horticultural crop and novel non-destructive three-dimensional scanning to measure in-season biomass development. The PBAT 32.7% formulation enabled greater above ground biomass production at both 50 and 100 kg N ha-1 equivalent application rates compared to conventional urea. For the sandy soil, plant scanning indicated that improved uptake performance with PBAT 32.7% was probably the result of greater N availability after 25 days than for conventional urea. Two of the encapsulated formulations (PHA and PBAT 19.4%) tended to decrease nitrogen leaching losses relative to urea (P < 0.05 for the red clay soil). However, decreased N leaching loss was accompanied by poorer N uptake performance, indicative of N being less available in these biopolymer formulations. A snapshot of nitrous oxide emissions collected during peak nitrate concentration (prior to planting and leaching) suggested that the biopolymers promoted N loss via gaseous emission relative to urea in the sandy soil (P < 0.05), and carbon dioxide emissions data suggested that biopolymer-carbon increased microbial activity (P < 0.1). Controlled testing of N release in water was a poor predictor of biomass production and leaching losses. The diverse behaviours of the tested formulations present the potential to optimise biopolymers and their N loadings by taking into account soil and environmental factors that influence the efficient delivery of N to target crops. The greater N uptake efficiency demonstrated for the PBAT 32.7% formulation confirms our hypothesis that matrix encapsulation can enable better synchronisation of N release with crop requirements and decrease leaching losses.

Sorbents can tailor nitrogen release from organic wastes to match the uptake capacity of crops.

Delivering nutrients from mineral or organic fertilizers out of synchrony with crop uptake causes inefficiencies and pollution. We explore methodologies for evaluating sorbents as additives to organic agricultural wastes to retain nitrogen in an exchangeable form and deliver at rates that approximate the uptake capacity of roots. Focussing on ammonium (NH4+) as the main inorganic nitrogen form in the studied wastes (sugarcane mill mud, poultry litter), we tested geo-sorbents and biochar for their ability to retain NH4+. Sorption capacity was ranked palagonite < bentonite, biochar, vermiculite < chabazite, clinoptilolite (5.7 to 24.3 mg NH4+ g-1 sorbent). Sorbent-waste formulations were analysed for sorption capacity, leaching and fluxes of NH4+. Ammonium-sorption capacity broadly translated to sorbent-waste formulations with clinoptilolite conferring the strongest NH4+ attenuation (80%), and palagonite the lowest (7%). A 1:1 ratio of sorbent:waste achieved stronger sorption than a 0.5:1 ratio, and similar sorption as a 1:1.5 ratio. In line with these results, clinoptilolite-amended wastes had the lowest in situ NH4+ fluxes, which exceeded the NH4+ uptake capacity (Imax) of sugarcane and sorghum roots 9 to 84-fold, respectively. Less efficient sorbent-waste formulations and un-amended wastes exceeded Imax of crop roots up to 274-fold. Roots preferentially colonized stronger sorbent-waste formulations and avoided weaker ones, suggesting that lower NH4+ fluxes generate a more favourable growth environment. This study contributes methodologies to identify suitable sorbents to formulate organic wastes as next-generation fertilizers with view of a crop's nutrient physiology. Efficient re-purposing of wastes can improve nutrient use efficiency in agriculture and support the circular nutrient economy.

Manure and sorbent fertilisers increase on-going nutrient availability relative to conventional fertilisers.

The key to better nutrient efficiency is to simultaneously improve uptake and decrease losses. This study sought to achieve this balance using sorbent additions and manure nutrients (spent poultry litter; SL) compared with results obtained using conventional sources (Conv; urea nitrogen, N; and phosphate-phosphorus; P). Two experiments were conducted. Firstly, a phosphorus pot trial involving two soils (sandy and clay) based on a factorial design (Digitaria eriantha/Pennisetum clandestinum). Subsequently, a factorial N and P field trial was conducted on the clay soil (D. eriantha/Lolium rigidum). In the pot trial, sorbent additions (26.2g of hydrotalcite [HT] gP(-1)) to the Conv treatment deferred P availability (both soils) as did SL in the sandy soil. In this soil, P delivery by the Conv treatments declined rapidly, and began to fall behind the HT and SL treatments. Addition of HT increased post-trial Colwell P. In the field trial low HT-rates (3.75 and 7.5g of HTgP(-1)) plus bentonite, allowed dry matter production and nutrient uptake to match that of Conv treatments, and increased residual mineral-N. The SL treatments performed similarly to (or better than) Conv treatments regarding nutrient uptake. With successive application, HT forms may provide better supply profiles than Conv treatments. Our findings, combined with previous studies, suggest it is possible to use manures and ion-exchangers to match conventional N and P source productivity with lower risk of nutrient losses.

Field measurement of beef pen manure methane and nitrous oxide reveals a surprise for inventory calculations.

Few data exist on direct greenhouse gas emissions from pen manure at beef feedlots. However, emission inventories attempt to account for these emissions. This study used a large chamber to isolate NO and CH emissions from pen manure at two Australian commercial beef feedlots (stocking densities, 13-27 m head) and related these emissions to a range of potential emission control factors, including masses and concentrations of volatile solids, NO, total N, NH, and organic C (OC), and additional factors such as total manure mass, cattle numbers, manure pack depth and density, temperature, and moisture content. Mean measured pen NO emissions were 0.428 kg ha d (95% confidence interval [CI], 0.252-0.691) and 0.00405 kg ha d (95% CI, 0.00114-0.0110) for the northern and southern feedlots, respectively. Mean measured CH emission was 0.236 kg ha d (95% CI, 0.163-0.332) for the northern feedlot and 3.93 kg ha d (95% CI, 2.58-5.81) for the southern feedlot. Nitrous oxide emission increased with density, pH, temperature, and manure mass, whereas negative relationships were evident with moisture and OC. Strong relationships were not evident between NO emission and masses or concentrations of NO or total N in the manure. This is significant because many standard inventory calculation protocols predict NO emissions using the mass of N excreted by the animal.

Large-chamber methane and nitrous oxide measurements are comparable to the backward lagrangian stochastic method.

Measurement of individual emission sources (e.g., animals or pen manure) within intensive livestock enterprises is necessary to test emission calculation protocols and to identify targets for decreased emissions. In this study, a vented, fabric-covered large chamber (4.5 × 4.5 m, 1.5 m high; encompassing greater spatial variability than a smaller chamber) in combination with on-line analysis (nitrous oxide [NO] and methane [CH] via Fourier Transform Infrared Spectroscopy; 1 analysis min) was tested as a means to isolate and measure emissions from beef feedlot pen manure sources. An exponential model relating chamber concentrations to ambient gas concentrations, air exchange (e.g., due to poor sealing with the surface; model linear when ≈ 0 m s), and chamber dimensions allowed data to be fitted with high confidence. Alternating manure source emission measurements using the large-chamber and the backward Lagrangian stochastic (bLS) technique (5-mo period; bLS validated via tracer gas release, recovery 94-104%) produced comparable NO and CH emission values (no significant difference at < 0.05). Greater precision of individual measurements was achieved via the large chamber than for the bLS (mean ± standard error of variance components: bLS half-hour measurements, 99.5 ± 325 µg CH s and 9.26 ± 20.6 µg NO s; large-chamber measurements, 99.6 ± 64.2 µg CH s and 8.18 ± 0.3 µg NO s). The large-chamber design is suitable for measurement of emissions from manure on pen surfaces, isolating these emissions from surrounding emission sources, including enteric emissions.

Effect of surface plasma treatments on the adhesion of Mars JSC 1 simulant dust to RTV 655, RTV 615, and Sylgard 184.

BACKGROUND: Dust accumulation on surfaces of critical instruments has been a major concern during lunar and Mars missions. Operation of instruments such as solar panels, chromatic calibration targets, as well as Extra Vehicular Activity (EVA) suits has been severely compromised in the past as a result of dust accumulation and adhesion. Wind storms with wind speeds of up to 70 mph have not been effective in removing significant amounts of the deposited dust. This is indeed an indication of the strength of the adhesion force(s) involved between the dust particles and the surface(s) that they have adhered to. Complications associated with dust accumulation are more severe for non-conducting surfaces and have been the focus of this work. METHODOLOGY: Argon plasma treatment was investigated as a mechanism for lowering dust accumulation on non-conducting polymeric surfaces. Polymers chosen for this study include a popular variety of silicones routinely used for space and terrestrial applications namely RTV 655, RTV 615, and Sylgard 184. Surface properties including wettability, surface potential, and surface charge density were compared before and after plasma treatment and under different storage conditions. Effect of ultraviolet radiation on RTV 655 was also investigated and compared with the effect of Ar plasma treatment. CONCLUSION/SIGNIFICANCE: Gravimetric measurements proved Ar plasma treatment to be an effective method for eliminating dust adhesion to all three polymers after short periods of exposure. No physical damage was detected on any of the polymer surfaces after Ar plasma treatment. The surface potential of all three polymers remained zero up to three months post plasma exposure. Ultraviolet radiation however was not effective in reducing surface and caused damage and significant discoloration to RTV 655. Therefore, Ar plasma treatment can be an effective and non-destructive method for treating insulating polymeric surfaces in order to eliminate dust adhesion and accumulation.

Presence and incidence of food-borne pathogens in Australian chicken litter.

1. Litter samples were collected at the end of the production cycle from spread litter in a single shed from each of 28 farms distributed across the three Eastern seaboard States of Australia. 2. The geometric mean for Salmonella was 44 Most Probable Number (MPN)/g for the 20 positive samples. Five samples were between 100 and 1000 MPN/g and one at 10(5) MPN/g, indicating a range of factors are contributing to these varying loads of this organism in litter. 3. The geometric mean for Campylobacter was 30 MPN/g for the 10 positive samples, with 7 of these samples being <100 MPN/g. The low prevalence and incidence of Campylobacter were possibly due to the rapid die-off of this organism. 4. E. coli values were markedly higher than the two key pathogens (geometric mean 20 x 10(5) colony forming units (cfu)/g) with overall values being more or less within the same range across all samples in the trial, suggesting a uniform contribution pattern of these organisms in litter. 5. Listeria monocytogenes was absent in all samples and this organism appears not to be an issue in litter. 6. The dominant (70% of the isolates) Salmonella serovar was S. Sofia (a common serovar isolated from chickens in Australia) and was isolated across all regions. Other major serovars were S. Virchow and S. Chester (at 10%) and S. Bovismorbificans and S. Infantis (at 8%) with these serovars demonstrating a spatial distribution across the major regions tested. 7. There is potential to re-use litter in the environment depending on end use and the support of relevant application practices and guidelines.

Estimating sludge loadings to land based on trace metal sorption in soil: effect of dissolved organo-metallic complexes.

This paper describes the results of research examining the effect of dissolved organo-metallic complexes of copper (Cu) and zinc (Zn) from sewage sludge leachate on sorption by a humic-gley soil A-horizon, and the influence of such complexes on resultant sludge loading estimates. Sorption was described with Linear, Freundlich or Langmuir equations, and compared between a sample of sludge leachate (containing 97.4% of Cu and 63.2% of Zn as dissolved organo-metallic complexes) and a reference solution (which mimicked the leachate, except for a lack of dissolved organic material). This comparison revealed that dissolved organo-metallic complexes significantly depressed Cu and Zn sorption in the study soil. The isotherm equations were then used to estimate sludge-derived Cu and Zn loadings to soil in order to result in an "allowable" output concentration from the soil solution to the surrounding environment. These loadings, together with soil bulk density and "availability" of sludge Cu and Zn, were incorporated in a preliminary model to estimate sludge application rates which are acceptable in terms of off-site movement of these metals through leaching losses. In the absence of dissolved organo-metallic complexes (sorption from the reference solution), levels of Cu and Zn sorption in the study soil indicated a sludge application rate of approximately 3500 kg/ha. However, when Cu and Zn sorption from the sludge leachate with dissolved organo-metallic complexes was considered, calculated loading rates were reduced to approximately 690 kg-sludge/ha. This suggests that for sludge loading estimates based on soil sorption characteristics to be relevant to environmental protection, the sorption depressing effect of dissolved organo-metallic complexes should be quantitatively considered.

Action research: a suitable method for promoting change in nurse education.

This paper arose from a research study and its follow-up in four schools of nursing and midwifery. The study was concerned with evaluating the extent to which a philosophy of health had been integrated into the educational curricula of nurses, midwives and health visitors. The purpose of the follow-up was to disseminate and implement the study findings in the four centres. The findings showed that the interpretation and implementation of a philosophy of health in nursing had been variable. Health was operationalized as both health education and health promotion ranging from individualized information giving and disease prevention. Action research was chosen as the appropriate methodology for the follow-up because of its emphasis on participation and partnership. As the follow-up study progressed a number of issues emerged which were indicative of the changes taking place in nurse education as its institutional base shifted into higher education. Other issues were associated with the gap between the rhetoric and reality of action research and the expectations and needs of the key partners. The authors conclude that the follow-up study presented both challenges and opportunities to nurse educators in their endeavour to undertaken research and implement educational change.

Theophylline does not shorten hospital stay for children admitted for asthma.

OBJECTIVE: To determine if the use of intravenous theophylline, in the form of aminophylline, when added to systemic corticosteroids and aerosolized beta 2-agonists, enhances the improvement of children with acute asthma exacerbations. DESIGN: A double-blind, placebo-controlled, randomized, clinical trial. SETTING: The University of Maryland Medical Center, Baltimore, an urban primary- and tertiary-care pediatric medical center. PATIENTS: Forty-two children, aged 2 to 18 years, admitted to the hospital for acute exacerbations of asthma. METHODS: Patients were randomized to receive either intravenous theophylline to maintain a serum level greater than 55 mumol/L or a placebo infusion. All patients received methylprednisolone and nebulized albuterol. A clinical severity score was assessed twice daily. RESULTS: The mean length of stay for the treatment and control groups was 52.3 +/- 32.3 hours and 48.2 +/- 26.6 hours, respectively (t = 0.45, P = .65). The rate of improvement of clinical scores was similar. CONCLUSION: These data suggest that the addition of theophylline to albuterol and corticosteroids does not enhance improvement of children admitted to the hospital with asthma.

Hypothalamic GABAergic influences on treadmill exercise responses in rats.

Microinjection of GABAergic antagonists in the posterior hypothalamus (PH) produces exercise-like adjustments in cardiovascular function. To test the hypothesis that a hypothalamic GABAergic mechanism within the PH modulates the cardiovascular adjustments to dynamic exercise in conscious animals, Sprague-Dawley rats (n = 10) were instrumented with bilateral guide cannula directed at the pH, an arterial cannula, and Doppler flow probes on the iliac and mesenteric arteries. Saline (100 nl) or the GABAA receptor agonist muscimol (125 ng.100 nl-1) was bilaterally injected into the PH during treadmill exercise (20 m.min-1). Microinjection of saline had no effect on mean arterial pressure (MAP), heart rate (HR), mesenteric vascular resistance (MR), or iliac vascular resistance (IR) during exercise. Microinjection of muscimol during exercise produced no significant changes in MAP (mean change +/- SE; +0 +/- 1 mmHg), HR (+17 +/- 12 b.min-1), or MR (+7 +/- 13%). However, microinjection of muscimol produced a significant increase in IR during exercise (16 +/- 6%). In addition, muscimol significantly decreased treadmill run time (saline = 19.6 +/- 0.4 min; muscimol = 17.8 +/- 0.6 min) and produced behavioral effects (including mild sedation) that were most evident after exercise. The results of these experiments suggest that while the posterior hypothalamic GABAergic system may modulate iliac blood flow during exercise in rats, this system does not modulate HR and MR responses to dynamic exercise.

Stimulatory and inhibitory regulation of DNA synthesis during spermatogenesis: studies in Squalus acanthias.

Spermatogenesis is a unique developmental sequence involving multiple cell to cell interactions and several categories of regulatory molecules. In contrast to conventional mammalian models in which testicular organization is highly complex, the testis of the dogfish shark Squalus acanthias is technically advantageous for elucidating stage-dependent structural and functional charactericsics and for in vitro regulatory studies. Using incorporation of [(3)H]thymidine into acid-insoluble molecules as a measure of DNA synthesis by spermatocysts (germ cell/Sertoli cell units) of premeiotic stages, we obtained evidence of a growth inhibitory bioactivity (chalone) within the testis. This activity is differentially distributed (postmeiotic > meiotic > premeiotic), suggesting that more advanced developmental stages, which are upstream in the vascular pathway within the testis, may control the size of the proliferating spermatocyst population and, hence, the advance of less mature stages. These data provide direct evidence for humoral communication between stages of spermatogenesis.

Acute open reduction and rigid internal fixation of proximal interphalangeal joint fracture dislocation.

We report the application and results of a technique of open reduction and rigid internal fixation of dorsal fracture/dislocation of the proximal interphalangeal joint with an interfragmentary screw in two cases. Articular congruity was restored, and the proximal interphalangeal joint was stabilized. This technique permitted immediate range-of-motion exercises. Excellent results were obtained in both cases. Previous descriptions have not detailed the indications, the surgical approach, or the results of this technique.