The dispersion-brightness relation for fast radio bursts from a wide-field survey.

Despite considerable efforts over the past decade, only 34 fast radio bursts-intense bursts of radio emission from beyond our Galaxy-have been reported1,2. Attempts to understand the population as a whole have been hindered by the highly heterogeneous nature of the searches, which have been conducted with telescopes of different sensitivities, at a range of radio frequencies, and in environments corrupted by different levels of radio-frequency interference from human activity. Searches have been further complicated by uncertain burst positions and brightnesses-a consequence of the transient nature of the sources and the poor angular resolution of the detecting instruments. The discovery of repeating bursts from one source3, and its subsequent localization4 to a dwarf galaxy at a distance of 3.7 billion light years, confirmed that the population of fast radio bursts is located at cosmological distances. However, the nature of the emission remains elusive. Here we report a well controlled, wide-field radio survey for these bursts. We found 20, none of which repeated during follow-up observations between 185-1,097 hours after the initial detections. The sample includes both the nearest and the most energetic bursts detected so far. The survey demonstrates that there is a relationship between burst dispersion and brightness and that the high-fluence bursts are the nearby analogues of the more distant events found in higher-sensitivity, narrower-field surveys5.

Retinoids in the treatment of photoageing: A histological study of topical retinoid efficacy in black skin.

BACKGROUND: Photoageing describes complex cutaneous changes that occur due to chronic exposure to solar ultraviolet radiation (UVR). The 'gold standard' for the treatment of photoaged white skin is all-trans retinoic acid (ATRA); however, cosmetic retinol (ROL) has also proven efficacious. Recent work has identified that black skin is susceptible to photoageing, characterized by disintegration of fibrillin-rich microfibrils (FRMs) at the dermal-epidermal junction (DEJ). However, the impact of topical retinoids for repair of black skin has not been well investigated. OBJECTIVES: To determine the potential of retinoids to repair photoaged black skin. METHODS: An exploratory intervention study was performed using an in vivo, short-term patch test protocol. Healthy but photoaged black volunteers (>45 years) were recruited to the study, and participant extensor forearms were occluded with either 0.025% ATRA (n = 6; 4-day application due to irritancy) or ROL (12-day treatment protocol for a cosmetic) at concentrations of 0.3% (n = 6) or 1% (n = 6). Punch biopsies from occluded but untreated control sites and retinoid-treated sites were processed for histological analyses of epidermal characteristics, melanin distribution and dermal remodelling. RESULTS: Treatment with ATRA and ROL induced significant acanthosis (all p < 0.001) accompanied by a significant increase in keratinocyte proliferation (Ki67; all p < 0.01), dispersal of epidermal melanin and restoration of the FRMs at the DEJ (all p < 0.01), compared to untreated control. CONCLUSIONS: This study confirms that topical ATRA has utility for the repair of photoaged black skin and that ROL induces comparable effects on epidermal and dermal remodelling, albeit over a longer timeframe. The effects of topical retinoids on black photoaged skin are similar to those reported for white photoaged skin and suggest conserved biology in relation to repair of UVR-induced damage. Further investigation of topical retinoid efficacy in daily use is warranted for black skin.

A large light-mass component of cosmic rays at 10(17)-10(17.5) electronvolts from radio observations.

Cosmic rays are the highest-energy particles found in nature. Measurements of the mass composition of cosmic rays with energies of 10(17)-10(18) electronvolts are essential to understanding whether they have galactic or extragalactic sources. It has also been proposed that the astrophysical neutrino signal comes from accelerators capable of producing cosmic rays of these energies. Cosmic rays initiate air showers--cascades of secondary particles in the atmosphere-and their masses can be inferred from measurements of the atmospheric depth of the shower maximum (Xmax; the depth of the air shower when it contains the most particles) or of the composition of shower particles reaching the ground. Current measurements have either high uncertainty, or a low duty cycle and a high energy threshold. Radio detection of cosmic rays is a rapidly developing technique for determining Xmax (refs 10, 11) with a duty cycle of, in principle, nearly 100 per cent. The radiation is generated by the separation of relativistic electrons and positrons in the geomagnetic field and a negative charge excess in the shower front. Here we report radio measurements of Xmax with a mean uncertainty of 16 grams per square centimetre for air showers initiated by cosmic rays with energies of 10(17)-10(17.5) electronvolts. This high resolution in Xmax enables us to determine the mass spectrum of the cosmic rays: we find a mixed composition, with a light-mass fraction (protons and helium nuclei) of about 80 per cent. Unless, contrary to current expectations, the extragalactic component of cosmic rays contributes substantially to the total flux below 10(17.5) electronvolts, our measurements indicate the existence of an additional galactic component, to account for the light composition that we measured in the 10(17)-10(17.5) electronvolt range.

Why do healthcare professionals fail to escalate as per the early warning system (EWS) protocol? A qualitative evidence synthesis of the barriers and facilitators of escalation.

BACKGROUND: Early warning systems (EWSs) are used to assist clinical judgment in the detection of acute deterioration to avoid or reduce adverse events including unanticipated cardiopulmonary arrest, admission to the intensive care unit and death. Sometimes healthcare professionals (HCPs) do not trigger the alarm and escalate for help according to the EWS protocol and it is unclear why this is the case. The aim of this qualitative evidence synthesis was to answer the question 'why do HCPs fail to escalate care according to EWS protocols?' The findings will inform the update of the National Clinical Effectiveness Committee (NCEC) National Clinical Guideline No. 1 Irish National Early Warning System (INEWS). METHODS: A systematic search of the published and grey literature was conducted (until February 2018). Data extraction and quality appraisal were conducted by two reviewers independently using standardised data extraction forms and quality appraisal tools. A thematic synthesis was conducted by two reviewers of the qualitative studies included and categorised into the barriers and facilitators of escalation. GRADE CERQual was used to assess the certainty of the evidence. RESULTS: Eighteen studies incorporating a variety of HCPs across seven countries were included. The barriers and facilitators to the escalation of care according to EWS protocols were developed into five overarching themes: Governance, Rapid Response Team (RRT) Response, Professional Boundaries, Clinical Experience, and EWS parameters. Barriers to escalation included: Lack of Standardisation, Resources, Lack of accountability, RRT behaviours, Fear, Hierarchy, Increased Conflict, Over confidence, Lack of confidence, and Patient variability. Facilitators included: Accountability, Standardisation, Resources, RRT behaviours, Expertise, Additional support, License to escalate, Bridge across boundaries, Clinical confidence, empowerment, Clinical judgment, and a tool for detecting deterioration. These are all individual yet inter-related barriers and facilitators to escalation. CONCLUSIONS: The findings of this qualitative evidence synthesis provide insight into the real world experience of HCPs when using EWSs. This in turn has the potential to inform policy-makers and HCPs as well as hospital management about emergency response system-related issues in practice and the changes needed to address barriers and facilitators and improve patient safety and quality of care.

A validated photonumeric scale for infraorbital dark circles and its application in evaluating the efficacy of a cosmetic treatment product in a split-face randomized clinical trial.

OBJECTIVE: As a result of their complex aetiology and periodicity, dark circles are difficult to characterize and measure, with current assessment techniques relying on specialist equipment, image analysis or proprietary grading scales. There is therefore a need to develop and validate a photonumeric scale for assessing infraorbital dark circles, which can provide an objective and consumer relevant tool for evaluating this condition and the efficacy of treatment products and procedures. METHODS: A panel of expert clinical evaluators reviewed approximately three thousand facial photographs collected over a 5-year period and selected images representing a dynamic range of dark circles. A 10-point photonumeric scale was created, with corresponding descriptors and images for each grade of the scale. To rigorously validate the scale, linearity, sensitivity and precision were assessed by colorimetry and in-clinic evaluation. Reproducibility was assessed photographically with both experienced and inexperienced clinical evaluators, whereas intragrader repeatability was assessed live in-clinic. The scale was then employed in a split-face randomized clinical trial on 58 subjects to evaluate the efficacy of a cosmetic treatment product over 8 weeks. RESULTS: Colour analysis of the images showed the scale was linear, with statistically significant correlations observed when colour data (CIElab; Individual Typology Angle) were plotted against the corresponding grades (r > 0.9, P < 0.001). Colour difference (Delta E) was calculated between the infraorbital zone and the surrounding skin, and when data were plotted against the grades, a statistically significant correlation was observed (r = 0.99, P < 0.01). The magnitude of the Delta E suggested that changes in grade are visibly perceptible to the human eye, and therefore, the scale is sensitive and clinically relevant. Intergrader reproducibility showed strong correlation (0.96) and >90% agreement between experienced evaluators, whereas intragrader repeatability assessment showed >90% perfect agreement between grades. Use of this scale in a clinical trial demonstrated the efficacy of a cosmetic product, with a mean statistically significant (P < 0.001) decrease in grade of 0.74 compared to baseline, and 0.59 versus the untreated control, after 8 weeks of treatment. CONCLUSION: Our photonumeric scale for infraorbital dark circles is sensitive and robust and provides an objective and easy-to-use tool to evaluate dark circles and their treatment.

OBJECTIF: En raison de leur étiologie et de leur périodicité complexes, les cernes sont difficiles à caractériser et à mesurer, les techniques d'évaluation actuelles reposant sur des équipements spécialisés, l'analyse d'images ou des échelles de notation exclusives. Il est donc nécessaire de développer et de valider une échelle photonumérique pour évaluer les cernes infraorbitaires, laquelle peut fournir un outil objectif et pertinent pour le consommateur et tester l'efficacité des produits et des procédures de traitement. MÉTHODES: Un panel d'évaluateurs cliniques experts a examiné environ trois mille photographies du visage recueillies sur une période de 5 ans, ainsi que des images sélectionnées représentant une plage dynamique de cernes. Une échelle photonumérique à 10 points a été créée, avec des descripteurs et des images correspondants à chaque grade de l'échelle. Afin de valider rigoureusement l'échelle, la linéarité, la sensibilité et la précision ont été évaluées par colorimétrie et en clinique. La reproductibilité a été évaluée sur le plan photographique par des évaluateurs cliniques expérimentés et inexpérimentés, tandis que la répétabilité intragrade a été évaluée en direct en clinique. L'échelle a ensuite été utilisée dans un essai clinique randomisé à deux parties sur 58 sujets, afin d'évaluer l'efficacité d'un produit de traitement cosmétique sur 8 semaines. RÉSULTATS: L'analyse des couleurs des images a montré que l'échelle était linéaire, avec des corrélations statistiquement significatives observées lorsque les données de couleurs (CIElab ; angle de typologie individuel) ont été tracées par rapport aux grades correspondants (r > 0,9, P < 0,001). La différence de couleur (Delta E) a été calculée entre la zone infraorbitaire et la peau environnante, et lorsque les données ont été tracées par rapport aux grades, une corrélation statistiquement significative a été observée (r = 0,99, P < 0,01). L'ampleur du delta E a suggéré que les changements de grade sont visiblement perceptibles à l'œil humain, l'échelle étant par conséquent sensible et cliniquement pertinente. La reproductibilité intergrade a montré une forte corrélation (0,96) et une concordance > 90 % entre les évaluateurs expérimentés, tandis que l'évaluation de la répétabilité intragrade a montré une concordance parfaite > 90 % entre les grades. L'utilisation de cette échelle lors d'un essai clinique a démontré l'efficacité d'un produit cosmétique, avec une diminution moyenne statistiquement significative (P < 0,001) du grade de 0,74 par rapport à la référence, et de 0,59 par rapport au témoin non traité, après 8 semaines de traitement. CONCLUSION: Notre échelle photonumérique pour les cernes infraorbitaires est sensible et robuste, fournissant un outil objectif et facile à utiliser afin d'évaluer les cernes et leur traitement.

On the use of Europium (Eu) for designing new metal-based anticancer drugs.

Europium oxide (Eu2O3) was used to evaluate the affinity of this rare earth element for interacting with double-stranded (ds) DNA molecules. To perform the study, we used single molecule force spectroscopy with optical tweezers and gel electrophoresis assays. Force spectroscopy experiments show that Eu2O3 presents a strong interaction with dsDNA, and the binding is independent on the ionic strength used in the surrounding environment. Among the main characteristics of the interaction, Eu2O3 tends to bind in a cooperative way, forming bound clusters of ∼ 3 molecules, and presents a high equilibrium association binding constant on the order of 105 M-1. In addition, gel electrophoresis confirm the weak electrostatic character of the interaction and explicit show that Eu2O3 does not interfere on drug intercalation into the double-helix. Such results demonstrate the potential of europium for interacting with nucleic acids and strongly suggest that this rare earth element may be considered for the design of new metal-based anticancer drugs in the future.

Estimating survival in advanced cancer: a comparison of estimates made by oncologists and patients.

PURPOSE: To compare estimates of expected survival time (EST) made by patients with advanced cancer and their oncologists. METHODS: At enrolment patients recorded their "understanding of how long you may have to live" in best-case, most-likely, and worst-case scenarios. Oncologists estimated survival time for each of their patients as the "median survival of a group of identical patients". We hypothesized that oncologists' estimates of EST would be unbiased (~ 50% longer or shorter than the observed survival time [OST]), imprecise (< 33% within 0.67 to 1.33 times OST), associated with OST, and more accurate than patients' estimates of their own survival. RESULTS: Twenty-six oncologists estimated EST for 179 patients. The median estimate of EST was 6.0 months, and the median OST was 6.2 months. Oncologists' estimates were unbiased (56% longer than OST), imprecise (27% within 0.67 to 1.33 times OST), and significantly associated with OST (HR 0.88, 95% CI 0.82 to 0.93, p < 0.01). Only 41 patients (23%) provided a numerical estimate of their survival with 107 patients (60%) responding "I don't know". The median estimate by patients for their most-likely scenario was 12 months. Patient estimates of their most-likely scenario were less precise (17% within 0.67 to 1.33 times OST) and more likely to overestimate survival (85% longer than OST) than oncologist estimates. CONCLUSION: Oncologists' estimates were unbiased and significantly associated with survival. Most patients with advanced cancer did not know their EST or overestimated their survival time compared to their oncologist, highlighting the need for improved prognosis communication training. Trial registration ACTRN1261300128871.

Baseline characteristics, disease severity and treatment history of patients with atopic dermatitis included in the German AD Registry TREATgermany.

BACKGROUND: The Atopic Dermatitis (AD) TREATgermany registry was initiated by the German Society for Dermatology (DDG) in 2011 to evaluate the 'real-life' situation of health care for patients with AD. OBJECTIVES: Interim data analysis on baseline characteristics as well as current and prescribed systemic treatments of the TREATgermany registry patients. METHODS: Patients (≥18 years) with moderate-to-severe AD [objective (o)SCORAD > 20], or with current or previous anti-inflammatory systemic treatment for AD within 24 months, were included and are followed up over at least 24 months. To assess clinical signs, the eczema area severity index (EASI, 0-72), the oSCORAD (0-83) and the Investigator Global Assessment (IGA; 6-point scale) were used. The disease severity was globally scored by the patients [Patient Global Assessment (PGA); six-step Likert scale]. Disease symptoms were assessed by the patient-oriented eczema measure (POEM, 0-28) and numeric rating scales (NRS, 0-10). Health-related quality of life was measured using the dermatological life quality index (DLQI, 0-30). RESULTS: A total of 612 patients were recruited across 32 sites between 06/2016 and 01/2019 (mean age: 42.6 ± 14.2 years; mean oSCORAD: 40.8 ± 16.3). The mean POEM score was 16.3 ± 7.5. Pruritus was rated highest among subjective symptoms (NRS: 5.4 ± 2.7). The mean DLQI value was 11.3 ± 7.5. The frequency of arterial hypertension was lower (20.8%) compared with the general population, whilst this was higher for depression (10%). More than 60% of the patients had received systemic glucocorticosteroids, and 36.8% had received cyclosporine A prior to inclusion. Dupilumab was the leading substance documented as either 'current' (12.1%) or 'prescribed' (31.4%) at baseline. CONCLUSIONS: These 'real-life' data clearly demonstrate the substantial disease burden. Most of TREATgermany patients were already treated with or prescribed dupilumab at baseline. Moreover, current findings indicate the urgent need for further alternative agents in order to achieve a perceptible improvement of quality of life of patients with moderate-to-severe AD.

A Rare Case of Infertility: SRY Positive 46, XX Testicular Disorder of Sexual Differentiation.

Aim To highlight the complexity of infertility causes by describing the rare case of a man with a testicular disorder of sexual differentiation. Diagnosis A 33 years old Caucasian male presented with a 3-year-old history of primary infertility. His investigations revealed a low testosterone and a raised LH and FSH levels. A sample sent for sperm analysis revealed azoospermia. Chromosomal analysis and karyotyping revealed a 46 XX SRY positive karyotype. Treatment The patient was initiated on testosterone replacement and on calcium/vitamin D supplements. Conclusion Fertility evaluation requires complex assessments and a broad knowledge of possible causes.

Sunscreen applied at ≥ 2 mg cm-2 during a sunny holiday prevents erythema, a biomarker of ultraviolet radiation-induced DNA damage and suppression of acquired immunity.

BACKGROUND: Sun protection factor (SPF) is assessed with sunscreen applied at 2 mg cm-2 . People typically apply around 0·8 mg cm-2 and use sunscreen daily for holidays. Such use results in erythema, which is a risk factor for skin cancer. OBJECTIVES: To determine (i) whether typical sunscreen use resulted in erythema, epidermal DNA damage and photoimmunosuppression during a sunny holiday, (ii) whether optimal sunscreen use inhibited erythema and (iii) whether erythema is a biomarker for photoimmunosuppression in a laboratory study. METHODS: Holidaymakers (n = 22) spent a week in Tenerife (very high ultraviolet index) using their own sunscreens without instruction (typical sunscreen use). Others (n = 40) were given SPF 15 sunscreens with instructions on how to achieve the labelled SPF (sunscreen intervention). Personal ultraviolet radiation (UVR) exposure was monitored electronically as the standard erythemal dose (SED) and erythema was quantified. Epidermal cyclobutane pyrimidine dimers (CPDs) were determined by immunostaining, and immunosuppression was assessed by contact hypersensitivity (CHS) response. RESULTS: There was no difference between personal UVR exposure in the typical sunscreen use and sunscreen intervention groups (P = 0·08). The former had daily erythema on five UVR-exposed body sites, increased CPDs (P < 0·001) and complete CHS suppression (20 of 22). In comparison, erythema was virtually absent (P < 0·001) when sunscreens were used at ≥ 2 mg cm-2 . A laboratory study showed that 3 SED from three very different spectra suppressed CHS by around ~50%. CONCLUSIONS: Optimal sunscreen use prevents erythema during a sunny holiday. Erythema predicts suppression of CHS (implying a shared action spectrum). Given that erythema and CPDs share action spectra, the data strongly suggest that optimal sunscreen use will also reduce CPD formation and UVR-induced immunosuppression.

Optimal sunscreen use, during a sun holiday with a very high ultraviolet index, allows vitamin D synthesis without sunburn.

BACKGROUND: Sunlight contains ultraviolet (UV)A and UVB radiation. UVB is essential for vitamin D synthesis but is the main cause of sunburn and skin cancer. Sunscreen use is advocated to reduce the sun's adverse effects but may compromise vitamin D status. OBJECTIVES: To assess the ability of two intervention sunscreens to inhibit vitamin D synthesis during a week-long sun holiday. METHODS: The impact of sunscreens on vitamin D status was studied during a 1-week sun holiday in Tenerife (28° N). Comparisons were made between two formulations, each with a sun protection factor (SPF) of 15. The UVA-protection factor (PF) was low in one case and high in the other. Healthy Polish volunteers (n = 20 per group) were given the sunscreens and advised on the correct application. Comparisons were also made with discretionary sunscreen use (n = 22) and nonholiday groups (51·8° N, n = 17). Sunscreen use in the intervention groups was measured. Behaviour, UV radiation exposure, clothing cover and sunburn were monitored. Serum 25-hydroxyvitamin D3 [25(OH)D3 ] was assessed by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Use of intervention sunscreens was the same (P = 0·60), and both equally inhibited sunburn, which was present in the discretionary use group. There was an increase (P < 0·001) in mean ± SD 25(OH)D3 (28·0 ± 16·5 nmol L-1 ) in the discretionary use group. The high and low UVA-PF sunscreen groups showed statistically significant increases (P < 0·001) of 19·0 ± 14·2 and 13·0 ± 11·4 nmol L-1 25(OH)D3 , respectively with P = 0·022 for difference between the intervention sunscreens. The nonholiday group showed a fall (P = 0·08) of 2·5 ± 5·6 nmol L-1 25(OH)D3 . CONCLUSIONS: Sunscreens may be used to prevent sunburn yet allow vitamin D synthesis. A high UVA-PF sunscreen enables significantly higher vitamin D synthesis than a low UVA-PF sunscreen because the former, by default, transmits more UVB than the latter. What's already known about this topic? Action spectra (wavelength dependence) for erythema and the cutaneous formation of vitamin D overlap considerably in the ultraviolet (UV)B region. Theoretically, sunscreens that inhibit erythema should also inhibit vitamin D synthesis. To date, studies on the inhibitory effects of sunscreens on vitamin D synthesis have given conflicting results, possibly, in part, because people typically apply sunscreen suboptimally. Many studies have design flaws. What does this study add? Sunscreens (sun protection factor, SPF 15) applied at sufficient thickness to inhibit sunburn during a week-long holiday with a very high UV index still allow a highly significant improvement of serum 25-hydroxyvitamin D3 concentration. An SPF 15 formulation with high UVA protection enables better vitamin D synthesis than a low UVA protection product. The former allows more UVB transmission.

An explanation for the mysterious distribution of melanin in human skin: a rare example of asymmetric (melanin) organelle distribution during mitosis of basal layer progenitor keratinocytes.

BACKGROUND: Melanin is synthesized by melanocytes in the basal layer of the epidermis. When transferred to surrounding keratinocytes melanin is the key ultraviolet radiation-protective biopolymer responsible for skin pigmentation. Most melanin is observable in the proliferative basal layer of the epidermis and only sparsely distributed in the stratifying/differentiating epidermis. The latter has been explained as 'melanin degradation' in suprabasal layers. OBJECTIVES: To re-evaluate the currently accepted basis for melanin distribution in human epidermis and to discover whether this pattern is altered after a regenerative stimulus. METHODS: Normal epidermis of adult human skin, at rest and after tape-stripping, was analysed by a range of (immuno)histochemical and high-resolution microscopy techniques. In vitro models of melanin granule uptake by human keratinocytes were attempted. RESULTS: We propose a different fate for melanin in the human epidermis. Our evidence indicates that the bulk of melanin is inherited only by the nondifferentiating daughter cell postmitosis in progenitor keratinocytes via asymmetric organelle inheritance. Moreover, this preferred pattern of melanin distribution can switch to a symmetric or equal daughter cell inheritance mode under conditions of stress, including regeneration. CONCLUSIONS: In this preliminary report, we provide a plausible and histologically supported explanation for how human skin pigmentation is efficiently organized in the epidermis. Steady-state epidermis pigmentation may involve much less redox-sensitive melanogenesis than previously thought, and at least some premade melanin may be available for reuse. The epidermal melanin unit may be an excellent example with which to study organelle distribution via asymmetric or symmetric inheritance in response to microenvironment and tissue demands.

Case-case analysis of Campylobacter and Salmonella - using surveillance data for outbreak investigations and monitoring routine risk factors.

Utilising routine surveillance data, this study presents a method for generating a baseline comparison that can be used in future foodborne outbreak investigations following a case-case methodology. Salmonella and Campylobacter cases (2012-2015) from Maricopa County, AZ were compared to determine differences in risk factors, symptoms and demographics. For foods and other risk factors, adjusted odds ratios were developed using Campylobacter as the reference. Comparisons were also made for three major Salmonella subtypes, Typhimurium, Enteritidis and Poona as compared with Campylobacter. Salmonella cases were younger, while Campylobacter cases were more Hispanic and female. Campylobacter cases reported consuming peppers, sprouts, poultry, queso fresco, eggs and raw nuts more and reported contact with animal products, birds, visiting a farm or dairy, owning a pet, a sick pet, swimming in a river, lake or pond, or handling multiple raw meats more. Salmonella cases reported visiting a petting zoo and contact with a reptile more. There were significant variations by Salmonella subtype in both foods and exposures. We recommend departments conduct this analysis to generate a baseline comparison and a running average of relevant odds ratios allowing staff to focus on trace-back of contaminated food items earlier in the outbreak investigation process.

Behavioral and subjective health changes in US and Mexico border residing participants in two promotora-led chronic disease preventive interventions.

Chronic diseases are the primary health burden among Mexican-origin populations and health promotion efforts have not been able to change negative population trends. This research presents behavioral and subjective health impacts of two related community health worker (CHW) interventions conducted in the US-Mexico border region. Pasos Adelante (United States) and Meta Salud (Mexico) are 12-13 week CHW-led preventive interventions implemented with Mexico-origin adults. Curricula include active learning modules to promote healthy dietary changes and increasing physical activity; they also incorporate strategies to promote social support, empowerment and group exercise components responsive to their communities. Questionnaire data at baseline (N = 347 for Pasos; 171 for Meta Salud), program completion and 3-month follow-up were analyzed. Results showed statistically significant improvements in multiple reported dietary, physical activity and subjective health indicators. Furthermore, at follow-up across both cohorts there were ≥10% improvements in participants' meeting recommended physical activity guidelines, consumption of whole milk, days of poor mental health and self-rated health. While this study identifies some robust health improvements and contributes to the evidence base for these interventions current dissemination, the lack of change observed for some targeted behaviors (e.g. time sitting) suggests they may have stronger overall impacts with curricula refinement.

Short communication: Development of an equation for estimating methane emissions of dairy cows from milk Fourier transform mid-infrared spectra by using reference data obtained exclusively from respiration chambers.

Evaluation and mitigation of enteric methane (CH4) emissions from ruminant livestock, in particular from dairy cows, have acquired global importance for sustainable, climate-smart cattle production. Based on CH4 reference measurements obtained with the SF6 tracer technique to determine ruminal CH4 production, a current equation permits evaluation of individual daily CH4 emissions of dairy cows based on milk Fourier transform mid-infrared (FT-MIR) spectra. However, the respiration chamber (RC) technique is considered to be more accurate than SF6 to measure CH4 production from cattle. This study aimed to develop an equation that allows estimating CH4 emissions of lactating cows recorded in an RC from corresponding milk FT-MIR spectra and to challenge its robustness and relevance through validation processes and its application on a milk spectral database. This would permit confirming the conclusions drawn with the existing equation based on SF6 reference measurements regarding the potential to estimate daily CH4 emissions of dairy cows from milk FT-MIR spectra. A total of 584 RC reference CH4 measurements (mean ± standard deviation of 400 ± 72 g of CH4/d) and corresponding standardized milk mid-infrared spectra were obtained from 148 individual lactating cows between 7 and 321 d in milk in 5 European countries (Germany, Switzerland, Denmark, France, and Northern Ireland). The developed equation based on RC measurements showed calibration and cross-validation coefficients of determination of 0.65 and 0.57, respectively, which is lower than those obtained earlier by the equation based on 532 SF6 measurements (0.74 and 0.70, respectively). This means that the RC-based model is unable to explain the variability observed in the corresponding reference data as well as the SF6-based model. The standard errors of calibration and cross-validation were lower for the RC model (43 and 47 g/d vs. 66 and 70 g/d for the SF6 version, respectively), indicating that the model based on RC data was closer to actual values. The root mean squared error (RMSE) of calibration of 42 g/d represents only 10% of the overall daily CH4 production, which is 23 g/d lower than the RMSE for the SF6-based equation. During the external validation step an RMSE of 62 g/d was observed. When the RC equation was applied to a standardized spectral database of milk recordings collected in the Walloon region of Belgium between January 2012 and December 2017 (1,515,137 spectra from 132,658 lactating cows in 1,176 different herds), an average ± standard deviation of 446 ± 51 g of CH4/d was estimated, which is consistent with the range of the values measured using both RC and SF6 techniques. This study confirmed that milk FT-MIR spectra could be used as a potential proxy to estimate daily CH4 emissions from dairy cows provided that the variability to predict is covered by the model.

Evaluation of the safety of daily administration of capromorelin in cats.

Capromorelin is a ghrelin receptor agonist that is FDA approved for appetite stimulation in dogs. The objective of this study was to evaluate the safety of daily oral administration of capromorelin to cats over a range of doses and for an extended period. Two randomized, controlled studies were conducted: in Study 1, cats (n = 6 per group) received placebo or capromorelin at a dose of 9, 15, 30 or 60 mg/kg once daily for 14 days; and in Study 2, cats received capromorelin at 6 mg/kg (n = 8) or placebo (n = 4) once daily for 91 days. Cats were evaluated using clinical observations and clinical pathology test results for both studies, with the addition of postmortem examination in Study 1 and measurements of growth hormone and insulin-like growth factor 1 in Study 2. Abnormal clinical observations were limited to emesis, hypersalivation, lethargy/depression, head shaking and lip smacking, which occurred more frequently in the capromorelin-treated groups than in the placebo group. There were no clinically relevant differences in clinical pathology test results between the capromorelin and placebo groups in either study.

A theoretical and experimental study of the temporal reduction in UV protection provided by a facial day cream.

OBJECTIVE: To investigate how the UV protection provided by a facial day cream reduces over the course of a day. METHODS: We developed a theoretical model using a Monte Carlo random sampling approach to estimate the variation in local thickness, and hence local effective SPF, at several different sites over the face. The input variables, which are labelled SPF, average application thickness, homogeneity of the product on the skin and the ability of the product to bind to the skin, allow examination of how these different factors affect the delivered photoprotection. We compared the results of our modelling with experimental determination of the binding of an oil-in-water moisturizing day cream with a rated SPF of 15 at various times over the course of a day by means of UV photography and digital image analysis. RESULTS: We demonstrated good agreement between our theoretical predictions of the temporal reduction in product thickness and the experimental observations. We used our modelling approach to show that a substantial reduction in lifetime UV burden on the face could be achieved by a daycare product delivering 3-fold (or greater) protection over the face. CONCLUSION: Comparison with experimental data confirmed the robustness and validity of our model, which predicts that products intended for daily use need to be formulated carefully and applied uniformly, and to have a half-life of binding to the skin of several hours. Products that bind less well to the skin, or are applied non-uniformly, are likely to be providing inadequate protection with regards to influencing the rate of photoaging of the skin. Our data suggest that after a single, realistic application of a day cream rated SPF15, consumers' faces remain protected to at least an average of 5-fold around the middle of the day, especially pertinent to indoor workers who are likely to be exposed to maximum UV levels as they venture outside during their lunch break.

[Decreased professional performance and quality of life in patients with moderate-to-severe atopic eczema : Results from the German atopic eczema registry TREATgermany]. / Verminderte berufliche Leistungsfähigkeit und Lebensqualität bei Patienten mit moderater bis schwerer Neurodermitis : Ergebnisse aus dem Deutschen Neurodermitisregister TREATgermany.

BACKGROUND: Clinical registries may provide high-quality evidence on the use and effectiveness of therapeutic interventions under real-life conditions. Adults with moderate-to-severe atopic eczema (atopic dermatitis [AD]) are enrolled into TREATgermany and prospectively followed over at least 2 years. This paper analyses the association between dermatological quality of life and work limitations. MATERIALS AND METHODS: Treatment modalities and a broad set of physician- and patient-reported outcome measures are documented using validated instruments to assess clinical disease severity (EASI [Eczema Area and Severity Index], objective SCORAD [objective-SCORing Atopic Dermatitis]), quality of life (DLQI [Dermatology Life Quality Index]), symptoms (POEM [Patient-oriented Eczema Measure]), global disease severity, as well as patient satisfaction and work limitations including presenteeism (WLQ [Work Limitation Questionnaire]). From 06/2016 until 12/2017, 241 individuals (mean age 43 ± 15 years, 38.6% female) were enrolled at 19 recruitment centers; 69% of the patients were employed. RESULTS: Employed persons had DLQI and WLQ scores of 10.6 ± 6.9 points and 17.7 ± 18.1%, respectively. Mean presenteeism was substantial accounting for 9.2%. With coefficients of 0.39 and 0.33 WLQ and presenteeism scores significantly correlate with DLQI (p < 0.000). Bootstrapped regression models showed that the limitations in coping with work requirements increase by 1.7% as DLQI increases by one point. Lower quality of life due to AD is most strongly associated with limitations in the area of physical and performance requirements in general. Presenteeism increases by 0.5% as DLQI increases by one point. CONCLUSION: Moderate-to-severe AD has substantial adverse economic impact with mean productivity loss of patients of almost 10%. Future analyses from TREATgermany will address the impact of innovative treatment modalities on quality of life and work productivity of patients with moderate-to-severe AD.

Runx1 Orchestrates Sphingolipid Metabolism and Glucocorticoid Resistance in Lymphomagenesis.

The three-membered RUNX gene family includes RUNX1, a major mutational target in human leukemias, and displays hallmarks of both tumor suppressors and oncogenes. In mouse models, the Runx genes appear to act as conditional oncogenes, as ectopic expression is growth suppressive in normal cells but drives lymphoma development potently when combined with over-expressed Myc or loss of p53. Clues to underlying mechanisms emerged previously from murine fibroblasts where ectopic expression of any of the Runx genes promotes survival through direct and indirect regulation of key enzymes in sphingolipid metabolism associated with a shift in the "sphingolipid rheostat" from ceramide to sphingosine-1-phosphate (S1P). Testing of this relationship in lymphoma cells was therefore a high priority. We find that ectopic expression of Runx1 in lymphoma cells consistently perturbs the sphingolipid rheostat, whereas an essential physiological role for Runx1 is revealed by reduced S1P levels in normal spleen after partial Cre-mediated excision. Furthermore, we show that ectopic Runx1 expression confers increased resistance of lymphoma cells to glucocorticoid-mediated apoptosis, and elucidate the mechanism of cross-talk between glucocorticoid and sphingolipid metabolism through Sgpp1. Dexamethasone potently induces expression of Sgpp1 in T-lymphoma cells and drives cell death which is reduced by partial knockdown of Sgpp1 with shRNA or direct transcriptional repression of Sgpp1 by ectopic Runx1. Together these data show that Runx1 plays a role in regulating the sphingolipid rheostat in normal development and that perturbation of this cell fate regulator contributes to Runx-driven lymphomagenesis. J. Cell. Biochem. 118: 1432-1441, 2017. © 2016 Wiley Periodicals, Inc.

Statistical controversies in cancer research: using standardized effect size graphs to enhance interpretability of cancer-related clinical trials with patient-reported outcomes.

Patient reported outcomes (PROs) are becoming increasingly important in cancer studies, particularly with the emphasis on patient centered outcome research. However, multiple PROs, using different scales, with different directions of favorability are often used within a trial, making interpretation difficult. To enhance interpretability, we propose the use of a standardized effect size graph, which shows all PROs from a study on the same figure, on the same scale. Plotting standardized effects with their 95% confidence intervals (CIs) on a single graph clearly showing the null value conveys a comprehensive picture of trial results. We demonstrate how to create such a graph using data from a randomized controlled trial that measured 12 PROs at two time points. The 24 effect sizes and CIs are shown on one graph and clearly indicate that the intervention is effective and sustained.