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Objective: To assess the impact of a structured educational programme for caregivers of children with cancer on their level of knowledge about the disease and patient's clinical outcome., Methods: This prospective, non-randomised, experimental study included caregivers of recently diagnosed children at two hospitals in Chile. Caregivers whose children were treated at the first centre were the structured education programme group (EPG), while the second hospital provided the standard care (SCG). We evaluated caregivers' level of knowledge on days 1, 10 and 90 as well as the children's clinical outcomes over 1 year of treatment., Results: A total of 102 caregivers were enrolled between 2014 and 2015. Only the EPG showed a significant increase in knowledge between days 1 and 90. The rate of central venous catheter infections was significantly lower in the EPG versus SCG (7% versus 26%; p = .01). The risk ratio was 0.35 (95% CI = 0.13-0.94), and a log-rank test showed a statistically significant difference between the two groups (p = .018). There were also fewer Emergency Department visits in the EPG for fever episodes., Conclusion: Providing a structured education to caregivers increased their level of knowledge and improved the clinical outcome of their children during the first year of treatment., (© 2020 John Wiley & Sons Ltd.)

A clinical study was designed to record a wide range of physiological values from patients undergoing haemodialysis treatment in the Renal Unit of the Churchill Hospital in Oxford. Video was recorded for a total of 84 dialysis sessions from 40 patients during the course of 1 year, comprising an overall video recording time of approximately 304.1 h. Reference values were provided by two devices in regular clinical use. The mean absolute error between the heart rate estimates from the camera and the average from two reference pulse oximeters (positioned at the finger and earlobe) was 2.8 beats/min for over 65% of the time the patient was stable. The mean absolute error between the respiratory rate estimates from the camera and the reference values (computed from the Electrocardiogram and a thoracic expansion sensor-chest belt) was 2.1 breaths/min for over 69% of the time for which the reference signals were valid. To increase the robustness of the algorithms, novel methods were devised for cancelling out aliased frequency components caused by the artificial light sources in the hospital, using auto-regressive modelling and pole cancellation. Maps of the spatial distribution of heart rate and respiratory rate information were developed from the coefficients of the auto-regressive models. Most of the periods for which the camera could not produce a reliable heart rate estimate lasted under 3 min, thus opening the possibility to monitor heart rate continuously in a clinical environment.

Background: Invasive fungal disease is a major cause of morbidity and mortality in children with cancer and high-risk febrile neutropenia (HRFN). Repeated serum galactomannan (sGM) measurements have been described as an effective tool to guide therapy in adults under suspicion of invasive aspergillosis. However, the utility of this approach has not been reported in paediatric population., Objectives: To evaluate the usefulness of sGM measurements in initiating and modifying antifungal therapy (AFT) in children with cancer and persistent HRFN., Patients/methods: Nested case-control study in children with cancer and persistent HRFN episodes, between July 2013 and January 2019. Patients were classified as cases and controls depending on if they received AFT or not, respectively. Through odds ratio analysis, we assessed the role of sGM positivity in the AFT initiation decision. Then, we analysed the group of patients that initiated AFT, and compared those who had AFT modifications and those who did not, analysing different sGM kinetics thresholds., Results: A total of 191 episodes from children with persistent HRFN were enrolled, of which 107 received AFT and 84 did not. The median age was 7 years (IQR 4-12), 52% were male and 89% had a haematologic malignancy as underlying disease. Positive sGM was not associated with AFT initiation (OR 0.99, 95% CI 0.43-2.33, P = .99). A difference threshold in sGM Δ ≥ 0.3 sGM was significantly associated with AFT modification (OR 5.07, 95% CI 1.02- 25.70, P = .04)., Conclusions: Our results suggest the utility of serial sGM sampling during AFT in children with persistent HRFN., (© 2020 Blackwell Verlag GmbH.)

Background: Viridans group streptococci (VGS) has acquired relevance as a microorganism causing febrile neutropenia, associated with significant morbidity., Aim: To characterize episodes of bacteremia caused by VGS in children with cancer who developed high-risk febrile neutropenia (HRFN) during the period from April 2004 to June 2018 in six pediatric hospitals of Santiago, Chile., Method: Database analysis of 4 successive, prospective and multicentric studies recording clinical and laboratory characteristics of patients, as well as antimicrobial susceptibility pattern of isolated strains., Results: 95 episodes of VGS bacteremia in 91 children with HRFN were analyzed. It emphasizes acute myeloid leukemia as cancer type, deep neutropenia, prolonged hospitalization (15 days), with extended use of antimicrobials (14 days) and use of cytarabine in chemotherapy schemes (86% episodes). The most frequent clinical manifestations were respiratory and gastrointestinal, associating up to 26% viridans group shock syndrome. There was high resistance to β lactams. As expected, there were not non-susceptible strains to vancomycin., Discussion: VGS is a relevant microorganism in children with cancer, fever and neutropenia, with a high percentage of sepsis. Resistance to β lactams is an issue that requires strict epidemiological surveillance in this population.

Every year thousands of horses from Mexico and the United States of America (USA) are transported to slaughter in Mexico, but little is known about their welfare or pre-slaughter logistics. In this study, we recorded the origin, sex, age and condition of horses (121 journeys, 2648 animals) upon arrival to an abattoir in northern Mexico, including transport details. Horse welfare was measured indirectly via individual scores for body condition, coat quality, lameness, ocular and nasal discharge, as well as reactivity to a chute restraint test, all performed shortly after unloading. The average journey duration was 9.69 (±7.6) hours for horses from Mexico and 16.77 (±4.51) hours for horses from the USA (77 % of all journeys). The prevalence of ocular discharge, nasal discharge, skin wounds, lameness and diarrhoea, were 23 %, 12 %, 11 %, 9 %, 1 % (respectively) of all the horses observed, with no significant differences between Mexican and American horses (P ≥ 0.05). During the chute test the American horses were calmer than the Mexican ones (P < 0.001), who were more restless and aggressive (P = 0.001). Likewise, vocalizations in their three variants during the restraint, neigh/whinny (P = 0.018), nicker (P < 0.001), and snort (P = 0.018), were more common in horses from Mexico. In order to help characterize fitness for transport, a two-step cluster analysis was applied using the welfare indicators, suggesting the existence of four clusters (C) evaluated on arrival at the abattoir (from good to very poor fitness): good (profile C4, n = 769, 29.1 %), average (profile C1, n = 799 horses, 30.2 %), poor (profile C3, n = 586, 22.1 %) and very poor (profile C2, n = 494, 18.6 %). In fact, the C4 best welfare group had 0% lame, 0% nasal discharge, 16.4 % ocular discharge, 7.9 % skin wounds. Instead, the C2 poorest welfare group had 45.8 % lame, 61.1 % nasal discharge, 42.8 % ocular discharge, and 19.9 % skin wounds. Results show potential for using nasal discharge, lameness and ocular discharge as key indicators of horse fitness and welfare on abattoir. The study provides detailed scientific data to help establish strategies regarding optimal days of recovery post-transport and fattening for homogenization of weights between animals of different origins, logistic planning, and optimization of logistic resources to minimize the biological cost of long-distance transport., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Skin perfusion varies in response to changes in the circulatory status. Blood flow to skin is reduced during haemodynamic collapse secondary to peripheral vasoconstriction, whereas increased skin perfusion is frequently observed when haemodynamics improve with resuscitation. These changes in perfusion may be monitored using non-contact image-based methods. Previous camera-derived physiological measurements have focused on accurate vital signs monitoring and extraction of physiological signals from environmental noise. One of the biggest challenges of camera-derived monitoring is artefacts from motion, which limits our understanding of what parameters may be derived from skin. In this study, we use phenylephrine and glyceryl trinitrate (GTN) to cause vasoconstriction and vasodilation in stationary healthy volunteers to describe directional changes in skin perfusion pattern., Methods and Analysis: We aim to recruit 30 healthy volunteers who will undergo protocolised infusions of phenylephrine and GTN, followed by the monitored and timed release of a thigh tourniquet. The experimental timeline will be identical for all participants. Measurements of traditionally used haemodynamic markers (heart rate, blood pressure and stroke volume) and camera-derived measurements will be taken concurrently throughout the experimental period. The parameters of interest from the image data are skin colour and pattern, skin surface temperature, pulsatile signal detected at the skin surface and skin perfusion index., Ethics and Dissemination: This study was reviewed and approved by the Oxford University Research and Ethics Committee and Clinical Trials and Research Governance teams (R63796/RE001). The results of this study will be presented at scientific conferences and published in peer-reviewed journals., Trial Registration Number: ISRCTN10417167., Competing Interests: Competing interests: PJW is Chief Medical Officer for Sensyne Health and holds share options in the company. His organisation has received research funding from Sensyne Health not associated with this work. LT is a non-executive Director of Sensyne Health and holds share options in the company. LT is a non-executive Director of Oxehealth and holds shares in the company., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Endoscopic retrograde cholangiography with biliary stenting is the generally recognized optimal treatment of malignant biliary obstruction. This procedure, though, is challenging in patients with surgically altered anatomy. Endoscopic ultrasound (EUS) enables tissue sampling by means of fine-needle aspiration and also represents an alternative recourse for biliary drainage in preference to a percutaneous approach. We aimed to report a case in which EUS enabled a definitive diagnosis of the recurrence of oncologic disease and the relief of biliary obstruction in a patient with a surgically altered anatomy.

Objective: There are multiple treatment options to enhance a patient's smile, from conservative bleaching procedures to composite resins, porcelain veneers, or full-coverage crowns. Treating patients with porcelain veneers is a commonly used approach in esthetic dentistry. Provisional restorations for veneers can be time-consuming to make and difficult to retain. This article illustrates a technique for fabricating indirect snap-on provisional restorations for veneer cases, describing both analog and digital approaches., Clinical Considerations: The present article presents an alternative provisionalization technique using snap-on restorations for dental veneers. Application of these techniques will allow for ease of cleansability by the patient leading to healthier soft tissues before the final cementation. Delivery of veneers is more predictable with healthy soft tissue, as bleeding and inflammation may affect the bonding process., Conclusions: This technique is an effective provisionalization option in most veneer cases. This approach seems to be well accepted by patients and a good alternative in helping to maintain optimal gingival health with interim restorations before delivery., Clinical Significance: The use of snap-on provisionals for veneer restorations will allow the clinician to have an efficient technique with better tissue response before cementation. This prevents inflammation and facilitates a controlled delivery process., (© 2020 Wiley Periodicals, Inc.)

Background: Postmenopausal women have higher severity of coronary heart disease (CHD) than premenopausal women and type 2 diabetes mellitus (T2DM) is an independent risk factor., Aim: To assess the severity of CHD in pre and postmenopausal patients undergoing coronary angiography and the impact of T2DM in both groups., Material and Methods: A coronary angiography was performed to 707 women due to suspected CHD during 2013 and 2014. Of these, 579 were older than 55 years and were considered as postmenopausal. Factors such as hypertension, obesity, smoking, creatinine and T2DM were registered. The severity of CHD in coronary angiography was evaluated according to the number of vessels with more than 50% stenosis., Results: Compared to their postmenopausal counterparts, premenopausal women had less frequency of T2DM (31% and 42% p < 0.033), hypertension (52 and 78%, p < 0.001) and alteration of renal function (11 vs. 39%, p < 0.001). Absence of coronary lesions was found in 44 and 32% of premenopausal and postmenopausal women, respectively (p < 0.01). Premenopausal women with T2DM had a higher frequency of multi-vessel disease than those without the disease (25 and 4.5%, p < 0.001). The frequency of multi-vessel disease was higher in postmenopausal than premenopausal women (24 and 11%, p < 0.01). Hypertension, T2DM and renal involvement were associated with a higher frequency multiple vessel disease., Conclusions: The severity of CHD is higher in postmenopausal women and T2DM is associated with the disease.

The implementation of video-based non-contact technologies to monitor the vital signs of preterm infants in the hospital presents several challenges, such as the detection of the presence or the absence of a patient in the video frame, robustness to changes in lighting conditions, automated identification of suitable time periods and regions of interest from which vital signs can be estimated. We carried out a clinical study to evaluate the accuracy and the proportion of time that heart rate and respiratory rate can be estimated from preterm infants using only a video camera in a clinical environment, without interfering with regular patient care. A total of 426.6 h of video and reference vital signs were recorded for 90 sessions from 30 preterm infants in the Neonatal Intensive Care Unit (NICU) of the John Radcliffe Hospital in Oxford. Each preterm infant was recorded under regular ambient light during daytime for up to four consecutive days. We developed multi-task deep learning algorithms to automatically segment skin areas and to estimate vital signs only when the infant was present in the field of view of the video camera and no clinical interventions were undertaken. We propose signal quality assessment algorithms for both heart rate and respiratory rate to discriminate between clinically acceptable and noisy signals. The mean absolute error between the reference and camera-derived heart rates was 2.3 beats/min for over 76% of the time for which the reference and camera data were valid. The mean absolute error between the reference and camera-derived respiratory rate was 3.5 breaths/min for over 82% of the time. Accurate estimates of heart rate and respiratory rate could be derived for at least 90% of the time, if gaps of up to 30 seconds with no estimates were allowed., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2019.)

Despite its theoretical relationship, the effect of body size on the performance of species distribution models (SDM) has only been assessed in a few studies, and to date, the evidence shows unclear results. In this context, Chilean fishes provide an ideal case to evaluate this relationship due to their short size (fishes between 5 cm and 40 cm) and conservation status, providing evidence for species at the lower end of the worldwide fish size distribution and representing a relevant management tool for species conservation. We assessed the effect of body size on the performance of SDM in nine Chilean river fishes, considering the number of records, performance metrics, and predictor importance. The study was developed in the Bueno and Valdivia basins of southern Chile. We used a neural network modeling algorithm, training models with a cross-validation scheme. The effect of fish size on selected metrics was assessed using linear models and beta regressions. While no relationship between fish size and the number of presences was found, our results indicate that the model specificity increases with fish size. Additionally, the predictive importance of Riparian Vegetation and Within-Channel Structures variables decreases for larger species. Our results suggest that the relationship between the grain of the dataset and the home range of the species could bias SDM, leading in our case, to overprediction of absences. We also suggest that evolutionary adaptation to low slopes among Chilean fishes increases the relevance of riparian vegetation in the SDMs of smaller species. This study provides evidence on how species size may bias SDM, which could potentially be corrected by adjusting the model grain., Competing Interests: Daniel Zamorano and Marcelo Villarroel were employed by Plataforma de Investigación en Ecohidrología y Ecohidráulica Limitada. Matías Peredo is director in chief of Plataforma de Investigación en Ecohidrología y Ecohidráulica Limitada. The other authors declare there are no competing interests., (©2019 Zamorano et al.)

Non-contact vital sign monitoring enables the estimation of vital signs, such as heart rate, respiratory rate and oxygen saturation (SpO 2 ), by measuring subtle color changes on the skin surface using a video camera. For patients in a hospital ward, the main challenges in the development of continuous and robust non-contact monitoring techniques are the identification of time periods and the segmentation of skin regions of interest (ROIs) from which vital signs can be estimated. We propose a deep learning framework to tackle these challenges., Approach: This paper presents two convolutional neural network (CNN) models. The first network was designed for detecting the presence of a patient and segmenting the patient's skin area. The second network combined the output from the first network with optical flow for identifying time periods of clinical intervention so that these periods can be excluded from the estimation of vital signs. Both networks were trained using video recordings from a clinical study involving 15 pre-term infants conducted in the high dependency area of the neonatal intensive care unit (NICU) of the John Radcliffe Hospital in Oxford, UK., Main Results: Our proposed methods achieved an accuracy of 98.8% for patient detection, a mean intersection-over-union (IOU) score of 88.6% for skin segmentation and an accuracy of 94.5% for clinical intervention detection using two-fold cross validation. Our deep learning models produced accurate results and were robust to different skin tones, changes in light conditions, pose variations and different clinical interventions by medical staff and family visitors., Significance: Our approach allows cardio-respiratory signals to be continuously derived from the patient's skin during which the patient is present and no clinical intervention is undertaken.

Knowledge of the pathological instabilities in the breathing pattern can provide valuable insights into the cardiorespiratory status of the critically-ill infant as well as their maturation level. This paper is concerned with the measurement of respiratory rate in premature infants. We compare the rates estimated from the chest impedance pneumogram, the ECG-derived respiratory rhythms, and the PPG-derived respiratory rhythms against those measured in the reference standard of breath detection provided by attending clinical staff during 165 manual breath counts. We demonstrate that accurate RR estimates can be produced from all sources for RR in the 40-80 bpm (breaths per min) range. We also conclude that the use of indirect methods based on the ECG or the PPG poses a fundamental challenge in this population due to their poor behavior at fast breathing rates (upward of 80 bpm).

The aim was to evaluate the effect of size (long or chopped wheat straw), type (barley or wheat) and presence/absence (1 week) of straw supplementation on behaviour and welfare of fattening lambs. Sixteen lambs (65 days) were individually housed to be used in two simultaneous experiments (8 lambs each) for 5 weeks of fattening. After a habituation period, they were offered straw that differed either in size (Experiment 1) or type (Experiment 2), which was followed by a week without straw and then reallocation of straw. Maintenance behaviours, play and stereotypies were analysed using video recording. Physiological stress responses were measured using blood samples taken at the end of the week without straw and after the reallocation of the straw. A preference test was performed during the last week. Concentrate and roughage consumption, average daily gain and conversion index were estimated. Lambs provided with long straw spent more time eating forage, playing and performed fewer stereotypies (Experiment 1). Lambs given wheat straw increased their play behaviour compared with those given barley straw, without affecting stereotypies (Experiment 2). When the straw was removed, lambs performed more behaviours associated with stress; however, this was not reflected in blood stress indicators. Lambs clearly preferred long straw over chopped straw, but no clear preference was observed between wheat and barley straw. The amount of forage intake was consistent with the time spent eating forage, but the amount of concentrate intake did not vary with eating concentrate behaviour, since the amount of concentrate intake was higher when the straw was removed, especially in Experiment 2. Our results show that size more than type of straw supplement impact the behaviour of lambs. Long straw reduces the stereotypies and increases play. This may improve the welfare and performance of fattening lambs, adding ethical value to a highly appreciated product., (© 2019 Blackwell Verlag GmbH.)

Background: Endoscopic mucosal resection is one of the most frequent therapeutic alternatives for large colorectal lateral spreading tumors. There are few data on the prevalence of synchronous lesions on these patients., Objective: To describe the prevalence of synchronous colorectal lesions in patients referred for endoscopic mucosal resection of lateral spreading tumors >20 mm., Methods: We reviewed the endoscopic database of our Department and identified adult patients who were referred for the resection of a colorectal lateral spreading tumor >20 mm and had a diagnostic colonoscopy performed up to six months before. The proportion of patients with at least one synchronous lesion was estimated. The following features were compared between patients with and without synchronous lesions: age, gender, bowel preparation quality and cecal intubation on index colonoscopy and therapeutic colonoscopy, serrated adenoma as index lesion., Results: From December 2016 to November 2017, we identified 70 patients who fulfilled inclusion criteria. Median size of lesions was 25 mm (20-45). Eighty percent were located in the right colon and 35.71% were serrated adenomas. Synchronous lesion rate was 38.57%. Bowel preparation quality was similar in both groups when comparing both index and therapeutic colonoscopies. Patients with synchronous lesions had a higher proportion of serrated adenoma as index lesion than patients without synchronous lesions [51.85% vs 25.58%, OR 3.13 (1.13-8.68), P=0.03]., Conclusion: We found a high prevalence of synchronous lesions among patients with a large colorectal lateral spreading tumor. This risk seems to be increased if index lesions are serrated adenomas.

Osteosarcomas are bone tumors that frequently metastasize to the lung. Aberrant expression of the transcription factor, runt-related transcription factor 2 (RUNX2), is a key pathological feature in osteosarcoma and associated with loss of p53 and miR-34 expression. Elevated RUNX2 may transcriptionally activate genes mediating tumor progression and metastasis, including the RUNX2 target gene osteopontin (OPN/SPP1). This gene encodes a secreted matricellular protein produced by osteoblasts to regulate bone matrix remodeling and tissue calcification. Here we investigated whether and how the RUNX2/OPN axis regulates lung metastasis of osteosarcoma. Importantly, RUNX2 depletion attenuates lung metastasis of osteosarcoma cells in vivo. Using next-generation RNA-sequencing, protein-based assays, as well as the loss- and gain-of-function approaches in selected osteosarcoma cell lines, we show that osteopontin messenger RNA levels closely correlate with RUNX2 expression and that RUNX2 controls the levels of secreted osteopontin. Elevated osteopontin levels promote heterotypic cell-cell adhesion of osteosarcoma cells to human pulmonary microvascular endothelial cells, but not in the presence of neutralizing antibodies. Collectively, these findings indicate that the RUNX2/OPN axis regulates the ability of osteosarcoma cells to attach to pulmonary endothelial cells as a key step in metastasis of osteosarcoma cells to the lung., (© 2019 Wiley Periodicals, Inc.)

There is an increasing need for fast and accurate transfer of readings from blood glucose metres and blood pressure monitors to a smartphone mHealth application, without a dependency on Bluetooth technology. Most of the medical devices recommended for home monitoring use a seven-segment display to show the recorded measurement to the patient. We aimed to achieve accurate detection and reading of the seven-segment digits displayed on these medical devices using an image taken in a realistic scenario by a smartphone camera. A synthetic dataset of seven-segment digits was developed in order to train and test a digit classifier. A dataset containing realistic images of blood glucose metres and blood pressure monitors using a variety of smartphone cameras was also created. The digit classifier was evaluated on a dataset of seven-segment digits manually extracted from the medical device images. These datasets along with the code for its development have been made public. The developed algorithm first preprocessed the input image using retinex with two bilateral filters and adaptive histogram equalisation. Subsequently, the digit segments were automatically located within the image by two techniques operating in parallel: Maximally Stable Extremal Regions (MSER) and connected components of a binarised image. A filtering and clustering algorithm was then designed to combine digit segments to form seven-segment digits. The resulting digits were classified using a Histogram of Orientated Gradients (HOG) feature set and a neural network trained on the synthetic digits. The model achieved 93% accuracy on digits found on the medical devices. The digit location algorithm achieved a F1 score of 0.87 and 0.80 on images of blood glucose metres and blood pressure monitors respectively. Very few assumptions were made of the locations of the digits on the devices so that the proposed algorithm can be easily implemented on new devices.

Fish normally undergo periods of food deprivation that are longer than non-hibernating mammals. In aquacultured rainbow trout (Oncorhynchus mykiss), it is unclear how fasting may affect their physiological adaptative response, especially when they are normally fed daily. In addition, that response may vary with temperature, making it necessary to express fasting duration in terms of degree days. In the current study, trout were fasted for 5, 10, and 20 days (55, 107, and 200 degree days (°C d), respectively). To assess the physiological response of fish to fasting, different biometric, blood, plasma, and metabolic parameters were measured, as well as liver fatty acid composition. The fish weight, condition factor, and the hepato-somatic index of 5-day fasted trout were not significantly different from those of control fish. Gastric pH increased as fasting progressed while plasma concentrations of glucose, triglycerides, and total proteins decreased significantly after 10 days of fasting, while the percentage of non-esterified fatty acids increased. There were no significant differences in plasma ions (sodium, potassium, and calcium), except for chloride ion which decreased after 5 days of fasting. Liver glycogen decreased after 5 days of fasting while glycogen concentration in muscle did not decrease until 20 days of fasting. Liver color presented a higher chroma after 5 days of fasting, suggesting a mobilization of reserves. Finally, acetylcholinesterase activity in the brain was not affected by food deprivation but increased after 10 days of fasting in liver and muscle, suggesting the mobilization of body reserves, but without severely affecting basal metabolism.

Thoracic electrical bioimpedance (TEB) and transthoracic echocardiography (TTE) are non-invasive methods to estimate stroke volume (SV) and cardiac output (CO). Thoracic electrical bioimpedance is not in widespread clinical use with reports of inaccurate cardiac output estimation compared to invasive monitors, particularly in non-healthy populations. We explore its use as a trend monitor by comparing it against thoracic echocardiography in fifteen healthy volunteers undergoing two physical challenges designed to vary cardiac output. Of all paired values, 54.6% showed gross trend agreement and only 1.9% showed direct disagreement between the two monitors. Our results show thoracic bioimpedance may have a role as a non-invasive cardiac output trend monitor in healthy volunteer studies.

The study aim was to identify consumer segmentation based on nonhuman animal welfare (AW) attitudes and their relationship with demographic features and willingness to pay (WTP) for welfare-friendly products (WFP) in Mexico. Personal interviews were conducted with 843 Mexican consumers who stated they purchased most of the animal products in their home. Respondents were selected using a quota sampling method with age, gender, education, and origin as quota control variables. The multivariate analysis suggested there were three clusters or consumer profiles labeled "skeptical," "concerned," and "ethical," which helped explain the association between AW attitudes, some demographic variables, and WTP for WFP. This study is one of the first to address consumer profiling in Latin America, and the findings could have implications for the commercialization of WFP. Hence, customers should receive information to consider welfare innovations when deciding to purchase animal products. The growth of the WFP food market establishes an element of a far more multifaceted phenomenon of sustainable consumption and support of a new paradigm called responsible marketing in emerging markets such as Mexico.

Objectives: To compare the efficacy of pre-emptive versus empirical antifungal therapy in children with cancer, fever and neutropenia., Methods: This was a prospective, multicentre, randomized clinical trial. Children presenting with persistent high-risk febrile neutropenia at five hospitals in Santiago, Chile, were randomized to empirical or pre-emptive antifungal therapy. The pre-emptive group received antifungal therapy only if the persistent high-risk febrile neutropenia was accompanied by clinical, laboratory, imaging or microbiological pre-defined criteria. The primary endpoint was overall mortality at day 30 of follow-up. Secondary endpoints included invasive fungal disease (IFD)-related mortality, number of days of fever, days of hospitalization and use of antifungal drugs, percentage of children developing IFD, requiring modification of initial treatment strategy and need for ICU. The trial was registered with Registro Brasileiro de Ensaios Clínicos (ReBEC) under trial number RBR-3m9d74., Results: A total of 149 children were randomized, 73 to empirical therapy and 76 to pre-emptive therapy. Thirty-two out of 76 (42%) children in the pre-emptive group received antifungal therapy. The median duration of antifungal therapy was 11 days in the empirical arm and 6 days in the pre-emptive arm (P < 0.001), with similar overall mortality (8% in the empirical arm and 5% in the pre-emptive arm, P = 0.47). IFD-related mortality was the same in both groups (3%, P = 0.97), as were the percentage of children with IFD (12%, P = 0.92) and the number of days of fever (9, P = 0.76). The number of days of hospitalization was 19 in the empirical arm and 17 in the pre-emptive arm (P = 0.15) and the need for ICU was 25% in the empirical arm and 20% in the pre-emptive arm (P = 0.47)., Conclusions: Pre-emptive antifungal therapy was as effective as empirical antifungal therapy in children with cancer, fever and neutropenia, significantly reducing the use of antifungal drugs.

Purpose: Health-related quality of life (HRQOL) improves throughout treatment of patients with nonmetastatic osteosarcoma. We compared HRQOL for patients in the United States and Chile treated on an international trial (OS99) with polychemotherapy and surgery, and we assessed the relationships among HRQOL measures, event-free survival (EFS), and overall survival (OS)., Materials and Methods: Patients with newly diagnosed, localized osteosarcoma and their parents completed three HRQOL instruments (PedsQL v.4, PedsQL Cancer v.3, and Symptom Distress Scale [SDS]). Data were collected at four time points throughout therapy. Repeated measures models were used to investigate the effect of treatment site on instrument scores. The log-rank test examined the impact of treatment site on survival outcomes, and Cox proportional hazards regression models evaluated baseline HRQOL measures as predictors of EFS and OS., Results: Of 71 eligible patients, 66 (93%) participated in the HRQOL studies in the United States (n = 44) and Chile (n = 22). The median age was 13.4 years (range, 5 to 23 years). Clinical characteristics were similar between treatment sites. US patients reported better scores for physical ( P = .030), emotional ( P = .027), and school functioning ( P < .001). Chilean patients reported poorer scores for worry ( P < .001) and nausea ( P = .007). Patient and parent nausea scores were similar between patients treated in the United States and Chile by the end of therapy. Differences in symptom distress were not observed between the countries. Neither HRQOL measures nor treatment site were associated with EFS or OS., Conclusion: Although significant differences in HRQOL were observed between countries, outcomes were similar, and HRQOL measures were not associated with prognosis.

The clavicular portion of the deltoid muscle (CPDM) in the human clavicle does not have a nomenclature in the Terminologia Anatomica (TA). This area is relevant in anatomy since the muscle participates in motions of glenohumeral articulation. The aim of this study was to describe the origin of the CPDM and to propose a name for the structure. Dry clavicles of 176 adults were studied, without distinction by sex. An osteometric board was used to measure the maximum length of the clavicles and a digital caliper to measure length of the CPDM's origin, distance from the origin to the sternal end, distance from the origin to the acromial end, distance of the lateral third and middle vertical diameter. The mean of maximum of the distances and CPDM's origin of left/right clavicle do not present significant differences. The CPDM s origin showed a high prevalence of structures as groove and roughened area (over 96% of cases). In conclusion, our definition of the CPDM shows the importance of clearly describing the observed groove and roughened area. Due to the high prevalence of the structures, the authors suggest that the terms "sulcus musculi deltoidei" and "tuberositas musculi deltoidei" be included in the TA to denominate the CPDM's origin on the human clavicle., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Resistance to atmospheric corrosion in different environments located in Chile and the corrosion's effect on the mechanical properties of SAE 1020 steel were studied. Atmospheric corrosivity categories at each station under study were determined. These categories were C2, for Laja; C3 and C4, for the Arica and Antarctic stations, respectively; and the most aggressive, C5 and higher at Quintero. These specific environments significantly influenced the mechanical responses of steel exposed for 36 months. Rupture elongation, the modulus of toughness, ultimate tensile strength, and hardness of the material all decreased as a function of environmental atmospheric aggressiveness. Lowered ductility is the result of the increased corrosion rate due to the high deposition of chlorides. This is due to the morphology of material degradation, which consequently occurs as pores, microstrains, and other defects that promote early rupture of the steel., Competing Interests: The authors declare no conflict of interest.

Background: Microorganisms isolated from blood cultures (BC) in patients with febrile neutropenia (NF) vary over time, requiring systematic monitoring to guide appropriate empirical therapy., Aim: To identify microorganisms isolated from BC and their antimicrobial resistance profile in children with cancer and high risk NF., Method: Prospective, multicenter study. The analysis included episodes of high-risk FN with positive BC in children under 18 years of age treated in five hospitals in Santiago, Chile, 2012-2015., Results: A total of 206 microorganisms were analyzed in 185 episodes of high-risk FN. The main isolates were Gram negative bacilli (46.6%) and Gram positive cocci (45.1%) and the most frequent microorganisms were Escherichia coli (22.8%), coagulase negative Staphylococcus (18.0%) and Klebsiella spp. (16.5%). Escherichia coli and Klebsiella spp showed 4.2% and 67.6% resistance to third generation cephalosporins (cefotaxime/ceftriaxone), 10.6% and 40.6% resistance to fluoroquinolones (ciprofloxacin) and 2.1% and 26.5% to amikacin, respectively. Coagulase negative Staphylococcus and Staphylococcus aureus had 86.4% and 22.2% resistance to oxacillin, Streptococcus viridans group had 71% resistance to penicillin., Discussion: This study updates the etiology and resistance profile of microorganisms isolated in BC from children with cancer and high risk FN, an essential tool for the adequate management of these patients.

Animal welfare has become an important subject of public, economic and political concern, leading to the need to validate indicators that are feasible to use at abattoirs. A systematic review was carried out, which identified 72 cattle welfare indicators (CWI) that were classified into four categories (physiological, morphometric, behavioral and meat quality). Their validity and feasibility for use in abattoirs were evaluated as potential measures of cattle welfare during transportation to the abattoir and at the abattoir itself. Several highly valid indicators were identified that are useful to assess welfare at abattoirs, including body condition score, human-animal interactions, vocalizations, falling, carcass bruising, and meat pH. In addition, some intermediate valid indicators are useful and should be investigated further. Information along the food chain could be used systematically to provide a basis for a more-risk-based meat inspection. An integrated system based on the use of key indicators defined for each inspection step with the setting of alarm thresholds could be implemented., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Livestock transport exposes animals to a range of potential stressors that may compromise their welfare and final product quality, and those effects typically increase with the distance travelled. In North America, producers often use pot-belly vehicles for long hauls but little is known about their suitability for transporting lambs. We followed two long-distance trips using pot-belly trailers carrying 500 lambs (each) from Northern to Central Mexico in winter, to measure possible effects on animal welfare and meat quality. Sixty lambs per trip were placed at different locations within the pot-belly trailer. Animals were equipped with iButton Thermochron® temperature devices, which registered body temperature throughout pre- and post-slaughter stages. Despite the rather cool winter conditions, lambs placed in the "belly" and "nose" compartments had higher body temperatures at loading, during transport and lairage and after slaughter (carcass temperature). Those lambs also had higher levels of plasma cortisol, glucose and creatine kinase (CK), and a higher neutrophil/lymphocyte ratio. Regarding meat quality, ultimate pH (24 h) was higher in all locations, especially in LT4 location. Overall, the results suggest a link between thermal stress during transport, elevated physiological indicators of stress and poorer meat quality.

Following previous metronomic meetings in Marseille (2011), Milano (2014), and Mumbai (2016), the first Latin American metronomic meeting was held in the School of Medical Sciences, National University of Rosario, Rosario, Argentina on 27 and 28 of May, 2016. For the first time, clinicians and researchers with experience in the field of metronomics, coming from different countries in Latin America, had the opportunity of presenting and discussing their work. The talks were organised in three main sessions related to experience in the pre-clinical, and clinical (paediatric and adult) areas. The different presentations demonstrated that the fields of metronomic chemotherapy and repurposing drugs in oncology, known as metronomics, constitute a branch of cancer therapy in permanent evolution, which have strong groups working in Latin America, both in the preclinical and the clinical settings including large, adequately designed randomised studies. It was shown that metronomics offers treatments, which, whether they are combined or not with the standard therapeutic approaches, are not only effective but also minimally toxic, with the consequent improvement of the patient's quality of life, and inexpensive, a feature very important in low resource clinical settings. The potential use of metronomic chemotherapy was proposed as a cost/effective treatment in low-/middle-income countries, for adjuvant therapy in selected tumours. The fundamental role of the governmental agencies and non-governmental alliances, as the Metronomic Global Health Initiative, in supporting this research with public interest was underlined.

Background: Respiratory viral infections in episodes of fever and neutropenia (FN) in children with cancer are not well characterized. We compared the clinical outcome of infections caused by different respiratory viruses (RVs) and by RV coinfection in this population., Methods: Children with cancer and FN at 3 hospitals in Chile were prospectively evaluated by clinical examination, blood cultures and detection of 17 RVs using multiplex polymerase chain reaction (nasopharyngeal samples). Clinical characterization and outcome variables were determined and compared by the type of RV detected., Results: A total of 1044 episodes of FN in 525 children were included. At least 1 RV was detected in 46%. In 350 of 1044 (34%) episodes, we detected only RVs, of which 284 (81%) were classified as a single-RV infection and 66 (19%) as a viral coinfection. Respiratory symptoms were present at admission in 65% of the episodes with any detected RV. Median age was 6 years (interquartile range, 3-10), and 51% were women. The most common RVs detected were rhinovirus, respiratory syncytial virus, parainfluenza, influenza, adenovirus and human metapneumovirus. Episodes caused by different types of RVs had no differences in the clinical outcome (days of hospitalization, days of fever, O2 requirement, admission to the intensive care unit and death) and when comparing single and viral coinfection., Conclusions: To our knowledge, this is the largest report comparing clinical outcome in FN episodes caused by different RVs in children with cancer. A positive polymerase chain reaction for RV at admission was significantly associated with the presence of respiratory symptoms. Our data showed a favorable outcome in all episodes with RV detection, including single and viral coinfections.

Introduction Women require effective contraception until they reach menopause. The long acting reversible contraceptives (LARC) and the depot-medroxyprogesterone acetate (DMPA, Depo-Provera®, Pfizer, Puurs, Belgium) are great options and can replace possible sterilizations. Purpose To assess the relationship between the use of LARCs and DMPA and terminations ascribed to menopause and sterilizations in a Brazilian clinic. Methods We reviewed the records of women between 12 and 50 years of age attending the clinic that chose to use a LARC method or DMPA. Cumulative termination rates due to sterilization or because the woman had reached menopause were computed using single decrement life-table analysis over 32 years. We also examined all records of surgical sterilization at our hospital between the years 1980-2012. Results Three hundred thirty-two women had continuously used the same contraceptive until menopause, and 555 women had discontinued the method because they or their partners underwent sterilization. From year 20 to year 30 of use, levonorgestrel intrauterine-releasing system (LNG-IUS - Mirena®, Bayer Oy, Turku, Finland; available since 1980), copper intrauterine device (IUD - available since 1980) and DMPA users showed a trend of cumulative higher discontinuation rates due to menopause when compared with the discontinuation rates due to sterilization. Over the study period, a steep decline in the use of sterilization occurred. Conclusion Over the past 15 years of research we have observed a trend: women usually preferred to continue using LARC methods or DMPA until menopause rather than decide for sterilization, be it their own, or their partners'. The annual number of sterilizations dropped in the same period. The use of LARC methods and DMPA until menopause is an important option to avoid sterilization, which requires a surgical procedure with potential complications., (Thieme Publicações Ltda Rio de Janeiro, Brazil.)

The effect of the fungicide tebuconazole (0.41, 0.52, 0.71 and 1.14mg/L) on survival, reproduction and growth of Daphnia magna organisms was monitored using 14 and 21 days exposure tests. A third experiment was performed by exposing D. magna to the fungicide for 14 days followed by 7 days of recovery (14+7). In order to test fungicide effects on D. magna, parameters as survival, mean whole body length, mean total number of neonates per female, mean number of broods per female, mean brood size per female, time to first brood/reproduction and intrinsic rate of natural increase (r) were used. Reproduction was seriously affected by tebuconazole. All tebuconazole concentrations tested affected the number of broods per female and day to first brood. At 14-days test, number of neonates per female and body size decreased by concentrations of tebuconazole higher than 0.52mg/L, whereas at 21-days test both parameters were affected at all the concentrations tested. Survival of the daphnids after 14 days fungicide exposure did not exhibited differences among experimental and control groups. In this experiment r value was reduced (in a 22%) when animals were exposed to concentrations of 0.71mg/L and 1.14mg/L. Survival of daphnids exposed during 21 days to 1.14mg/L declined, and the intrinsic rate of natural increase (r) decreased in a 30 % for tebuconazole concentrations higher than 0.41mg/L. Longevity of daphnids pre-exposed to tebuconazole for 14 days and 7 days in clean water did not show differences from control values and all of them survived the 21 days of the test. However, after 7 days in fungicide free medium animals were unable to restore control values for reproductive parameters and length. The maximum acceptable toxicant concentration (MATC) was calculated using the r values as parameter of evaluation. MATC estimations were 0.61mg/L and 0.46mg/L for 14 and 21 days, respectively. Results showed that the number of neonates per female was the highest sensitive parameter to the effects of tebuconazole on D. magna. On the other hand, a recovery period of 7 days in a free toxicant medium would not be longer enough to reestablish normal reproduction parameters in pre-exposed tebuconazole daphnids., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: XSome authors have assessed the link between obesity and colon adenoma risk. Moreover, it has been reported that obesity could increase the risk of proximal adenoma development. Accordingly, obese patients may have a distinctive pattern of adenoma recurrence. AIM: To determine whether metachronous adenoma features differ between obese and non-obese subjects submitted to colonoscopy surveillance., Materials and Methods: We prospectively evaluated all patients over 18 years old that underwent surveillance colonoscopy at our institution between June 2013 and June 2014. Date of prior colonoscopy was registered. A body mass index ≥ 30 was used to define obesity. Analysis looking for variables significantly associated with metachronous adenoma was performed. Metachronous adenoma rate was compared between obese and non-obese subjects, as well as size, location, morphological and histopathological characteristics., Results: Overall, 825 subjects were enrolled. Median time of surveillance colonoscopy was 38.9 months. Obesity was statistically more frequent in those subjects with metachronous adenomas (40% vs 25.71%, p < 0.001). On multivariate analysis, obesity [OR 1.7 (1.01-2.9)] and age [OR 1.02 (1-1.05)] were independently associated with metachronous adenoma presence. Obesity was also significantly associated with a higher risk of right colon adenomas [OR 2.4 (1.76-3.26)] and advanced adenoma [OR 1.99 (1.29-3.06)]. The risk is significantly higher in men and in those with a family history of colorectal cancer/adenoma., Conclusion: Obesity was associated with a higher risk of metachronous adenomas on surveillance colonoscopy. A higher risk of right-sided lesions and advanced adenomas was also found in this population.

A novel method (Sophia) is presented to track oxygen saturation changes in a controlled environment using an RGB camera placed approximately 1.5 m away from the subject. The method is evaluated on five healthy volunteers (Fitzpatrick skin phenotypes II, III, and IV) whose oxygen saturations were varied between 80% and 100% in a purpose-built chamber over 40 minutes each. The method carefully selects regions of interest (ROI) in the camera image by calculating signal-to-noise ratios for each ROI. This allows it to track changes in oxygen saturation accurately with respect to a conventional pulse oximeter (median coefficient of determination, 0.85).

The fungi of the order Mucorales cause mucormycosis, which usually presents as an invasive fungal disease with rapid angioinvasion in immunocompromised patients. Rhinocerebral is the most common presentation. The lipid formulations of amphotericin B are used as primary treatment in invasive mucormycosis; the combined use of posaconazole could allow a reduction in the dose of amphotericin B improving tolerance and adherence to treatment. Caspofungin and amphotericin B association has been shown to be synergistic in vitro and effective in murine models. We present the case of a preschool patient that during the debut of acute lymphoblastic leukemia developed a rhinocerebral mucormycosis successfully responding to antifungal treatment with the combination of liposomal amphotericin and caspofungin.

Introduction: Immune response against vaccine antigens may be impaired in children with cancer. The aim of this study was to evaluate the seroconversion response against hepatitis B vaccination (HBV) at the time of chemotherapy onset and/or remission in children with cancer., Patients and Method: Prospective, two-centre, controlled, non-randomised study conducted on children recently diagnosed with cancer, paired with healthy subjects. Cases received HBV at time 0, 1 and 6 months with DNA recombinant HBV at a dose of 20 and 40 μg if < or > than 10 years of age, respectively, at the time of diagnosis for solids tumours and after the remission in case of haematological tumours. Controls received the same schedule, but at of 10 and 20 μg doses, respectively. HBs antibodies were measured in serum samples obtained at 2, 8 and 12 months post-vaccination. Protective titres were defined as > 10 mIU/ml at 8th month of follow up., Results: A total of 78 children with cancer and 25 healthy controls were analysed at month 8th of follow up. Seroconversion rates in the cancer group reached 26.9%, with no differences by age, gender or type of tumour (P = .13, .29, and .44, respectively). Control group seroconversion was 100% at the 8th month, with P < .0001 compared with the cancer group. At month 12 of follow up, just 31.9% of children with cancer achieved anti-HBs antibodies > 10 mIU/ml., Conclusions: Vaccination against hepatitis B with three doses of DNA recombinant vaccine at an increased concentration, administrated at the time of onset of chemotherapy and/or remission provided an insufficient immune response in a majority of children with cancer. More immunogenic vaccines should be evaluated in this special population, such as a third generation, with more immunogenic adjuvants, enhanced schedules at 0, 1, 2, 6 month, evaluation of antibody titres at month 8 and 12h to evaluate the need for further booster doses., (Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Subcutaneous mycoses in freshwater fish are rare infections usually caused by oomycetes of the genus Saprolegnia and some filamentous fungi. To date, Fusarium infections in farmed fish have only been described in marine fish. Here, we report the presence of Fusarium oxysporum in subcutaneous lesions of Nile tilapia (Oreochromis niloticus). Histopathologic evaluation revealed granuloma formation with fungal structures, and the identity of the etiological agent was demonstrated by morphological and molecular analyses. Some of the animals died as a result of systemic coinfection with Aeromonas hydrophila.

Postweaning management strategies that include an element of social enrichment may reduce weaning stress and improve welfare and productive performance. We analyzed the effect of postweaning handling strategies on welfare and production traits in lambs. After weaning, 36 lambs were assigned to 3 experimental groups with 12 lambs each (control [C], fattening with gentle human female contact [H], and fattening with 2 adult ewes [E]). The average daily gain (ADG) was estimated. Blood samples were taken, and infrared thermography was used to estimate stress variables. There were significant differences among treatments (in favor of alternative strategies) regarding production and stress variables (cortisol, glucose, and creatine kinase). The results suggest that the lambs handled gently during the fattening were less reactive and better able to modulate their physiological stress. The E group adapted better to acute stress than the C group but was less efficient in modulating chronic stress. Both treatments showed higher slaughter live weights and better ADGs compared with the control. The use of social enrichment at weaning, especially to establish a positive human-nonhuman animal bond, alleviates lamb weaning stress and improves welfare and performance.

Current technologies to allow continuous monitoring of vital signs in pre-term infants in the hospital require adhesive electrodes or sensors to be in direct contact with the patient. These can cause stress, pain, and also damage the fragile skin of the infants. It has been established previously that the colour and volume changes in superficial blood vessels during the cardiac cycle can be measured using a digital video camera and ambient light, making it possible to obtain estimates of heart rate or breathing rate. Most of the papers in the literature on non-contact vital sign monitoring report results on adult healthy human volunteers in controlled environments for short periods of time. The authors' current clinical study involves the continuous monitoring of pre-term infants, for at least four consecutive days each, in the high-dependency care area of the Neonatal Intensive Care Unit (NICU) at the John Radcliffe Hospital in Oxford. The authors have further developed their video-based, non-contact monitoring methods to obtain continuous estimates of heart rate, respiratory rate and oxygen saturation for infants nursed in incubators. In this Letter, it is shown that continuous estimates of these three parameters can be computed with an accuracy which is clinically useful. During stable sections with minimal infant motion, the mean absolute error between the camera-derived estimates of heart rate and the reference value derived from the ECG is similar to the mean absolute error between the ECG-derived value and the heart rate value from a pulse oximeter. Continuous non-contact vital sign monitoring in the NICU using ambient light is feasible, and the authors have shown that clinically important events such as a bradycardia accompanied by a major desaturation can be identified with their algorithms for processing the video signal.

New developments in livestock transport within the pre-slaughter chain are discussed in terms of three logistic nodes: origin, stopovers and slaughterhouse. Factors as transport cost, haulier, truck specifications, micro-environment conditions, loading density, route planning, vehicle accidents and journey length are discussed as well as causes of morbidity, mortality, live weight and carcass damage. Taking into account current trends towards increased transport times, logistics stopovers and mixed transport, there is a need to develop systems of evaluation and decision-making that provide tools and protocols that can minimize the biological cost to animals, which may have been underestimated in the past., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The ovarian, or coelomic, fluid that is released with the egg mass of many fishes is increasingly found to play an important role in several biological processes crucial for reproductive success. These include maintenance of oocyte fertility and developmental competence, prolonging of sperm motility, and enhancing sperm swimming speed. Here we examined if and how the proteome of chinook salmon (Oncorhynchus tshawytscha) ovarian fluid varied among females and then sought to examine the composition of this fluid. Ovarian fluid in chinook salmon was analyzed using 1D SDS PAGE and LC-MS/MS tryptic digest screened against Mascot and Sequest databases. We found marked differences in the number and concentrations of proteins in salmon ovarian fluid across different females. A total of 174 proteins were identified in ovarian fluid, 47 of which were represented by six or more peptides, belonging to one of six Gene Ontology pathways. The response to chemical stimulus and response to hypoxia pathways were best represented, accounting for 26 of the 174 proteins. The current data set provides a resource that furthers our understanding of those factors that influence successful egg production and fertilisation in salmonids and other species.

Introduction: Leukemia is the most common cancer in Chilean children. Acute lymphoblastic leukemia (ALL) is more prevalent and longer survival compared to acute myeloid leukemia (AML)., Aims: To describe episodes of febrile neutropenia (FN) in children with AML, determining frequency of infections as agent, focus and evolution, comparing children with ALL episodes., Method: A prospective multicenter study. Children presenting with FN at six hospitals in Santiago, Chile, were invited to participate in two consecutive FONDECYT projects, from April 2004 to June 2011. All patients were uniformly evaluated, recording epidemiological, clinical and laboratory variables. Information regarding FN episodes of children with LMA and LLA was used to this study., Results: We evaluated 506 episodes of FN in children with leukemia: 173 children with AML and 333 in children with ALL. NF episodes in children with ALML showed significantly greater depth and duration of neutropenia, febrile remained a > period of time and had a worse clinical outcome, as evidenced by > hemodynamic instability, > sepsis, CRP > 90 mg/L for a longer time, more days of hospitalization, > frequency of hospitalization in ICU, > bacteremia, mainly by Streptococcus viridans group, > change of antimicrobial treatment, > use of antifungal therapy., Conclusions: This study demonstrates that FN episodes in children with ALML further evolve unfavorably, compared with episodes of FN in children with ALL. FN episodes in children with ALML require a more aggressive diagnostic and therapeutic approach, related to its severity.

Background: Mercaptopurine (6-MP) plays a pivotal role in treatment of childhood acute lymphoblastic leukemia (ALL); however, interindividual variability in toxicity of this drug due to genetic polymorphism in 6-MP metabolizing enzymes has been described. We determined the prevalence of the major genetic polymorphisms in 6-MP metabolizing enzymes in Chilean children with ALL., Methods: 103 Chilean pediatric patients with a confirmed diagnosis of ALL were enrolled. DNA was isolated from whole blood and genetic polymorphism in thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) coding genes were detected by polymorphism chain reaction-restriction fragment length (PCR-RFLP) assay., Results: The total frequency of variant TPMT alleles was 8%. TPMT*2, TPMT*3A and TPMT*3B alleles were found in 0%, 7%, and 1% of patients, respectively. For ITPA, the frequency of P32T allele was 3%. We did not observe any homozygous variant for TPMT and ITPA alleles. We also analyzed a subgroup of 40 patients who completed the maintenance phase of ALL treatment, and we found that patients carrying a TPMT gene variant allele required a significantly lower median cumulative dosage and median daily dosage of 6-MP than patients carrying wild type alleles., Conclusion: TMPT genotyping appears an important tool to further optimize 6-MP treatment design in Chilean patients with ALL.

Background: In a previous uncontrolled study, continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA) improved vision in patients with diabetic macular oedema., Objectives: We investigated whether the above improvement in vision (or visual processing) might have been due to reduced sleepiness, rather than a true improvement in retinal function., Methods: Twelve normal control subjects and 20 patients with OSA were tested for their ability to recognise degraded words, by means of a computer programme displaying 5-letter words every 4 s for 10 min, with variable amounts of the bottom half of the word missing; the percentage of the word necessary to achieve correct identification on average half the time was 'hunted' (the test score). All subjects were tested twice, 2-3 weeks apart; the OSA group after the commencement of CPAP. The Epworth Sleepiness Score (ESS) in patients was measured at the same visit., Results: The test score at visit 1 was 26.7% for normal subjects and 31.6% for patients with OSA. At visit 2, the test score was 25.0% for normal subjects and 29.9% for patients with OSA. The groups showed a small and identical improvement over the trial period in the test score, of 1.7% (p = 0.01 and p = 0.03 for the normal and OSA groups, respectively). The group with OSA experienced a drop in ESS of 7.5 (SD 5.5) points following treatment., Conclusion: The small and identical improvement in both groups suggests only a similar learning effect rather than any improvement due to reduced sleepiness.

Astaxanthin (AST) is a valued molecule because of its high antioxidant properties. However, AST is extremely sensitive to oxidation, causing the loss of its bioactive properties. The purposes of this study were to define conditions for microencapsulating AST in oil bodies (OB) from Brassica napus to enhance its oxidative stability, and to test the bioactivity of the microencapsulated AST (AST-M) in cells. Conditions for maximising microencapsulation efficiency (ME) were determined using the Response Surface Methodology, obtaining a high ME (>99%). OB loaded with AST showed a strong electrostatic repulsion in a wide range of pH and ionic strengths. It was found that AST-M exposed to air and light was more stable than free AST. In addition, the protective effect of AST against intracellular ROS production was positively influenced by microencapsulation in OB. These results suggest that OB offer a novel option for stabilising and delivering AST.

Wnt signaling is one of the key oncogenic pathways in multiple cancers, and targeting this pathway is an attractive therapeutic approach. However, therapeutic success has been limited because of the lack of therapeutic agents for targets in the Wnt pathway and the lack of a defined patient population that would be sensitive to a Wnt inhibitor. We developed a screen for small molecules that block Wnt secretion. This effort led to the discovery of LGK974, a potent and specific small-molecule Porcupine (PORCN) inhibitor. PORCN is a membrane-bound O-acyltransferase that is required for and dedicated to palmitoylation of Wnt ligands, a necessary step in the processing of Wnt ligand secretion. We show that LGK974 potently inhibits Wnt signaling in vitro and in vivo, including reduction of the Wnt-dependent LRP6 phosphorylation and the expression of Wnt target genes, such as AXIN2. LGK974 is potent and efficacious in multiple tumor models at well-tolerated doses in vivo, including murine and rat mechanistic breast cancer models driven by MMTV-Wnt1 and a human head and neck squamous cell carcinoma model (HN30). We also show that head and neck cancer cell lines with loss-of-function mutations in the Notch signaling pathway have a high response rate to LGK974. Together, these findings provide both a strategy and tools for targeting Wnt-driven cancers through the inhibition of PORCN.

Background: We previously created a risk prediction model for severe sepsis not clinically apparent during the first 24 hours of hospitalization in children with high-risk febrile neutropenia (HRFN), which identified 3 variables, age ≥ 12 years, serum C-reactive protein (CRP) ≥ 90 mg/L and interleukin-8 ≥ 300 pg/mL, evaluated at the time of admission and at 24 hours of hospitalization. The combination of these 3 variables identified a risk for severe sepsis ranging from 8% to 73% with a relative risk of 3.15 (95% confidence interval: 1.1-9.06). The aim of this study was to validate prospectively our risk prediction model for severe sepsis in a new cohort of children with cancer and HRFN., Methods: Predictors of severe sepsis identified in our previous model (age, CRP and interleukin-8) were evaluated at admission and at 24 hours of hospitalization in a new cohort of children with HRFN between April 2009 and July 2011. Diagnosis of severe sepsis, not clinically apparent during the first 24 hours of hospitalization, was made after discharge by a blind evaluator., Results: A total of 447 HRFN episodes were studied, of which 76 (17%) had a diagnosis of severe sepsis. The combination of age ≥ 12 years, CRP ≥ 90 mg/L and interleukin-8 ≥ 300 pg/mL at admission and/or at 24 hours in the new cohort identified a risk for severe sepsis ranging from 7% to 46% with an RR of 6.7 (95% CI: 2.3-19.5)., Conclusions: We validated a risk prediction model for severe sepsis applicable to children with HRFN episodes within the first 24 hours of admission. We propose to incorporate this model in the initial patient assessment to offer a more selective management for children at risk for severe sepsis.