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The first palliative care services were started in Uganda 30 years ago with services continuing to develop since then. The Ministry of Health and the Palliative Care Association of Uganda have played key roles in the development of paediatric palliative care in the country. There are a range of paediatric palliative care service providers in Uganda, and these have developed alongside educational programmes and research in PPC. Care is provided across the Uganda health system and across the age range from neonates through to adolescents and young adults. Whilst recognising the importance of shared decision-making there is little literature with regards to this in the Ugandan context. However, a variety of factors have been shown to influence decision-making, along with the challenges and recommendations for the future. Uganda has made significant strides in the provision of paediatric palliative care although there is still a way to go before all children with palliative care needs, and their families, can access palliative care.
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Comunicación , Cuidados Paliativos , Recién Nacido , Adolescente , Adulto Joven , Niño , Humanos , UgandaRESUMEN
Skewness values for the pressure time derivative are greater at ground-based measurements near a tactical aircraft than they are at nearby off-ground locations. A possible explanation for this phenomenon is the occurrence of nonlinear, irregular shock reflections at the ground. Propagation angle, source location, and corresponding angle of incidence relative to the ground are estimated using a two-point cross correlation of windowed shock events. Nonlinear reflections are likely to occur based on the combination of angles of incidence and measured shock strengths and cause a pressure increase at the shock that is greater than twice the free-field pressure. The associated pressure increase at the shocks appears to enhance shock-related metrics at the ground compared to off-ground locations.
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INTRODUCTION: Self-report is the gold standard for measuring children's health-related outcomes. Design of such measures is complex and challenging. This review aims to systematically appraise the evidence on recall period, response scale format, mode of administration and approaches needed to enable children and young people < 19 years to participate in valid and reliable self-reporting of their health outcomes. METHOD: PsycInfo, Medline, CINAHL and Embase were searched from 1 January 1990 to 15 March 2020, and citation searching undertaken in Scopus. Articles were included if they were primary research or case reports of ≥ 3 participants reporting the following: recall period, response scale selection, administration modality. Quality was assessed using QualSyst, and results synthesised narratively. This review was conducted and reported according to PRISMA guidelines. RESULTS: 81 of 13,215 retrieved articles met the inclusion criteria. Children < 5 years old cannot validly and reliably self-report health outcomes. Face scales demonstrate better psychometric properties than visual analogue or Likert scales. Computerised and paper scales generally show equivalent construct validity. Children prefer computerised measures. Children ≤ 7 years old think dichotomously so need two response options. Those > 8 years old can reliably use a 3-point scale. CONCLUSION: The results of this review have both clinical and research implications. They can be used to inform appropriate choice of PROM for use with CYP in the clinical setting. We also give eight recommendations for future development of self-reported outcome measures for children and young people.
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Evaluación de Resultado en la Atención de Salud/métodos , Medición de Resultados Informados por el Paciente , Psicometría/métodos , Calidad de Vida/psicología , Niño , Preescolar , Humanos , Lactante , Reproducibilidad de los Resultados , AutoinformeRESUMEN
Noise from a tactical aircraft can impact operations due to concerns regarding military personnel noise exposure and community annoyance and disturbance. The efficacy of mission planning can increase when the distinct, complex acoustic source mechanisms creating the noise are better understood. For each type of noise, equivalent acoustic source distributions are obtained from a tied-down F-35B operating at various engine conditions using the hybrid method for acoustic source imaging of Padois, Gauthier, and Berry [J. Sound Vib. 333, 6858-6868 (2014)]. The source distributions for the distinct noise types are obtained using different sections of a 71 element, ground-based linear array. Using a subarray close to the nozzle exit plane, source distributions are obtained for fine-scale turbulent mixing noise and broadband shock-associated noise, although grating lobes complicate interpretations at higher frequencies. Results for a subarray spanning the maximum sound region show that the multiple frequency peaks in tactical aircraft noise appear to originate from overlapping source regions. The observation of overlapping spatial extent of competing noise sources is supported by the coherence properties of the source distributions for the different subarrays.
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Broadband shock-associated noise (BBSAN) is a prominent noise component from nonideally expanded jets in the forward and sideline directions. BBSAN from laboratory-scale jets has been studied extensively, and spatial trends in BBSAN spectral peak characteristics-frequency, level, and width-have been established. These laboratory-scale trends are compared to those for BBSAN from a tied-down F-35B operated at four engine conditions. While the peak frequency varies as expected, both spatially and across engine condition, the peak level and width do not, pointing to the need for additional research into BBSAN for high-performance military aircraft.
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Acoustic shocks have been previously documented in high-amplitude jet noise, including both the near and far fields of military jet aircraft. However, previous investigations into the nature and formation of shocks have historically concentrated on stationary, ground run-up measurements, and previous attempts to connect full-scale ground run-up and flyover measurements have omitted the effect of nonlinear propagation. This paper shows evidence for nonlinear propagation and the presence of acoustic shocks in acoustical measurements of F-35 flyover operations. Pressure waveforms, derivatives, and statistics indicate nonlinear propagation, and the resulting shock formation is significant at high engine powers. Variations due to microphone size, microphone height, and sampling rate are considered, and recommendations for future measurements are made. Metrics indicating nonlinear propagation are shown to be influenced by changes in sampling rate and microphone size, and exhibit less variation due to microphone height.
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Free-range laying hen systems are increasing within Australia. The pullets for these systems are typically reared indoors before being provided first range access around 21 to 26 weeks of age. Thus, the rearing and laying environments are disparate and hens may not adapt well to free-range housing. In this study, we reared 290 Hy-Line® Brown day-old chicks divided into two rooms each with feed, water and litter. In the enriched room, multiple structural, manipulable, visual and auditory stimuli were also provided from 4 to 21 days, the non-enriched room had no additional objects or stimuli. Pullets were transferred to the laying facility at 12 weeks of age and divided into six pens (three enriched-reared, three non-enriched-reared) with identical indoor resources and outdoor range area. All birds were first provided range access at 21 weeks of age. Video observations of natural disturbance behaviours on the range at 22 to 23 and 33 to 34 weeks of age showed no differences in frequency of disturbance occurrences between treatment groups (P=0.09) but a decrease in disturbance occurrences over time (P<0.0001). Radio-frequency identification tracking of individually tagged birds from 21 to 37 weeks of age showed enriched birds on average, spent less time on the range each day (P<0.04) but with a higher number of range visits than non-enriched birds from 21 to 24 weeks of age (P=0.01). Enriched birds accessed the range on more days (P=0.03) but over time, most birds in both treatment groups accessed the range daily. Basic external health scoring showed minimal differences between treatment groups with most birds in visibly good condition. At 38 weeks of age all birds were locked inside for 2 days and from 40 to 42 weeks of age the outdoor range was reduced to 20% of its original size to simulate stressful events. The eggs from non-enriched birds had higher corticosterone concentrations following lock-in and 2 weeks following range reduction compared with the concentrations within eggs from enriched birds (P<0.0001). Correspondingly, the enriched hens showing a greater increase in the number of visits following range area reduction compared to non-enriched hens (P=0.02). Only one rearing room per treatment was used but these preliminary data indicate 3 weeks of early enrichment had some long-term effects on hen ranging behaviour and enhanced hen's adaptability to environmental stressors.
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Bienestar del Animal , Conducta Animal , Pollos/fisiología , Animales , Australia , Corticosterona/sangre , Ambiente , Femenino , Dispositivo de Identificación por Radiofrecuencia , Estrés FisiológicoRESUMEN
BACKGROUND: Communication is complex in endocrine care, particularly during transition from paediatric to adult services. The aims of this study were to examine the feasibility of interventions to support young people to interact with clinicians. METHODS: Development and evaluation of a complex intervention in 2 phases: Pre-intervention observational study; Intervention feasibility study. Purposive sample of recordings of 62 consultations with 58 young people aged 11-25 years with long-term endocrine conditions in two paediatric and two adult endocrine clinics. Proportion of time talked during consultations, number and direction of questions asked; Paediatric Consultation Assessment Tool (PCAT); OPTION shared decision making tool; Medical Information Satisfaction Scale (MISS- 21). Young people were invited to use one or more of: a prompt sheet to help them influence consultation agendas and raise questions; a summary sheet to record key information; and the www.explain.me.uk website. RESULTS: Nearly two thirds of young people (63%) chose to use at least one communication intervention. Higher ratings for two PCAT items (95% CI 0.0 to 1.1 and 0.1 to 1.7) suggest interventions can support consultation skills. A higher proportion of accompanying persons (83%) than young people (64%) directed questions to clinicians. The proportion of young people asking questions was higher (84%) in the intervention phase than in the observation phase (71%). CONCLUSIONS: Interventions were acceptable and feasible. The Intervention phase was associated with YP asking more questions, which implies that the availability of interventions could promote interactivity.
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Servicios de Salud del Adolescente , Comunicación , Participación del Paciente , Adolescente , Niño , Toma de Decisiones , Endocrinología/métodos , Estudios de Factibilidad , Femenino , Humanos , MasculinoRESUMEN
Acute megakaryoblastic leukemia in patients without Down syndrome is a rare malignancy with a poor prognosis. RNA sequencing of fourteen pediatric cases previously identified novel fusion transcripts that are predicted to be pathological including CBFA2T3-GLIS2, GATA2-HOXA9, MN1-FLI and NIPBL-HOXB9. In contrast to CBFA2T3-GLIS2, which is insufficient to induce leukemia, we demonstrate that the introduction of GATA2-HOXA9, MN1-FLI1 or NIPBL-HOXB9 into murine bone marrow induces overt disease in syngeneic transplant models. With the exception of MN1, full penetrance was not achieved through the introduction of fusion partner genes alone, suggesting that the chimeric transcripts possess a unique gain-of-function phenotype. Leukemias were found to exhibit elements of the megakaryocyte erythroid progenitor gene expression program, as well as unique leukemia-specific signatures that contribute to transformation. Comprehensive genomic analyses of resultant murine tumors revealed few cooperating mutations confirming the strength of the fusion genes and their role as pathological drivers. These models are critical for both the understanding of the biology of disease as well as providing a tool for the identification of effective therapeutic agents in preclinical studies.
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Transformación Celular Neoplásica/genética , Regulación Leucémica de la Expresión Génica/genética , Leucemia Megacarioblástica Aguda/genética , Proteínas de Fusión Oncogénica/fisiología , Factores de Transcripción/fisiología , Animales , Médula Ósea/patología , Autorrenovación de las Células , Femenino , Perfilación de la Expresión Génica , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/patología , Humanos , Ratones , Ratones Endogámicos C57BL , Modelos Genéticos , Células Mieloides/patología , Trasplante de Neoplasias , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Proteínas de Fusión Oncogénica/genética , Fenotipo , ARN Interferente Pequeño/genética , Quimera por Radiación , Trombopoyesis/genética , Factores de Transcripción/genéticaRESUMEN
To determine the clinical significance of minimal residual disease (MRD) in patients with prognostically relevant subtypes of childhood acute lymphoblastic leukemia (ALL), we analyzed data from 488 patients treated in St Jude Total Therapy Study XV with treatment intensity based mainly on MRD levels measured during remission induction. MRD levels on day 19 predicted treatment outcome for patients with hyperdiploid >50 ALL, National Cancer Institute (NCI) standard-risk B-ALL or T-cell ALL, while MRD levels on day 46 were prognostic for patients with NCI standard-risk or high-risk B-ALL. Patients with t(12;21)/(ETV6-RUNX1) or hyperdiploidy >50 ALL had the best prognosis; those with a negative MRD on day 19 had a particularly low risk of relapse: 1.9% and 3.8%, respectively. Patients with NCI high-risk B-ALL or T-cell ALL had an inferior outcome; even with undetectable MRD on day 46, cumulative risk of relapse was 12.7% and 15.5%, respectively. Among patients with NCI standard-risk B-ALL, the outcome was intermediate overall but was poor if MRD was ⩾1% on day 19 or MRD was detectable at any level on day 46. Our results indicate that the clinical impact of MRD on treatment outcome in childhood ALL varies considerably according to leukemia subtype and time of measurement.
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Neoplasia Residual/patología , Neoplasia Residual/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Terapia Combinada , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Lactante , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Pronóstico , Recurrencia , Inducción de Remisión , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Free-range laying hen systems are increasing within Australia and research is needed to determine optimal outdoor stocking densities. Six small (n=150 hens) experimental flocks of ISA Brown laying hens were housed with access to ranges simulating one of three outdoor stocking densities with two pen replicates per density: 2000 hens/ha, 10 000 hens/ha or 20 000 hens/ha. Birds were provided daily range access from 21 to 36 weeks of age and the range usage of 50% of hens was tracked using radio-frequency identification technology. Throughout the study, basic external health assessments following a modified version of the Welfare Quality® protocol showed most birds were in visibly good condition (although keel damage was increasingly present with age) with few differences between stocking densities. Toenail length at 36 weeks of age was negatively correlated with hours spent ranging for all pens of birds (all r⩾-0.23, P⩽0.04). At 23 weeks of age, there were no differences between outdoor stocking densities in albumen corticosterone concentrations (P=0.44). At 35 weeks of age, density effects were significant (P<0.001) where the eggs from hens in the highest outdoor stocking density showed the highest albumen corticosterone concentrations, although eggs from hens in the 10 000 hens/ha density showed the lowest concentrations (P<0.017). Behavioural observations of hens both on the range and indoors showed more dust bathing and foraging (scratching followed by ground-pecking) was performed outdoors, but more resting indoors (all P<0.001). Hens from the 2000 hens/ha densities showed the least foraging on the range but the most resting outdoors, with hens from the 20 000 hens/ha densities showing the least amount of resting outdoors (all P<0.017). Proportions of dust bathing outdoors tended to differ between the stocking densities (P=0.08). For each of the health and behavioural measures there were differences between pen replicates within stocking densities. These data show outdoor stocking density has some effects on hen welfare, and it appears that consideration of both individual and group-level behaviour is necessary when developing optimal stocking density guidelines and free-range system management practices.
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Bienestar del Animal , Conducta Animal , Pollos/fisiología , Corticosterona/análisis , Vivienda para Animales , Crianza de Animales Domésticos , Animales , Australia , Femenino , Óvulo , Densidad de PoblaciónRESUMEN
Somatic mutations that lead to constitutive activation of NRAS and KRAS proto-oncogenes are among the most common in human cancer and frequently occur in acute myeloid leukemia (AML). An inducible NRAS(V12)-driven AML mouse model has established a critical role for continued NRAS(V12) expression in leukemia maintenance. In this model genetic suppression of NRAS(V12) expression results in rapid leukemia remission, but some mice undergo spontaneous relapse with NRAS(V12)-independent (NRI) AMLs providing an opportunity to identify mechanisms that bypass the requirement for Ras oncogene activity and drive leukemia relapse. We found that relapsed NRI AMLs are devoid of NRAS(V12) expression and signaling through the major oncogenic Ras effector pathways, phosphatidylinositol-3-kinase and mitogen-activated protein kinase, but express higher levels of an alternate Ras effector, Ralb, and exhibit NRI phosphorylation of the RALB effector TBK1, implicating RALB signaling in AML relapse. Functional studies confirmed that inhibiting CDK5-mediated RALB activation with a clinically relevant experimental drug, dinaciclib, led to potent RALB-dependent antileukemic effects in human AML cell lines, induced apoptosis in patient-derived AML samples in vitro and led to a 2-log reduction in the leukemic burden in patient-derived xenograft mice. Furthermore, dinaciclib potently suppressed the clonogenic potential of relapsed NRI AMLs in vitro and prevented the development of relapsed AML in vivo. Our findings demonstrate that Ras oncogene-independent activation of RALB signaling is a therapeutically targetable mechanism of escape from NRAS oncogene addiction in AML.
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GTP Fosfohidrolasas/genética , Regulación Neoplásica de la Expresión Génica , Leucemia Experimental/patología , Leucemia Mieloide Aguda/patología , Proteínas de la Membrana/genética , Mutación/genética , Proteínas de Unión al GTP ral/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Femenino , Humanos , Leucemia Experimental/genética , Leucemia Experimental/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Masculino , Ratones , Ratones SCID , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas de Unión al GTP Monoméricas/genética , Proteínas de Unión al GTP Monoméricas/metabolismo , Invasividad Neoplásica , Oncogenes , Transducción de Señal , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas de Unión al GTP ral/genéticaRESUMEN
The International Children's Palliative Care Network held its second international conference on children's palliative care in Buenos Aires, Argentina, from the 18th-21st May 2016. The theme of the conference was 'Children's Palliative Care . Now!' emphasising the need for palliative care for children now, as the future will be too late for many of them. Six pre-conference workshops were held, addressing issues connected to pain assessment and management, adolescent palliative care, ethics and decision-making, developing programmes, the basics of children's palliative care, and hidden aspects of children's palliative care. The conference brought together 410 participants from 40 countries. Plenary, concurrent, and poster presentations covered issues around the status of children's palliative care, genetics, perinatal and neonatal palliative care, the impact of children's palliative care and the experiences of parents and volunteers, palliative care as a human right, education in children's palliative care, managing complex pain in children, spiritual care and when to initiate palliative care. The 'Big Debate' explored issues around decision-making and end of life care in children, and gave participants the opportunity to explore a sensitive and thought provoking topic. At the end of the conference, delegates were urged to sign the Commitment of Buenos Aires which called for governments to implement the WHA resolution and ensure access to palliative care for neonates, children and their families, and also commits us as palliative care providers to share all that we can and collaborate with each other to achieve the global vision of palliative care for all children who need it. The conference highlighted the ongoing issues in children's palliative care and participants were continually challenged to ensure that children can access palliative care NOW.
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We compared whole exome sequencing (WES, n = 176 patients) and whole genome sequencing (WGS, n = 68) and clinical genotyping (DMET array-based approach) for interrogating 13 genes with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. We focused on 127 CPIC important variants: 103 single nucleotide variations (SNV), 21 insertion/deletions (Indel), HLA-B alleles, and two CYP2D6 structural variations. WES and WGS provided interrogation of nonoverlapping sets of 115 SNV/Indels with call rate >98%. Among 68 loci interrogated by both WES and DMET, 64 loci (94.1%, confidence interval [CI]: 85.6-98.4%) showed no discrepant genotyping calls. Among 66 loci interrogated by both WGS and DMET, 63 loci (95.5%, CI: 87.2-99.0%) showed no discrepant genotyping calls. In conclusion, even without optimization to interrogate pharmacogenetic variants, WES and WGS displayed potential to provide reliable interrogation of most pharmacogenes and further validation of genome sequencing in a clinical lab setting is warranted.
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Exoma/genética , Genoma Humano/genética , Técnicas de Genotipaje , Secuenciación de Nucleótidos de Alto Rendimiento , Farmacogenética/métodos , HumanosRESUMEN
BACKGROUND: There is a global need to expand palliative care services to reach the increasing number requiring end of life care. In developing countries where the incidences of cancer are rising there is an urgent need to develop the palliative care workforce. This paper reports on a UK Department for international development (DFID) initiative funded through the Tropical Health Education Trust (THET) where palliative care staff, both clinical and academic, volunteered to help to develop, support and deliver a degree in palliative care in sub-Saharan Africa. The objective of the study was to explore the personal impact on the health care professionals of being part of this initiative. METHODS: An evaluation approach using a confidential electronic survey containing quantitative and qualitative questions was distributed to all 17 volunteers on the programme, three months after completion of the first cohort. Data were analysed using descriptive statistics and content thematic analysis. Ethical review deemed the study to be service evaluation. RESULTS: 82 % (14) responded and several themes emerged from the data including the positive impact on teaching and educational skills; clinical practice and finally personal development. Using a score of 1-10 (1-no impact, 10 maximum impact) 'Lifestyle choices - life work balance' (rating 7.83) had the most impact. CONCLUSIONS: This approach to supporting the development of palliative care in Sub-Saharan Africa through skill sharing in supporting the delivery of a degree programme in palliative care was successful in terms of delivery of the degree programme, material development and mentorship of local staff. Additionally, this study shows it provided a range of positive impacts on the volunteer health care professionals from the UK. Professional impacts including increased management skills, and being better prepared to undertake a senior role. However it is the personal impact including lifestyle choices which the volunteers reported as the highest impact. Interestingly, several of the faculty have joined other volunteer programmes to continue to support the international development of palliative care.
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Curriculum , Personal de Salud/psicología , Cuidados Paliativos , Desarrollo de Programa/métodos , Enseñanza/métodos , África del Sur del Sahara , Humanos , Cooperación Internacional , Reino UnidoRESUMEN
BACKGROUND: Cytomegalovirus (CMV) infection in transplant recipients is reported to replicate with a doubling time of 1.2-2 days, and weekly screening is recommended for early diagnosis. We re-evaluated these features in our cohort of transplant recipients. METHODS: The CMV doubling time of the first CMV infection in the first year post-transplant could be calculated for 193 recipients of haematopoietic stem cell or solid organ transplantation. Factors determining the proportion of recipients with a high diagnostic CMV viral load (≥ 18,200 IU/mL) were explored using mathematical simulation. FINDINGS: The overall median doubling time was 4.3 days (IQR 2.5-7.8) and was not influenced by prior CMV immunity, or type of transplantation (p > 0.4). Assuming a fixed doubling time of 1.3 days and screening intervals of 7 or 10 days, 11.1% and 33.3% were projected to have a high CMV viral load at diagnosis, compared to 1.4% and 4.3% if the doubling time varies as observed in our cohort. Consistently, 1.9% of recipients screened weekly had a high diagnostic virus load. INTERPRETATION: Screening intervals can be extended to 10 days in cohorts with comparable CMV doubling time, whereas shorter than 7 days is required in cohorts with shorter doubling times to maintain pre-emptive screening quality.
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Infecciones por Citomegalovirus/virología , Citomegalovirus/fisiología , Trasplante , Replicación Viral , Adulto , Estudios de Cohortes , Simulación por Computador , Infecciones por Citomegalovirus/diagnóstico , Femenino , Humanos , Cinética , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
The effects of dietary electrolyte balance (DEB) and electrolyte-betaine (El-Be) supplements on heat-stressed broiler performance, acid-base balance and water retention were evaluated during the period 31-40 d of age in a 2 × 3 factorial arrangement of treatments. A total of 240 broilers were assigned to 6 treatment groups each with 8 replicates of 5 birds per cage and were exposed to cyclic high temperature (32 - 24 ± 1°C). Birds were provided with diets having DEB of either 180 or 220 mEq/kg. El-Be supplements were either added to the diet, water or not added to either of them to complete the array of 6 treatment groups. An additional 80 birds were kept at thermoneutral temperature (20 ± 1°C) and were provided with tap water and diets with DEB of either 180 or 220 mEq/kg to serve as negative controls. Exposure to high temperature depressed growth performance, increased rectal temperature and decreased potassium (K(+)) retention. In high-temperature room, birds fed on diets with DEB of 220 mEq/kg tended to increase BW from 35-40 d of age. However, at thermoneutral temperature, broilers fed on diets with DEB of 220 mEq/kg increased K(+) retention. Adding El-Be supplements in feed or water improved feed conversion ratio (FCR), enhanced water consumption and increased K(+) and sodium (Na(+)) retention. Interactions between DEB and El-Be supplements tended to affect body weight gain and FCR during the periods 35-40 and 31-40 d of age, respectively. It is suggested that when using a diet with DEB of 180 mEq/kg, adding the El-Be supplements in drinking water was more beneficial than in feed. Adding the supplements in feed or water was equally useful when using DEB of 220 mEq/kg.
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Betaína/metabolismo , Pollos/fisiología , Suplementos Dietéticos , Electrólitos/metabolismo , Respuesta al Choque Térmico , Equilibrio Ácido-Base , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Betaína/administración & dosificación , Temperatura Corporal , Pollos/crecimiento & desarrollo , Dieta/veterinaria , Relación Dosis-Respuesta a Droga , Electrólitos/administración & dosificación , Masculino , Carne/análisis , Agua/metabolismoRESUMEN
With improved contemporary therapy, we reassess long-term outcome in patients completing treatment for childhood acute lymphoblastic leukemia (ALL) to determine when cure can be declared with a high degree of confidence. In six successive clinical trials between 1984 and 2007, 1291 (84.5%) patients completed all therapies in continuous complete remission. The post-therapy cumulative risk of relapse or development of a second neoplasm and the event-free survival rate and overall survival were analyzed according to the presenting features and the three treatment periods defined by relative outcome. Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs 74.8% vs 85.1% (P<0.001)) and overall survival (76.5% vs 81.1% vs 91.7% (P<0.001)) at 10 years. The most important predictor of outcome after completion of therapy was the type of treatment. In the most recent treatment period, which omitted the use of prophylactic cranial irradiation, the post-treatment cumulative risk of relapse was 6.4%, death in remission 1.5% and development of a second neoplasm 2.3% at 10 years, with all relapses except one occurring within 4 years of therapy. None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy. These findings demonstrate that with contemporary effective therapy that excludes cranial irradiation, approximately 6% of children with ALL may relapse after completion of treatment, and those who remain in remission at 4 years post treatment may be considered cured (that is, less than 1% chance of relapse).
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Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Niño , Preescolar , Ensayos Clínicos como Asunto , Terapia Combinada/efectos adversos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Mortalidad , Neoplasias Primarias Secundarias , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Recurrencia , Inducción de Remisión , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
The International Children's Palliative Care Network (ICPCN) held its first international conference on children's palliative care, in conjunction with Tata Memorial Centre, in Mumbai, India, from 10-12 February 2014. The theme of the conference, Transforming children's palliative care-from ideas to action, reflected the vision of the ICPCN to live in a world where every child who needs it, can access palliative care, regardless of where they live. Key to this is action, to develop service provision and advocate for children's palliative care. Three pre-conference workshops were held on 9 February, aimed at doctors, nurses, social workers, and volunteers, and focused around the principles of children's palliative care, and in particular pain and symptom management. The conference brought together 235 participants representing 38 countries. Key themes identified throughout the conference included: the need for advocacy and leadership; for education and research, with great strides having been taken in the development of an evidence base for children's palliative care, along with the provision of education; the importance of communication and attention to spirituality in children, and issues around clinical care, in particular for neonates. Delegates were continually challenged to transform children's palliative care in their parts of the world and the conference culminated in the signing of the ICPCN Mumbai Declaration. The Declaration calls upon governments around the world to improve access to quality children's palliative care services and made a call on the Belgian government not to pass a bill allowing children to be euthanised in that country. The conference highlighted many of the ongoing developments in children's palliative care around the world, and as she closed the conference, Joan Marston (ICPCN CEO) challenged participants to take positive action and be the champions that the children need, thus transforming children's palliative care.