Intensive care for extreme prematurity--moving beyond gestational age.

BACKGROUND: Decisions regarding whether to administer intensive care to extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients. METHODS: We prospectively studied a cohort of 4446 infants born at 22 to 25 weeks' gestation (determined on the basis of the best obstetrical estimate) in the Neonatal Research Network of the National Institute of Child Health and Human Development to relate risk factors assessable at or before birth to the likelihood of survival, survival without profound neurodevelopmental impairment, and survival without neurodevelopmental impairment at a corrected age of 18 to 22 months. RESULTS: Among study infants, 3702 (83%) received intensive care in the form of mechanical ventilation. Among the 4192 study infants (94%) for whom outcomes were determined at 18 to 22 months, 49% died, 61% died or had profound impairment, and 73% died or had impairment. In multivariable analyses of infants who received intensive care, exposure to antenatal corticosteroids, female sex, singleton birth, and higher birth weight (per each 100-g increment) were each associated with reductions in the risk of death and the risk of death or profound or any neurodevelopmental impairment; these reductions were similar to those associated with a 1-week increase in gestational age. At the same estimated likelihood of a favorable outcome, girls were less likely than boys to receive intensive care. The outcomes for infants who underwent ventilation were better predicted with the use of the above factors than with use of gestational age alone. CONCLUSIONS: The likelihood of a favorable outcome with intensive care can be better estimated by consideration of four factors in addition to gestational age: sex, exposure or nonexposure to antenatal corticosteroids, whether single or multiple birth, and birth weight. (ClinicalTrials.gov numbers, NCT00063063 [ClinicalTrials.gov] and NCT00009633 [ClinicalTrials.gov].).

Evaluation of Cage Designs and Feeding Regimes for Honey Bee (Hymenoptera: Apidae) Laboratory Experiments

The aim of this study was to improve cage systems for maintaining adult honey bee (Apis mellifera L.) workers under in vitro laboratory conditions. To achieve this goal, we experimentally evaluated the impact of different cages, developed by scientists of the international research network COLOSS (Prevention of honey bee COlony LOSSes), on the physiology and survival of honey bees. We identified three cages that promoted good survival of honey bees. The bees from cages that exhibited greater survival had relatively lower titers of deformed wing virus, suggesting that deformed wing virus is a significant marker reflecting stress level and health status of the host. We also determined that a leak- and drip-proof feeder was an integral part of a cage system and a feeder modified from a 20-ml plastic syringe displayed the best result in providing steady food supply to bees. Finally, we also demonstrated that the addition of protein to the bees' diet could significantly increase the level ofvitellogenin gene expression and improve bees' survival. This international collaborative study represents a critical step toward improvement of cage designs and feeding regimes for honey bee laboratory experiments.

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

BACKGROUND Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

Detection of haemorrhagic shock: Are vital signs obsolete? A commentary by Dr M. Luginbühl

The ATLS program by the American college of surgeons is probably the most important globally active training organization dedicated to improve trauma management. Detection of acute haemorrhagic shock belongs to the key issues in clinical practice and thus also in medical teaching. (In this issue of the journal William Schulz and Ian McConachrie critically review the ATLS shock classification Table 1), which has been criticized after several attempts of validation have failed [1]. The main problem is that distinct ranges of heart rate are related to ranges of uncompensated blood loss and that the heart rate decrease observed in severe haemorrhagic shock is ignored [2]. Table 1. Estimated blood loos based on patient's initial presentation (ATLS Students Course Manual, 9th Edition, American College of Surgeons 2012). Class I Class II Class III Class IV Blood loss ml Up to 750 750–1500 1500–2000 >2000 Blood loss (% blood volume) Up to 15% 15–30% 30–40% >40% Pulse rate (BPM) <100 100–120 120–140 >140 Systolic blood pressure Normal Normal Decreased Decreased Pulse pressure Normal or ↑ Decreased Decreased Decreased Respiratory rate 14–20 20–30 30–40 >35 Urine output (ml/h) >30 20–30 5–15 negligible CNS/mental status Slightly anxious Mildly anxious Anxious, confused Confused, lethargic Initial fluid replacement Crystalloid Crystalloid Crystalloid and blood Crystalloid and blood Table options In a retrospective evaluation of the Trauma Audit and Research Network (TARN) database blood loss was estimated according to the injuries in nearly 165,000 adult trauma patients and each patient was allocated to one of the four ATLS shock classes [3]. Although heart rate increased and systolic blood pressure decreased from class I to class IV, respiratory rate and GCS were similar. The median heart rate in class IV patients was substantially lower than the value of 140 min−1 postulated by ATLS. Moreover deterioration of the different parameters does not necessarily go parallel as suggested in the ATLS shock classification [4] and [5]. In all these studies injury severity score (ISS) and mortality increased with in increasing shock class [3] and with increasing heart rate and decreasing blood pressure [4] and [5]. This supports the general concept that the higher heart rate and the lower blood pressure, the sicker is the patient. A prospective study attempted to validate a shock classification derived from the ATLS shock classes [6]. The authors used a combination of heart rate, blood pressure, clinically estimated blood loss and response to fluid resuscitation to classify trauma patients (Table 2) [6]. In their initial assessment of 715 predominantly blunt trauma patients 78% were classified as normal (Class 0), 14% as Class I, 6% as Class II and only 1% as Class III and Class IV respectively. This corresponds to the results from the previous retrospective studies [4] and [5]. The main endpoint used in the prospective study was therefore presence or absence of significant haemorrhage, defined as chest tube drainage >500 ml, evidence of >500 ml of blood loss in peritoneum, retroperitoneum or pelvic cavity on CT scan or requirement of any blood transfusion >2000 ml of crystalloid. Because of the low prevalence of class II or higher grades statistical evaluation was limited to a comparison between Class 0 and Class I–IV combined. As in the retrospective studies, Lawton did not find a statistical difference of heart rate and blood pressure among the five groups either, although there was a tendency to a higher heart rate in Class II patients. Apparently classification during primary survey did not rely on vital signs but considered the rather soft criterion of “clinical estimation of blood loss” and requirement of fluid substitution. This suggests that allocation of an individual patient to a shock classification was probably more an intuitive decision than an objective calculation the shock classification. Nevertheless it was a significant predictor of ISS [6]. Table 2. Shock grade categories in prospective validation study (Lawton, 2014) [6]. Normal No haemorrhage Class I Mild Class II Moderate Class III Severe Class IV Moribund Vitals Normal Normal HR > 100 with SBP >90 mmHg SBP < 90 mmHg SBP < 90 mmHg or imminent arrest Response to fluid bolus (1000 ml) NA Yes, no further fluid required Yes, no further fluid required Requires repeated fluid boluses Declining SBP despite fluid boluses Estimated blood loss (ml) None Up to 750 750–1500 1500–2000 >2000 Table options What does this mean for clinical practice and medical teaching? All these studies illustrate the difficulty to validate a useful and accepted physiologic general concept of the response of the organism to fluid loss: Decrease of cardiac output, increase of heart rate, decrease of pulse pressure occurring first and hypotension and bradycardia occurring only later. Increasing heart rate, increasing diastolic blood pressure or decreasing systolic blood pressure should make any clinician consider hypovolaemia first, because it is treatable and deterioration of the patient is preventable. This is true for the patient on the ward, the sedated patient in the intensive care unit or the anesthetized patients in the OR. We will therefore continue to teach this typical pattern but will continue to mention the exceptions and pitfalls on a second stage. The shock classification of ATLS is primarily used to illustrate the typical pattern of acute haemorrhagic shock (tachycardia and hypotension) as opposed to the Cushing reflex (bradycardia and hypertension) in severe head injury and intracranial hypertension or to the neurogenic shock in acute tetraplegia or high paraplegia (relative bradycardia and hypotension). Schulz and McConachrie nicely summarize the various confounders and exceptions from the general pattern and explain why in clinical reality patients often do not present with the “typical” pictures of our textbooks [1]. ATLS refers to the pitfalls in the signs of acute haemorrhage as well: Advanced age, athletes, pregnancy, medications and pace makers and explicitly state that individual subjects may not follow the general pattern. Obviously the ATLS shock classification which is the basis for a number of questions in the written test of the ATLS students course and which has been used for decades probably needs modification and cannot be literally applied in clinical practice. The European Trauma Course, another important Trauma training program uses the same parameters to estimate blood loss together with clinical exam and laboratory findings (e.g. base deficit and lactate) but does not use a shock classification related to absolute values. In conclusion the typical physiologic response to haemorrhage as illustrated by the ATLS shock classes remains an important issue in clinical practice and in teaching. The estimation of the severity haemorrhage in the initial assessment trauma patients is (and was never) solely based on vital signs only but includes the pattern of injuries, the requirement of fluid substitution and potential confounders. Vital signs are not obsolete especially in the course of treatment but must be interpreted in view of the clinical context. Conflict of interest None declared. Member of Swiss national ATLS core faculty.

When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study.

OBJECTIVE To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). DESIGN Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. METHODS Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9-12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. RESULTS In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -5.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. CONCLUSIONS Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.

Determination of suitable irrigation lengths and intervals using capacitance humidity sensors for a sandy soil

production, during the summer of 2010. This farm is integrated at the Spanish research network for the sugar beet development (AIMCRA) which regarding irrigation, focuses on maximizing water saving and cost reduction. According to AIMCRA 0 s perspective for promoting irrigation best practices, it is essential to understand soil response to irrigation i.e. maximum irrigation length for each soil infiltration capacity. The Use of Humidity Sensors provides foundations to address soil 0 s behavior at the irrigation events and, therefore, to establish the boundaries regarding irrigation length and irrigation interval. In order to understand to what extent farmer 0 s performance at Tordesillas farm could have been potentially improved, this study aims to address suitable irrigation length and intervals for the given soil properties and evapotranspiration rates. In this sense, several humidity sensors were installed: (1) A Frequency Domain Reflectometry (FDR) EnviroScan Probe taking readings at 10, 20, 40 and 60cm depth and (2) different Time Domain Reflectometry (TDR) Echo 2 and Cr200 probes buried in a 50cm x 30cm x 50cm pit and placed along the walls at 10, 20, 30 and 40 cm depth. Moreover, in order to define soil properties, a textural analysis at the Tordesillas Farm was conducted. Also, data from the Tordesillas meteorological station was utilized.

Mapping of the Music Ontology to the Media Value Chain Ontology and the PROV Ontology

Mapping of the Music Ontology to the Media Value Chain Ontology and the PROV Ontology

Conformance monitoring, contract of objectives, tube in the sky

Ponencia invitada sobre asignacion y gestion de losts en el curso de verano de la UPM Research in Decisión Support Systems for future Air Traffic Management

Air Traffic Management - Historic background and present situation

Ponencia invitada sobre gestion de trafico aereo en el curso de verano de la UPM Research in Decision Support Systems for future Air Traffic Management

Replication types: towards a shared taxonomy

Context: The software engineering community is becoming more aware of the need for experimental replications. In spite of the importance of this topic, there is still much inconsistency in the terminology used to describe replications. Objective: Understand the perspectives of empirical researchers about various terms used to characterize replications and propose a consistent taxonomy of terms. Method: A survey followed by plenary discussion during the 2013 International Software Engineering Research Network meeting. Results: We propose a taxonomy which consolidates the disparate terminology. This taxonomy had a high level of agreement among workshop attendees. Conclusion: Consistent terminology is important for any field to progress. This work is the first step in that direction. Additional study and discussion is still necessary.

Participación Directa y Aprendizaje de los Trabajadores en Mejoras Tecnológicas a Empresas Bajo Gestión Colectiva. Aplicación en Industrias Metalúrgicas de Venezuela y Argentina

La industria metalúrgica estatal venezolana ha vivido, desde sus inicios, procesos cíclicos de cambios y ajustes tecnológicos. Estos procesos no han sido objeto de sistematización que asegure el aprendizaje y apropiación del conocimiento. Este hecho, aún hoy, ha obstaculizado los procesos de apropiación y mejora de las tecnologías asociadas al sector. A partir del acompañamiento a iniciativas de participación de grupos de interés surgidos del seno de los trabajadores, se planteó esta investigación que tuvo como propósito la determinación de condiciones y relaciones para su participación directa en los procesos de mejora de las tecnologías existentes y el fortalecimiento del aprendizaje asociado. Se consideraron dos ámbitos Latinoamericanos donde hay manifestación de gestión colectiva y participación: Venezuela y Argentina. En el caso venezolano, el abordaje se realizó bajo la Investigación Acción Participativa (IAP), desarrollando la “investigación próxima”, como estrategia de acompañamiento, mediante “talleres de formación-investigación” y la sistematización de experiencias considerando la perspectiva y necesidades de los actores. En el caso argentino, el abordaje se realizó mediante visitas, entrevistas, reuniones y encuentros. Los talleres realizados en Venezuela, en un contexto de diálogo de saberes, facilitaron el surgimiento de herramientas prácticas para la sistematización de su propia experiencia (“Preguntas generadoras”, “Mi historia con la tecnología”, “Bitácora de aprendizaje”). El intercambio con los pares argentinos ha generado una red que plantea la posibilidad de construcción y nucleación conjunta de saberes y experiencia, tanto para los trabajadores como para los investigadores. Los casos estudiados referidos a las empresas recuperadas por los trabajadores (ERTs) argentinos evidencian un proceso de participación marcada por su autonomía en la gestión de la empresa, dadas las circunstancias que los llevó a asumirla para conservar sus puestos de trabajo. De estos casos emergieron categorías asociadas con elementos de gestión de un proceso técnico–tecnológico, como la participación en la planificación, concepción o diseño de la mejora. La participación en general está asociada al hecho asambleario, vinculado a las prácticas de toma de decisiones autogestionarias como expresión de una alta participación. La Asamblea, como máxima instancia de participación, y el Consejo de Administración son las formas de participación prevalecientes. En cuanto al aprendizaje, los trabajadores de las ERTs argentinas aportaron categorías de gran significación a los procesos de socialización del conocimiento: conocimiento colectivo y cooperación del conocimiento, rescate de los saberes y formación de trabajadores que tomen el relevo. Las categorías surgidas de las ERTs argentinas, los referentes teóricos y el interés de los trabajadores venezolanos fueron la base para la valoración tanto de su grado de participación en las mejoras a procesos tecnológicos emprendidas, como del aprendizaje asociado. Ésta valoración se realizó bajo una aproximación borrosa dado el carácter ambiguo de estas categorías que fueron trabajadas como conjuntos que se relacionan, más que como variables. Se encontró que la participación, se configura como un sub-conjunto del aprendizaje para contribuir a su fortalecimiento. Las condiciones y relaciones para fortalecer la participación en los asuntos tecnológicos surgieron a partir de la sistematización y síntesis de ambas experiencias (Venezuela y Argentina) conjugando una estructura que contempla la formación para la nucleación de colectivos de saberes (proyectos de mejora o innovaciones), las redes por afinidad, la sistematización de su propia experiencia técnica y los enlaces institucionales. Estos resultados dan cuenta de la integración de los intereses de las partes (trabajadores, investigadores, instituciones), mediante las estrategias de encuentro, de sistematización de los propios métodos y de conformación de los “colectivos de saberes”, la red de IAP en la industria (IAP Industrial) considerando la “deriva de la investigación”, bajo discursos práctico–teóricos propios, como posibilidad de posicionamiento de su participación en los asuntos tecnológicos de sus respectivas organizaciones, abriendo una oportunidad de ampliación de la experiencia en otros ámbitos y sectores. ABSTRACT Venezuelan's state owned steel industry has experienced since its earliest years, cycles of change and technological adjustments. These processes have not been systematized to ensure learning and knowledge in those organizations. This fact, even today, has hindered the processes of appropriation and improving the technologies associated with the sector. In order to support initiatives involving metalworker interest groups, this research was aimed at determining conditions and relations for their direct participation in process improvements to existing technologies and strengthening the associated learning. Two Latin American countries, Venezuela and Argentina, were considered on the base of their collective management and participation experiences. The Venezuelan approach was carried out under the Participatory Action Research (PAR) strategy, through the ‘proximal research’ as support strategy, by means of ‘workshops–research’ and systematization of experiences considering the perspective and needs of actors. Workshops were carried out in metallurgical enterprises from steel and aluminum at Guayana, Venezuela and its affiliates in the Central region. Those industries have been promoted collective management. The Argentine approach was carried out through visits, interviews, meetings and gatherings. The workshops held in Venezuela, in a dialogue of knowledge context, facilitated the emergence of tools for the systematization of their own experience (‘generating questions’, ‘My history with technology’, ‘Learning Log’). The relation with Argentine peers has generated a network that creates opportunities of knowledge and experience construction and its nucleation for both, workers and researchers. The cases studied relating to Argentine workers’ recuperated enterprises show a participatory process marked by autonomy in the management of the factory, given the circumstances that led them to take it in order to maintain their jobs. From these cases emerged categories associated with management aspects about technical-technology process, such as participation in planning, design or implementation of the improvement. Participation, in general, is associated with assemblies, joined to the practices of self-management decision-making as an expression of a high participation. The Cooperative General Assembly, as the highest instance of participation, and the Board of Directors are the prevalent forms of participation. In relation to learning, Argentine workers’ recuperated enterprises provided categories of great significance to the process of socialization of knowledge: collective knowledge and knowledge cooperation, recovery of knowledge and training workers for replacement. Based on categories arising from the Argentine experience, theoretical framework and the interest of the Venezuelan workers the assessment of both, their degree of participation on technical improvements and the associated technological learning were made considering a fuzzy approach, given the ambiguous nature of these categories that were worked as sets rather than variables. It was found that participation is configured as a subset of learning to contribute to its strengthening. The conditions and relations to strengthen participation in technology issues emerged from the systematization and synthesis of both experiences (Venezuela and Argentina) combining a structure which provides training for the nucleation of collectives of knowledge (improvement projects or innovations), affinity networks, systematization of their own expertise and institutional links. These results show the integration of the interests of stakeholders (workers, researchers, institutions) through strategies like meetings, systematization of their own methods, forming ‘collectives of technological knowledge’ and a participative action research network in this industry (Industrial PAR) considering the ‘research drift’, under their own practical-theoretical discourses positioned as a possibility of their participation in technological activities in their respective organizations, opening an opportunity for scaling to other areas and sectors.

Antibiotic treatment for intermittent bladder catheterisation with once daily prophylaxis (the AnTIC study) : Study protocol for a randomised controlled trial

Funder statement This article/paper/report presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the UK Government’s Department of Health. Acknowledgements We would like to acknowledge Dr Graeme MacLennan, Mr Simon Skene, Mr Julian Shah and Dr Nadine Dougall (past member) for their valuable contribution to the study as DMC members. We would like to thank Professor Chris Butler, Dr Emma Hall, Mr Roland Morley, Mr Dan Wood, Ms Jane Laws and Ms Sarah Bittlestone for their oversight of the AnTIC study as members of the TSC, and we would like to thank Ms Heather Armstrong for her contributions as a patient group representative. We thank all Principal Investigators and site staff for their commitment in recruitment for the AnTIC study. Finally, we would like to thank Hazel Wilde for secretarial support. The trial is funded by the NIHR Health Technology Assessment Programme (project reference: 11-72-01) and will be published in full in the Health Technology Assessment journal series. The authors also acknowledge the support of the National Institute for Health Research through the Comprehensive Clinical Research Network.