Evolution of superficial lake water temperature profile under diurnal radiative forcing

In lentic water bodies, such as lakes, the water temperature near the surface typically increases during the day, and decreases during the night as a consequence of the diurnal radiative forcing (solar and infrared radiation). These temperature variations penetrate vertically into the water, transported mainly by heat conduction enhanced by eddy diffusion, which may vary due to atmospheric conditions, surface wave breaking, and internal dynamics of the water body. These two processes can be described in terms of an effective thermal diffusivity, which can be experimentally estimated. However, the transparency of the water (depending on turbidity) also allows solar radiation to penetrate below the surface into the water body, where it is locally absorbed (either by the water or by the deployed sensors). This process makes the estimation of effective thermal diffusivity from experimental water temperature profiles more difficult. In this study, we analyze water temperature profiles in a lake with the aim of showing that assessment of the role played by radiative forcing is necessary to estimate the effective thermal diffusivity. To this end we investigate diurnal water temperature fluctuations with depth. We try to quantify the effect of locally absorbed radiation and assess the impact of atmospheric conditions (wind speed, net radiation) on the estimation of the thermal diffusivity. The whole analysis is based on the results of fiber optic distributed temperature sensing, which allows unprecedented high spatial resolution measurements (∼4 mm) of the temperature profile in the water and near the water surface.

Tumor heterogeneity and cancer stem cell paradigm: updates in concept, controversies and clinical relevance.

Although tumor heterogeneity is widely accepted, the existence of cancer stem cells (CSCs) and their proposed role in tumor maintenance has always been challenged and remains a matter of debate. Recently, a path-breaking chapter was added to this saga when three independent groups reported the in vivo existence of CSCs in brain, skin and intestinal tumors using lineage-tracing and thus strengthens the CSC concept; even though certain fundamental caveats are always associated with lineage-tracing approach. In principle, the CSC hypothesis proposes that similar to normal stem cells, CSCs maintain self renewal and multilineage differentiation property and are found at the central echelon of cellular hierarchy present within tumors. However, these cells differ from their normal counterpart by maintaining their malignant potential, alteration of genomic integrity, epigenetic identity and the expression of specific surface protein profiles. As CSCs are highly resistant to chemotherapeutics, they are thought to be a crucial factor involved in tumor relapse and superficially appear as the ultimate therapeutic target. However, even that is not the end; further complication is attributed by reports of bidirectional regeneration mechanism for CSCs, one from their self-renewal capability and another from the recently proposed concept of dynamic equilibrium between CSCs and non-CSCs via their interconversion. This phenomenon has currently added a new layer of complexity in understanding the biology of tumor heterogeneity. In-spite of its associated controversies, this area has rapidly emerged as the center of attention for researchers and clinicians, because of the conceptual framework it provides towards devising new therapies.

Angiogenic activity of breast cancer patients' monocytes reverted by combined use of systems modeling and experimental approaches.

Angiogenesis plays a key role in tumor growth and cancer progression. TIE-2-expressing monocytes (TEM) have been reported to critically account for tumor vascularization and growth in mouse tumor experimental models, but the molecular basis of their pro-angiogenic activity are largely unknown. Moreover, differences in the pro-angiogenic activity between blood circulating and tumor infiltrated TEM in human patients has not been established to date, hindering the identification of specific targets for therapeutic intervention. In this work, we investigated these differences and the phenotypic reversal of breast tumor pro-angiogenic TEM to a weak pro-angiogenic phenotype by combining Boolean modelling and experimental approaches. Firstly, we show that in breast cancer patients the pro-angiogenic activity of TEM increased drastically from blood to tumor, suggesting that the tumor microenvironment shapes the highly pro-angiogenic phenotype of TEM. Secondly, we predicted in silico all minimal perturbations transitioning the highly pro-angiogenic phenotype of tumor TEM to the weak pro-angiogenic phenotype of blood TEM and vice versa. In silico predicted perturbations were validated experimentally using patient TEM. In addition, gene expression profiling of TEM transitioned to a weak pro-angiogenic phenotype confirmed that TEM are plastic cells and can be reverted to immunological potent monocytes. Finally, the relapse-free survival analysis showed a statistically significant difference between patients with tumors with high and low expression values for genes encoding transitioning proteins detected in silico and validated on patient TEM. In conclusion, the inferred TEM regulatory network accurately captured experimental TEM behavior and highlighted crosstalk between specific angiogenic and inflammatory signaling pathways of outstanding importance to control their pro-angiogenic activity. Results showed the successful in vitro reversion of such an activity by perturbation of in silico predicted target genes in tumor derived TEM, and indicated that targeting tumor TEM plasticity may constitute a novel valid therapeutic strategy in breast cancer.

Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study.

BACKGROUND: Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance. METHODS: We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis. RESULTS: Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5-98.8), 80.8% specificity (72.6-87.1), positive likelihood ratio 4.9 (3.4-7.1), negative likelihood ratio 0.083 (0.022-0.32), and misclassification rate 0.20 (standard error 0.038). CONCLUSIONS: In Tanzanian children with WHO-defined clinical pneumonia, combinations of host biomarkers distinguished between end-point pneumonia, other infiltrates, and normal chest x-ray, whereas clinical variables did not. These findings generate pathophysiological hypotheses and may have potential research and clinical utility.

Spontaneous cell polarization: Feedback control of Cdc42 GTPase breaks cellular symmetry.

Spontaneous polarization without spatial cues, or symmetry breaking, is a fundamental problem of spatial organization in biological systems. This question has been extensively studied using yeast models, which revealed the central role of the small GTPase switch Cdc42. Active Cdc42-GTP forms a coherent patch at the cell cortex, thought to result from amplification of a small initial stochastic inhomogeneity through positive feedback mechanisms, which induces cell polarization. Here, I review and discuss the mechanisms of Cdc42 activity self-amplification and dynamic turnover. A robust Cdc42 patch is formed through the combined effects of Cdc42 activity promoting its own activation and active Cdc42-GTP displaying reduced membrane detachment and lateral diffusion compared to inactive Cdc42-GDP. I argue the role of the actin cytoskeleton in symmetry breaking is not primarily to transport Cdc42 to the active site. Finally, negative feedback and competition mechanisms serve to control the number of polarization sites.

Helping medical students to acquire a deeper understanding of truth-telling.

PROBLEM: Truth-telling is an important component of respect for patients' self-determination, but in the context of breaking bad news, it is also a distressing and difficult task. INTERVENTION: We investigated the long-term influence of a simulated patient-based teaching intervention, integrating learning objectives in communication skills and ethics into students' attitudes and concerns regarding truth-telling. We followed two cohorts of medical students from the preclinical third year to their clinical rotations (fifth year). Open-ended responses were analysed to explore medical students' reported difficulties in breaking bad news. CONTEXT: This intervention was implemented during the last preclinical year of a problem-based medical curriculum, in collaboration between the doctor-patient communication and ethics programs. OUTCOME: Over time, concerns such as empathy and truthfulness shifted from a personal to a relational focus. Whereas 'truthfulness' was a concern for the content of the message, 'truth-telling' included concerns on how information was communicated and how realistically it was received. Truth-telling required empathy, adaptation to the patient, and appropriate management of emotions, both for the patient's welfare and for a realistic understanding of the situation. LESSONS LEARNED: Our study confirms that an intervention confronting students with a realistic situation succeeds in making them more aware of the real issues of truth-telling. Medical students deepened their reflection over time, acquiring a deeper understanding of the relational dimension of values such as truth-telling, and honing their view of empathy.

Laparoscopic technique to perform a true Stamm gastrostomy in children.

PURPOSE: A surgical gastrostomy is mandatory in cases where a PEG is not feasible. Various minimally invasive techniques have been described, but many involve unusable materials in small children and/or have risk of disunion. We describe a technique for true Stamm gastrostomy performed by laparoscopy (LSG) with a purse string suture and four points of attachment onto the wall. METHOD: We reviewed 20 children who underwent an LSG from 2010 to 2013. After incision of the skin at the location planned for the gastrostomy, using three 3-5mm ports the stomach is fixed to the wall by three suspension stitches, which are entered and then emerged subcutaneously. A fourth stitch of attachment is used to make an award on the stomach and tie around the gastrostomy tube. RESULTS: Mean age was 4.2years, with 70% aged <2years. All children were malnourished, most often severely. All but two underwent a concomitant fundoplication. Feeding through the gastrostomy started on D0 or D1. Total feeding by gastrostomy was achieved in a mean duration of 2.9day. Mean hospital stay was 4.5days. There was no perioperative complication. Mean follow-up was 14months. Once, the balloon was accidently deflated and reinflated in the wall leading to its necrosis. Five peristomial granulomas were noticed. It was always possible to replace the tube by a gastrostomy device at least 6weeks after surgery. CONCLUSION: This new technique for true Stamm gastrostomy by laparoscopy reproduces exactly the one done by laparotomy, without special equipment. It can be made since the neonatal period, in all the circumstances when a laparoscopy is possible.

Management Control for Corporate Sustainability Execution: The Role of Employee Compensation

The research described in this thesis examines the characteristics, the benefits and the challenges associated with the implementation of management accounting systems in the field of Corporate Social Responsibility (CSR). Applied to the CSR context, management accounting relates to the identification, elaboration and communication of information about an organization's interactions with the society and the environment. Based on this information, firms are able to make decisions to achieve social and environmental objectives and provide evidence justifying the benefits and the costs of such actions. The study begins by focusing on green management and exploring the characteristics of Environmental Management Accounting (EMA) systems within firms. The first chapter informs the reader about the growing body of EMA research and reveals unexplored relevant aspects that need to be further investigated. The work also emphasizes the importance of developing new theoretical hypotheses and appropriate research designs to empirically tackle new aspects of EMA and gain understanding on the use of these practices. Subsequently, given the acknowledged importance of control systems in influencing the behaviour of individuals within organizations, the remaining two chapters of the dissertation focus on the functioning of CSR-linked incentives assigned to employees in the form of compensation plans. The second chapter examines the determinants influencing corporate provision of incentives for the attainment of environmental targets. Empirical analysis of a sample of international firms reveals that companies are likely to use green incentives as mechanisms to increase the efficacy in contracting with their employees as well as to respond to social influences. Finally, the third chapter investigates the effectiveness of contracting associated with the use of CSR-linked executive compensation. Empirical analysis of a sample of US-based companies shows that corporate choice to tie senior executives' pay to CSR targets promotes the firm's CSR performance. Cette thèse examine les caractéristiques, avantages et défis associés à l'utilisation des systèmes de contrôle de gestion dans le domaine de la Responsabilité Sociale des Entreprises (RSE). Dans le contexte de la RSE, les activités du contrôle de gestion impliquent l'identification, l'élaboration et la communication d'informations qui concernent les interactions des organisations avec la société et l'environnement. Avec ces informations les entreprises sont en mesure de prendre des décisions visant à atteindre les objectifs sociaux et environnementaux de l'organisation et de documenter les bénéfices et coûts de ces actions. Dès le début, la thèse se concentre sur les caractéristiques des systèmes de contrôle de gestion environnementale au sein des entreprises. Le premier chapitre passe en revue la littérature existante et révèle des aspects inexplorés. Pour ce faire, le travail suggère le développement de nouvelles théories ainsi que l'utilisation de méthodes appropriées. Ces dernières doivent permettre d'aborder empiriquement de nouveaux aspects des systèmes de contrôle environnemental et faciliter la compréhension sur l'utilisation de ces pratiques. Considérant l'importance des systèmes de contrôle pour influencer le comportement des individus au sein des organisations, la suite du travail se concentre sur le fonctionnement des contrats de rémunération des employées liées aux résultats de la RSE. Plus particulièrement, le deuxième chapitre examine les facteurs qui influencent la décision des entreprises d'assigner des objectifs environnementaux aux employées. L'analyse empirique d'un échantillon d'entreprises internationales montre que les entreprises sont susceptibles d'utiliser des mécanismes incitatifs écologiques pour augmenter l'efficacité des contrats ainsi que pour répondre aux influences sociales. Finalement, le troisième chapitre analyse l'efficacité des contrats de rémunération des dirigeants liés aux résultats de la RSE. L'analyse empirique d'un échantillon de sociétés américaines indique que le choix de l'entreprise de lier la rémunération des dirigeants à des objectifs de la RSE favorise la performance RSE de l'organisation.

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Our lives and careers are becoming ever more unpredictable. The "life-design paradigm" described in detail in this ground-breaking handbook helps counselors and others meet people's increasing need to develop and manage their own lives and careers. Life-design interventions, suited to a wide variety of cultural settings, help individuals become actors in their own lives and careers by activating, stimulating, and developing their personal resources. This handbook first addresses life-design theory, then shows how to apply life designing to different age groups and with more at-risk people, and looks at how to train life-design counselors.

Handbook of life design : from practice to theory and from theory to practice

Our lives and careers are becoming ever more unpredictable. The "life-design paradigm" described in detail in this ground-breaking handbook helps counselors and others meet people's increasing need to develop and manage their own lives and careers. Life-design interventions, suited to a wide variety of cultural settings, help individuals become actors in their own lives and careers by activating, stimulating, and developing their personal resources. This handbook first addresses life-design theory, then shows how to apply life designing to different age groups and with more at-risk people, and looks at how to train life-design counselors

Emotions in International Politics. Beyond Mainstream International Relations

In recent years, social scientists have increasingly recognized the interconnectedness of thought on emotions. Nowhere is the role of passions more evident than international politics, where pride, anger, guilt, fear, empathy, and other feelings are routinely on display. But in the absence of an overarching theory of emotions, how can we understand their role at the international level? Emotions in International Politics fills the need for theoretical tools in the new and rapidly growing subfield of international relations. Eminent scholars from a range of disciplines consider how emotions can be investigated from an international perspective involving collective players, drawing evidence from such emotionally fraught events as the Rwandan genocide, World War II, the 9/11 attacks, and the Iranian nuclear standoff. The path-breaking research collected in Emotions in International Politics will be a valuable theoretical guide to understanding conflict and cooperation in international relations.