Gestão integrada de recursos humanos em farmácia comunitária e seus fundamentos

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

O perfil de personalidade dos estudantes de engenharia informática

Dissertação apresentada à Universidade Fernando Pessoa, como parte dos requisitos necessários para a obtenção do grau Mestre em Psicologia, ramo de Psicologia do Trabalho e das Organizações

A gestão na medicina dentária

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária

Micro-Anatomical Quantitative Imaging Towards Enabling Automated Diagnosis of Thick Tissues at the Point of Care

Histopathology is the clinical standard for tissue diagnosis. However, histopathology has several limitations including that it requires tissue processing, which can take 30 minutes or more, and requires a highly trained pathologist to diagnose the tissue. Additionally, the diagnosis is qualitative, and the lack of quantitation leads to possible observer-specific diagnosis. Taken together, it is difficult to diagnose tissue at the point of care using histopathology.

Several clinical situations could benefit from more rapid and automated histological processing, which could reduce the time and the number of steps required between obtaining a fresh tissue specimen and rendering a diagnosis. For example, there is need for rapid detection of residual cancer on the surface of tumor resection specimens during excisional surgeries, which is known as intraoperative tumor margin assessment. Additionally, rapid assessment of biopsy specimens at the point-of-care could enable clinicians to confirm that a suspicious lesion is successfully sampled, thus preventing an unnecessary repeat biopsy procedure. Rapid and low cost histological processing could also be potentially useful in settings lacking the human resources and equipment necessary to perform standard histologic assessment. Lastly, automated interpretation of tissue samples could potentially reduce inter-observer error, particularly in the diagnosis of borderline lesions.

To address these needs, high quality microscopic images of the tissue must be obtained in rapid timeframes, in order for a pathologic assessment to be useful for guiding the intervention. Optical microscopy is a powerful technique to obtain high-resolution images of tissue morphology in real-time at the point of care, without the need for tissue processing. In particular, a number of groups have combined fluorescence microscopy with vital fluorescent stains to visualize micro-anatomical features of thick (i.e. unsectioned or unprocessed) tissue. However, robust methods for segmentation and quantitative analysis of heterogeneous images are essential to enable automated diagnosis. Thus, the goal of this work was to obtain high resolution imaging of tissue morphology through employing fluorescence microscopy and vital fluorescent stains and to develop a quantitative strategy to segment and quantify tissue features in heterogeneous images, such as nuclei and the surrounding stroma, which will enable automated diagnosis of thick tissues.

To achieve these goals, three specific aims were proposed. The first aim was to develop an image processing method that can differentiate nuclei from background tissue heterogeneity and enable automated diagnosis of thick tissue at the point of care. A computational technique called sparse component analysis (SCA) was adapted to isolate features of interest, such as nuclei, from the background. SCA has been used previously in the image processing community for image compression, enhancement, and restoration, but has never been applied to separate distinct tissue types in a heterogeneous image. In combination with a high resolution fluorescence microendoscope (HRME) and a contrast agent acriflavine, the utility of this technique was demonstrated through imaging preclinical sarcoma tumor margins. Acriflavine localizes to the nuclei of cells where it reversibly associates with RNA and DNA. Additionally, acriflavine shows some affinity for collagen and muscle. SCA was adapted to isolate acriflavine positive features or APFs (which correspond to RNA and DNA) from background tissue heterogeneity. The circle transform (CT) was applied to the SCA output to quantify the size and density of overlapping APFs. The sensitivity of the SCA+CT approach to variations in APF size, density and background heterogeneity was demonstrated through simulations. Specifically, SCA+CT achieved the lowest errors for higher contrast ratios and larger APF sizes. When applied to tissue images of excised sarcoma margins, SCA+CT correctly isolated APFs and showed consistently increased density in tumor and tumor + muscle images compared to images containing muscle. Next, variables were quantified from images of resected primary sarcomas and used to optimize a multivariate model. The sensitivity and specificity for differentiating positive from negative ex vivo resected tumor margins was 82% and 75%. The utility of this approach was further tested by imaging the in vivo tumor cavities from 34 mice after resection of a sarcoma with local recurrence as a bench mark. When applied prospectively to images from the tumor cavity, the sensitivity and specificity for differentiating local recurrence was 78% and 82%. The results indicate that SCA+CT can accurately delineate APFs in heterogeneous tissue, which is essential to enable automated and rapid surveillance of tissue pathology.

Two primary challenges were identified in the work in aim 1. First, while SCA can be used to isolate features, such as APFs, from heterogeneous images, its performance is limited by the contrast between APFs and the background. Second, while it is feasible to create mosaics by scanning a sarcoma tumor bed in a mouse, which is on the order of 3-7 mm in any one dimension, it is not feasible to evaluate an entire human surgical margin. Thus, improvements to the microscopic imaging system were made to (1) improve image contrast through rejecting out-of-focus background fluorescence and to (2) increase the field of view (FOV) while maintaining the sub-cellular resolution needed for delineation of nuclei. To address these challenges, a technique called structured illumination microscopy (SIM) was employed in which the entire FOV is illuminated with a defined spatial pattern rather than scanning a focal spot, such as in confocal microscopy.

Thus, the second aim was to improve image contrast and increase the FOV through employing wide-field, non-contact structured illumination microscopy and optimize the segmentation algorithm for new imaging modality. Both image contrast and FOV were increased through the development of a wide-field fluorescence SIM system. Clear improvement in image contrast was seen in structured illumination images compared to uniform illumination images. Additionally, the FOV is over 13X larger than the fluorescence microendoscope used in aim 1. Initial segmentation results of SIM images revealed that SCA is unable to segment large numbers of APFs in the tumor images. Because the FOV of the SIM system is over 13X larger than the FOV of the fluorescence microendoscope, dense collections of APFs commonly seen in tumor images could no longer be sparsely represented, and the fundamental sparsity assumption associated with SCA was no longer met. Thus, an algorithm called maximally stable extremal regions (MSER) was investigated as an alternative approach for APF segmentation in SIM images. MSER was able to accurately segment large numbers of APFs in SIM images of tumor tissue. In addition to optimizing MSER for SIM image segmentation, an optimal frequency of the illumination pattern used in SIM was carefully selected because the image signal to noise ratio (SNR) is dependent on the grid frequency. A grid frequency of 31.7 mm-1 led to the highest SNR and lowest percent error associated with MSER segmentation.

Once MSER was optimized for SIM image segmentation and the optimal grid frequency was selected, a quantitative model was developed to diagnose mouse sarcoma tumor margins that were imaged ex vivo with SIM. Tumor margins were stained with acridine orange (AO) in aim 2 because AO was found to stain the sarcoma tissue more brightly than acriflavine. Both acriflavine and AO are intravital dyes, which have been shown to stain nuclei, skeletal muscle, and collagenous stroma. A tissue-type classification model was developed to differentiate localized regions (75x75 µm) of tumor from skeletal muscle and adipose tissue based on the MSER segmentation output. Specifically, a logistic regression model was used to classify each localized region. The logistic regression model yielded an output in terms of probability (0-100%) that tumor was located within each 75x75 µm region. The model performance was tested using a receiver operator characteristic (ROC) curve analysis that revealed 77% sensitivity and 81% specificity. For margin classification, the whole margin image was divided into localized regions and this tissue-type classification model was applied. In a subset of 6 margins (3 negative, 3 positive), it was shown that with a tumor probability threshold of 50%, 8% of all regions from negative margins exceeded this threshold, while over 17% of all regions exceeded the threshold in the positive margins. Thus, 8% of regions in negative margins were considered false positives. These false positive regions are likely due to the high density of APFs present in normal tissues, which clearly demonstrates a challenge in implementing this automatic algorithm based on AO staining alone.

Thus, the third aim was to improve the specificity of the diagnostic model through leveraging other sources of contrast. Modifications were made to the SIM system to enable fluorescence imaging at a variety of wavelengths. Specifically, the SIM system was modified to enabling imaging of red fluorescent protein (RFP) expressing sarcomas, which were used to delineate the location of tumor cells within each image. Initial analysis of AO stained panels confirmed that there was room for improvement in tumor detection, particularly in regards to false positive regions that were negative for RFP. One approach for improving the specificity of the diagnostic model was to investigate using a fluorophore that was more specific to staining tumor. Specifically, tetracycline was selected because it appeared to specifically stain freshly excised tumor tissue in a matter of minutes, and was non-toxic and stable in solution. Results indicated that tetracycline staining has promise for increasing the specificity of tumor detection in SIM images of a preclinical sarcoma model and further investigation is warranted.

In conclusion, this work presents the development of a combination of tools that is capable of automated segmentation and quantification of micro-anatomical images of thick tissue. When compared to the fluorescence microendoscope, wide-field multispectral fluorescence SIM imaging provided improved image contrast, a larger FOV with comparable resolution, and the ability to image a variety of fluorophores. MSER was an appropriate and rapid approach to segment dense collections of APFs from wide-field SIM images. Variables that reflect the morphology of the tissue, such as the density, size, and shape of nuclei and nucleoli, can be used to automatically diagnose SIM images. The clinical utility of SIM imaging and MSER segmentation to detect microscopic residual disease has been demonstrated by imaging excised preclinical sarcoma margins. Ultimately, this work demonstrates that fluorescence imaging of tissue micro-anatomy combined with a specialized algorithm for delineation and quantification of features is a means for rapid, non-destructive and automated detection of microscopic disease, which could improve cancer management in a variety of clinical scenarios.

Violence Exposure and Welfare over Time: Evidence from the Burundi Civil War

We investigate the relationship between exposure to conflict and poverty dynamics over time, using original three-waves panel data for Burundi which tracked individuals and reported local-level violence exposure from 1998 to 2012. Firstly, the data reveal that headcount poverty has not changed since 1998 while we observe multiple transitions into and out of poverty. Moreover, households exposed to the war exhibit a lower level of welfare than non-exposed households, with the difference between the two groups predicted to remain significant at least until 2017, i.e. twelve years after the conflict termination. The correlation between violence exposure and deprivation over time is confirmed in a household-level panel setting. Secondly, our empirical investigation shows how violence exposure over different time spans interacts with households' subsequent welfare. Our analysis of the determinants of households' likelihood to switch poverty status (i.e. to fall into poverty or escape poverty) combined with quantile regressions suggest that, (i) exposure during the first phase of the conflict has affected the entire distribution, and (ii) exposure during the second phase of the conflict has mostly affected the upper tail of the distribution: initially non-poor households have a higher propensity to fall into poverty while initially poor households see their propensity to pull through only slightly decrease with recent exposure to violence. Although not directly testable with the data at hand, these results are consistent with the changing nature of violence in the course of the Burundi civil war, from relatively more labour-destructive to relatively more capital-destructive.

Public-public partnerships (PUPs) in water

Water operators need to be efficient, accountable, honest public institutions providing a universal service. Many water services however lack the institutional strength, the human resources, the technical expertise and equipment, or the financial or managerial capacity to provide these services. They need support to develop these capacities. The vast majority of water operators in the world are in the public sector – 90% of all major cities are served by such bodies. This means that the largest pool of experience and expertise, and the great majority of examples of good practice and sound institutions, are to be found in existing public sector water operators. Because they are public sector, however, they do not have any natural commercial incentive to provide international support. Their incentive stems from solidarity, not profit. Since 1990, however, the policies of donors and development banks have focussed on the private companies and their incentives. The vast resources of the public sector have been overlooked, even blocked by pro-private policies. Out of sight of these global policy-makers, however, a growing number of public sector water companies have been engaged, in a great variety of ways, in helping others develop the capacity to be effective and accountable public services. These supportive arrangements are now called 'public-public partnerships' (PUPs). A public-public partnership (PUP) is simply a collaboration between two or more public authorities or organisations, based on solidarity, to improve the capacity and effectiveness of one partner in providing public water or sanitation services. They have been described as: “a peer relationship forged around common values and objectives, which exclude profit-seeking”.1 Neither partner expects a commercial profit, directly or indirectly. This makes PUPs very different from the public–private partnerships (PPPs) which have been promoted by the international financial institutions (IFIs) like the World Bank. The problems of PPPs have been examined in a number of reports. A great advantage of PUPs is that they avoid the risks of such partnerships: transaction costs, contract failure, renegotiation, the complexities of regulation, commercial opportunism, monopoly pricing, commercial secrecy, currency risk, and lack of public legitimacy.2 PUPs are not merely an abstract concept. The list in the annexe to this paper includes over 130 PUPs in around 70 countries. This means that far more countries have hosted PUPs than host PPPs in water – according to a report from PPIAF in December 2008, there are only 44 countries with private participation in water. These PUPs cover a period of over 20 years, and been used in all regions of the world. The earliest date to the 1980s, when the Yokohama Waterworks Bureau first started partnerships to help train staff in other Asian countries. Many of the PUP projects have been initiated in the last few years, a result of the growing recognition of PUPs as a tool for achieving improvements in public water management. This paper attempts to provide an overview of the typical objectives of PUPs; the different forms of PUPs and partners involved; a series of case studies of actual PUPs; and an examination of the recent WOPs initiative. It then offers recommendations for future development of PUPs.

Discourses on Modernization in the Employment Public Services: Towards a New Form of Governance?

The “crisis of the social issue” in the EU has led to a certain consensus in the need to renew the organizational and institutional model of public administration. The core of the reform implies important administrative changes in most of the European welfare states. Those changes are inspired on theories such as the new public management, management by objectives or partnership. Such changes involve both semantic (“sharing responsibilities”, “effective costs”, or the substitution of “citizen under an administration” by “consumer”) and political (predominance of scattered forms of power and the individualization of responsibilities) transformations which operate in the framework of individuals and State relations. The paradigms of activation and flexicurity have been central in this public administration modernization project. This commitment with new forms of governance of social issues has important consequences for the political and moral foundations of social cohesion, and the Spanish case is not an exception. This paper aims at looking at those representations of “modernization” (as they appear in debates about the employment services restructuring policies) in detail as well as providing references to the trajectory of such reforms of public services since the early eighties to the beginning of the crisis.

Unemployment Duration: Competing and Defective Risks

This paper examines the determinants of unemployment duration in a competing risks framework with two destination states: inactivity and employment. The innovation is the recognition of defective risks. A polynomial hazard function is used to differentiate between two possible sources of infinite durations. The first is produced by a random process of unlucky draws, the second by workers rejecting a destination state. The evidence favors the mover-stayer model over the search model. Refinement of the former approach, using a more flexible baseline hazard function, produces a robust and more convincing explanation for positive and zero transition rates out of unemployment.

Video games in the classrooms: implications of a disruptive innovation to develop the Multiple Intelligences

The present study aims to identify the framework of personal, organizational and technical variables that contribute to the viability and successful of innovative educational practices with video games within the school context to enhance the multiple intelligences. For this purpose, advantage was taken on the information previously collected through a questionnaire about the views, thoughts and experiences of a group of teachers of childhood and primary education (N=25) who voluntarily participated in a blended training activity from Center of Teachers (CEFIRE) of Valencia, around a community of practice aimed at promoting and advising projects for implementing educational video games in the classroom. The mixed methodology adopted has allowed the following: a) describe the relationship between their degree of development and daily use made of ICT in the classroom, their level of familiarity with video games,  their previous experience to integrate them for educational purposes..., and their participation in projects that focus on game-based learning; b) conduct content analysis of the opinions and thoughts expressed in a forum for teachers on innovation on and methodological strategies adopted reflected in a virtual board; and c) develop a SWOT analysis: Strengths, Weaknesses, Opportunities and Threats inherent in the implementation of experience with video games in the classroom. Among the conclusions, it is highlighted that, even though most did not have specific training or enough technological resources and the planning and implementation of innovation required them a great investment of time, their personal interest, the support given by members of the online community of practice, helped to encourage their activity, along with receptivity, positive attitude and high motivation of students with the experience. These aspects have been crucial to promote successful innovative practices with video games.

The global pharmacy workforce: a systematic review of the literature.

Hawthorne N, Anderson C. (2009) The global pharmacy workforce: a systematic review of the literature. Human Resources for Health, 7:48.

Developing tomorrow's leaders-Evidence of global talent management in multinational enterprises

Organizations are becoming relentless in managing and developing their key talent. This is a view, however, largely based on anecdote rather than reliable empirical evidence. Utilizing data from 260 multinational enterprises (MNEs), this paper helps redress this deficit. Specifically, this paper explores the extent to which MNEs engage in global talent management (GTM) and deciphers some of the factors which may explain the use and non-use of GTM practices. In so doing, we find that although a significant number of MNEs have systems and mechanisms in place to strategically identify and develop their talent many more seemingly adopt an ad hoc or haphazard approach. For instance, less than half of all MNEs have both global succession planning and formal management development programs for their high-potentials. Consequently it seems that there is a considerable distance yet to be travelled to arrive at a universal appreciation of the need to strategically manage one's key employees. We find the size of the MNE has a significant effect on GTM system usage-larger MNEs are more likely to undertake GTM. Other significant, positive influences include whether products or services are standardized regionally or globally, and if the MNE has a global human resources policy formation body. Of considerable interest is the finding that MNEs operating in the low-tech/low-cost sectors are significantly more likely to have formal global systems to identify and develop high-potentials. © 2009 Elsevier Inc. All rights reserved.

Was Personalverantwortliche über das Verbot der mittelbaren Geschlechtsdiskriminierung wissen sollten

This chapter introduces the uses of indirect discrimination on grounds of sex for human resources management.