Towards optimal clinical and epidemiological registration of haematological malignancies: Guidelines for recording progressions, transformations and multiple diagnoses

Haematological malignancies (HM) represent over 6% of the total cancer incidence in Europe and affect all ages, ranging between 45% of all cancers in children and 7% in the elderly. Thirty per cent of childhood cancer deaths are due to HM, 8% in the elderly. Their registration presents specific challenges, mainly because HM may transform or progress in the course of the disease into other types of HM. In the context of cancer registration decisions have to be made about classifying subsequent notifications on the same patient as the same tumour (progression), a transformation or a new tumour registration. Allocation of incidence date and method of diagnosis must also be standardised. We developed European Network of Cancer Registries (ENCR) recommendations providing specific advice for cancer registries to use haematology and molecular laboratories as data sources, conserve the original date of incidence in case of change of diagnosis, make provision for recording both the original as well as transformed tumour and to apply precise rules for recording and counting multiple diagnoses. A reference table advising on codes which reflect a potential transformation or a new tumour is included. This work will help to improve comparability of data produced by population-based cancer registries, which are indispensable for aetiological research, health care planning and clinical research, an increasing important area with the application of targeted therapies.

Impact of tooth replacement on the nutritional status of partially dentate elders

OBJECTIVES: The aim of this study was to compare the impact of two different tooth replacement strategies on the nutritional status of partially dentate older patients. Nutritional status was measured using the full version of the Mini Nutritional Assessment (MNA) and the short form of the Mini Nutritional Assessment (MNA-SF).

MATERIALS AND METHODS: A randomised controlled clinical trial was conducted (Trial Registration no. ISRCTN26302774). Partially dentate patients aged 65 years and older were recruited and randomly allocated to the two different treatment groups: the removable partial dentures (RPD) group and the shortened dental arch (SDA) group. Nutritional status was measured using the MNA and MNA-SF administered at baseline and 1, 6 and 12 months after treatment intervention by a research nurse blinded to the treatment group allocation of all participants.

RESULTS: Data collected using the full version of the MNA showed significant improvements in mean MNA scores over the length of the study (p < 0.05). For the entire patient group, there was a mean increase of 0.15 points at 6 months and a further increase of 0.19 points at 12 months. These increases were similar within the treatment groups (p > 0.05). For MNA-SF, the analysis showed that there were no significant differences recorded over the data collection points after treatment intervention (p < 0.05).

CONCLUSION: Tooth replacement using conventional and functionally orientated treatment for the partially dentate elderly showed significant improvements in MNA score 12 months after intervention.

CLINICAL RELEVANCE: Prosthodontic rehabilitation may play an important role in the nutritional status of partially dentate elders.

Chapter Three – Host–Parasite Interactions and the Evolution of Immune Defense

Parasites and pathogens are ubiquitous and act as an important selection pressure on animals. Here, drawing primarily on our own research, mostly on insects, we illustrate how host-parasite interactions have played a role in the evolution of a range of phenomena, including animal coloration, social behavior, foraging ecology, sexual selection, and life-history tradeoffs, as well as how variation in host behavior and ecology can drive variation in parasitism risk and host allocation of resources to immunity and other antiparasite defenses. We conclude by identifying key areas for future study.

Understanding Risk: Contributions from the Journal of Risk and Governance

During recent years, news headlines have been rife with criticisms of the risk management practices of public and private sector entities. These criticisms have often been accompanied by calls for greater transparency in the way government entities manage risks and communicate dangers to the public. Similarly, in the private sector, the internationalisation of economic activity has heightened concerns over the potential adverse implications of mismanagement and financial scandals, and has led to calls for greater regulation and supervision. While the responses of public sector agencies and private sector actors to these challenges have differed, they share a common acknowledgement that effective governance relies on the pro-active identification, assessment, and management of risks as well as appropriate regulatory frameworks.

This edited book covers a number of divergent topics illustrating the emergence of several novel themes in the area of economic and social risks. As a communality, these novel themes relate to the complexity in which human activity in this late stage of capitalist development is embedded. This risk-generating complexity, in turn, can be observed at several levels, including workplace hazards, governance problems within the private sector or the intersection between public and private, and in relation to the economic risks faced by larger entities such as national governments.

The value of tests in the diagnosis and management of glaucoma.

PURPOSE:

To assess the noneconomic value of tests used in the diagnosis and management of glaucoma, and explore the contexts and factors that determine such value.

DESIGN:

Perspective.

METHODS:

Selected articles from primary and secondary sources were reviewed and interpreted in the context of the authors' clinical and research experience, influenced by our perspectives on the tasks of reducing the global problem of irreversible blindness caused by glaucoma. The value of any test used in glaucoma is addressed by 3 questions regarding: its contexts, its kind of value, and its implicit or explicit benefits.

RESULTS:

Tonometry, slit-lamp gonioscopy, and optic disc evaluation remain the foundation of clinic-based case finding, whether in areas of more or less abundant resources. In resource-poor areas, there is urgency in identifying patients at risk for severe functional loss of vision; screening strategies have proven ineffective, and efforts are hindered by the inadequate allocation of support. In resource-abundant areas, the wider spectrum of glaucoma is addressed, with emphasis on early detection of structural changes of little functional consequence; these are increasingly the focus of new and expensive technologies whose clinical value has not been established in longitudinal and population-based studies. These contrasting realities in part reflect differences among the value ascribed, often implicitly, to the tests used in glaucoma.

CONCLUSIONS:

The value of any test is determined by 3 aspects: its context of usage; its comparative worth and to whom its benefit accrues; and how we define historically what we are testing. These multiple factors

Organic contaminants in urban soils: major inputs and potential risks

Urban soil quality may be severely affected by hydrophobic organic contaminants (HOCs), impairing environmental quality and human health. A comprehensive study was conducted in two contrasting Portuguese urban areas (Lisbon and Viseu) in order to assess the levels and potential risks of these contaminants, to identify sources and study their behaviour in soils. The concentrations of HOCs were related to the size of the city, with much higher contamination levels observed in Lisbon urban area. Source apportionment was performed by studying the HOCs profiles, their relationship with potentially toxic elements and general characteristics of soil using multivariate statistical methods. Lisbon seems to be affected by nearby sources (traffic, industry and incineration processes) whereas in Viseu the atmospheric transport may be playing an important role. In a first tier of risk assessment (RA) it was possible to identify polycyclic aromatic hydrocarbons (PAHs) in Lisbon soils as a potential hazard. The levels of PAHs in street dusts were further studied and allowed to clarify that traffic, tire and pavement debris can be an important source of PAHs to urban soils. Street dusts were also identified as being a potential concern regarding human and environmental health, especially if reaching the nearby aquatic bodies. Geostatistical tools were also used and their usefulness in a RA analysis and urban planning was discussed. In order to obtain a more realistic assessment of risks of HOCs to environment and human health it is important to evaluate their available fraction, which is also the most accessible for organisms. Therefore, a review of the processes involved on the availability of PAHs was performed and the outputs produced by the different chemical methods were evaluated. The suitability of chemical methods to predict bioavailability of PAHs in dissimilar naturally contaminated soils has not been demonstrated, being especially difficult for high molecular weight compounds. No clear relationship between chemical and biological availability was found in this work. Yet, in spite of the very high total concentrations found in some Lisbon soils, both the water soluble fraction and the body residues resulting from bioaccumulation assays were generally very low, which may be due to aging phenomena. It was observed that the percentage of soluble fraction of PAHs in soils was found to be different among compounds and mostly regulated by soil properties. Regarding bioaccumulation assays, although no significant relationship was found between soil properties and bioavailability, it was verified that biota-to-soil bioaccumulation factors were sample dependent rather than compound dependent. In conclusion, once the compounds of potential concern are targeted, then performing a chemical screening as a first tier can be a simple and effective approach to start a RA. However, reliable data is still required to improve the existing models for risk characterization.

Effect of high CO2 and ocean acidification on photosynthesis and response to oxidative stress in seagrasses

Climate change scenarios comprise significant modifications of the marine realm, notably ocean acidification and temperature increase, both direct consequences of the rising atmospheric CO2 concentration. These changes are likely to impact marine organisms and ecosystems, namely the valuable seagrass-dominated coastal habitats. The main objective of this thesis was to evaluate the photosynthetic and antioxidant responses of seagrasses to climate change, considering CO2, temperature and light as key drivers of these processes. The methodologies used to determine global antioxidant capacity and antioxidant enzymatic activity in seagrasses were optimized for the species Cymodocea nodosa and Posidonia oceanica, revealing identical defence mechanisms to those found in terrestrial plants. The detailed analysis and identification of photosynthetic pigments in Halophila ovalis, H.stipulacea, Zostera noltii, Z marina, Z. capricorni, Cymodocea nodosa and Posidonia oceanica, sampled across different climatic zones and depths, also revealed a similarity with terrestrial plants, both in carotenoid composition and in the pigment-based photoprotection mechanisms. Cymodocea nodosa plants from Ria Formosa were submitted to the combined effect of potentially stressful light and temperature ranges and showed considerable physiological tolerance, due to the combination of changes in the antioxidant system, activation of the VAZ cycle and accumulation of leaf soluble sugars, thus preventing the onset of oxidative stress. Cymodocea nodosa plants living in a naturally acidified environment near submarine volcanic vents in Vulcano Island (Italy) showed to be under oxidative stress despite the enhancement of the antioxidant capacity, phenolics concentration and carotenoids. Posidonia oceanica leaves loaded with epiphytes showed a significant increase in oxidative stress, despite the increase of antioxidant responses and the allocation of energetic resources to these protection mechanisms. Globally, the results show that seagrasses are physiologically able to deal with potentially stressful conditions from different origins, being plastic enough to avoid stress in many situations and to actively promote ulterior defence and repair mechanisms when under effective oxidative stress.

An exploration of pre-attentive visual discrimination using event-related potentials

The Mismatch Negativity (MMN) has been characterised as a ‘pre-attentive’ component of an Event-Related Potential (ERP) that is related to discriminatory processes. Although well established in the auditory domain, characteristics of the MMN are less well characterised in the visual domain. The five main studies presented in this thesis examine visual cortical processing using event-related potentials. Novel methodologies have been used to elicit visual detection and discrimination components in the absence of a behavioural task. Developing paradigms in which a behavioural task is not required may have important clinical applications for populations, such as young children, who cannot comply with the demands of an active task. The ‘pre-attentive’ nature of visual MMN has been investigated by modulating attention. Generators and hemispheric lateralisation of visual MMN have been investigated by using pertinent clinical groups. A three stimulus visual oddball paradigm was used to explore the elicitation of visual discrimination components to a change in the orientation of stimuli in the absence of a behavioural task. Monochrome stimuli based on pacman figures were employed that differed from each other only in terms of the orientation of their elements. One such stimulus formed an illusory figure in order to capture the participant’s attention, either in place of, or alongside, a behavioural task. The elicitation of a P3a to the illusory figure but not to the standard or deviant stimuli provided evidence that the illusory figure captured attention. A visual MMN response was recorded in a paradigm with no task demands. When a behavioural task was incorporated into the paradigm, a P3b component was elicited consistent with the allocation of attentional resources to the task. However, visual discrimination components were attenuated revealing that the illusory figure was unable to command all attentional resources from the standard deviant transition. The results are the first to suggest that the visual MMN is modulated by attention. Using the same three stimulus oddball paradigm, generators of visual MMN were investigated by recording potentials directly from the cortex of an adolescent undergoing pre-surgical evaluation for resection of a right anterior parietal lesion. To date no other study has explicitly recorded activity related to the visual MMN intracranially using an oddball paradigm in the absence of a behavioural task. Results indicated that visual N1 and visual MMN could be temporally and spatially separated, with visual MMN being recorded more anteriorly than N1. The characteristic abnormality in retinal projections in albinism afforded the opportunity to investigate each hemisphere in relative isolation and was used, for the first time, as a model to investigate lateralisation of visual MMN and illusory contour processing. Using the three stimulus oddball paradigm, no visual MMN was elicited in this group, and so no conclusions regarding the lateralisation of visual MMN could be made. Results suggested that both hemispheres were equally capable of processing an illusory figure. As a method of presenting visual test stimuli without conscious perception, a continuous visual stream paradigm was developed that used a briefly presented checkerboard stimulus combined with masking for exploring stimulus detection below and above subjective levels of perception. A correlate of very early cortical processing at a latency of 60-80 ms (CI) was elicited whether stimuli were reported as seen or unseen. Differences in visual processing were only evident at a latency of 90 ms (CII) implying that this component may represent a correlate of visual consciousness/awareness. Finally, an oddball sequence was introduced into the visual stream masking paradigm to investigate whether visual MMN responses could be recorded without conscious perception. The stimuli comprised of black and white checkerboard elements differing only in terms of their orientation to form an x or a +. Visual MMN was not recorded when participants were unable to report seeing the stimulus. Results therefore suggest that behavioural identification of the stimuli was required for the elicitation of visual MMN and that visual MMN may require some attentional resources. On the basis of these studies it is concluded that visual MMN is not entirely independent of attention. Further, the combination of clinical and non-clinical investigations provides a unique opportunity to study the characterisation and localisation of putative mechanisms related to conscious and non-conscious visual processing.

Diversification, size and risk: The case of bank acquisitions of nonbank financial firms

We investigate the risk effects of bank acquisitions of insurance companies and securities firms between 1991 and 2012 using a newly constructed dataset of M&A deals. We examine risk changes before and after deal announcements by decomposing risk into systematic and idiosyncratic components. Subsequently, we investigate the relationship between risk and diversification by modelling the determinants of risks. We find that bank combinations with securities firms yield higher risks than combinations with insurance companies. Bank size is an important and consistent determinant of risk whereas diversification is not. Our results inform the continuing debate on diversification versus functional separation of bank activities.

Chancen und herausforderungen der rückversicherung in der gesetzlichen krankenversicherung (Chances and challenges of reinsurance in the social health scheme)

In 2009 a so-called morbidity orientated risk structure equalization scheme was installed for the German statutory health insurance in order to minimize structural differences between different providers with respect to revenue and expenditures. Even with this mechanism some risks to the individual health insurance providers remain. Reinsurance could be a way to mitigate these risks, but so far only very few contracts have been signed. Moreover the existing reinsurance contracts only focus on the periphery of the statutory health insurance system such as travel health insurance. In this article we therefore analyse existing risks for individual health insurance providers and evaluate their (re-)insurability. Hereafter the potential for reinsurance solutions in the German statutory health insurance itself as well as in newer forms of healthcare provision (e.g. integrated health care and managed care) is discussed. We find that reinsurance may be a reasonable solution for many of the risks in the statutory health insurance scheme. But as research in this area is very young further analysis of the nature of risks is necessary.

GTS allocation analysis in IEEE 802.15.4 for real-time wireless sensor networks

The IEEE 802.15.4 protocol proposes a flexible communication solution for Low-Rate Wireless Personal Area Networks including sensor networks. It presents the advantage to fit different requirements of potential applications by adequately setting its parameters. When enabling its beacon mode, the protocol makes possible real-time guarantees by using its Guaranteed Time Slot (GTS) mechanism. This paper analyzes the performance of the GTS allocation mechanism in IEEE 802.15.4. The analysis gives a full understanding of the behavior of the GTS mechanism with regards to delay and throughput metrics. First, we propose two accurate models of service curves for a GTS allocation as a function of the IEEE 802.15.4 parameters. We then evaluate the delay bounds guaranteed by an allocation of a GTS using Network Calculus formalism. Finally, based on the analytic results, we analyze the impact of the IEEE 802.15.4 parameters on the throughput and delay bound guaranteed by a GTS allocation. The results of this work pave the way for an efficient dimensioning of an IEEE 802.15.4 cluster.

Assessment of non-steroidal anti-inflammatory and analgesic pharmaceuticals in seawaters of North of Portugal: Occurrence and environmental risk

The occurrence of seven pharmaceuticals and two metabolites belonging to non-steroidal anti-inflammatory drugs and analgesics therapeutic classes was studied in seawaters. A total of 101 samples covering fourteen beaches and five cities were evaluated in order to assess the spatial distribution of pharmaceuticals among north Portuguese coast. Seawaters were selected in order to embrace different bathing water quality (excellent, good and sufficient). Acetaminophen, ketoprofen and the metabolite hydroxyibuprofen were detected in all the seawater samples at maximum concentrations of 584, 89.7 and 287 ng L− 1, respectively. Carboxyibuprofen had the highest seawater concentration (1227 ng L− 1). The temporal distribution of the selected pharmaceuticals during the bathing season showed that, in general, higher concentrations were detected in August and September. The environmental risk posed by the pharmaceuticals detected in seawaters towards different trophic levels (fish, daphnids and algae) was also assessed. Only diclofenac showed hazard quotients above one for fish, representing a potential risk for aquatic organisms. These results were observed in seawaters classified as excellent bathing water. Additional data is needed in order to support the identification and prioritization of risks posed by pharmaceuticals in marine environment.

Continuous improvement logidtics project: A study on the increase of the finished goods warehouse of Unilever at Sta. Iria

This project is called Improvement Logistics Project and aims to study an opportunity of expansion of the output in 80% of the Unilever warehouse at Sta. Iria via an increase in exportations for the next two years. This has been done using the Distibuidora Luís Simões tariff rates as basis of comparison for the as-is and to-be situations. For this matter, an allocation of all the costs of the warehouse is prepared and described with the goal of comparing the differences with and without expansion. The results show that a better outcome is achieved with the investment, but the warehouse is yet to prove its efficiency against the distribution company.

Reallocation of resources between the tradable and non-tradable sector in Portugal: Assessing the degree of structural transformation in the Portuguese economy

Portugal implemented a large number of structural reforms in the recent years, which are expected to enhance the allocation of resources in the economy, namely from the non-tradable to tradable sector. We argue that the methodology to identify the tradable sector used by some international institutions is outdated and may hamper an accurate assessment of the progress achieved so far. Based on an enhanced methodology to identify the tradable sector, we are able to provide a more accurate, clearer picture of the recent structural developments of the Portuguese economy.

Contingent contracts

International businesses bring with them additional negotiation complexities and extra risks, thus calling for negotiation integrative solutions and additional legal protection. The recent economic crisis forced, companies, including SMEs, to look for international markets and face these additional complexities and issues. In the search for a practical and simplified solution, to serve less sophisticated companies, this paper brings insights from the negotiation literature to a specific legal issue. Specifically, I investigate the negotiation and use of contingent agreements as a tool for facilitating the negotiation process and managing risk in international deals. Looking into an international sale of goods from Portugal to Brazil, this paper proposes the structuring of two contingent contracts related to two category of products in order to demonstrate the potential benefits of some of its relevant features, specifically the creation of incentives and identification and allocation of future risks. In general, the structuring of contingent agreements is likely to provide positive results in mitigating the issues of lack of trust and dealing with the additional risks derived from international deals, therefore facilitating and improving the overall quality of the deal.