Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior

There is a growing recognition of the importance of the commensal intestinal microbiota in the development and later function of the central nervous system. Research using germ-free mice (mice raised without any exposure to microorganisms) has provided some of the most persuasive evidence for a role of these bacteria in gut-brain signalling. Key findings show that the microbiota is necessary for normal stress responsivity, anxiety-like behaviors, sociability, and cognition. Furthermore, the microbiota maintains central nervous system homeostasis by regulating immune function and blood brain barrier integrity. Studies have also found that the gut microbiota influences neurotransmitter, synaptic, and neurotrophic signalling systems and neurogenesis. The principle advantage of the germ-free mouse model is in proof-of-principle studies and that a complete microbiota or defined consortiums of bacteria can be introduced at various developmental time points. However, a germ-free upbringing can induce permanent neurodevelopmental deficits that may deem the model unsuitable for specific scientific queries that do not involve early-life microbial deficiency. As such, alternatives and complementary strategies to the germ-free model are warranted and include antibiotic treatment to create microbiota-deficient animals at distinct time points across the lifespan. Increasing our understanding of the impact of the gut microbiota on brain and behavior has the potential to inform novel management strategies for stress-related gastrointestinal and neuropsychiatric disorders.

Structured professional judgement approach to risk assessment: generalisability across patient groups for the prediction of adverse outcomes in secure mental health care

This is a redacted version of the the final thesis. Copyright material has been removed to comply with UK Copyright Law.

From a traditionally open access fishery to modern restrictions: Portuguese anglers' perceptions about newly implemented recreational fishing regulations

Saltwater recreational fishing (SRF) in Portugal was for a long time an open-access activity, without restrictions of any kind. Restrictions to control the recreational harvest were first implemented in 2006 and were highly criticized by the angler community, for being highly restrictive and lacking scientific support. The present study aimed to obtain socio-economic data on the recreational shore anglers and gauge their perceptions about recreational fishing regulations and the newly implemented restrictions in Portugal. Roving creel surveys were conducted along the south and south-west coasts of Portugal, during pre and post regulation periods (2006-2007). A total of 1298 valid face-to-face interviews were conducted. Logit models were fitted to identify which characteristics influence anglers' perceptions about recreational fishing regulations. The majority of the interviewed anglers was aware and agreed with the existence of recreational fishing regulations. However, most were against the recreational fishing regulations currently in place. The logit models estimates revealed that Portuguese anglers with a higher level of formal education and income are more likely to agree with the existence of recreational fishing regulations. In contrast, anglers who perceive that more limitations and a better enforcement of commercial fishing would improve fishing in the area are less likely to agree with the existence of SRF regulations. The findings from this study will contribute to inform decision-makers about anglers' potential behaviour towards the new and future regulations. Although the existence of fishing regulations is a good starting point for effective management, the lack of acceptance and detailed knowledge of the regulations in place by fishers may result in lack of compliance, and ultimately hinder the success of recreational fishing regulations in Portugal. (C) 2013 Elsevier Ltd. All rights reserved.

Surveillance risks in IoT applied to smart cities

Nowadays, cities deal with unprecedented pollution and overpopulation problems, and Internet of Things (IoT) technologies are supporting them in facing these issues and becoming increasingly smart. IoT sensors embedded in public infrastructure can provide granular data on the urban environment, and help public authorities to make their cities more sustainable and efficient. Nonetheless, this pervasive data collection also raises high surveillance risks, jeopardizing privacy and data protection rights. Against this backdrop, this thesis addresses how IoT surveillance technologies can be implemented in a legally compliant and ethically acceptable fashion in smart cities. An interdisciplinary approach is embraced to investigate this question, combining doctrinal legal research (on privacy, data protection, criminal procedure) with insights from philosophy, governance, and urban studies. The fundamental normative argument of this work is that surveillance constitutes a necessary feature of modern information societies. Nonetheless, as the complexity of surveillance phenomena increases, there emerges a need to develop more fine-attuned proportionality assessments to ensure a legitimate implementation of monitoring technologies. This research tackles this gap from different perspectives, analyzing the EU data protection legislation and the United States and European case law on privacy expectations and surveillance. Specifically, a coherent multi-factor test assessing privacy expectations in public IoT environments and a surveillance taxonomy are proposed to inform proportionality assessments of surveillance initiatives in smart cities. These insights are also applied to four use cases: facial recognition technologies, drones, environmental policing, and smart nudging. Lastly, the investigation examines competing data governance models in the digital domain and the smart city, reviewing the EU upcoming data governance framework. It is argued that, despite the stated policy goals, the balance of interests may often favor corporate strategies in data sharing, to the detriment of common good uses of data in the urban context.

Development of a relationship between physical parameters of tsunami waves and tsunami intensity based on macroscopic effects and its application to the Italian tsunami database

Tsunamis are rare events. However, their impact can be devastating and it may extend to large geographical areas. For low-probability high-impact events like tsunamis, it is crucial to implement all possible actions to mitigate the risk. The tsunami hazard assessment is the result of a scientific process that integrates traditional geological methods, numerical modelling and the analysis of tsunami sources and historical records. For this reason, analysing past events and understanding how they interacted with the land is the only way to inform tsunami source and propagation models, and quantitatively test forecast models like hazard analyses. The primary objective of this thesis is to establish an explicit relationship between the macroscopic intensity, derived from historical descriptions, and the quantitative physical parameters measuring tsunami waves. This is done first by defining an approximate estimation method based on a simplified 1D physical onshore propagation model to convert the available observations into one reference physical metric. Wave height at the coast was chosen as the reference due to its stability and independence of inland effects. This method was then implemented for a set of well-known past events to build a homogeneous dataset with both macroseismic intensity and wave height. By performing an orthogonal regression, a direct and invertible empirical relationship could be established between the two parameters, accounting for their relevant uncertainties. The target relationship is extensively tested and finally applied to the Italian Tsunami Effect Database (ITED), providing a homogeneous estimation of the wave height for all existing tsunami observations in Italy. This provides the opportunity for meaningful comparison for models and simulations, as well as quantitatively testing tsunami hazard models for the Italian coasts and informing tsunami risk management initiatives.

[recommendations For Physical Exercise Practice During Pregnancy: A Critical Review].

Physical exercise is recommended for all healthy pregnant women. Regular practice of exercises during pregnancy can provide many physical and psychological benefits, with no evidence of adverse outcomes for the fetus or the newborn when exercise is performed at mild to moderate intensity. However, few pregnant women engage in this practice and many still have fears and doubts about the safety of exercise. The objective of the present study was to inform the professionals who provide care for Brazilian pregnant women about the current recommendations regarding physical exercise during pregnancy based on the best scientific evidence available. In view of the perception that few systematic models are available about this topic and after performing several studies in this specific area, we assembled practical information of interest to both the professionals and the pregnant women. We also provide recommendations about the indications, contraindications, modalities (aerobics, resistance training, stretching and pelvic floor training), frequency, intensity and duration indicated for each gestational trimester. The review addresses physical exercise recommendation both for low risk pregnant women and for special populations, such as athletes and obese, hypertensive and diabetic subjects. The advantages of an active and healthy lifestyle should be always reinforced during and after gestation since pregnancy is an appropriate period to introduce new habits because pregnant women are usually more motivated to adhere to recommendations. Thus, routine exams, frequent returns and supervision are recommended in order to provide new guidelines that will have long-term beneficial effects for both mother and child.

Innovation and entrepreneurship in scientific research

This research wants to lay emphasis on topics that historicize and rescue concepts, in addition, shows the relation between innovation and socioeconomic development resulted; reviews the legal framework to stimulate new innovation into Brazilian society; considers the definition and the entrepreneur university's new paradigm; and finally, this research highlights the importance of teaching entrepreneur at universities, with straight society benefits. The results suggests that innovation is directly enrolled with a successful development of certain society, as well, is actually the biggest business competitive differential into corporative universe. In one way of getting results of social advancement to inform entrepreneur research practice, it appears that entrepreneurs concepts, necessarily, must be incorporated into the array of Science/Technology/Innovation for the effective development of supported formula. This article develops a thought about actual scientific researches paradigm, the way that is built on today, and if it's sufficient to effectively get the results that society expects from main bodies to create human resource and researches, especially those with innovation aspects, at Brazilian economic improvement.

Environmental Risk Factors for Parkinson's Disease

Parkinson’s disease (PD) is a progressive, degenerative, neurological disease. The progressive disability associated with PD results in substantial burdens for those with the condition, their families and society in terms of increased health resource use, earnings loss of affected individuals and family caregivers, poorer quality of life, caregiver burden, disrupted family relationships, decreased social and leisure activities, and deteriorating emotional well-being. Currently, no cure is available and the efficacy of available treatments, such as medication and surgical interventions, decreases with longer duration of the disease. Whilst the cause of PD is unknown, genetic and environmental factors are believed to contribute to its aetiology. Descriptive and analytical epidemiological studies have been conducted in a number of countries in an effort to elucidate the cause, or causes, of PD. Rural residency, farming, well water consumption, pesticide exposure, metals and solvents have been implicated as potential risk factors for PD in some previous epidemiological studies. However, there is substantial disagreement between the results of existing studies. Therefore, the role of environmental exposures in the aetiology of PD remains unclear. The main component of this thesis consists of a case-control study that assessed the contribution of environmental exposures to the risk of developing PD. An existing, previously unanalysed, dataset from a local case-control study was analysed to inform the design of the new case-control study. The analysis results suggested that regular exposure to pesticides and head injury were important risk factors for PD. However, due to the substantial limitations of this existing study, further confirmation of these results was desirable with a more robustly designed epidemiological study. A new exposure measurement instrument (a structured interviewer-delivered questionnaire) was developed for the new case-control study to obtain data on demographic, lifestyle, environmental and medical factors. Prior to its use in the case-control study, the questionnaire was assessed for test-retest repeatability in a series of 32 PD cases and 29 healthy sex-, age- and residential suburb-matched electoral roll controls. High repeatability was demonstrated for lifestyle exposures, such as smoking and coffee/tea consumption (kappas 0.70-1.00). The majority of environmental exposures, including use of pesticides, solvents and exposure to metal dusts and fumes, also showed high repeatability (kappas >0.78). A consecutive series of 163 PD case participants was recruited from a neurology clinic in Brisbane. One hundred and fifty-one (151) control participants were randomly selected from the Australian Commonwealth Electoral Roll and individually matched to the PD cases on age (± 2 years), sex and current residential suburb. Participants ranged in age from 40-89 years (mean age 67 years). Exposure data were collected in face-to-face interviews. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression for matched sets in SAS version 9.1. Consistent with previous studies, ever having been a regular smoker or coffee drinker was inversely associated with PD with dose-response relationships evident for packyears smoked and number of cups of coffee drunk per day. Passive smoking from ever having lived with a smoker or worked in a smoky workplace was also inversely related to PD. Ever having been a regular tea drinker was associated with decreased odds of PD. Hobby gardening was inversely associated with PD. However, use of fungicides in the home garden or occupationally was associated with increased odds of PD. Exposure to welding fumes, cleaning solvents, or thinners occupationally was associated with increased odds of PD. Ever having resided in a rural or remote area was inversely associated with PD. Ever having resided on a farm was only associated with moderately increased odds of PD. Whilst the current study’s results suggest that environmental exposures on their own are only modest contributors to overall PD risk, the possibility that interaction with genetic factors may additively or synergistically increase risk should be considered. The results of this research support the theory that PD has a multifactorial aetiology and that environmental exposures are some of a number of factors to contribute to PD risk. There was also evidence of interaction between some factors (eg smoking and welding) to moderate PD risk.

Should the health community promote smokeless tobacco (snus) as a harm reduction measure?

Background to the debate: The tobacco control community is divided on whether or not to inform the public that using oral, smokeless tobacco (Swedish snus) is less hazardous to health than smoking tobacco. Proponents of 'harm reduction' point to the Swedish experience. Snus seems to be widely used as an alternative to cigarettes in Sweden, say these proponents, contributing to the low overall prevalence of smoking and smoking-related disease. Harm reduction proponents thus argue that the health community should actively inform inveterate cigarette smokers of the benefits of switching to snus. However, critics of harm reduction say that snus has its own risks, that no form of tobacco should ever be promoted, and that Sweden’s experience is likely to be specific to that culture and not transferable to other settings. Critics also remain deeply suspicious that the tobacco industry will use snus marketing as a 'gateway' to promote cigarettes. In the interests of promoting debate, the authors (who are collaborators on a research project on the future of tobacco control) have agreed to outline the strongest arguments for and against promoting Swedish snus as a form of harm reduction.

Is there a role for axillary dissection for patients with operable breast cancer in this era of conservatism?

Background: The trend in breast cancer surgery is toward more conservative operative procedures. The new staging technique of sentinel node biopsy facilitates the identification of pathological node-negative patients in whom axillary dissection may be avoided. However, patients with a positive sentinel node biopsy would require a thorough examination of their nodal status. An axillary dissection provides good local control, and accurate staging and prognostic information to inform decisions about adjuvant therapy. In addition, the survival benefit of axillary treatment is still debated. The objectives of the present study were to examine the pattern of lymph node metastases in the axilla, and evaluate the merits of a level III axillary dissection. Methods : Between June 1997 and May 2000, 308 patients underwent a total of 320 level III dissections as part of their treatment for operable invasive breast cancer. The three axillary levels were marked intraoperatively, and the contents in each level were submitted and examined separately. The patterns of axillary lymph node (ALN) metastases were examined, and factors associated with 4 positive nodes, and level III ALN metastases were evaluated by univariate and multivariate analyses. Results: An average of 25 lymph nodes were examined per case (range: 8-54), and using strict anatomical criteria, the mean numbers of ALN found in levels I, II and III were 18 (range: 2-43), 4 (range: 0 19), and 3 ( range: 0-11), respectively. Axillary lymph node involvement was found in 45% of the cases (143/320). Of the 143 cases, 78% (n = 111) had involvement of level I nodes only, and 21% (n = 30) had positive ALN in levels II and, or, III, in addition to level I. Involvement of lymph nodes in level II or III without a level I metastasis was found in two cases only (0.6%). By including level II, in addition to level I, in the dissection, four cases (1%) were converted from one to three positive nodes to 4 positive nodes (P = 0.64). By the inclusion of level III to a level I and II dissection, three cases (1%) were converted from one to three positive nodes to 4 positive nodes (P = 0.74). Involvement of lymph nodes in level III was found in 22 cases (7%), and 51 cases (16%) had 4 positive nodes. Palpability of ALN, pathological tumour size, and lymphovascular invasion (LVI), were significantly associated with level III involvement and 4 positive nodes by univariate and multivariate analyses. The frequencies of level III involvement and 4 positive nodes in patients with palpable ALN were 22% and 42%, respectively. The corresponding frequencies in patients with a clinically negative axilla, and a primary tumour which was >20 mm and LVI positive, were over 14% and 31%, respectively. Conclusion: Level III axillary dissection is appropriate for patients with palpable ALN, and in those with a tumour which is >20 mm and LVI positive, principally to reduce the risk of axillary recurrence. Staging accuracy is achieved with a level II dissection, or even a level I dissection alone based on strict anatomical criteria. Sentinel node biopsy is a promising technique in identifying pathological node-positive patients in whom an axillary clearance provides optimal local control and staging information.

A note on the decomposition of the health concentration index

In recent work, the concentration index has been widely used as a measure of income-related health inequality. The purpose of this note is to illustrate two different methods for decomposing the overall health concentration index using data collected from a Short Form (SF-36) survey of the general Australian population conducted in 1995. For simplicity, we focus on the physical functioning scale of the SF-36. Firstly we examine decomposition 'by component' by separating the concentration index for the physical functioning scale into the ten items on which it is based. The results show that the items contribute differently to the overall inequality measure, i.e. two of the items contributed 13% and 5%, respectively, to the overall measure. Second, to illustrate the 'by subgroup' method we decompose the concentration index by employment status. This involves separating the population into two groups: individuals currently in employment; and individuals not currently employed. We find that the inequality between these groups is about five times greater than the inequality within each group. These methods provide insights into the nature of inequality that can be used to inform policy design to reduce income related health inequalities. Copyright (C) 2002 John Wiley Sons, Ltd.

Pharmacy Asthma Care Program. Final Report.

The purpose of the project is to identify the role and value of professional services that community pharmacy can provide to people who are at risk of asthma or present with the disease. A literature review has been conducted to inform the development of a Pharmacy Asthma Care Module to pilot in the project

Equity in regional service provision

Most transportation agencies stipulate that an important planning goal is to provide equitable and just public transport services. However, who is to be served and the type of service that should be provided has been ambiguous. This paper develops a methodology for examining equity in the provision of public transportation services. An approach for identifying areas in need of public transport is developed based upon the use of socio-demographic and economic information. Public transport need is then related to levels of access to service. This approach makes it possible to establish the degree to which public transport services may be considered equitable in relation to need and suitable access. A detailed analysis of the southeast Queensland region of Australia illustrates how this approach may be used to inform public transport decision making.

Ethical dilemmas confronting dentists in Queensland, Australia

Background: This paper details contemporary ethical dilemmas encountered by Queensland dentists. Methods: An age-stratified sample of 499 dentists resident in Queensland was surveyed. The questionnaire contained scenarios of five common ethical dilemmas. In addition, open-ended questions sought the respondent's most frequent, difficult and recent ethical dilemmas, and where they would seek guidance in dealing with ethical problems. Results: Respondents acknowledged the patient's rights in treatment decisions and the dentist's right to refuse demands for inappropriate treatment. However, responses varied in the extent to which dentists may influence treatment decisions. Few respondents would ignore evidence of poor dental treatment but they are evenly divided in choosing to inform the patient, the dentist or both. Poor quality treatment is the most frequent and difficult dilemma, and half have experienced this problem recently. Requests by patients for fraudulent receipts occur in a third of responses. Dentists develop ethical values from multiple sources but for help with dental ethical problems, 90 per cent of respondents would consult another dentist. Conclusions: Of the ethical dilemmas discussed in this survey, those relating to poor quality treatment confronted most respondents. Also the actions of dentists in dealing with these dilemmas were most varied.

Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis

Objective: To review the literature regarding the effectiveness of 5-hydroxytryptophan (5-HT) and L-tryptophan in the treatment of unipolar depression. Methods: A systematic review of the literature from 1966 to 2000 using the search terms 'tryptophan', 5-hydroxytryptophan', '5-HTP', '5-HT' and 'depression'. We extracted and grouped data for meta-analysis by pooling odds ratios (OR) and relative risks where possible. Results: One hundred and eight studies were located of which only two studies, one of 5-HT and one of L-tryptophan, with a total of 64 patients met sufficient quality criteria to be included. These studies suggest 5-HT and L-tryptophan are better than placebo at alleviating depression (Peto OR = 4.1, 95% CI = 1.3-13.2). However, the small size of the studies, and the large number of inadmissible, poorly executed studies, casts doubt on the result from potential publication bias, and suggests that they are insufficiently evaluated to assess their effectiveness. Conclusions: A large body of evidence was subjected to very basic criteria for assessing reliability and validity, and was found to largely be of insufficient quality to inform clinical practice. More well-designed studies are urgently required to enable an assessment of what may be an effective class of agents.