Defining Paternalism

Much of the philosophical engagement with the issue of paternalism, especially in the last couple of decades, has focused on important normative issues such as: 'what, if anything, is morally problematic about paternalism?', 'when is paternalism justified?', and 'how concerned should we be, morally speaking, with paternalism?'. My thesis seeks to take a step back and asks a more fundamental, conceptual question, upon which these more practical, normative issues supervene: What precisely defines an act of paternalism? To this end, this thesis is divided into five parts; an introduction followed by four chapters. As well as setting out the aims of the thesis, the introduction outlines some of the basic, uncontroversial features of paternalism. Chapters 1, 2, and 3 then examine the rich philosophical literature on defining paternalism; each chapter examining a different approach to defining paternalism. Through the outlining of some of the uncontroversial features of paternalism, and subsequent investigation of where philosophers have gone wrong in defining paternalism, I develop seven 'Challenges' an accurate definition of paternalism must meet. I also argue that no definition of paternalism currently in the philosophical literature, can meet each of these Challenges (or even just meet Challenges 5, 6, and 7; three connected Challenges that are particularly important). Finally, in Chapter 4, I present an original definition of paternalism consisting of three individually necessary, and together sufficient conditions. I argue that this definition can in fact meet each of the seven 'Challenges'

Exercise alters and beta-alanine combined with exercise augments histidyl dipeptide levels and scavenges lipid peroxidation products in human skeletal muscle

Title on article: Exercise alters and β-alanine combined with exercise augments histidyl dipeptide levels and scavenges lipid peroxidation products in human skeletal muscl

Titania-based Photocatalytic Coatings on Stainless Steel Hospital Fixtures

A scaled-up pulsed-pressure MOCVD system was used to deposit TiO2 coatings from tetra-isopropoxide precursor solution on stainless steel substrates and on 3- D objects. The objective of the work is the production of antimicrobial coatings for handles in health care facilities. Antimicrobial coatings are sought to manage the transmission of hospital acquired infections (HAI’s), which are reported to cost around one million pounds per annum in the UK alone. Titania is a promising material for this application due to the photocatalytic production of reactive oxygen species that are crucial for the destruction of organic pathogens. TiO2 coatings of 0.2 to 13 μm thickness were deposited at temperatures between 375 oC and 475 oC. The crystallite size and photocatalytic activity are influenced by deposition temperature. No dependence of stoichiometry on the deposition temperature has been observed. The films on stainless steel exhibit reasonably good photocatalytic performance. The photocatalytic performance and the stoichiometry improve with the film thickness. A three dimensional object (door handle) was coated with good conformity. The reactor scale-up for coating production on door handles is proposed for future wear and hygiene performance testing

k is the Magic Number -- Inferring the Number of Clusters Through Nonparametric Concentration Inequalities

Most convex and nonconvex clustering algorithms come with one crucial parameter: the $k$ in $k$-means. To this day, there is not one generally accepted way to accurately determine this parameter. Popular methods are simple yet theoretically unfounded, such as searching for an elbow in the curve of a given cost measure. In contrast, statistically founded methods often make strict assumptions over the data distribution or come with their own optimization scheme for the clustering objective. This limits either the set of applicable datasets or clustering algorithms. In this paper, we strive to determine the number of clusters by answering a simple question: given two clusters, is it likely that they jointly stem from a single distribution? To this end, we propose a bound on the probability that two clusters originate from the distribution of the unified cluster, specified only by the sample mean and variance. Our method is applicable as a simple wrapper to the result of any clustering method minimizing the objective of $k$-means, which includes Gaussian mixtures and Spectral Clustering. We focus in our experimental evaluation on an application for nonconvex clustering and demonstrate the suitability of our theoretical results. Our \textsc{SpecialK} clustering algorithm automatically determines the appropriate value for $k$, without requiring any data transformation or projection, and without assumptions on the data distribution. Additionally, it is capable to decide that the data consists of only a single cluster, which many existing algorithms cannot

Two Theileria parva CD8 T Cell Antigen Genes Are More Variable in Buffalo than Cattle Parasites, but Differ in Pattern of Sequence Diversity

<p><b>Background:</b> Theileria parva causes an acute fatal disease in cattle, but infections are asymptomatic in the African buffalo (Syncerus caffer). Cattle can be immunized against the parasite by infection and treatment, but immunity is partially strain specific. Available data indicate that CD8(+) T lymphocyte responses mediate protection and, recently, several parasite antigens recognised by CD8(+) T cells have been identified. This study set out to determine the nature and extent of polymorphism in two of these antigens, Tp1 and Tp2, which contain defined CD8(+) T-cell epitopes, and to analyse the sequences for evidence of selection.</p> <p><b>Methodology/Principal Findings:</b> Partial sequencing of the Tp1 gene and the full-length Tp2 gene from 82 T. parva isolates revealed extensive polymorphism in both antigens, including the epitope-containing regions. Single nucleotide polymorphisms were detected at 51 positions (similar to 12%) in Tp1 and in 320 positions (similar to 61%) in Tp2. Together with two short indels in Tp1, these resulted in 30 and 42 protein variants of Tp1 and Tp2, respectively. Although evidence of positive selection was found for multiple amino acid residues, there was no preferential involvement of T cell epitope residues. Overall, the extent of diversity was much greater in T. parva isolates originating from buffalo than in isolates known to be transmissible among cattle.</p> <p><b>Conclusions/Significance:</b> The results indicate that T. parva parasites maintained in cattle represent a subset of the overall T. parva population, which has become adapted for tick transmission between cattle. The absence of obvious enrichment for positively selected amino acid residues within defined epitopes indicates either that diversity is not predominantly driven by selection exerted by host T cells, or that such selection is not detectable by the methods employed due to unidentified epitopes elsewhere in the antigens. Further functional studies are required to address this latter point.</p&gt

Two Theileria parva CD8 T Cell Antigen Genes Are More Variable in Buffalo than Cattle Parasites, but Differ in Pattern of Sequence Diversity

<p><b>Background:</b> Theileria parva causes an acute fatal disease in cattle, but infections are asymptomatic in the African buffalo (Syncerus caffer). Cattle can be immunized against the parasite by infection and treatment, but immunity is partially strain specific. Available data indicate that CD8(+) T lymphocyte responses mediate protection and, recently, several parasite antigens recognised by CD8(+) T cells have been identified. This study set out to determine the nature and extent of polymorphism in two of these antigens, Tp1 and Tp2, which contain defined CD8(+) T-cell epitopes, and to analyse the sequences for evidence of selection.</p> <p><b>Methodology/Principal Findings:</b> Partial sequencing of the Tp1 gene and the full-length Tp2 gene from 82 T. parva isolates revealed extensive polymorphism in both antigens, including the epitope-containing regions. Single nucleotide polymorphisms were detected at 51 positions (similar to 12%) in Tp1 and in 320 positions (similar to 61%) in Tp2. Together with two short indels in Tp1, these resulted in 30 and 42 protein variants of Tp1 and Tp2, respectively. Although evidence of positive selection was found for multiple amino acid residues, there was no preferential involvement of T cell epitope residues. Overall, the extent of diversity was much greater in T. parva isolates originating from buffalo than in isolates known to be transmissible among cattle.</p> <p><b>Conclusions/Significance:</b> The results indicate that T. parva parasites maintained in cattle represent a subset of the overall T. parva population, which has become adapted for tick transmission between cattle. The absence of obvious enrichment for positively selected amino acid residues within defined epitopes indicates either that diversity is not predominantly driven by selection exerted by host T cells, or that such selection is not detectable by the methods employed due to unidentified epitopes elsewhere in the antigens. Further functional studies are required to address this latter point.</p&gt

Piloting the Global Subsidy: The Impact of Subsidized Artemisinin-Based Combination Therapies Distributed through Private Drug Shops in Rural Tanzania

BACKGROUND: WHO estimates that only 3% of fever patients use recommended artemisinin-based combination therapies (ACTs), partly reflecting their high prices in the retail sector from where many patients seek treatment. To overcome this challenge, a global ACT subsidy has been proposed. We tested this proposal through a pilot program in rural Tanzania. METHODS/PRINCIPAL FINDINGS: Three districts were assigned to serve either as a control or to receive the subsidy plus a package of supporting interventions. From October 2007, ACTs were sold at a 90% subsidy through the normal private supply chain to intervention district drug shops. Data were collected at baseline and during intervention using interviews with drug shop customers, retail audits, mystery shoppers, and audits of public and NGO facilities. The proportion of consumers in the intervention districts purchasing ACTs rose from 1% at baseline to 44.2% one year later (p<0.001), and was significantly higher among consumers purchasing for children under 5 than for adults (p = 0.005). No change in ACT usage was observed in the control district. Consumers paid a mean price of $0.58 for ACTs, which did not differ significantly from the price paid for sulphadoxine-pyrimethamine, the most common alternative. Drug shops in population centers were significantly more likely to stock ACTs than those in more remote areas (p<0.001). CONCLUSIONS: A subsidy introduced at the top of the private sector supply chain can significantly increase usage of ACTs and reduce their retail price to the level of common monotherapies. Additional interventions may be needed to ensure access to ACTs in remote areas and for poorer individuals who appear to seek treatment at drug shops less frequently. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN39125414

Application of Acoustic Telemetry to Assess Residency and Movements of Rockfish and Lingcod at Created and Natural Habitats in Prince William Sound

Loss and/or degradation of nearshore habitats have led to increased efforts to restore or enhance many of these habitats, particularly those that are deemed essential for marine fishes. Copper rockfish (Sebastes caurinus) and lingcod (Ophiodon enlongatus) are dominant members of the typical reef fish community that inhabit rocky and high-relief substrates along the Pacific Northwest. We used acoustic telemetry to document their residency and movements in the nearshore waters of Prince William Sound, Alaska in order to assess use of created reef habitat in an individual-based manner. A total of 57 fish were surgically implanted with acoustic transmitters. Forty-five fish were captured and monitored in three habitats: artificial reef, low-relief natural reef, and patchy high-relief natural reef. Within each habitat, both rockfish and lingcod exhibited long periods of residency with limited movements. Twelve rockfish were captured at the natural reefs and displaced a distance of 4.0 km to the artificial reef. Five of the 12 rockfish returned within 10 d of their release to their initial capture site. Another five of the 12 displaced fish established residency at the artificial reef through the duration of our study. Our results suggest the potential for artificial reefs to provide rockfish habitat in the event of disturbances to natural habitat

Expression Analysis of the Theileria parva Subtelomere-Encoded Variable Secreted Protein Gene Family

Background The intracellular protozoan parasite Theileria parva transforms bovine lymphocytes inducing uncontrolled proliferation. Proteins released from the parasite are assumed to contribute to phenotypic changes of the host cell and parasite persistence. With 85 members, genes encoding subtelomeric variable secreted proteins (SVSPs) form the largest gene family in T. parva. The majority of SVSPs contain predicted signal peptides, suggesting secretion into the host cell cytoplasm. Methodology/Principal Findings We analysed SVSP expression in T. parva-transformed cell lines established in vitro by infection of T or B lymphocytes with cloned T. parva parasites. Microarray and quantitative real-time PCR analysis revealed mRNA expression for a wide range of SVSP genes. The pattern of mRNA expression was largely defined by the parasite genotype and not by host background or cell type, and found to be relatively stable in vitro over a period of two months. Interestingly, immunofluorescence analysis carried out on cell lines established from a cloned parasite showed that expression of a single SVSP encoded by TP03_0882 is limited to only a small percentage of parasites. Epitope-tagged TP03_0882 expressed in mammalian cells was found to translocate into the nucleus, a process that could be attributed to two different nuclear localisation signals. Conclusions Our analysis reveals a complex pattern of Theileria SVSP mRNA expression, which depends on the parasite genotype. Whereas in cell lines established from a cloned parasite transcripts can be found corresponding to a wide range of SVSP genes, only a minority of parasites appear to express a particular SVSP protein. The fact that a number of SVSPs contain functional nuclear localisation signals suggests that proteins released from the parasite could contribute to phenotypic changes of the host cell. This initial characterisation will facilitate future studies on the regulation of SVSP gene expression and the potential biological role of these enigmatic proteins