Predicting crashes using traffic offences. A meta-analysis that examines potential bias between self-report and archival data

Background Traffic offences have been considered an important predictor of crash involvement, and have often been used as a proxy safety variable for crashes. However the association between crashes and offences has never been meta-analysed and the population effect size never established. Research is yet to determine the extent to which this relationship may be spuriously inflated through systematic measurement error, with obvious implications for researchers endeavouring to accurately identify salient factors predictive of crashes. Methodology and Principal Findings Studies yielding a correlation between crashes and traffic offences were collated and a meta-analysis of 144 effects drawn from 99 road safety studies conducted. Potential impact of factors such as age, time period, crash and offence rates, crash severity and data type, sourced from either self-report surveys or archival records, were considered and discussed. After weighting for sample size, an average correlation of r = .18 was observed over the mean time period of 3.2 years. Evidence emerged suggesting the strength of this correlation is decreasing over time. Stronger correlations between crashes and offences were generally found in studies involving younger drivers. Consistent with common method variance effects, a within country analysis found stronger effect sizes in self-reported data even controlling for crash mean. Significance The effectiveness of traffic offences as a proxy for crashes may be limited. Inclusion of elements such as independently validated crash and offence histories or accurate measures of exposure to the road would facilitate a better understanding of the factors that influence crash involvement.

Structural and functional studies of Bacillus stearothermophilus serine hydroxymethyl transferase: the role of N341, Y60 and F351 in tetrahydrofolate binding.

SHMT (serine hydoxymethyltransferase), a type I pyridoxal 5'-phosphate-dependent enzyme, catalyses the conversion of L-serine and THF (tetrahydrofolate) into glycine and 5,10 -methylene THE SHMT also catalyses several THF-independent side reactions such as cleavage of P-hydroxy amino acids, trans-amination, racemization and decarboxylation. In the present study, the residues Asn(341), Tyr(60) and Phe(351), which are likely to influence THF binding, were mutated to alanine, alanine and glycine respectively, to elucidate the role of these residues in THF-dependent and -independent reactions catalysed by SHMT. The N341A and Y60A bsSHMT (Bacillus stearothermophilus SHMT) mutants were inactive for the THF-dependent activity, while the mutations had no effect on THF-independent activity. However, mutation of Phe(351) to glycine did not have any effect oil either of the activities. The crystal structures of the glycine binary complexes of the mutants showed that N341A bsSHMT forms an external aldimine as in bsSHMT, whereas Y60A and F351G bsSHMTs exist as a Mixture of internal/external aldimine and gem-diamine forms. Crystal structures of all of the three Mutants obtained in the presence of L-allo-threonine were similar to the respective glycine binary complexes. The structure of the ternary complex of F351G bsSHMT with glycine and FTHF (5-formyl THF) showed that the monoglutamate side chain of FTHF is ordered in both the subunits of the asymmetric unit, unlike in the wild-type bsSHMT. The present studies demonstrate that the residues Asn(341) and Tyr(60) are pivotal for the binding of THF/FTHF, whereas Phe(351) is responsible for the asymmetric binding of FTHF in the two subunits of the dimer.

Nature of the Oxygen Species at Ni(110) and Ni(100) Surfaces Revealed by Exposure to Oxygen and Oxygen-Ammonia Mixtures: Evidence for the Surface Reactivity of O- Type Species

Adsorption of dioxygen at clean Ni(110) and Ni(100) surfaces gives rise to two prominent features in the O(1s) spectra at 530 and 531 eV due to O2- and O- type species, respectively. Interaction of ammonia with a Ni(100)-O surface where theta(oxygen) < 0.1 ML favors the dissociation of NH3 giving NHn, (n = 1, 2) and N(a) species. This is accompanied by a decrease in the intensity of the 531 eV feature. On the other hand. a Ni(100)-O surface where the oxygen species are mainly of the O2- type is unreactive, Coadsorption studies of NH3-O-2 mixtures show that at Ni(110) surfaces the uptake of both oxygen and ammonia increase with the proportion of oxygen in the NH3-O-2 mixture. The surface concentrations of the O- species and the NHn species also increase with the increase in the O-2/NH3 ratio while the slope of the plot of sigma(N) versus sigma(O-) is around unity. The results demonstrate the high surface reactivity of the O- species and its role in the dissociation of ammonia. Based on these observations, the possibility of the formation of a surface complex between ammonia and oxygen (specifically O-) is suggested. Results from vibrational spectroscopic studies of the coadsorption of NH3-O-2 mixtures are consistent with those from core-level spectroscopic studies.

Mixed convection in non-Newtonian fluids along a horizontal plate in a porous medium

The problem of mixed convection from horizontal surfaces in a porous medium saturated with a power-law-type non-Newtonian fluid is investigated. The transformed conservation laws are solved numerically for the case of variable wall hear pur conditions. Results for the details of the velocity and temperature fields as well as the Nusselt number have been presented. The viscosity index ranged from 0.5-1.5.

Nonsimilar solutions for mixed convection in non-Newtonian fluids along horizontal surfaces in porous media

A nonsimilar boundary layer analysis is presented for the problem of mixed convection in power-law type non-Newtonian fluids along horizontal surfaces with variable heat flux distribution. The mixed convection regime is divided into two regions, namely, the forced convection dominated regime and the free convection dominated regime. The two solutions are matched. Numerical results are presented for the details of the velocity and temperature fields. A discussion is provided for the effect of viscosity index on the surface heat transfer rate.

Nonsimilar solutions for free convection in non-Newtonian fluids along a vertical plate in a porous medium

A nonsimilar boundary layer analysis is presented for the problem of free convection in power-law type non-Newtonian fluids along a permeable vertical plate with variable wall temperature or heat flux distribution. Numerical results are presented for the details of the velocity and temperature fields. A discussion is provided for the effect of viscosity index on the surface heat transfer rate.

Synthesis and biological activity of anticoagulant heparan sulfate glycopolymers

Heparin has been used as an anticoagulant drug for more than 70 years. The global distribution of contaminated heparin in 2007, which resulted in adverse clinical effects and over 100 deaths, emphasizes the necessity for safer alternatives to animal-sourced heparin. The structural complexity and heterogeneity of animal-sourced heparin not only impedes safe access to these biologically active molecules, but also hinders investigations on the significance of structural constituents at a molecular level. Efficient methods for preparing new synthetic heparins with targeted biological activity are necessary not only to ensure clinical safety, but to optimize derivative design to minimize potential side effects. Low molecular weight heparins have become a reliable alternative to heparin, due to their predictable dosages, long half-lives, and reduced side effects. However, heparin oligosaccharide synthesis is a challenging endeavor due to the necessity for complex protecting group manipulation and stereoselective glycosidic linkage chemistry, which often result in lengthy synthetic routes and low yields. Recently, chemoenzymatic syntheses have produced targeted ultralow molecular weight heparins with high-efficiency, but continue to be restricted by the substrate specificities of enzymes.

To address the need for access to homogeneous, complex glycosaminoglycan structures, we have synthesized novel heparan sulfate glycopolymers with well-defined carbohydrate structures and tunable chain length through ring-opening metathesis polymerization chemistry. These polymers recapitulate the key features of anticoagulant heparan sulfate by displaying the sulfation pattern responsible for heparin’s anticoagulant activity. The use of polymerization chemistry greatly simplifies the synthesis of complex glycosaminoglycan structures, providing a facile method to generate homogeneous macromolecules with tunable biological and chemical properties. Through the use of in vitro chromogenic substrate assays and ex vivo clotting assays, we found that the HS glycopolymers exhibited anticoagulant activity in a sulfation pattern and length-dependent manner. Compared to heparin standards, our short polymers did not display any activity. However, our longer polymers were able to incorporate in vitro and ex vivo characteristics of both low-molecular-weight heparin derivatives and heparin, displaying hybrid anticoagulant properties. These studies emphasize the significance of sulfation pattern specificity in specific carbohydrate-protein interactions, and demonstrate the effectiveness of multivalent molecules in recapitulating the activity of natural polysaccharides.

Estudo de atributos de virulência e resistência a antimicrobianos em amostras de P. aeruginosa

P. aeruginosa é um importante agente de infecções relacionadas à assistência em saúde. Habitualmente, o estabelecimento de infecções agudas é precedido pela colonização das mucosas dos pacientes. Não se sabe, porém, se os processos infecciosos são causados pelas próprias cepas bacterianas colonizadoras ou por outras com que os pacientes entrem em contato, dotadas ou não de maior potencial de virulência ou de resistência a antimicrobianos que as tornem mais eficientes como agentes infecciosos. Assim, este estudo teve como objetivos i) investigar a existência de potenciais diferenças entre amostras de P. aeruginosa que causaram apenas colonização e aquelas responsáveis por infecção, isoladas de um mesmo paciente, quanto a seus fenótipos de virulência e de não susceptibilidade a antimicrobiamos; ii) pesquisar a existência de associação entre características dos paciente, incluindo o tipo de evolução clínica, com as demais variáveis estudadas. No estudo foram incluídos 21 pacientes que desenvolveram infecção por P. aeruginosa durante sua internação no Centro de Terapia Intensiva do Hospital Universitário Clementino Fraga Filho, entre abril de 2007 e abril de 2008. De cada paciente foram selecionadas duas amostras bacterianas: a primeira isolada durante o episódio de infecção e a amostra colonizadora obtida imediatamente antes da ocorrência da infecção. As amostras selecionadas foram estudadas quanto a i) expressão de três mecanismos de virulência (citotoxicidade, aderência a células epiteliais respiratórias humanas e capacidade de formação de biofilme); ii) presença de genes codificadores das proteínas efetoras do sistema de secreção do tipo 3 (SST3 - exoS, exoT, exoU e exoY); iii) perfil de susceptibilidade a antimicrobianos, iv) perfil de fragmentação do DNA cromossômico por eletroforese em gel de campo pulsado (PFGE). As amostras bacterianas obtidas de infecções agudas foram significativamente mais citotóxicas que aquelas obtidas de colonização. Embora sem diferença estatística, a citotoxicidade das amostras que causaram infecção em pacientes que evoluíram para óbito foi superior à citotoxicidade das amostras de pacientes que sobreviveram. O gene que codifica a toxina ExoU foi detectado em 16 amostras (38%), sendo nove de colonização e sete de infecção. Não houve diferença significativa entre as amostras de colonização e infecção quanto à aderência, produção de biofilme, expressão dos genes do SST3 e não-susceptibilidade às diferentes classes de antimicrobianos. Também não foi encontrada associação entre a não-susceptibilidade à quinolona, ou a outras classes de antimicrobianos, e a presença do gene exoU. As 42 amostras de P. aeruginosa estudadas foram incluídas em 20 genótipos. Em 10 deles foi detectado o gene exoU. Amostras de um mesmo genótipo foram uniformes quanto à expressão dos genes do SST3 e a não-susceptibilidade aos antimicrobianos, mas não quanto às outras variáveis estudadas. Em apenas sete pacientes (33,3%), as amostras de colonização e de infecção pertenciam ao mesmo genótipo. Assim, nesse estudo, o estabelecimento do processo infeccioso resultou não da perda do equilíbrio estabelecido entre os mecanismos de agressão das amostras colonizadoras e os de defesa do hospedeiro e sim da introdução de nova cepa bacteriana no organismo hospedeiro, cepa esta dotada de maior potencial citotóxico.

中国松鼠科 Sciuridae (Non-flying squirrels) 动物的分类和分布及系统发育研究

松鼠科隶属于哺乳纲、啮齿目，是一类世界广布性动物，全世界共计36 属 234 种。本文通过形态分析及分子生物学方法，研究了我国松鼠科动物的分类及 系统发育关系，内容包括以下两个方面： 一、中国松鼠科动物的分类 本研究查看了中科院昆明动物研究所、中科院动物研究所、云南大学、四川 省林业科学研究院、四川大学、陕西师范大学、陕西动物研究所、西北大学、上 海自然历史博物馆、广东昆虫所馆藏该科各类群标本。同时，结合相关文献，对 各类群的外形特征进行了详细的描述和系统分类整理，我国共计10 属34 种。测 取可量性状数据共计20800 个（完整头骨共计1300 号），而且还运用多变量及单 变量分析方法进行数据分析，对部分类群的种下分类结果进行分析：1.探讨了分 布于中国境内的明纹花鼠（Tamiops mcclellandii）3 亚种的有效性。2.研究了 隐纹花鼠（Tamiops swinhoei）在中国的分化并描记了分布于四川马尔康地区的 隐纹花鼠为一新亚种（Tamiops swinhoei markamensis）。3.描记了分布于云南 省东北部昭通地区的赤腹松鼠为一新亚种：昭通亚种（Callosciurus erythraeus zhaotongensis）。4. 提出了分布于云南省无量山区的泊氏长吻松鼠为一新亚种： 无量山亚种（Dremomys pernyi wuliangshanensis）。 二、中国松鼠科动物的系统发育研究 2004－2005 年相继到滇西北高黎贡山、香格里拉，滇西南临沧地区，滇东 南马关、麻栗坡、富宁，滇东北昭通地区进行标本采集，基本收集到我国南方松 鼠科属、种样品进行分子生物学研究。 1.中国松鼠科动物各属的系统发育关系 在分析线粒体细胞色数b 基因（1040bp）序列的基础上，运用贝叶斯法 （Bayesian phylogenetic reconstruction approaches）、最简约法（Maximum parsimony method）、邻接法（Neighbor Joining method）构建中国松鼠科动物 所有属间系统发育树。结果表明：所分析的10 属分别聚集为3 群，巨松鼠属Ratufa单独成为一群，丽松鼠属Callosciurus、长吻松鼠属Dremomys、花松鼠属 Tamiops 以及线松鼠属Menetes 成为一群，松鼠属Sciurus、岩松鼠属 Sciurotamias、花鼠属Tamias、旱獭属Marmota 以及黄鼠属Spermophilus 成 为一群。在此基础上我们进一步探讨了中国松鼠科动物的分化与环境变化的关 系。 2.长吻松鼠属的系统发育关系 在分析线粒体细胞色数b 基因（378bp）序列的基础上，我们重建了长吻松 鼠属内5 个类群间的系统发育关系，结合对5 类群外部形态特征的详细比较，我 们探讨并论证了红腿长吻松鼠、橙喉长吻松鼠作为种的地位的有效性，同时论证 了该属内泊氏长吻松鼠最早分化，其次为橙腹长吻松鼠，第三是红腿长吻松鼠， 红颊长吻松鼠和橙喉长吻松鼠是最后分化的类群。

Using participant or non-participant observation to explain information behaviour

Cooper, J., Lewis, R. & Urquhart, C. (2004). Using participant or non-participant observation to explain information behaviour. Information Research, 9(4). Retrieved August 3, 2006 from http://informationr.net/ir/9-4/paper184.html Sponsorship: AHRC (Cooper).

Private health care coverage and increased risk of obstetric intervention

Background: When clinically indicated, common obstetric interventions can greatly improve maternal and neonatal outcomes. However, variation in intervention rates suggests that obstetric practice may not be solely driven by case criteria. Methods: Differences in obstetric intervention rates by private and public status in Ireland were examined using nationally representative hospital discharge data. A retrospective cohort study was performed on childbirth hospitalisations occurring between 2005 and 2010. Multivariate logistic regression analysis with correction for the relative risk was conducted to determine the risk of obstetric intervention (caesarean delivery, operative vaginal delivery, induction of labour or episiotomy) by private or public status while adjusting for obstetric risk factors. Results: 403,642 childbirth hospitalisations were reviewed; approximately one-third of maternities (30.2%) were booked privately. After controlling for relevant obstetric risk factors, women with private coverage were more likely to have an elective caesarean delivery (RR: 1.48; 95% CI: 1.45-1.51), an emergency caesarean delivery (RR: 1.13; 95% CI: 1.12-1.16) and an operative vaginal delivery (RR: 1.25; 95% CI: 1.22-1.27). Compared to women with public coverage who had a vaginal delivery, women with private coverage were 40% more likely to have an episiotomy (RR: 1.40; 95% CI: 1.38-1.43). Conclusions: Irrespective of obstetric risk factors, women who opted for private maternity care were significantly more likely to have an obstetric intervention. To better understand both clinical and non-clinical dynamics, future studies of examining health care coverage status and obstetric intervention would ideally apply mixed-method techniques.

Reforming the legal framework for clinical trials with neonates in Ireland: a children’s rights approach

This thesis assesses the current regulatory framework regarding clinical trials with neonates in Ireland from a children’s rights perspective, as derived from the UN Convention on the Rights of the Child 1989 (UN CRC) and its supporting instruments. The focus on neonates in the thesis is due to the particular need for clinical research with this group of children, their dependency on others for their protection and the lack of attention which has been given to them in the regulatory framework. The importance of children’s rights in this area is linked to the role of human rights in the regulation of clinical research in general. A rights-based approach is of great practical relevance in reforming law, policy and practice. For example, the CRC contains a set of commonly agreed legal benchmarks which can be used to assess the current framework and shape recommendations for reform. In this way, it provides a set of binding norms under international law, which must be complied with by states and state actors in all law, policy and practice affecting children. However, the contribution which a children’s rights approach could make to the regulation of research with children has not, to date, been explored in detail. This thesis aims to address this gap by developing a set of children’s rights-based benchmarks, which are used to assess the Irish regulatory framework for clinical trials with neonates and to develop recommendations for reform. The purpose of the analysis and recommendations is to assess Ireland’s compliance with international children’s rights law in the area and to analyse the potential of children’s rights to effectively address inadequacies in the Irish framework. The recommendations ultimately aim to develop a framework which will enhance the protection of neonates’ rights in this important area of children’s lives.

Economics of new oncology drug development.

PURPOSE: Review existing studies and provide new results on the development, regulatory, and market aspects of new oncology drug development. METHODS: We utilized data from the US Food and Drug Administration (FDA), company surveys, and publicly available commercial business intelligence databases on new oncology drugs approved in the United States and on investigational oncology drugs to estimate average development and regulatory approval times, clinical approval success rates, first-in-class status, and global market diffusion. RESULTS: We found that approved new oncology drugs to have a disproportionately high share of FDA priority review ratings, of orphan drug designations at approval, and of drugs that were granted inclusion in at least one of the FDA's expedited access programs. US regulatory approval times were shorter, on average, for oncology drugs (0.5 years), but US clinical development times were longer on average (1.5 years). Clinical approval success rates were similar for oncology and other drugs, but proportionately more of the oncology failures reached expensive late-stage clinical testing before being abandoned. In relation to other drugs, new oncology drug approvals were more often first-in-class and diffused more widely across important international markets. CONCLUSION: The market success of oncology drugs has induced a substantial amount of investment in oncology drug development in the last decade or so. However, given the great need for further progress, the extent to which efforts to develop new oncology drugs will grow depends on future public-sector investment in basic research, developments in translational medicine, and regulatory reforms that advance drug-development science.

Adult personality inconsistency and problems with parents: uncovering the roots of the false self

Research has established that individuals who tend to vary their personality depending on who they are with, show a variety of signs of psychological maladjustment in comparison to those who do not; they show more negative affect (Baird, Le and Lucas, 2006), lower life satisfaction (Suh, 2002), lower self-esteem (Sheldon et al., 1997), lower role-satisfaction (Donahue et al., 1993), higher rates of depression (Lutz and Ross, 2003), more anxiety (Diehl, Hastings and Stanton, 2001) and poorer physical health (Cross, Gore and Morris, 2003). It has also been shown that personality variability is positively related to the experience of inauthenticity and falsity (Sheldon et al., 1997). Donahue, Roberts, Robins and John (1993) found that personality inconsistency of this type is related to tension within the family. Psychoanalytic theory has also linked the operation of an adult false self to experiences with parents, particularly in early life (Winnicott, 1960). It was hypothesized that personality variability and the adult experience of falsity in social situations would be related to an emotionally unstable relationship with parents. The method to test this comprised a questionnaire-based survey given to a non-clinical population. The final sample comprised 305, with 193 women and 112 men, aged from 19 to 55. The first questionnaire asked participants to rate personality traits, including emotional stability, in three social contexts - with parents, with friends and with work colleagues. The second part involved 3 questions; participants were asked to select in which of the aforementioned three social contexts they felt “most themselves”; in which they were “most authentic” and in which they “put on a front”. It was found, consistent with predictions, that an index of overall personality variability calculated from the personality questionnaire correlated strongly with emotional instability around parents (r = 0.46, p<0.001), while not correlating with emotional instability in either of the other two contexts measured. This suggests a specific link between a person’s relationship with their parents and their overall personality integration. Furthermore, it was found that participants who cited one of the three social contexts (parents, friends, work colleagues) as being one in which they were “more themselves” or “more authentic” had significantly higher ratings of emotional instability with parents than those participants who found that they were equally authentic across settings (F = 9.8, p<0.005). The results suggest a clear link between a person’s relationships with their parents and their adult personality integration. An explanation is that individuals who experience an anxious or ambiguous attachment with their parents in childhood may fear rejection or abandonment in later life, and so habitually adapt their personality to fit in to social contexts as adults, in order to be accepted by others and to minimize the possibility of social rejection. These individuals meanwhile retain an emotionally unstable relationship with their parents in adulthood. This interpretation is speculative but is open to empirical testing. Clinicians should be aware that attachment problems with parents may underlie poor personality integration in adulthood.

Nutrient regulation of pancreatic beta-cell function in diabetes: problems and potential solutions

increasing prevalence of obesity combined with longevity will produce an epidemic of Type 2 (non-insulin-dependent) diabetes in the next 20 years. This. disease is associated with defects in insulin secretion, specifically abnormalities of insulin secretory kinetics and pancreatic beta-cell glucose responsiveness. Mechanisms underlying beta-cell dysfunction include glucose toxicity, lipotoxicity and beta-cell hyperactivity. Defects at various sites in beta-cell signal transduction pathways contribute, but no single lesion can account for the common form of Type 2 diabetes. Recent studies highlight diverse beta-cell actions of GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). These intestinal hormones target the beta-cell to stimulate glucose-dependent insulin secretion through activation of protein kinase A and associated pathways. Both increase gene expression and proinsulin biosynthesis, protect against apoptosis and stimulate replication/neogenesis of beta-cells. Incretin hormones therefore represent an exciting future multi-action solution to correct beta-cell defect in Type 2 diabetes.