Generalised Osteoporosis in the Aged: Diagnosis, Incidence and Aetiology

Abstract Not Provided

Smoke-free legislation and hospitalizations for childhood asthma

<b>BACKGROUND:</b> Previous studies have shown that after the adoption of comprehensive smoke-free legislation, there is a reduction in respiratory symptoms among workers in bars. However, it is not known whether respiratory disease is also reduced among people who do not have occupational exposure to environmental tobacco smoke. The aim of our study was to determine whether the ban on smoking in public places in Scotland, which was initiated in March 2006, influenced the rate of hospital admissions for childhood asthma.<br></br> <b>METHODS:</b> Routine hospital administrative data were used to identify all hospital admissions for asthma in Scotland from January 2000 through October 2009 among children younger than 15 years of age. A negative binomial regression model was fitted, with adjustment for age group, sex, quintile of socioeconomic status, urban or rural residence, month, and year. Tests for interactions were also performed. <br></br> <b>RESULTS:</b> Before the legislation was implemented, admissions for asthma were increasing at a mean rate of 5.2% per year (95% confidence interval [CI], 3.9 to 6.6). After implementation of the legislation, there was a mean reduction in the rate of admissions of 18.2% per year relative to the rate on March 26, 2006 (95% CI, 14.7 to 21.8; P<0.001). The reduction was apparent among both preschool and school-age children. There were no significant interactions between hospital admissions for asthma and age group, sex, urban or rural residence, region, or quintile of socioeconomic status. <b>CONCLUSIONS:</b> In Scotland, passage of smoke-free legislation in 2006 was associated with a subsequent reduction in the rate of respiratory disease in populations other than those with occupational exposure to environmental tobacco smoke. (Funded by NHS Health Scotland.

Collaborate or thread the eye of the needle

Abstract: Th

Halting the hallmarks: a cellular automaton model of early cancer growth inhibition

Cancer treatment is a fragmented and varied process, as ‘‘cancer’’ is really hundreds of different diseases. The ‘‘hallmarks of cancer’’ proposed by Hanahan and Weinberg (Cell 100(1):57–70, 2000) are a framework for viewing cancer within a common set of underlying principles—ten properties that are common to almost all cancers, allowing them to grow uncontrollably and ravage the body. We used a cellular automaton model of tumour growth paired with lattice Boltzmann methods modelling oxygen flow to simulate combination drugs targeted at knocking out pairs of hallmarks. We found that knocking out some pairs of cancer-enabling hallmarks did not prevent tumour formation, while other pairs significantly prevent tumour growth (p ¼ 0:0004 using Wilcoxon signed-rank adjusted with the Bonferroni correction for multiple comparisons). This is not what would be expected from models of knocking out the hallmarks individually, as many pairs did not have an additive effect but had either no statistically significant effect or a multiplicative one. We propose that targeting certain pairs of cancer hallmarks, specifically cancers ability to induce blood vessel development paired with another cancer hallmark, could prove an effective cancer treatment option

The Impact of Future CO2 Emission Reduction Targets on U.S. Electric Sector Water Use

The U.S. electric sector's reliance on water makes it vulnerable to the impacts of climate change on water resources. Here we analyze how constraints on U.S. energy system carbon dioxide (CO2) emissions could affect water withdrawal and consumption in the U.S. electric sector through 2055. We use simulations of the EPA's U.S. 9-region (EPAUS9r) MARKAL least-cost optimization energy systems model with updated water use factors for electricity generating technologies. Model results suggest CO2 constraints could force the retirement of old power plants and drive increased use of low water-use renewable and nuclear power as well as natural gas CCS plants with more advanced cooling systems. These changes in electric sector technology mix reduce water withdrawal in all scenarios but increase water consumption in aggressive scenarios. Decreased electric sector water withdrawal would likely reduce electric sector vulnerability to climate change, but the rise in consumption could increase competition with other users.Master of Scienc

The Synthesis and Fine Structure Studies of Polycyclic Aromatic Hydrocarbons

The main part of this thesis has dealt with benzylic coupling in a large number of methyl derivatives of polycyclic aromatic hydrocarbons. It has been shown previously that a coupling constant of ~1.0 Hz. between the methyl protons and the ortho aromatic proton is indicative of a high degree of localisation and double bond character in the intervening bond. This idea has been extended by examining a series of symmetrical 6-dimethyl derivatives which involved synthesising 2' ,3'-dimethyl-1,2;6,7-dibenzo-pyrene, (I) and 6,7-dimethy1-1,2:3-4-dibenzanthracene (II). 9,10-Dimethyl-3,4-benzotetraphene (III) was obtained as a byproduct in the latter synthesis. The couplings in these derivatives add further evidence to the idea that there is only one true double bond in each ring which occupies the lowest energy orbital. The remaining 4 pi-electrons are divided into two higher energy levels with one pair remaining delocalised within the ring,and the third pair, in the highest level, delocalised outside the ring and capable of migrating from ring to ring. An annellation effect is thus observed in passing from o-xylene to 2,3-dimethylanthracene (IV)(V)(VI) which can be explained by the increased linear annellation reducing the influence of those delocalised pi-electrons which are free to migrate, as they are spread over more rings. The distribution of the true double bond can also be considerably affected by substitution in the ring. This is reflected by considerable -changes in the magnitude of the benzylic coupling and supports the additivity of only one true double bond in each ring. The electronic arrangement in pyridazine is in the opposite sense to naphthalene and anthracene. There is a high degree of double bond character in the 4,5 position and a correspondingly low value in the 3,4 and 5,6 positions. This is borne out on examination of a number of methylpyridazines and adds further evidence to the above ideas. Finally, the unusual asymmetry of the methyl resonance in alpha-methyl derivatives was investigated. During this work an explanation was published on the basis of computer analysis of the methyl signal and it appears that the asymmetry is inherent with this combination of couplings to the ortho, para and meta protons on the ring. The apparent lack of long-range coupling in aromatic hydrocarbons has been attributed to 2nd order interactions. In this work halogen derivatives of anthracene and tetracene were examined. Decoupling indicates the absence of para coupling between the protons on non-terminal rings, although there is substantial trans-peri coupling between the protons of a terminal and non-terminal ring. However a methyl group on a non-terminal ring is found to he strongly coupled only to the para proton with J= 0.8-1.0Hz. This value is as large as the coupling constant observed for the localised double bond in 9-methylphenanthrene 1.0 Hz. This evidence is compared with other methyl derivatives and several possible explanations are discussed. The reductive dimerisation of 6-naphthanthrone yielded the known hydrocarbons, dinaphtho-(7', 1' : 1,13): (1", 7" :6, 8) -peropyrene , dinaphtho- -peropyrene and 2,3-trimethylenepyrene along with two new hydrocarbons (VIl) and(VIIl). Circobiphenyl (VII) is a highly condensed hydrocarbon which can be considered as a double coronene. The U.V. spectrum is similar to coronene, however its low solubility has proved a stumbling block in efforts to obtain the n. m. r. spectrum. It was hoped that the protons of this molecule would resonate at low field thus indicating a "superaromaticity" effect analogous to coronene. A new purple hydrocarbon was also obtained and U.V. evidence favours the structure dibenzisoviolanthrene (VIIl). Application of Robinsons aromatic sextet to this structure does not indicate any localised dienophilic regions and therefore this molecule should not react with maleic anhydride. Contrary to expectations, two-fold addition of maleic anhydride does occur in a similar manner to 2,3:4,5:8,9:10,11-tetrabenzoperylene and on this basis the possibility of structure (IX) cannot be excluded. However closer examination of structure (IX) shows that a complete Kekule structure is not possible, despite the fact that alternant marking predicts an equal number of marked and unmarked carbon atoms. The former finding leads to the theoretical prediction of a diradical or higher structure with an inherent instability as shown by triangulene, yet from the alternant marking sbbeme (IXa) a bond across the middle ring involving electrons of opposite spin might be possible. In order to test the above predictions and to try and clarify the reactivity of the purple hydrocarbon with maleic anhydride, an unambiguous synthesis of (IX) was attempted. A series of examples which show the asymmetric annellation of two diphenyl complexes to an acene have been built up over the years. Two of the remaining members of this series are 1,2:3,4:11,12: 13,14-hetrabenzheptacene (x) and 1,2:3,4-dibenzhexacene (xi). A synthesis of the former compound was undertaken to increase the scope of the above series and in an effort to obtain a reasonably stable heptacene derivative

Molecular Cloning, Characterisation, and Gene Targeting Vector Design for the Murine Preprotachykinin-A (PPT-A) and Neurokinin-1 Receptor (NK1-R) Genes

The neuropeptide substance P, recently re-named neurokinin-1 and abbreviated to NK-1, is a member of a family of neuropeptides called the tachykinins. Those neuropeptides are distributed throughout both the mammalian central and peripheral nervous systems and have likely roles in a myriad of cellular functions ranging from nociception to development. Neurokinin-1 has been localised to several interesting regions of the brain, regions that show phenotypic changes in line with the progression of clinical neurodegenerative diseases such as Huntingdons disease for example. NK-1 is encoded by the preprotachykinin-A (PPT-A) gene. The neurokinin-1 receptor (NK-1R) gene encodes the G-protein- coupled receptor for NK-1. In order to investigate the proposed involvement of the PPT-A and NK-1R genes in diseases of the nervous system and other cellular activities, it is important to firstly understand the normal function and regulation of those genes at the molecular level. This project sets out to examine the normal function and regulation of the PPT-A and NK-1R genes by molecularly cloning the murine PPT-A and NK-1R genes and provisionally characterising those genes. Gene targeting vectors for both genes will then be described. Vectors were designed for use in homologous recombination experiments, which is the first step required in order to generate transgenic mice bearing specifically altered forms of those genes. This objective was pursued by firstly cloning the murine NK-1 precursor (PPT-A) gene from a genomic bacteriophage library. A 423 bp probe was generated by polymerase chain reaction (PGR) from mouse genomic DNA template and was subcloned and sequenced. Optimal hybridisation conditions were then determined and the probe used to isolate lambda bacteriophage clones from a library. Similarly, positively-hybridising clones of the NK-1R (receptor) gene were isolated from another bacteriophage library using an 865 bp rat NK-1 R cDNA-derived probe. Secondly, the PPT-A bacteriophage clones were analysed by restriction mapping, PCR and by hybridisation to exon-specific probes. The exons of the murine PPT-A gene were then subcloned, restriction mapped and positioned relative to each other on linear restriction maps. Some mouse PPT-A sequence was obtained and aligned with other species to determine the extent of identity and homology. A similar approach was used for the NK-1R bacteriophage clones. Thirdly, gene targeting vectors for use in homologous recombination experiments in mouse embryonic stem cells were then constructed for each of the genes. Multiple cloning and subcloning steps were required to do this. Several endonuclease recognition sequences were altered by ligation of DNA linker sequences. A neomycin (G418) resistance gene with its own promoter was introduced into PPT-A exon 3, or in the the other vector, the neomycin resistance gene was introduced in place of a deleted 2.4 kb genomic sequence containing PPT-A exons 3 and 4. For the NK-1R vector, exons 3 and 4 were deleted and replaced by the neo resistance gene. In each vector, a thymidine kinase (TK) counter-selection gene from herpes simplex I virus (HSV1) was also inserted

Prognostic Value of Computed Tomography : Measured Parameters of Body Composition in Primary Operable Gastrointestinal Cancers

Professor Graeme Murray, Department of Pathology, University of Aberdeen provided us access to the colorectal cancer pathology databases from which the colorectal component of the research was based. Conflict of interest There are no conflicts of interest.Peer reviewedPublisher PD