Political marketing and the British Labour Party 1994-2010: Applying the product life-cycle model to a political party

This thesis explores the merits of applying a marketing model, the product life-cycle model, to a political party. The product life-cycle model details a product during its introduction, growth, maturity and decline cycles. For this thesis I apply this model to the British Labour Party between 1994 and 2010 under the leadership of Tony Blair and Gordon Brown. The product life-cycle model, adapted to political science from the political marketing literature, shows that a political party does go through an introduction, growth, maturity and decline phase. To avoid moving into the decline phase, a political party must learn how to rejuvenate during the maturity cycle. This thesis concludes that the product life-cycle model does have merits when applied to political parties. In the case of the British Labour Party, it began with a strong market-orientation, but the longer it stayed in power this market-orientation shifted. The New Labour brand and its primary brand agent, Tony Blair, were both strong assets to the party. However, during the lifetime of the product these assets became liabilities. The longer that New Labour stayed in power, the more it shifted away from its relationship with the political market. The product life-cycle model should be tested in other political systems to further strengthen its explanatory power

corona Is Required for Higher-Order Assembly of Transverse Filaments into Full-Length Synaptonemal Complex in Drosophila Oocytes

The synaptonemal complex (SC) is an intricate structure that forms between homologous chromosomes early during the meiotic prophase, where it mediates homolog pairing interactions and promotes the formation of genetic exchanges. In Drosophila melanogaster, C(3)G protein forms the transverse filaments (TFs) of the SC. The N termini of C(3)G homodimers localize to the Central Element (CE) of the SC, while the C-termini of C(3)G connect the TFs to the chromosomes via associations with the axial elements/lateral elements (AEs/LEs) of the SC. Here, we show that the Drosophila protein Corona (CONA) co-localizes with C(3)G in a mutually dependent fashion and is required for the polymerization of C(3)G into mature thread-like structures, in the context both of paired homologous chromosomes and of C(3)G polycomplexes that lack AEs/LEs. Although AEs assemble in cona oocytes, they exhibit defects that are characteristic of c(3)G mutant oocytes, including failure of AE alignment and synapsis. These results demonstrate that CONA, which does not contain a coiled coil domain, is required for the stable ‘zippering’ of TFs to form the central region of the Drosophila SC. We speculate that CONA's role in SC formation may be similar to that of the mammalian CE proteins SYCE2 and TEX12. However, the observation that AE alignment and pairing occurs in Tex12 and Syce2 mutant meiocytes but not in cona oocytes suggests that the SC plays a more critical role in the stable association of homologs in Drosophila than it does in mammalian cells

Interplay between Synaptonemal Complex, Homologous Recombination, and Centromeres during Mammalian Meiosis

The intimate synapsis of homologous chromosome pairs (homologs) by synaptonemal complexes (SCs) is an essential feature of meiosis. In many organisms, synapsis and homologous recombination are interdependent: recombination promotes SC formation and SCs are required for crossing-over. Moreover, several studies indicate that initiation of SC assembly occurs at sites where crossovers will subsequently form. However, recent analyses in budding yeast and fruit fly imply a special role for centromeres in the initiation of SC formation. In addition, in budding yeast, persistent SC–dependent centromere-association facilitates the disjunction of chromosomes that have failed to become connected by crossovers. Here, we examine the interplay between SCs, recombination, and centromeres in a mammal. In mouse spermatocytes, centromeres do not serve as SC initiation sites and are invariably the last regions to synapse. However, centromeres are refractory to de-synapsis during diplonema and remain associated by short SC fragments. Since SC–dependent centromere association is lost before diakinesis, a direct role in homolog segregation seems unlikely. However, post–SC disassembly, we find evidence of inter-centromeric connections that could play a more direct role in promoting homolog biorientation and disjunction. A second class of persistent SC fragments is shown to be crossover-dependent. Super-resolution structured-illumination microscopy (SIM) reveals that these structures initially connect separate homolog axes and progressively diminish as chiasmata form. Thus, DNA crossing-over (which occurs during pachynema) and axis remodeling appear to be temporally distinct aspects of chiasma formation. SIM analysis of the synapsis and crossover-defective mutant Sycp1−/− implies that SCs prevent unregulated fusion of homolog axes. We propose that SC fragments retained during diplonema stabilize nascent bivalents and help orchestrate local chromosome reorganization that promotes centromere and chiasma function

an international multi center serum protein electrophoresis accuracy and m protein isotyping study part i factors impacting limit of quantitation of serum protein electrophoresis

AbstractBackgroundSerum protein electrophoresis (SPEP) is used to quantify the serum monoclonal component or M-protein, for diagnosis and monitoring of monoclonal gammopathies. Significant imprecision and inaccuracy pose challenges in reporting small M-proteins. Using therapeutic monoclonal antibody-spiked sera and a pooled beta-migrating M-protein, we aimed to assess SPEP limitations and variability across 16 laboratories in three continents.MethodsSera with normal, hypo- or hypergammaglobulinemia were spiked with daratumumab, Dara (cathodal migrating), or elotuzumab, Elo (central-gamma migrating), with concentrations from 0.125 to 10 g/L (n = 62) along with a beta-migrating sample (n = 9). Provided with total protein (reverse biuret, Siemens), laboratories blindly analyzed samples according to their SPEP and immunofixation (IFE) or immunosubtraction (ISUB) standard operating procedures. Sixteen laboratories reported the perpendicular drop (PD) method of gating the M-protein, while 10 used tangent skimming (TS). A mean percent recovery range of 80%–120% was set as acceptable. The inter-laboratory %CV was calculated.ResultsGamma globulin background, migration pattern and concentration all affect the precision and accuracy of quantifying M-proteins by SPEP. As the background increases, imprecision increases and accuracy decreases leading to overestimation of M-protein quantitation especially evident in hypergamma samples, and more prominent with PD. Cathodal migrating M-proteins were associated with less imprecision and higher accuracy compared to central-gamma migrating M-proteins, which is attributed to the increased gamma background contribution in M-proteins migrating in the middle of the gamma fraction. There is greater imprecision and loss of accuracy at lower M-protein concentrations.ConclusionsThis study suggests that quantifying exceedingly low concentrations of M-proteins, although possible, may not yield adequate accuracy and precision between laboratories

Political marketing and the British Labour Party 1994-2010: Applying the product life-cycle model to a political party

This thesis explores the merits of applying a marketing model, the product life-cycle model, to a political party. The product life-cycle model details a product during its introduction, growth, maturity and decline cycles. For this thesis I apply this model to the British Labour Party between 1994 and 2010 under the leadership of Tony Blair and Gordon Brown. The product life-cycle model, adapted to political science from the political marketing literature, shows that a political party does go through an introduction, growth, maturity and decline phase. To avoid moving into the decline phase, a political party must learn how to rejuvenate during the maturity cycle. This thesis concludes that the product life-cycle model does have merits when applied to political parties. In the case of the British Labour Party, it began with a strong market-orientation, but the longer it stayed in power this market-orientation shifted. The New Labour brand and its primary brand agent, Tony Blair, were both strong assets to the party. However, during the lifetime of the product these assets became liabilities. The longer that New Labour stayed in power, the more it shifted away from its relationship with the political market. The product life-cycle model should be tested in other political systems to further strengthen its explanatory power.</p

Reversion of a methicillin resistant staphylococcus aureus strain to sensitivity in vivo : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Microbiology at Massey University

In 1986 during an outbreak of MRSA infection at Palmerston North Hospital an MRSA strain (PN MRSA) was recovered from a patient who was treated and subsequently discharged. In 1990 prior to readmission an isolate of S.aureus which produced small colonies typical of MRSA was recovered from the same patient. This isolate was resistant to several antibiotics but unexpectedly was sensitive to methicillin. This investigation examines the possibility that this atypical methicillin sensitive S.aureus (AMSSA) strain was derived in vivo from the resistant strain, possibly by a reversible mutation, and examines the possibility that exposure of this sensitive strain to analogues of methicillin may lead to reversion to resistance. The PN MRSA and the AMSSA strain were compared with various other methicillin resistant and sensitive staphylococci by phage typing, reverse phage typing, plasmid profiles, and total genomic digests using the restriction enzymes Hindlll and Smal. In all instances results showed that the PN MRSA and the AMSSA strain were more similar to each other than they were to any of the other staphylococci examined. Probing of total genomic and SmaI-digested DNA with the methicillin resistance gene mec showed that the gene was present in all the 'high level multiply resistant' and 'low level singularly resistant' MRSA strains examined but absent from the AMSSA strain and the other methicillin sensitive isolates. The 143 kb fragment which contained the mec gene in the PN MRSA was absent from the SmaI restriction profile of the AMSSA strain. The loss of this fragment and another fragment (104 kb) followed by the gain of a 203 kb fragment in the profile of the AMSSA strain was consistant with a deletion (44 kilobases) which spans a SmaI site. The deletion corresponds to the estimated size of the mec gene complex. Overall the results suggest that the AMSSA strain was derived in vivo from the PN MRSA strain and in the process 44 kilobases of DNA was deleted from the mec region. As sensitivity in the AMSSA strain was not due to an easily reversible point mutation or small deletion it is unlikely that the isolate will rapidly develop resistance to methicillin following exposure to the drug. However the results suggest that the mec region is unstable and that under the appropriate conditions the mec region may be lost from the chromosome of MRSA strain in vivo

Political marketing and the British Labour Party 1994-2010: Applying the product life-cycle model to a political party

This thesis explores the merits of applying a marketing model, the product life-cycle model, to a political party. The product life-cycle model details a product during its introduction, growth, maturity and decline cycles. For this thesis I apply this model to the British Labour Party between 1994 and 2010 under the leadership of Tony Blair and Gordon Brown. The product life-cycle model, adapted to political science from the political marketing literature, shows that a political party does go through an introduction, growth, maturity and decline phase. To avoid moving into the decline phase, a political party must learn how to rejuvenate during the maturity cycle. This thesis concludes that the product life-cycle model does have merits when applied to political parties. In the case of the British Labour Party, it began with a strong market-orientation, but the longer it stayed in power this market-orientation shifted. The New Labour brand and its primary brand agent, Tony Blair, were both strong assets to the party. However, during the lifetime of the product these assets became liabilities. The longer that New Labour stayed in power, the more it shifted away from its relationship with the political market. The product life-cycle model should be tested in other political systems to further strengthen its explanatory power

A meta-analysis of differences in IL-6 and IL-10 between people with and without depression: exploring the causes of heterogeneity

Epidemiological evidence for the inflammatory hypothesis of depression is largely cross-sectional; people with depression have elevated levels of circulating pro-inflammatory markers compared to people without depression. The limitation of cross sectional research is the potential for extraneous factors to influence observed effects. The purpose of this meta-analysis of cross-sectional studies of interleukin(IL)-6 and IL-10 in people with and without depression is to provide a targeted analysis of potential moderator factors relating to the diagnosis of depression and to physical and psychiatric comorbidity. Electronic searches of Embase and Medline databases were conducted using subject headings “interleukin-6” or “interleukin-10” and those relating to depression. Studies were included if they measured circulating marker levels in serum or plasma in a group of people with and without depressive symptoms (99 studies for IL-6, 19 studies for IL-10). IL-6 was elevated in depressed compared to non-depressed groups (d = 0.46, 99% CI 0.34 to 0.58, I2 = 85.9%). This effect was larger in subgroups where depressive disorders were diagnosed compared to those with only depressive symptoms via standardized inventory, and subgroups where participants were recruited from inpatient or outpatient settings compared to the general community. The effect was also larger in those who were not selected for a particular comorbidity compared to those selected for cardiovascular disease. IL-10 effect size was not significant (d = −0.31, 99% CI −0.95 to 0.32, I2 = 94.1%) which was not accounted for in subgroup analyses or meta-regression, indicating there is not a global elevation in cytokines. These data highlight that comorbidity and behavioral aspects of depression need to be measured and controlled in future prospective and experimental research testing the inflammatory hypothesis of depression

Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis

Background: Cross-sectional studies support an association between depression and inflammatory markers. However, little is known of their relationship in the context of antidepressant treatment. Our aim was to explore via meta-analysis whether antidepressant treatment is associated with a reduction in three inflammatory markers associated with depression. Method: A computerized search of EMBASE, Medline, PsycINFO and Cochrane Library databases was completed using subject headings for depression and either interleukin-6, C-reactive protein or interleukin-10, selecting studies which reported circulating levels of inflammatory markers before and after antidepressant treatment for people with depression. Outcome and moderator variables were coded for analysis, including inflammatory marker change, depression severity change, age, gender ratio, assay brand, treatment response and weight change. Results: Pooled effect sizes showed a significant decrease in interleukin-6 (n=14, d=-0.42, p=0.02), marginally significant decrease in C-reactive protein (n=8, d=-0.57, p=0.05) and a non-significant decrease in interleukin-10 (n=3, d=-0.45, p=0.14) after treatment. High levels of heterogeneity were observed, which may be associated with clinical variations between the studies such as weight gain, anxiety, incomplete remission and other individual differences and co-morbidities. Conclusions: The findings of this meta-analysis indicate that there may be a normalization of overactive inflammatory processes following antidepressant treatment

The role of inflammatory markers in explaining the association between depression and cardiovascular hospitalisations

This study investigated whether inflammation may explain the relationship between depression and incident cardiovascular hospitalisations. Participants (55-85 years) completed baseline depression and physical assessment. Those without self-reported cardiovascular events were followed prospectively for hospital admissions for angina, myocardial infarction and cerebral infarction (median 937 days). Across 5140 person-years of risk (N = 1692), there were 47 incident cardiovascular hospitalisations (2.8 %). Controlling for age and gender, interleukin (IL)-6, C-reactive protein (CRP), body mass index (BMI) and waist-to-hip ratio were associated with future cardiovascular events. Mediation analysis showed that CRP accounted for 8.1 % and IL-6 10.9 % of the effect of depression on cardiovascular events, and including the indirect effect in the model substantially reduced the direct relationship between depression and cardiovascular hospitalisations. BMI and waist-to-hip ratio accounted for indirect effects of 7.7 and 10.4 %, respectively. Inflammatory markers partly explain the association between depression and cardiovascular events, although other shared factors also likely contribute