"A palace within a Palace": the Speaker's House at Westminster, 1794–1834

The thesis provides the first detailed study of the original Speaker’s House within the Palace of Westminster. In 1794, the Speaker of the House of Commons appropriated a large mansion which stood immediately adjacent to the Commons chamber. During 1802–08 the house was extensively remodelled by James Wyatt. It remained the official residence of the Speaker until 1834, when the old Palace of Westminster was effectively destroyed by fire. This interdisciplinary thesis will explore the history of the house from both political and architectural perspectives. It will examine how successive Speakers used the house to support their political role, with particular emphasis on its vital part in their hospitality and sociability, both official and unofficial. It will also explain how successive Speakers used the increased prestige of their office to support their personal ambitions for social advancement. It argues that the Speaker’s House helped the Speaker to consolidate their position as the symbolic figurehead of the House of Commons. Architecturally, this thesis will concentrate on Wyatt’s decision—which was fully embraced by his patron, Speaker Abbot—to adopt a Gothic style for his alterations. It will consider the reasons for his choice, and the long-term impact of his work. It will also consider the Speaker’s House in relation to contemporary debates about architectural conservation, for which the Palace of Westminster was a significant flashpoint. This thesis presents the Speaker’s House as a case study of changing attitudes to architectural style and conservation in early nineteenth-century Britain. It argues that Wyatt’s interventions changed the architectural destiny of the old palace, creating a newfound sense that Gothic was the ‘proper’ style both for the Palace of Westminster as a complex of buildings, and for Parliament as an institution. This newfound sensibility ultimately determined the design of the present Palace of Westminster

Obesity related metabolic endotoxemia is associated with oxidative stress and impaired sperm DNA integrity

© The Author(s). 2019 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Obesity is known to be associated with inflammation, oxidative stress and a resulting reduction in sperm DNA integrity. Importantly, obesity is also reported to be associated with an increase in intestinal permeability with the passage of intestinal bacteria into the circulation (metabolic endotoxemia) that triggers a systemic state of inflammation and resultant oxidative stress. Therefore, we hypothesised that this obesity related increase in intestinal permeability and resultant metabolic endotoxemia (ME) may activate inflammation within the male reproductive tract, leading to increased reactive oxygen species production, sperm oxidative stress and a decline in DNA integrity. Results Our pilot study of 37 infertile men confirmed a significant positive correlation between body mass index (BMI), increased intestinal permeability (serum zonulin), metabolic endotoxaemia (LBP), sperm DNA oxidative damage (seminal 8 OhDG) and increasing levels of sperm DNA fragmentation (Halosperm). Metabolic endotoxemia was positively correlated with increasing levels of sperm DNA oxidative damage with this relationship remaining significant, even after adjustment for relevant confounders such as age, BMI and days of abstinence. These observations suggest that metabolic endotoxemia and its associated oxidative stress may be a key driver of sperm DNA damage in obese men. Conclusion This study confirms a link between obesity, increasing intestinal permeability and endotoxin exposure, and oxidative mediated sperm DNA damage. This warrants further investigation to fully understand the effect of metabolic endotoxemia on male reproductive function which could result in the new therapies to improve male fertility potential

Double trouble: Should double embryo transfer be banned?

What role should legislation or policy play in avoiding the complications of in-vitro fertilization? In this article, we focus on single versus double embryo transfer, and assess three arguments in favour of mandatory single embryo transfer: risks to the mother, risks to resultant children, and costs to society. We highlight significant ethical concerns about each of these. Reproductive autonomy and non-paternalism are strong enough to outweigh the health concerns for the woman. Complications due to non-identity cast doubt on the extent to which children are harmed. Twinning may offer an overall benefit rather than burden to society. Finally, including the future health costs for children (not yet born) in reproductive policy is inconsistent with other decisions. We conclude that mandatory single embryo transfer is not justified and that a number of countries should reconsider their current embryo transfer policy

Male seminal parameters are not associated with Leydig cell functional capacity in men

Background: Insulin-like peptide 3 (INSL3) is a constitutive, secreted peptide produced in the male uniquely by the Leydig cells of the testes. It is a biomarker for Leydig cell functional capacity, which is a measure of the numbers and differentiation status of these steroidogenic cells and lacks the biological and technical variance of the steroid testosterone. This retrospective study was carried out to examine the relationship between seminal parameters and the Leydig cell compartment, and secondarily to assess other factors responsible for determining Leydig cell functional capacity. Methods: INSL3 was assessed together with seminal, anthropometric, and hormonal parameters in a Swedish cohort of 18-year-old men, representing the average population, and in a smaller, more heterogeneous cohort of men visiting an Australian infertility clinic. Results and discussion: Average INSL3 concentration at 18years is greater than that reported at younger or older ages and indicated a large 10-fold variation. In neither cohort was there a relationship between INSL3 concentration and any semen parameter. For the larger, more uniform Swedish cohort of young men, there was a significant negative relationship between INSL3 and BMI, supporting the idea that adult Leydig cell functional capacity may be established during puberty. In both cohorts, there was a significant relationship between INSL3 and FSH, but not LH concentration. No relationship was found between INSL3 and androgen receptor trinucleotide repeat polymorphisms, reinforcing the notion that Leydig cell functional capacity is unlikely to be determined by androgen influence alone. Nor did INSL3 correlate with the T/LH ratio, an alternative measure of Leydig cell functional capacity, supporting the view that these are independent measures of Leydig cell function

Seminal “priming” for protection from pre-eclampsia-a unifying hypothesis

Abstract Conventional belief holds that an immune response to ejaculate antigens should interfere with fertilisation and establishment of pregnancy. However, emerging evidence now supports the opposing view */that insemination acts to activate maternal immune mechanisms exerting a positive effect on reproductive events. In a response well documented in rodents, semen triggers an influx of antigen-presenting cells into the female reproductive tract which process and present paternal ejaculate antigens to elicit activation of lymphocytes in the adaptive immune compartment. Transforming growth factor beta (TGFb), a cytokine present in abundance in seminal plasma, initiates this inflammatory response by stimulating the synthesis of pro-inflammatory cytokines and chemokines in uterine tissues. Lymphocyte activation is evident in lymph nodes draining the uterus and leads to hypo-responsiveness in T-cells reactive with paternal alloantigens. TGFb has potent immune-deviating effects and is likely to be the key agent in skewing the immune response against a Type-1 bias. Prior exposure to semen in the context of TGFb can be shown to be associated with enhanced fetal Á/placental development late in gestation. In this paper, we review the experimental basis for these claims and propose the hypothesis that, in women, the partner-specific protective effect of insemination in pre-eclampsia might be explained by induction of immunological hyporesponsiveness conferring tolerance to histocompatibility antigens present in the ejaculate and shared by the conceptus.

Anti-Müllerian hormone measurement for the diagnosis of polycystic ovary syndrome

Objective: Anti-Müllerian hormone (AMH) is derived from the small antral follicles, and an elevated level has been suggested to add value to the Rotterdam criteria for the diagnosis of PCOS in cases of diagnostic uncertainty. Therefore, the role of AMH in the classical phenotype of PCOS was defined within a Caucasian population. Design: This was a cross-sectional study. Patients: Sixty Five women without PCOS and 110 women with PCOS fulfilling all 3 diagnostic Rotterdam criteria. Measurements: The main outcomes were the utility of serum AMH for the diagnosis of PCOS and its relationship to the metabolic parameters. Results: Anti-Müllerian hormone was increased in PCOS compared to controls (P  < .001). Areas under the receiver operator curve showed AMH to be predictive of PCOS (0.76) using a cut-off AMH of 46 pmol/L, which is derived from the 95 th percentile of the controls that gave a 41% sensitivity and 86% specificity; an AMH cut-off of 35 pmol/L gave a 55% sensitivity and 79% specificity. Age- and BMI-adjusted multiple logistic regression showed that AMH was more predictive of PCOS independently of either serum testosterone (T) (OR = 4.04; 95% CI 1.42-11.11; P =.007) or free androgen index (FAI) (OR = 3.90; 95% CI 1.40-10.83; P =.009). Conclusion: Whilst an elevated AMH has poor sensitivity, it is fourfold more likely to be associated with a diagnosis of PCOS, and supplementary to biochemical parameters will make a positive diagnosis of PCOS in 22% of patients when neither serum testosterone nor FAI is elevated

Effect of Intralipid infusion on peripheral blood T cells and plasma cytokines in women undergoing assisted reproduction treatment

Objectives: Intravenous infusion of Intralipid is an adjunct therapy in assisted reproduction treatment (ART) when immune-associated infertility is suspected. Here, we evaluated the effect of Intralipid infusion on regulatory T cells (Treg cells), effector T cells and plasma cytokines in peripheral blood of women undertaking IVF. Methods: This prospective, observational pilot study assessed Intralipid infusion in 14 women exhibiting recurrent implantation failure, a clinical sign of immune-associated infertility. Peripheral blood was collected immediately prior to and 7 days after intravenous administration of Intralipid. Plasma cytokines were measured by Luminex, and T-cell subsets were analysed by flow cytometry. Results: A small increase in conventional CD8+ T cells occurred after Intralipid infusion, but no change was seen in CD4+ Treg cells, or naïve, memory or effector memory T cells. Proliferation marker Ki67, transcription factors Tbet and RORγt, and markers of suppressive capacity CTLA4 and HLA-DR were unchanged. Dimensionality-reduction analysis using the tSNE algorithm confirmed no phenotype shift within Treg cells or other T cells. Intralipid infusion increased plasma CCL2, CCL3, CXCL8, GM-CSF, G-CSF, IL-6, IL-21, TNF and VEGF. Conclusion: Intralipid infusion elicited elevated pro-inflammatory cytokines, and a minor increase in CD8+ T cells, but no change in pro-tolerogenic Treg cells. Notwithstanding the limitation of no placebo control, the results do not support Intralipid as a candidate intervention to attenuate the Treg cell response in women undergoing ART. Future placebo-controlled studies are needed to confirm the potential efficacy and clinical significance of Intralipid in attenuating cytokine induction and circulating CD8+ T cells.Kerrie L Foyle, David J Sharkey, Lachlan M Moldenhauer, Ella S Green, Jasmine J Wilson, Cassandra J Roccisano ... et al

A systematic review of the evidence for complementary and alternative medicine in infertility

BackgroundThe use of complementary and alternative medicine (CAM) by patients and physicians has increased markedly in recent years. Many case reports, case series, and uncontrolled trials of varying quality have been completed; however, there is now a slowly increasing number of randomized controlled trials (RCTs) examining the use of CAM.ObjectivesTo identify, survey, and review RCTs investigating the use of CAM for infertility treatment.Search strategyThe MEDLINE and Cochrane databases were electronically searched.Selection criteriaRCTs examining modalities for treatment or improvement of health status were reviewed.Data collection and analysisRCTs were included based on use of objective measures, articles written in English, availability through the University of Michigan database, and clear published clinical outcomes.Main resultsThirty‐seven articles assessing a variety of CAM modalities met inclusion criteria. Acupuncture, selenium supplementation, weight loss, and psychotherapeutic intervention had 3 or more studies demonstrating beneficial effect. Other interventions had been studied less and evidence for them was limited.ConclusionsAlthough there is preliminary evidence of the effectiveness of some CAM interventions among infertile patients, many of these interventions require further investigation before they can be considered for routine clinical use.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135426/1/ijgo202.pd