Property assessment in the Commonwealth of Massachusetts - an analysis of present conditions and proposals.

Thesis (M.B.A.)--Boston Universit

The importance of age, sex and place in understanding socioeconomic inequalities in allostatic load: Evidence from the Scottish Health Survey (2008–2011)

Background  Given the broad spectrum of health and wellbeing outcomes that are patterned by socioeconomic position (SEP), it has been suggested that there may be common biological pathways linking SEP and health. Allostatic load is one such pathway, which aims to measure cumulative burden/dysregulation across multiple physiological systems. This study aimed to determine the contextual and demographic factors (age, sex and place) that may be important in better understanding the links between lower SEP and higher allostatic load.  Methods  Data were from a nationally representative sample of adults (18+): the Scottish Health Survey (2008–2011). Higher SEP (‘1’) was defined as having ‘Higher’-level, secondary school qualifications versus having lower level or no qualifications (‘0’). For allostatic load, a range of 10 biomarkers across the cardiovascular, metabolic and immune systems were used. Respondents were scored “1” for each biomarker that fell into the highest quartile of risk. Linear regressions were run in STATA, including SEP, age (continuous and as a 7-category variable), sex (male/female), urbanity (a 5-category variable ranging from primary cities to remote rural areas) and geographical location (based on 10 area-level healthboards). Interactions between SEP and each predictor, as well as stratified analyses, were tested.  Results  Lower SEP was associated with higher allostatic load even after adjusting for age, sex and place (b = −0.631, 95% CI −0.795, −0.389,p < 0.001). There was no significant effect moderation between SEP and age, sex or place. Stratified analysis did show that the inequality identified in the baseline models widened with age, becoming significant at ages 35–44, before narrowing at older ages (75+). There was no difference by sex, but more mixed findings with regards place (urbanity or geographical location), with a mix of significant and non-significant results by SEP that did not appear to follow any pattern.  Conclusions  Inequalities in allostatic load by educational attainment, as a measure of SEP, are consistent with age, sex and place. However, these stratified analyses showed that these inequalities did widen with age, before narrowing in later life, matching the patterns seen with other objective and subjective health measures. However, effect moderation analysis did not support evidence of a statistically significant interaction between age and SEP. Context remains an important feature in understanding and potentially addressing inequalities, although may be less of an issue in terms of physiological burden

Characterization of peptides and proteins by ultraviolet photodissociation mass spectrometry for biotechnology applications

Given the rapid and ubiquitous growth of biotechnology as a field, expanding the capabilities for the characterization of peptides and proteins remains paramount. Extending the breadth of applications for advanced tandem mass spectrometry methods has been critical to improving the understanding of biomolecules. The research presented in this dissertation focuses on the characterization of peptides and proteins with ultraviolet photodissociation-mass spectrometry (UVPD-MS). In addition to enhancing the body of knowledge on the applications of UVPD, this results in improved tools to characterize biotherapeutics and other biomolecules relevant to the biotechnology industry, including antibody drug conjugates (ADCs), synthetic selenoproteins, and human leukocyte antigen (HLA) immunopeptides. Through this work, improved localization of drug conjugation sites is presented for both cysteine- and lysine-linked ADCs, complete characterization of sequence and diselenide bond locations is reported for synthetic selenoproteins, and comprehensive sequence information, including leucine and isoleucine differentiation, is established for HLA immunopeptides. Various sample preparation techniques are explored to suit each application, including bottom-up and middle-down proteolysis as well as top-down analysis. High resolution mass spectrometry instrumentation and modern tandem mass spectrometry platforms are integral to the research presented in this dissertation. In addition to UVPD, a variety of tandem mass spectrometry techniques are explored including collisional and electron transfer dissociation. External collaborations have contributed greatly to the impact of this work, ensuring the development of industry-relevant applications. Access to application-specific software suits has also facilitated and enhanced the analysis and presentation of high-quality data. Overall, the work represents a step forward in both the understanding of key biomolecules as well as the applicability of UVPD to key areas in biotechnology research.Chemistr

Church attendance and alloparenting: an analysis of fertility, social support and child development among English mothers

Many aspects of religious rituals suggest they provide adaptive benefits. Studies across societies consistently find that investments in ritual behaviour return high levels of cooperation. Another line of research finds that alloparental support to mothers increases maternal fertility and improves child outcomes. Although plausible, whether religious cooperation extends to alloparenting and/or affects child development remains unclear. Using 10 years of data collected from the Avon Longitudinal Study of Parents and Children (ALSPAC), we test the predictions that church attendance is positively associated with social support and fertility (n = 8207 to n = 8209), and that social support is positively associated with fertility and child development (n = 1766 to n = 6561). Results show that: (i) relative to not attending, church attendance is positively related to a woman's social network support and aid from co-religionists, (ii) aid from co-religionists is associated with increased family size, while (iii) fertility declines with extra-religious social network support. Moreover, while extra-religious social network support decreased over time, co-religionist aid remained constant. These findings suggest that religious and secular networks differ in their longevity and have divergent influences on a woman's fertility. We find some suggestive evidence that support to mothers and aid from co-religionists is positively associated with a child's cognitive ability at later stages of development. Findings provide mixed support for the premise that ritual, such as church attendance, is part of a strategy that returns high levels of support, fertility and improved child outcomes. Identifying the diversity and scope of cooperative breeding strategies across global religions presents an intriguing new horizon in the evolutionary study of religious systems. This article is part of the theme issue 'Ritual renaissance: new insights into the most human of behaviours'

Circulating free testosterone and risk of aggressive prostate cancer : Prospective and Mendelian randomisation analyses in international consortia

Publisher Copyright: © 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet =.0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.Peer reviewe

The relationship between lipoprotein A and other lipids with prostate cancer risk:A multivariable Mendelian randomisation study

BACKGROUND: Numerous epidemiological studies have investigated the role of blood lipids in prostate cancer (PCa) risk, though findings remain inconclusive to date. The ongoing research has mainly involved observational studies, which are often prone to confounding. This study aimed to identify the relationship between genetically predicted blood lipid concentrations and PCa. METHODS AND FINDINGS: Data for low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), apolipoprotein A (apoA) and B (apoB), lipoprotein A (Lp(a)), and PCa were acquired from genome-wide association studies in UK Biobank and the PRACTICAL consortium, respectively. We used a two-sample summary-level Mendelian randomisation (MR) approach with both univariable and multivariable (MVMR) models and utilised a variety of robust methods and sensitivity analyses to assess the possibility of MR assumptions violation. No association was observed between genetically predicted concentrations of HDL, TG, apoA and apoB, and PCa risk. Genetically predicted LDL concentration was positively associated with total PCa in the univariable analysis, but adjustment for HDL, TG, and Lp(a) led to a null association. Genetically predicted concentration of Lp(a) was associated with higher total PCa risk in the univariable (OR(weighted median) per standard deviation (SD) = 1.091; 95% CI 1.028 to 1.157; P = 0.004) and MVMR analyses after adjustment for the other lipid traits (OR(IVW) per SD = 1.068; 95% CI 1.005 to 1.134; P = 0.034). Genetically predicted Lp(a) was also associated with advanced (MVMR OR(IVW) per SD = 1.078; 95% CI 0.999 to 1.163; P = 0.055) and early age onset PCa (MVMR OR(IVW) per SD = 1.150; 95% CI 1.015,1.303; P = 0.028). Although multiple estimation methods were utilised to minimise the effect of pleiotropy, the presence of any unmeasured pleiotropy cannot be excluded and may limit our findings. CONCLUSIONS: We observed that genetically predicted Lp(a) concentrations were associated with an increased PCa risk. Future studies are required to understand the underlying biological pathways of this finding, as it may inform PCa prevention through Lp(a)-lowering strategies

Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank

Background: Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank. Methods: A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure. Results: After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death. Conclusion: We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.</p

A novel preference-informed complementary trial (PICT) design for clinical trial research influenced by strong patient preferences

Background: Patients and their families often have preferences for medical care that relate to wider considerations beyond the clinical effectiveness of the proposed interventions. Traditionally, these preferences have not been adequately considered in research. Research questions where patients and families have strong preferences may not be appropriate for traditional randomized controlled trials (RCTs) due to threats to internal and external validity, as there may be high levels of drop-out and non-adherence or recruitment of a sample that is not representative of the treatment population. Several preference-informed designs have been developed to address problems with traditional RCTs, but these designs have their own limitations and may not be suitable for many research questions where strong preferences and opinions are present. Methods: In this paper, we propose a novel and innovative preference-informed complementary trial (PICT) design which addresses key weaknesses with both traditional RCTs and available preference-informed designs. In the PICT design, complementary trials would be operated within a single study, and patients and/or families would be given the opportunity to choose between a trial with all treatment options available and a trial with treatment options that exclude the option which is subject to strong preferences. This approach would allow those with strong preferences to take part in research and would improve external validity through recruiting more representative populations and internal validity. Here we discuss the strengths and limitations of the PICT design and considerations for analysis and present a motivating example for the design based on the use of opioids for pain management for children with musculoskeletal injuries. Conclusions: PICTs provide a novel and innovative design for clinical trials with more than two arms, which can address problems with existing preference-informed trial designs and enhance the ability of researchers to reflect shared decision-making in research as well as improving the validity of trials of topics with strong preferences