Censors and society: the Roman censorship, 443 - 21 BC

The censorship was one of the Roman Republic's most significant magistracies. The range and importance of their duties – the census, the lectio senatus and recognitio equitum, letting public contracts and initiating public works, and the ceremony of the lustrum – meant that the office had a profound impact on Roman society. There is much modern scholarship on the censorship. But some of the arguments and conclusions put forward by earlier scholars, while valuable, need to be updated and certain misconceptions corrected. In particular, what is required is a greater focus on placing the censorship in its political and social context, into the political culture of the Roman Republic, in order to properly analyse the office, its wider function(s), and its influence on Roman society. At the same time, a careful consideration of what precisely the censors' duties involved and how each pair of censors carried these out is necessary. The present work hopes to address both aspects of this important magistracy. To that end, this thesis is divided into seven chapters. Five of which deal with the censors' individual responsibilities. Chapter 1 is a diachronic survey of the censorship across the whole period of its existence. It aims to highlight the development of the office over time and to ground the subsequent discussion of the magistracy in its proper chronological context. Chapter 2 highlights the infrastructure – assistants, schedule, records, headquarters etc – through which the censors were able to carry out their tasks. Chapter 3 is a study of the censors' most important task, the taking of the census, and its importance for the Roman community. Chapter 4 looks at the censors as guardians of the mos maiorum, and the activities through which this role was expressed. Chapter 5 investigates the censors' responsibility for letting public contracts of various kinds, and the impact this had on the Roman state and its economy. Chapter 6 focuses in more detail on the most significant and costly element of the censors' contracting duties – public works. It attempts to assess what contribution the censors made to the ever-changing face of the city of Rome, as compared to the other magistrates. Finally, Chapter 7 considers the lustrum, the sacred rite which closed each pair of censors' term in office. It asks both what the ceremony involved, and what its meaning and significance for the community might have been

Comparative adsorption of saturated and unsaturated fatty acids at the iron oxide/oil interface

A detailed comparison of the adsorption behavior of long straight chain saturated and unsaturated fatty acids at the iron oxide/oil interface has been considered using a combination of surface study techniques. Both depletion isotherms and polarized neutron reflectometry (PNR) show that the extent of adsorption decreases as the number of double bonds in the alkyl chains increases. Sum frequency generation spectroscopic measurements demonstrate that there is also an increase in chain disorder within the adsorbed layer as the unsaturation increases. However, for the unsaturated analogues, a decrease in peak intensity is seen for the double bond peak upon heating, which is thought to arise from isomerization in the surface-bound layer. The PNR study of oleic acid adsorption indicates chemisorbed monolayer adsorption, with a further diffuse reversible adsorbed layer formed at higher concentrations.Mary Wood is grateful for funding from the Oppenheimer Trust. The PNR data were collected using the V6 instrument at the Helmholtz-Zentrum Berlin (experiment number MAT-04-2131).This is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/acs.langmuir.5b0443

Weight loss surgery for non-morbidly obese populations with type 2 diabetes: is this an acceptable option for patients?

Aim To explore the views of non-morbidly obese people (BMI 30-40 kg/m2) with type 2 diabetes regarding: (a) the acceptability of bariatric surgery (BS) as a treatment for type 2 diabetes, and (b) willingness to participate in randomised controlled trials comparing BS versus non-surgical intervention. BACKGROUND: Despite weight management being a key therapeutic goal in type 2 diabetes, achieving and sustaining weight loss is problematic. BS is an effective treatment for people with morbid obesity and type 2 diabetes; it is less certain whether non-morbidly obese patients (BMI 30-39.9 kg/m2) with type 2 diabetes benefit from this treatment and whether this approach would be cost-effective. Before evaluating this issue by randomised trials, it is important to understand whether BS and such research are acceptable to this population. METHODS: Non-morbidly obese people with type 2 diabetes were purposively sampled from primary care and invited to participate in semi-structured interviews. Interviews explored participants' thoughts surrounding their diabetes and weight, the acceptability of BS and the willingness to participate in BS research. Data were analysed using Framework Analysi

Use of the cell cycle progression (CCP) score for predicting systemic disease and response to radiation of biochemical recurrence

BACKGROUND: Determining the optimal treatment for biochemical recurrence (BCR) after radical prostatectomy (RP) is challenging. OBJECTIVE: We evaluated the ability of CCP score (a prognostic RNA expression signature) to discriminate between systemic disease and local recurrence in patients with BCR after RP. METHODS: Sixty patients with BCR after RP were selected for analysis based on: 1) metastatic disease, 2) non-response to salvage external beam radiotherapy (EBRT), and 3) durable response to salvage EBRT. CCP scores were generated from the RNA expression of 46 genes. Logistic regression assessed the association between CCP score and patient group. RESULTS: Passing CCP scores were generated for 47 patients with complete clinical and pathologic data. CCP score predicted clinical status when comparing patients with metastatic disease or non-responders to salvage therapy to patients with durable response (p = 0.006). CCP score remained significantly predictive of clinical status after accounting for time to BCR, PSA level at BCR, and Gleason score (p = 0.0031). CONCLUSIONS: Elevated CCP score was associated with increased risk of systemic disease, indicating that CCP score may be useful in identifying patients with BCR who are most likely to benefit from salvage radiation therapy

The circularly permuted globin domain of androglobin exhibits atypical heme stabilization and nitric oxide interaction

In the decade since the discovery of androglobin, a multi-domain hemoglobin of metazoans associated with ciliogenesis and spermatogenesis, there has been little advance in the knowledge of the biochemical and structural properties of this unusual member of the hemoglobin superfamily. Using a method for aligning remote homologues, coupled with molecular modelling and molecular dynamics, we have identified a novel structural alignment to other hemoglobins. This has led to the first stable recombinant expression and characterization of the circularly permuted globin domain. Exceptional for eukaryotic globins is that a tyrosine takes the place of the highly conserved phenylalanine in the CD1 position, a critical point in stabilizing the heme. A disulfide bond, similar to that found in neuroglobin, forms a closed loop around the heme pocket, taking the place of androglobin's missing CD loop and further supporting the heme pocket structure. Highly unusual in the globin superfamily is that the heme iron binds nitric oxide as a five-coordinate complex similar to other heme proteins that have nitric oxide storage functions. With rapid autoxidation and high nitrite reductase activity, the globin appears to be more tailored toward nitric oxide homeostasis or buffering. The use of our multi-template profile alignment method to yield the first biochemical characterisation of the circularly permuted globin domain of androglobin expands our knowledge of the fundamental functioning of this elusive protein and provides a pathway to better define the link between the biochemical traits of androglobin with proposed physiological functions

Involving lay and professional stakeholders in the development of a research intervention for the DEPICTED Study

Aim: This paper focuses on stakeholders’ active involvement at key stages of the research as members of a Stakeholder Action Group (SAG), particularly in the context of lay stakeholder involvement. Some challenges that can arise and wider issues (e.g. empowerment, the impact of user involvement) are identified and explored within the literature on service user involvement in health care research, reflecting on the implications for researchers. Background: In the DEPICTED study, lay and professional stakeholders were actively involved in developing a complex research intervention. Lay stakeholders comprised teenage and adult patients with diabetes, parents and patient organization representatives. Professional stakeholders were from a range of disciplines. Methods: Three 1-day research meetings were attended by 13–17 lay stakeholders and 10–11 professional stakeholders (plus researchers). The SAG was responsible for reviewing evidence, advising on developing ideas for the research intervention and guiding plans for evaluation of the intervention in a subsequent trial. Formal evaluations were completed by stakeholders following each SAG meeting. Results: Throughout the first (developmental) stage of this two-stage study, lay and professional stakeholders participated or were actively involved in activities that provided data to inform the research intervention. Lay stakeholders identified the need for and contributed to the design of a patient-held tool, strongly influenced the detailed design and content of the research intervention and outcome questionnaire, thus making a major contribution to the trial design. Conclusion: Stakeholders, including teenagers, can be actively involved in designing a research intervention and impact significantly on study outcomes

The mechanism of formation, structure and physiological relevance of covalent hemoglobin attachment to the erythrocyte membrane

Covalent hemoglobin binding to membranes leads to band 3 (AE1) clustering and the removal of erythrocytes from the circulation; it is also implicated in blood storage lesions. Damaged hemoglobin, with the heme being in a redox and oxygen-binding inactive hemichrome form, has been implicated as the binding species. However, previous studies used strong non-physiological oxidants. In vivo hemoglobin is constantly being oxidised to methemoglobin (ferric), with around 1% of hemoglobin being in this form at any one time. In this study we tested the ability of the natural oxidised form of hemoglobin (methemoglobin) in the presence or absence of the physiological oxidant hydrogen peroxide to initiate membrane binding. The higher the oxidation state of hemoglobin (from Fe(III) to Fe(V)) the more binding was observed, with approximately 50% of this binding requiring reactive sulphydryl groups. The hemoglobin bound was in a high molecular weight complex containing spectrin, ankyrin and band 4.2, which are common to one of the cytoskeletal nodes. Unusually, we showed that hemoglobin bound in this way was redox active and capable of ligand binding. It can initiate lipid peroxidation showing the potential to cause cell damage. In vivo oxidative stress studies using extreme endurance exercise challenges showed an increase in hemoglobin membrane binding, especially in older cells with lower levels of antioxidant enzymes. These are then targeted for destruction. We propose a model where mild oxidative stress initiates the binding of redox active hemoglobin to the membrane. The maximum lifetime of the erythrocyte is thus governed by the redox activity of the cell; from the moment of its release into the circulation the timer is set

Identification and Characterization of the Host Protein DNAJC14 as a Broadly Active Flavivirus Replication Modulator

Viruses in the Flavivirus genus of the Flaviviridae family are arthropod-transmitted and contribute to staggering numbers of human infections and significant deaths annually across the globe. To identify cellular factors with antiviral activity against flaviviruses, we screened a cDNA library using an iterative approach. We identified a mammalian Hsp40 chaperone protein (DNAJC14) that when overexpressed was able to mediate protection from yellow fever virus (YFV)-induced cell death. Further studies revealed that DNAJC14 inhibits YFV at the step of viral RNA replication. Since replication of bovine viral diarrhea virus (BVDV), a member of the related Pestivirus genus, is also known to be modulated by DNAJC14, we tested the effect of this host factor on diverse Flaviviridae family members. Flaviviruses, including the pathogenic Asibi strain of YFV, Kunjin, and tick-borne Langat virus, as well as a Hepacivirus, hepatitis C virus (HCV), all were inhibited by overexpression of DNAJC14. Mutagenesis showed that both the J-domain and the C-terminal domain, which mediates self-interaction, are required for anti-YFV activity. We found that DNAJC14 does not block YFV nor HCV NS2-3 cleavage, and using non-inhibitory mutants demonstrate that DNAJC14 is recruited to YFV replication complexes. Immunofluorescence analysis demonstrated that endogenous DNAJC14 rearranges during infection and is found in replication complexes identified by dsRNA staining. Interestingly, silencing of endogenous DNAJC14 results in impaired YFV replication suggesting a requirement for DNAJC14 in YFV replication complex assembly. Finally, the antiviral activity of overexpressed DNAJC14 occurs in a time- and dose-dependent manner. DNAJC14 overexpression may disrupt the proper stoichiometry resulting in inhibition, which can be overcome upon restoration of the optimal ratios due to the accumulation of viral nonstructural proteins. Our findings, together with previously published work, suggest that the members of the Flaviviridae family have evolved in unique and important ways to interact with this host Hsp40 chaperone molecule

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Censors and society: the Roman censorship, 443 - 21 BC

The censorship was one of the Roman Republic's most significant magistracies. The range and importance of their duties – the census, the lectio senatus and recognitio equitum, letting public contracts and initiating public works, and the ceremony of the lustrum – meant that the office had a profound impact on Roman society. There is much modern scholarship on the censorship. But some of the arguments and conclusions put forward by earlier scholars, while valuable, need to be updated and certain misconceptions corrected. In particular, what is required is a greater focus on placing the censorship in its political and social context, into the political culture of the Roman Republic, in order to properly analyse the office, its wider function(s), and its influence on Roman society. At the same time, a careful consideration of what precisely the censors' duties involved and how each pair of censors carried these out is necessary. The present work hopes to address both aspects of this important magistracy. To that end, this thesis is divided into seven chapters. Five of which deal with the censors' individual responsibilities. Chapter 1 is a diachronic survey of the censorship across the whole period of its existence. It aims to highlight the development of the office over time and to ground the subsequent discussion of the magistracy in its proper chronological context. Chapter 2 highlights the infrastructure – assistants, schedule, records, headquarters etc – through which the censors were able to carry out their tasks. Chapter 3 is a study of the censors' most important task, the taking of the census, and its importance for the Roman community. Chapter 4 looks at the censors as guardians of the mos maiorum, and the activities through which this role was expressed. Chapter 5 investigates the censors' responsibility for letting public contracts of various kinds, and the impact this had on the Roman state and its economy. Chapter 6 focuses in more detail on the most significant and costly element of the censors' contracting duties – public works. It attempts to assess what contribution the censors made to the ever-changing face of the city of Rome, as compared to the other magistrates. Finally, Chapter 7 considers the lustrum, the sacred rite which closed each pair of censors' term in office. It asks both what the ceremony involved, and what its meaning and significance for the community might have been