Self-love and sociability: the ‘rudiments of commerce’ in the state of nature

Istvan Hont’s classic work on the theoretical links between the seventeenth-century natural jurists Hugo Grotius and Samuel Pufendorf and the eighteenth-century Scottish political economists remains a popular trope among intellectual and economic historians of various stamps. Despite this, a common criticism levelled at Hont remains his relative lack of engagement with the relationship between religion and economics in the early modern period. This paper challenges this aspect of Hont’s narrative by drawing attention to an alternative, albeit complementary, assessment of the natural jurisprudential heritage of eighteenth-century British political economy. Specifically, the article attempts to map on to Hont’s thesis the Christian Stoic interpretation of Grotius and Pufendorf which has gained greater currency in recent years. In doing so, the paper argues that Grotius and Pufendorf’s contributions to the ‘unsocial sociability’ debate do not necessarily lead directly to the Scottish school of political economists, as is commonly assumed. Instead, it contends that a reconsideration of Grotius and Pufendorf as neo-Stoic theorists, particularly via scrutiny of their respective adaptations of the traditional Stoic theory of oikeiosis, steers us towards the heart of the early English ‘clerical’ Enlightenment

Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway

The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient’s life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn’s disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFβ1 reduces production of proinflammatory cytokines, including TNFα, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses. PAPERCLIP

(Dis)located Olympic patriots: sporting connections, administrative communications and imperial ether in interwar New Zealand

During the interwar period (1919-1939) protagonists of the early New Zealand Olympic Committee NZOC worked to renegotiate and improve the country's international sporting participation and involvement in the International Olympic Committee IOC. To this end, NZOC effectively used its locally based administrators and well-placed expatriates in Britain to variously assert the organisation's nascent autonomy, independence and political power, progress Antipodean athlete's causes, and, counter any potential doubt about the nation's peripheral position in imperial sporting dialogues. Adding to the corpus of scholarship on New Zealand's ties and tribulations with imperial Britain (in and beyond sport) (e.g. Beilharz and Cox 2007; Belich 2001, 2007; Coombes 2006; MacLean 2010; Phillips 1984, 1987; Ryan 2004, 2005, 2007), in this paper I examine how the political actions and strategic location of three key NZOC agents (specifically, administrator Harry Amos and expatriates Arthur Porritt and Jack Lovelock) worked in their own particular ways to assert the position of the organisation within the global Olympic fraternity. I argue that the efforts of Amos, Porritt and Lovelock also concomitantly served to remind Commonwealth sporting colleagues (namely Britain and Australia) that New Zealand could not be characterised as, or relegated to being, a distal, subdued, or subservient colonial sporting partner. Subsequently I contend that NZOC's development during the interwar period, and particularly the utility of expatriate agents, can be contextualised against historiographical shifts that encourage us to rethink, reimagine, and rework narratives of empire, colonisation, national identity, commonwealth and belonging

Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-Regulated Pathway

The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient’s life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn’s disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFb1 reduces production of proinflammatory cytokines, including TNFa, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses

Bone mineral density, body mass index and cigarette smoking among Iranian women: implications for prevention

BACKGROUND: While risk factors of osteoporosis in Western populations have been extensively documented, such a profile has not been well studied in Caucasians of non-European origin. This study was designed to estimate the modifiable distribution and determinants of bone mineral density (BMD) among Iranian women in Australia. METHODS: Ninety women aged 35 years and older completed a questionnaire on socio-demographic and lifestyle factors. BMD was measured at the lumbar spine (LS) and femoral neck (FN) using DXA (GE Lunar, WI, USA), and was expressed in g/cm(2 )as well as T-score. RESULTS: In multiple regression analysis, advancing age, lower body mass index (BMI), and smoking were independently associated with LS and FN BMD, with the 3 factors collectively accounting for 30% and 38% variance of LS and FN BMD, respectively. LS and FN BMD in smokers was 8% lower than that in non-smokers. Further analysis of interaction between BMI and smoking revealed that the effect of smoking was only observed in the obese group (p = 0.029 for LSBMD and p = 0.007 for FNBMD), but not in the overweight and normal groups. Using T-scores from two bone sites the prevalence of osteoporosis (T-scores ≤ -2.5) was 3.8% and 26.3% in pre-and post-menopausal women, respectively. Among current smokers, the prevalence was higher (31.3%) than that among ex-smokers (28.6%) and non-smokers (7.5%). CONCLUSION: These data, for the first time, indicate that apart from advancing age and lower body mass index, cigarette smoking is an important modifiable determinant of bone mineral density in these Caucasians of non-European origin

Libertà politica e virtù civile. Significati e percorsi del repubblicanesimo classico

Tra storia e filosofia della politica, il volume analizza il ruolo delle idee politiche repubblicane nella formazione delle repubbliche moderne e propone spunti di riflessione sul significato del repubblicanesimo per il futuro delle democrazie.- Indice #5- Introduzione, Maurizio Viroli #9- Il repubblicanesimo di Machiavelli, Maurizio Viroli #19- Declino e durata delle repubbliche e delle idee repubblicane nell’Italia del Cinquecento, Elena Fasano Guarini #49- Patriottismo e riforma politica, Rosario Villari #113- Le idee repubblicane e la Rivoluzione inglese, Blair Worden #127- Cittadini, clienti e creditori: la repubblica come critica del mutamento storico, John G. A. Pocock #151- Le trasformazioni del repubblicanesimo classico nella Francia del Settecento, Keith Michael Baker #167- Virtù e Vittorianesimo. I valori repubblicani del liberalismo inglese, 1860/1890, Eugenio F. Biagini #195- Tra virtù e libertà: percorsi dell’idea repubblicana nella Francia ottocentesca (1830/1875), Mirella Larizza #217- La tradizione repubblicana nell’Italia dell’Ottocento e del Novecento, Massimo L. Salvadori #245- Considerazioni sulla libertà repubblicana, Quentin Skinner #267- “Moderno repubblicanesimo”? La promessa della società civile, Benjamin R. Barber #279- La moderna repubblica: mito o realtà?, Jean Fabien Spitz #30

Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials

<p>Abstract</p> <p>Background</p> <p>Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome.</p> <p>Methods</p> <p>We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the <it>New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine</it>, and <it>BMJ </it>as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes.</p> <p>Discussion</p> <p>A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials.</p

Cost effectiveness of first-line oral therapies for pulmonary arterial hypertension: A modelling study

Background: In recent years, a significant number of costly oral therapies have become available for the treatment of pulmonary arterial hypertension (PAH). Funding decisions for these therapies requires weighing up their effectiveness and costs. Objective: The aim of this study was to assess the cost effectiveness of monotherapy with oral PAH-specific therapies versus supportive care as initial therapy for patients with functional class (FC) II and III PAH in Canada. Methods: A cost-utility analysis, from the perspective of a healthcare system and based on a Markov model, was designed to estimate the costs and quality-adjusted life-years (QALYs) associated with bosentan, ambrisentan, riociguat, tadalafil, sildenafil and supportive care for PAH in treatment-naïve patients. Separate analyses were conducted for cohorts of patients commencing therapy at FC II and III PAH. Transition probabilities, based on the relative risk of improving and worsening in FC with treatment versus placebo, were derived from a recent network meta-analysis. Utility values and costs were obtained from published data and clinical expert opinion. Extensive sensitivity analyses were conducted. Results: Analysis suggests that sildenafil is the most cost-effective therapy for PAH in patients with FC II or III. Sildenafil was both the least costly and most effective therapy, thereby dominating all other treatments. Tadalafil was also less costly and more effective than supportive care in FC II and III; however, sildenafil was dominant over tadalafil. Even given the uncertainty within the clinical inputs, the probabilistic sensitivity analysis showed that apart from sildenafil and tadalafil, the other PAH therapies had negligible probability of being the most cost effective. Conclusion: The results show that initiation of therapy with sildenafil is likely the most cost-effective strategy in PAH patients with either FC II or III disease.This research was supported by funds from the Canadian Agency for Drugs and Technologies in Health (CADTH)

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Background: High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods: We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK-based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. Findings: Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants' systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p&lt;0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups. Interpretation: Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultra-acute prehospital setting

β3-adrenergic receptor gene, body mass index, bone mineral density and fracture risk in elderly men and women: the Dubbo Osteoporosis Epidemiology Study (DOES)

BACKGROUND: Recent studies have suggested that the Arg allele of β3-adrenergic receptor (ADRB3) gene is associated with body mass index (BMI), which is an important predictor of bone mineral density (BMD) and fracture risk. However, whether the ADRB3 gene polymorphism is associated with fracture risk has not been investigated. The aim of study was to examine the inter-relationships between ADRB3 gene polymorphisms, BMI, BMD and fracture risk in elderly Caucasians. METHODS: Genotypes of the ADRB3 gene were determined in 265 men and 446 women aged 60+ in 1989 at entry into the study, whose BMD were measured by DXA (GE Lunar, WI USA) at baseline. During the follow-up period (between 1989 and 2004), fractures were ascertained by reviewing radiography reports and personal interviews. RESULTS: The allelic frequencies of the Trp and the Arg alleles were 0.925 and 0.075 respectively, and the relative frequencies of genotypes Trp/Trp, Trp/Arg and Arg/Arg 0.857, 0.138 and 0.006 respectively. There was no significant association between BMI and ADRB3 genotypes (p = 0.10 in women and p = 0.68 in men). There was also no significant association between ADRB3 genotypes and lumbar spine or femoral neck BMD in either men and women. Furthermore, there were no significant association between ADRB3 genotypes and fracture risk in both women and men, either before or after adjusting for and, BMD and BMI. CONCLUSION: The present data suggested that in Caucasian population the contribution of ADRB3 genotypes to the prediction of BMI, BMD and fracture risk is limited