The new resilience of emerging and developing countries: systemic interlocking, currency swaps and geoeconomics

The vulnerability/resilience nexus that defined the interaction between advanced and developing economies in the post-WWII era is undergoing a fundamental transformation. Yet, most of the debate in the current literature is focusing on the structural constraints faced by the Emerging and Developing Countries (EDCs) and the lack of changes in the formal structures of global economic governance. This paper challenges this literature and its conclusions by focusing on the new conditions of systemic interlocking between advanced and emerging economies, and by analysing how large EDCs have built and are strengthening their economic resilience. We find that a significant redistribution of ‘policy space’ between advanced and emerging economies have taken place in the global economy. We also find that a number of seemingly technical currency swap agreements among EDCs have set in motion changes in the very structure of global trade and finance. These developments do not signify the end of EDCs’ vulnerability towards advanced economies. They signify however that the economic and geoeconomic implications of this vulnerability have changed in ways that constrain the options available to advanced economies and pose new challenges for the post-WWII economic order

A palladium-catalyzed domino reaction to access 3-amino-2H-indazoles from hydrazines and 2-halobenzonitriles

The development of a novel selective synthesis of 3-amino-2H-indazoles from readily available 2-halobenzonitriles is presented. The reaction proceeds through a domino reaction sequence, consisting of a regioselective palladium-catalyzed coupling of monosubstituted hydrazines with 2-halobenzonitriles, followed by an intramolecular hydroamination through a 5-exo-dig cyclization and subsequent isomerization to directly afford a wide variety of substituted 2H-indazole analogues in good to excellent yields

Bleeding peptic ulcer: characteristics and outcomes in Newcastle, NSW

Background: Peptic ulcer disease risk factors have changed, as has the impact of treatment on morbidity and mortality. Recent data on clinical presentation and outcome are sparse in Australia. Aim: To determine the characteristics and outcome of patients presenting with a bleeding peptic ulcer to a tertiary referral centre. Methods: We evaluated patients diagnosed with peptic ulcer bleeding between 2004 and 2008 at a tertiary referral hospital. Variables assessed included demographic data, comorbidities, medication use and Rockall score. Outcomes of interest were the time to endoscopy, peptic ulcer treatment, transfusion requirements, urgent surgery and survival. Results: Peptic ulcers were confirmed in 265 patients (55% male), of which 145 were gastric and 119 duodenal.The mean age was 71 years. On admission 38% of patients had haemodynamic instability and 92% had one or more comorbidity. Consumption of ulcerogenic medications at the time of admission was frequent (non-steroidal anti-inflammatory drugs (NSAIDs) 22%, aspirin 41%, clopidogrel or warfarin 10%) and proton pump inhibitors infrequent (15%). A gastroenterologist managed all patients according to their usual practice. Only a minority of patients received over three units of packed red cells. Few patients were referred for surgery (3%) or died (3%), but both events were significantly higher for the duodenal ulcer group. Conclusion: The characteristics and outcomes in patients with peptic ulcer bleeding have changed. Peptic ulcer disease remains a public health problem with modifiable risk factors, such as Helicobacter pylori infection and NSAIDs, which should be targeted to reduce the burden of illness

A case-control study of childhood trauma in the development of irritable bowel syndrome

Background: The etiology of irritable bowel syndrome (IBS) is not been fully elucidated, but childhood trauma may disturb the brain–gut axis and therefore be important. Thus, we conducted a family based case–control study of IBS cases and their relatives with the aims to (i) determine the frequency of childhood trauma among IBS cases and controls as well as their relatives, and (ii) assess childhood trauma among IBS cases with affected relatives (familial IBS). Methods: Outpatients with IBS, matched controls, and their first-degree relatives completed a self-report version of Bremner' Early Trauma Inventory. Percent of cases and controls with a family history were compared and odds ratios were computed using chi-squared test; recurrence risks to relatives were computed using logistic regression and generalized estimating equations. Key Results: Data were collected from 409 cases, 415 controls, 825 case relatives, and 921 control relatives. IBS cases had a median age of 50 and 83% were women. Of IBS cases, 74% had experienced any general trauma compared to 59% among controls, yielding an odds ratio of 1.56 (95% CI: 1.13–2.15, p < 0.008). There were no statistical differences between IBS relatives and control relatives with regards to lifetime trauma. Conclusions & Inferences: IBS is associated with childhood trauma, and these traumas often occur prior to onset of IBS symptoms. This provides further insight into how traumatic childhood events are associated with development of adult IBS

Short- and long-term outcomes for patients with variceal haemorrhage in a tertiary hospital

Background/Aim: To determine short- and long-term outcomes among a cohort of patients with variceal haemorrhage at a tertiary referral centre, and to determine the predictive value of the model for end-stage liver disease (MELD) score for mortality in these patients. Methods: Prospective database hospital audit that captured patients who presented with or were transferred with variceal haemorrhage between 2004 and 2008, and a retrospective review of long-term outcomes. Patients who presented to or were transferred to John Hunter Hospital, a tertiary referral hospital, with confirmed variceal bleeding were included. The main outcome measures were in-hospital, 6 weeks and end-of-audit mortality. We also recorded cause, location and degree of planning surrounding the deaths in this patient group. We analysed the MELD score for patients with complete survival data. Results: We recorded 93 episodes of variceal haemorrhage from 78 unique patients during the initial study period. The in-hospital mortality, 6 weeks mortality and end-of-audit mortality were 2.6, 9.0 and 59, respectively, and median survival time was 3.2 years (95% confidence interval 0.0, 6.1). The most frequent cause of death was related to complications of end-stage liver disease at 74%, followed by variceal bleeding (19%) and unknown (6%). A Cox proportional hazard model showed that the risk of mortality is increased by 1.06 (1.01–1.11) for each unit increase in MELD score. Conclusions: Short-term outcomes for patients with variceal bleeding continue to improve, but long-term prognosis remains guarded and should prompt further emphasis on advanced care planning to optimise patient care

Rational design of highly potent, selective, and bioavailable SGK1 protein kinase inhibitors for the treatment of osteoarthritis

The serine/threonine kinase SGK1 is an activator of the β-catenin pathway and a powerful stimulator of cartilage degradation that is found to be upregulated under genomic control in diseased osteoarthritic cartilage. Today, no oral disease-modifying treatments are available and chronic treatment in this indication sets high requirements for the drug selectivity, pharmacokinetic, and safety profile. We describe the identification of a highly selective druglike 1(H)-pyrazolo[3,4-d]pyrimidine SGK1 inhibitor 17a that matches both safety and pharmacokinetic requirements for oral dosing. Rational compound design was facilitated by a novel hSGK1 co-crystal structure, and multiple ligand-based computer models were applied to guide the chemical optimization of the compound ADMET and selectivity profiles. Compounds were selected for subchronic proof of mechanism studies in the mouse femoral head cartilage explant model, and compound 17a emerged as a druglike SGK1 inhibitor, with a highly optimized profile suitable for oral dosing as a novel, potentially disease-modifying agent for osteoarthritis