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BACKGROUND: Ibrutinib is an irreversible inhibitor of Burton's tyrosine kinase (BTK) in the B-cell receptor (BCR) signaling cascade and is a practice changing treatment for chronic lymphocytic leukemia (CLL) and other B-cell malignancies. Ibrutinib also inhibits Interleukin-2 Inducible Kinase (ITK) in T-cells and has demonstrated immunomodulatory effects. Recently, cases of opportunistic infections (OI) have been reported during ibrutinib treatment including pneumocystis jirovecii pneumonia (PJP), cryptococcus, and fusarium. To date there are no reports on OI in large unselected cohorts of patients taking ibrutinib. We conducted a single-institution retrospective study to determine the incidence and type of OI during ibrutinib treatment as well as outcomes and characteristics associated with risk. METHODS: We reviewed medical records of all patients treated with ibrutinib at the Ohio State University between June 1st 2010 and March 31st 2016. Patients who received ibrutinib for graft versus host disease were excluded. All charts were initially reviewed by one of the investigators and patients with OI were independently reviewed by a second investigator. Baseline patient and disease characteristics were captured at time of starting ibrutinib. All OI occurring after the first dose of ibrutinib were recorded. Onset of OI was considered as the time of first presentation for a complaint related to OI. Time to OI was calculated from the date of starting ibrutinib until the onset of OI or censored at the last assessment date, discontinuation of ibrutinib, or death prior to OI as competing risks. The cumulative incidence of OI was estimated and the Fine and Gray regression models were used to examine the association between patient characteristics and risk of OI. Covariates with significance level of p RESULTS: The cohort included 566 patients. Median age was 65 (range 23-89) and 70.1% (397/566) were men. The majority of patients had CLL (73.7%, 417/566). Other diagnoses included mantle cell lymphoma (9.9%, 56/566), indolent B-cell malignancies (8.1%, 46/566; 11 Waldenström's Macroglobulinemia, 13 Hairy Cell Leukemia, 15 Follicular Lymphoma, 6 Marginal Zone Lymphoma, and 1 Prolymphocytic Leukemia), and aggressive lymphoma (8.3%, 47/566; 35 diffuse large B-cell or transformed lymphoma and 12 Richter's syndrome). Median number of prior treatments was 3 (range 0-18) and 6.5% (37/566) of patients were treatment naïve. Ibrutinib was prescribed on clinical trial for 80.9% (458/566) of patients with the rest receiving it as standard of care. A second agent was given with ibrutinib in 30.9% (175/566) of cases and was most often a monoclonal antibody (81.7%, 143/175). Use of antiviral prophylaxis was common (78.6%, 445/566) with fewer patients receiving PJP (44.9%, 254/566) or fungal (11.5%, 65/566) prophylaxis. The most utilized prophylactic antifungal agent was fluconazole (70.8%, 46/65). Total ibrutinib exposure for the cohort was 1,225 person-years with a median exposure of 1.98 (range 0.008-6.40) years. Median duration of follow-up was 2.69 (range 0.03-6.40) years. Twenty-three of 566 (4.1%) patients developed an OI at a median of 0.39 (range 0.03-4.33) years after starting ibrutinib. The cumulative incidence of OI was 2.3% (95% CI: 1.3-3.8%) at 0.5 years and increased to 4.7% (95% CI: 3.0-7.0-%) at 5 years. Types of OI and outcomes are detailed in Table 1. Median survival of the entire cohort was not reached. Among 23 OI patients, the median survival after infection was 1.39 years. Univariable analysis revealed ≥3 prior treatments (HR 2.61), diabetes (HR 3.03), pulmonary disease (HR 2.81), chronic kidney disease (HR 2.56), and liver disease (HR 6.42) were associated with an increased risk for OI (p CONCLUSIONS: The cumulative incidence of OI during ibrutinib treatment was low (4.7% at 5 years) and the most common type was invasive fungal (61%) with no PJP cases. Three or greater prior treatments, diabetes, and liver disease were independently associated with risk for OI. Disclosures Byrd: Janssen: Research Funding; The Ohio State University: Patents & Royalties: OSU-2S; Genentech: Research Funding; Acerta Pharma: Research Funding; Pharmacyclics: Research Funding.

We analyze definitions used by researchers about a single concept: Sovereign Wealth Funds (SWF). It is still a matter of recent controversy and debate. We place these definitions into one of eleven categories. The results show full agreement (what we have called ‘the core’) for just two characteristics: SWFs are owned by governments and they are investment funds. Beyond the core, there are three layers commanding general consensus: SWFs are (1) international investors; (2) without explicit pension liabilities; (3) determined by the source of funding. But the debate remains open. The dynamic nature of SWFs, morphing institutions in a continuous evolution led us to conclude that there is no definition capturing the essence of these "new" instruments of state intervention.

No longer do the highest economic growth rates belong exclusively to the BRICS countries. Lesser known economies, the so-called frontier markets such as Nigeria and Vietnam, are key players in global economic growth and are expected to continue to be so for several decades. These states base their economic growth on the combination of low labour costs and abundant natural resources. In the past, frontier markets were characterised by instability, restricted market accessibility and low liquidity. Nowadays, their governments are opting to create sovereign wealth funds and tech hubs in order to avoid excessive commodity dependence and guarantee sustainable growth over time. Spain could take advantage of the opportunity that frontier markets represent, just as it once did with the Latin American market.

Brief description of ten economic trends shaping the global economy in the medium-long term.

Since the early 1960s, Colombia has suffered the consequences of armed conflict. He has left behind the destruction of much of the endowments of human and physical capital of the country. In this work, and from a perspective that has not received the same attention from researchers, we evaluated the relationship that has existed between the violence of the three main guerrilla groups who are operating in the country, (FARC, ELN and AUC), and the economic growth experienced by the thirty-two departments and the capital district that make up the State of Colombia. To do this, we build an index of violence for each of the guerrillas and develop a growth accounting exercise at the departmental level. From the pooling of the two exercises, we find thatthe average of the total factor productivity of the departments that suffered more guerrillera violence, has been lower than those that suffered lesser extent this.