Essays in information design

A relatively recent strand of economic literature studies the design of information. Classical economic models analyze optimal decision-making (e.g., profit-maximizing firms choosing prices or quantities) taking a particular economic environment as given. Such an environment, and in particular the knowledge of its characteristics by decision-makers, is usually endogenous in the real world. The information that decision-makers process plays a role in determining their decisions. Therefore, it is fundamental to understand what is the content of the information available to decision-makers and why

Reconstruction of upper limb soft-tissue defects after sarcoma resection with free flaps: A systematic review

BACKGROUND AND OBJECTIVES: Upper limb preservation after soft tissue sarcoma (STS) surgical excision is now the accepted gold standard and it often requires reconstruction with free flaps. The purpose of this review is to summarize current literature on upper limb reconstruction with free flaps after STS resection.METHODS: A systematic review was performed in July 2019 in PubMed and MedLine Ovid databases according to the PRISMA guidelines.RESULTS: A total of 17 studies were included in the final analysis, with 132 patients. The most common diagnosis was Malignant Fibrous Histiocytoma. The most frequent timing of flap coverage was immediate. The success rate was almost always 100%. The length of follow-up was reported in 11 studies with a range of 2-187 months. The most commonly reported patient-centered outcome was the MSTS Score. Based on the evidence of the literature collected, we divided the upper limb into four parts (shoulder, elbow and arm, forearm and wrist, and hand) and described the most common and functional free flaps used for reconstruction after STS resection.CONCLUSIONS: Free flaps in the treatment of STS of the upper extremity have a good overall outcome, with a low postoperative complication rate. A wide array of free flaps is available for reconstruction, and the choice of flap is based on defect size, types of tissue required, postoperative functional goal, and surgeon preference. A greater degree of standardization is needed in the reporting of patient-centered outcomes to facilitate future comparative studies

Can knowledge of germline markers of toxicity optimize dosing and efficacy of cancer therapy?

The systemic treatment of cancer with traditional cytotoxic chemotherapeutic agents and more targeted agents is often complicated by the onset of adverse drug reactions. Pharmacogenetic prediction of adverse drug reactions might have consequences for dosing and efficacy. This review discusses relevant examples where the germline variant–toxicity relationship has been validated as an initial step in developing clinically useful pharmacogenetic markers and provides examples where germline variants have influenced dosing strategies and/or survival or other outcomes of efficacy. This review will also provide insight into the reasons why more pharmacogenetic markers have not been routinely integrated into clinical practice

The influence of UGT polymorphisms as biomarkers in solid organ transplantation

In solid organ transplant patients, it is important to maintain a fine balance between preventing rejection and reducing adverse effects. Several immunosuppressive agents such tacrolimus, cyclosporine, sirolimus and everolimus require therapeutic drug monitoring. The study of germline variation of the genome has opened novel opportunities to individualize therapy. Among the currently available immunosuppressive agents, cyclosporine, tacrolimus and mycophenolic acid are in vitro substrates of the UGT1A and 2B families of glucuronidation enzymes. Mycophenolic acid, either given as mycophenolate mofetil or mycophenolate sodium, is the most frequently used antiproliferative immunosuppressant. Mycophenolic acid is a prodrug which is rapidly de-esterified in the gut wall, blood, liver and tissue to the active moiety, mycophenolic acid (MPA). MPA undergoes significant hepatic metabolism to several metabolites. The 7-hydroxyglucuronide MPA is the major metabolite and is inactive. This paper reviews the current status of the genetic associations between germline UGT variants and the pharmacokinetics and pharmacodynamics of mycophenolic acid. Our conclusive assessment of the studies conducted so far is that these germline markers are not ready to be used in the clinic to individualize mycophenolic acid dosing and improve outcome. Novel approaches are required to identify new genetic determinants of outcomes in transplantation

Implications of genome-wide association studies in cancer therapeutics

Genome wide association studies (GWAS) provide an agnostic approach to identifying potential genetic variants associated with disease susceptibility, prognosis of survival and/or predictive of drug response. Although these techniques are costly and interpretation of study results is challenging, they do allow for a more unbiased interrogation of the entire genome, resulting in the discovery of novel genes and understanding of novel biological associations. This review will focus on the implications of GWAS in cancer therapy, in particular germ-line mutations, including findings from major GWAS which have identified predictive genetic loci for clinical outcome and/or toxicity. Lessons and challenges in cancer GWAS are also discussed, including the need for functional analysis and replication, as well as future perspectives for biological and clinical utility. Given the large heterogeneity in response to cancer therapeutics, novel methods of identifying mechanisms and biology of variable drug response and ultimately treatment individualization will be indispensable

Unidirectional endobronchial valves for management of persistent air-leaks. Results of a multicenter study

Background: To evaluate the efficacy of Endo-Bronchial Valves in the management of persistent air-leaks (PALs) and the procedural cost. Methods: It was a retrospective multicenter study including consecutive patients with PALs for alveolar pleural fistula (APF) undergoing valve treatment. We assessed the efficacy and the cost of the procedure. Results: Seventy-four patients with persistent air leaks due to various etiologies were included in the analysis. In all cases the air leaks were severe and refractory to standard treatments. Sixty-seven (91%) patients underwent valve treatment obtaining a complete resolution of air-leaks in 59 (88%) patients; a reduction of air-leaks in 6 (9%); and no benefits in 2 (3%). The comparison of data before and after valve treatment showed a significant reduction of air-leak duration (16.2±8.8 versus 5.0±1.7 days; P<0.0001); chest tube removal (16.2±8.8 versus 7.3±2.7 days; P<0.0001); and length of hospital stay (LOS) (16.2±8.8 versus 9.7±2.8 days; P=0.004). Seven patients not undergoing valve treatment underwent pneumo-peritoneum with pleurodesis (n=6) or only pleurodesis (n=1). In only 1 (14%) patient, the chest drainage was removed 23 days later while the remaining 6 (86%) were discharged with a domiciliary chest drainage removed after 157±41 days. No significant difference was found in health cost before and after endobronchial valve (EBV) implant (P=0.3). Conclusions: Valve treatment for persistent air leaks is an effective procedure. The reduction of hospitalization costs related to early resolution of air-leaks could overcome the procedural cost

Discovery and functional assessment of gene variants in the vascular endothelial growth factor pathway

Angiogenesis is a host-mediated mechanism in disease pathophysiology. The vascular endothelial growth factor (VEGF) pathway is a major determinant of angiogenesis, and a comprehensive annotation of the functional variation in this pathway is essential to understand the genetic basis of angiogenesis-related diseases. We assessed the allelic heterogeneity of gene expression, population specificity of cis expression quantitative trait loci (eQTLs), and eQTL function in luciferase assays in CEU and Yoruba people of Ibadan, Nigeria (YRI) HapMap lymphoblastoid cell lines in 23 resequenced genes. Among 356 cis-eQTLs, 155 and 174 were unique to CEU and YRI, respectively, and 27 were shared between CEU and YRI. Two cis-eQTLs provided mechanistic evidence for two genome-wide association study findings. Five eQTLs were tested for function in luciferase assays and the effect of two KRAS variants was concordant with the eQTL effect. Two eQTLs found in each of PRKCE, PIK3C2A, and MAP2K6 could predict 44%, 37%, and 45% of the variance in gene expression, respectively. This is the first analysis focusing on the pattern of functional genetic variation of the VEGF pathway genes in CEU and YRI populations and providing mechanistic evidence for genetic association studies of diseases for which angiogenesis plays a pathophysiologic role. (C) 2013 Wiley Periodicals, Inc

Pharmacodynamic genes do not influence risk of neutropenia in cancer patients treated with moderately high-dose irinotecan

A recent study found that variation in camptothecin pharmacodynamic genes (TOP1, PARP1, TDP1 and XRCC1) correlated with efficacy and risk of neutropenia in irinotecan-treated cancer patients (median dose: 180 mg/m2), which suggests that these genes might predict outcomes to irinotecan-based therapies. The present study was conducted to evaluate previous gene associations using an independent sample of patients receiving irinotecan