19 research outputs found
A framework for vulnerability analysis in sustainability science
Global environmental change and sustainability science increasingly recognize the need to address the consequences of changes taking place in the structure and function of the biosphere. These changes raise questions such as: Who and what are vulnerable to the multiple environmental changes underway, and where? Research demonstrates that vulnerability is registered not by exposure to hazards (perturbations and stresses) alone but also resides in the sensitivity and resilience of the system experiencing such hazards. This recognition requires revisions and enlargements in the basic design of vulnerability assessments, including the capacity to treat coupled human–environment systems and those linkages within and without the systems that affect their vulnerability. A vulnerability framework for the assessment of coupled human–environment systems is presented
Brain development in children with new onset epilepsy: A prospective controlled cohort investigation
The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease
The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm probability (MAP), derived from 2 serum biomarkers, measures damage to crypts in the gastrointestinal tract during graft-versus-host disease (GVHD). We hypothesized that changes in MAP after treatment could validate it as a response biomarker. We prospectively collected serum samples and clinical stages of acute GVHD from 615 patients receiving hematopoietic cell transplantation in 20 centers at initiation of first-line systemic treatment and 4 weeks later. We computed MAPs and clinical responses and compared their abilities to predict 6-month nonrelapse mortality (NRM) in the validation cohort (n = 367). After 4 weeks of treatment, MAPs predicted NRM better than the change in clinical symptoms in all patients and identified 2 groups with significantly different NRM in both clinical responders (40% vs 12%, P < .0001) and nonresponders (65% vs 25%, P < .0001). MAPs successfully reclassified patients for NRM risk within every clinical grade of acute GVHD after 4 weeks of treatment. At the beginning of treatment, patients with a low MAP that rose above the threshold of 0.290 after 4 weeks of treatment had a significant increase in NRM, whereas patients with a high MAP at onset that fell below that threshold after treatment had a striking decrease in NRM that translated into clear differences in overall survival. We conclude that a MAP measured before and after treatment of acute GVHD is a response biomarker that predicts long-term outcomes more accurately than change in clinical symptoms. MAPs have the potential to guide therapy for acute GVHD and may function as a useful end point in clinical trials