The Novelty Paradox & Bias for Normal Science: Evidence from Randomized Medical Grant Proposal Evaluations

Central to any innovation process is the evaluation of proposed projects and allocation of resources. We investigate whether novel research projects, those deviating from existing research paradigms, are treated with a negative bias in expert evaluations. We analyze the results of a peer review process for medical research grant proposals at a leading medical research university, in which we recruited 142 expert university faculty members to evaluate 150 submissions, resulting in 2,130 randomly-assigned proposal-evaluator pair observations. Our results confirm a systematic penalty for novel proposals; a standard deviation increase in novelty drops the expected rank of a proposal by 4.5 percentile points. This discounting is robust to various controls for unobserved proposal quality and alternative explanations. Additional tests suggest information effects rather than strategic effects account for the novelty penalty. Only a minority of the novelty penalty could be related to perceptions of lesser feasibility of novel proposals

Colocation and Scientific Collaboration: Evidence from a Field Experiment

We present the results of a field experiment conducted within the Harvard Medical School system of hospitals and research centers to understand how colocation impacts the likelihood of scientific collaboration. We introduce exogenous colocation and face-to-face interactions for a random subset of biomedical researchers responding to an opportunity to apply for a research grant. While the overall baseline likelihood of any two researchers collaborating is small, we find that random colocation significantly increases the likelihood of pair-level co-application by almost 70%. The effect of exogenous colocation on subsequent collaboration was greater for previous coauthors, pairs including a woman, and pairs researching similar clinical areas. Our results suggest that matching between scientists may be subject to considerable frictions—even among those in relatively close geographic proximity and in the same organizational system. At the same time, even a brief and focused intervention facilitating face-to-face interactions can provide information that impacts the formation of scientific collaborations

Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade

Allogeneic hematopoietic stem cell transplantation (AHSCT) offers the best chance of cure for many patients with congenital and acquired hematologic diseases. Unfortunately, transplantation of alloreactive donor T cells which recognize and damage healthy patient tissues can result in Graft-versus-Host Disease (GvHD)1. One challenge to successful AHSCT is the prevention of GvHD without associated impairment of the beneficial effects of donor T cells, particularly immune reconstitution and prevention of relapse. GvHD can be prevented by non-specific depletion of donor T cells from stem cell grafts or by administration of pharmacological immunosuppression. Unfortunately these approaches increase infection and disease relapse2-4. An alternative strategy is to selectively deplete alloreactive donor T cells after allostimulation by recipient antigen presenting cells (APC) before transplant. Early clinical trials of these allodepletion strategies improved immune reconstitution after HLA-mismatched HSCT without excess GvHD5, 6. However, some allodepletion techniques require specialized recipient APC production6, 7and some approaches may have off-target effects including depletion of donor pathogen-specific T cells8and CD4 T regulatory cells9.One alternative approach is the inactivation of alloreactive donor T cells via induction of alloantigen-specific hyporesponsiveness. This is achieved by stimulating donor cells with recipient APC while providing blockade of CD28-mediated co-stimulation signals10.This "alloanergization" approach reduces alloreactivity by 1-2 logs while preserving pathogen- and tumor-associated antigen T cell responses in vitro11. The strategy has been successfully employed in 2 completed and 1 ongoing clinical pilot studies in which alloanergized donor T cells were infused during or after HLA-mismatched HSCT resulting in rapid immune reconstitution, few infections and less severe acute and chronic GvHD than historical control recipients of unmanipulated HLA-mismatched transplantation12. Here we describe our current protocol for the generation of peripheral blood mononuclear cells (PBMC) which have been alloanergized to HLA-mismatched unrelated stimulator PBMC. Alloanergization is achieved by allostimulation in the presence of monoclonal antibodies to the ligands B7.1 and B7.1 to block CD28-mediated costimulation. This technique does not require the production of specialized stimulator APC and is simple to perform, requiring only a single and relatively brief ex vivo incubation step. As such, the approach can be easily standardized for clinical use to generate donor T cells with reduced alloreactivity but retaining pathogen-specific immunity for adoptive transfer in the setting of AHSCT to improve immune reconstitution without excessive GvHD

Stepwise Distributed Open Innovation Contests for Software Development: Acceleration of Genome-Wide Association Analysis

Abstract Background: The association of differing genotypes with disease-related phenotypic traits offers great potential to both help identify new therapeutic targets and support stratification of patients who would gain the greatest benefit from specific drug classes. Development of low-cost genotyping and sequencing has made collecting large-scale genotyping data routine in population and therapeutic intervention studies. In addition, a range of new technologies is being used to capture numerous new and complex phenotypic descriptors. As a result, genotype and phenotype datasets have grown exponentially. Genome-wide association studies associate genotypes and phenotypes using methods such as logistic regression. As existing tools for association analysis limit the efficiency by which value can be extracted from increasing volumes of data, there is a pressing need for new software tools that can accelerate association analyses on large genotype-phenotype datasets. Results: Using open innovation (OI) and contest-based crowdsourcing, the logistic regression analysis in a leading, community-standard genetics software package (PLINK 1.07) was substantially accelerated. OI allowed us to do this in <6 months by providing rapid access to highly skilled programmers with specialized, difficult-to-find skill sets. Through a crowd-based contest a combination of computational, numeric, and algorithmic approaches was identified that accelerated the logistic regression in PLINK 1.07 by 18- to 45-fold. Combining contest-derived logistic regression code with coarse-grained parallelization, multithreading, and associated changes to data initialization code further developed through distributed innovation, we achieved an end-to-end speedup of 591-fold for a data set size of 6678 subjects by 645 863 variants, compared to PLINK 1.07's logistic regression. This represents a reduction in run time from 4.8 hours to 29 seconds. Accelerated logistic regression code developed in this project has been incorporated into the PLINK2 project. Conclusions: Using iterative competition-based OI, we have developed a new, faster implementation of logistic regression for genome-wide association studies analysis. We present lessons learned and recommendations on running a successful OI process for bioinformatics

Changing factors associated with parent activation after pediatric hematopoietic stem cell transplant

To identify factors associated with parent activation in parents of children undergoing pediatric hematopoietic stem cell transplant (HSCT) in the 6 months following HSCT, and to address if their association with parent activation changes over time

Factors Associated With Parental Activation in Pediatric Hematopoietic Stem Cell Transplant

Patient activation, the extension of self-efficacy into self-management, is an essential component of effective chronic care. In pediatric populations, caregiver activation is also needed for proper disease management. This study investigates the relationships between parental activation and other characteristics of parent–child dyads (N = 198) presenting for pediatric hematopoietic stem cell transplant. Parental activation concerning their child’s health was assessed using the Parent Patient Activation Measure (Parent-PAM), a modified version of the well-validated Patient Activation Measure (PAM). Using hierarchical linear regression and following the Belsky process model for determining parenting behaviors, a multivariate model was created for parental activation on behalf of their child that showed that the parent’s age, rating of their own general health, self-activation, and duration of the child’s illness were significantly related to Parent-PAM score. Our findings characterize a potentially distinct form of activation in a parent–child cohort preparing for a demanding clinical course

Engineering serendipity:When does knowledge sharing lead to knowledge production?

Research Summary: We investigate how knowledge similarity between two individuals is systematically related to the likelihood that a serendipitous encounter results in knowledge production. We conduct a field experiment at a medical research symposium, where we exogenously varied opportunities for face-to-face encounters among 15,817 scientist-pairs. Our data include direct observations of interaction patterns collected using sociometric badges, and detailed, longitudinal data of the scientists' postsymposium publication records over 6 years. We find that interacting scientists acquire more knowledge and coauthor 1.2 more papers when they share some overlapping interests, but cite each other's work between three and seven times less when they are from the same field. Our findings reveal both collaborative and competitive effects of knowledge similarity on knowledge production outcomes. Managerial Summary: Managers often try to stimulate innovation by encouraging serendipitous interactions between employees, for example by using office space redesigns, conferences and similar events. Are such interventions effective? This article proposes that an effective encounter depends on the degree of common knowledge shared by the individuals. We find that scientists who attend the same conference are more likely to learn from each other and collaborate effectively when they have some common interests, but may view each other competitively when they work in the same field. Hence, when designing opportunities for face-to-face interactions, managers should consider knowledge similarity as a criteria for fostering more productive exchanges.</p

Colocation and Scientific Collaboration: Evidence from a Field Experiment

We present the results of a field experiment conducted within the Harvard Medical School system of hospitals and research centers to understand how colocation impacts the likelihood of scientific collaboration. We introduce exogenous colocation and face-to-face interactions for a random subset of biomedical researchers responding to an opportunity to apply for a research grant. While the overall baseline likelihood of any two researchers collaborating is small, we find that random colocation significantly increases the likelihood of pair-level co-application by almost 70%. The effect of exogenous colocation on subsequent collaboration was greater for previous coauthors, pairs including a woman, and pairs researching similar clinical areas. Our results suggest that matching between scientists may be subject to considerable frictions—even among those in relatively close geographic proximity and in the same organizational system. At the same time, even a brief and focused intervention facilitating face-to-face interactions can provide information that impacts the formation of scientific collaborations