We introduce flash teams, a framework for dynamically assembling and managing paid experts from the crowd. Flash teams advance a vision of expert crowd work that accomplishes complex, interdependent goals such as engineering and design. These teams consist of sequences of linked modular tasks and handoffs that can be computationally managed. Interactive systems reason about and manipulate these teams' structures: for example, flash teams can be recombined to form larger organizations and authored automatically in response to a user's request. Flash teams can also hire more people elastically in reaction to task needs, and pipeline intermediate output to accelerate completion times. To enable flash teams, we present Foundry, an end-user authoring platform and runtime manager. Foundry allows users to author modular tasks, then manages teams through handoffs of intermediate work. We demonstrate that Foundry and flash teams enable crowdsourcing of a broad class of goals including design prototyping, course development, and film animation, in half the work time of traditional self-managed teams.

The objective of this study was to enhance the angiogenic capacity of endothelial cells (ECs) using nano-scale signaling cues from aligned nanofibrillar scaffolds in the setting of tissue ischemia. Thread-like nanofibrillar scaffolds with porous structure were fabricated from aligned-braided membranes generated under shear from liquid crystal collagen solution. Human ECs showed greater outgrowth from aligned scaffolds than from non-patterned scaffolds. Integrin α1 was in part responsible for the enhanced cellular outgrowth on aligned nanofibrillar scaffolds, as the effect was abrogated by integrin α1 inhibition. To test the efficacy of EC-seeded aligned nanofibrillar scaffolds in improving neovascularization in vivo, the ischemic limbs of mice were treated with: EC-seeded aligned nanofibrillar scaffold; EC-seeded non-patterned scaffold; ECs in saline; aligned nanofibrillar scaffold alone; or no treatment. After 14 days, laser Doppler blood spectroscopy demonstrated significant improvement in blood perfusion recovery when treated with EC-seeded aligned nanofibrillar scaffolds, in comparison to ECs in saline or no treatment. In ischemic hindlimbs treated with scaffolds seeded with human ECs derived from induced pluripotent stem cells (iPSC-ECs), single-walled carbon nanotube (SWNT) fluorophores were systemically delivered to quantify microvascular density after 28 days. Near infrared-II (NIR-II, 1000–1700 nm) imaging of SWNT fluorophores demonstrated that iPSC-EC-seeded aligned scaffolds group showed significantly higher microvascular density than the saline or cells groups. These data suggest that treatment with EC-seeded aligned nanofibrillar scaffolds improved blood perfusion and arteriogenesis, when compared to treatment with cells alone or scaffold alone, and have important implications in the design of therapeutic cell delivery strategies

Hereditary haemolytic anaemias are genetically and phenotypically heterogeneous disorders characterized by increased red cell destruction, with consequences ranging from innocuous to severe life-threatening anaemia. Diagnostic laboratories endeavour to assist clinicians reach the exact patient diagnosis by using tests principally based on morphological and biochemical techniques. However, these routine studies may be inconclusive, particularly in newborn infants and when transfusions have recently been administered. Large numbers and size of the potentially involved genes also impose a practical challenge for molecular diagnosis using routine sequencing approaches. To overcome these diagnostic shortcomings, we have utilized next-generation sequencing to provide a high-throughput, highly sensitive assay. We developed a panel interrogating 28 genes encoding cytoskeletal proteins and enzymes with sequencing coverage of the coding regions, splice site junctions, deep intronic and regulatory regions. We then evaluated 19 samples, including infants with unexplained extreme hyperbilirubinaemia and patients with transfusion-dependent haemolytic anaemia. Where possible, inheritance patterns of pathogenic mutations were determined by sequencing of immediate relatives. We conclude that this next-generation sequencing panel could be a cost-effective approach to molecular diagnosis of hereditary haemolytic anaemia, especially when the family history is uninformative or when routine laboratory testing fails to identify the causative haemolytic process.

Germline DDX41 variants are the most common mutations predisposing to acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) in adults, but the causal variant (CV) landscape and clinical spectrum of hematologic malignancies (HM) remain unexplored. Here, we analyzed the genomic profiles of 176 HM patients carrying 82 distinct presumably germline DDX41 variants among a group of 9,821 unrelated patients. Using our proposed DDX41 specific variant classification, we identified features distinguishing 116 HM patients with CV from 60 HM patients with variant of uncertain significance (VUS): an older age (median 69 years), male predominance (74% in CV versus 60% in VUS, P=0.03), frequent concurrent somatic DDX41 variants (79% in CV versus 5% in VUS, p<0.0001), a lower somatic mutation burden (1.4 ± 0.1 in CV versus 2.9 ± 0.04 in VUS, P=0.012), near exclusion of canonical recurrent genetic abnormalities including mutations in NPM1, CEBPA and FLT3 in AML, and favorable overall survival (OS) in AML/MDS patients. This superior OS was determined independent of blast count, abnormal karyotypes, and concurrent variants, including TP53 in AML/MDS patients, regardless of patient's sex, age or specific germline CV, suggesting that germline DDX41 variants define a distinct clinical entity. Furthermore, unrelated patients with myeloproliferative neoplasm (MPN) and B-cell lymphoma were linked by DDX41 CV, thus expanding the known disease spectrum. This study outlines the CV landscape, expands the phenotypic spectrum in unrelated DDX41-mutated patients, and underscores the urgent need for gene-specific diagnostic and clinical management guidelines.