Supply chain logistics with quantum and classical annealing algorithms.

Noisy intermediate-scale quantum (NISQ) hardware is almost universally incompatible with full-scale optimization problems of practical importance which can have many variables and unwieldy objective functions. As a consequence, there is a growing body of literature that tests quantum algorithms on miniaturized versions of problems that arise in an operations research setting. Rather than taking this approach, we investigate a problem of substantial commercial value, multi-truck vehicle routing for supply chain logistics, at the scale used by a corporation in their operations. Such a problem is too complex to be fully embedded on any near-term quantum hardware or simulator; we avoid confronting this challenge by taking a hybrid workflow approach: we iteratively assign routes for trucks by generating a new binary optimization problem instance one truck at a time. Each instance has [Formula: see text] quadratic binary variables, putting it in a range that is feasible for NISQ quantum computing, especially quantum annealing hardware. We test our methods using simulated annealing and the D-Wave Hybrid solver as a place-holder in wait of quantum hardware developments. After feeding the vehicle routes suggested by these runs into a highly realistic classical supply chain simulation, we find excellent performance for the full supply chain. Our work gives a set of techniques that can be adopted in contexts beyond vehicle routing to apply NISQ devices in a hybrid fashion to large-scale problems of commercial interest.

Multicenter study of crystalloid boluses and transfusion in pediatric trauma-When to go to blood?

BACKGROUND: The 9th edition of Advanced Trauma Life Support recommends up to three crystalloid boluses in pediatric trauma patients with consideration of transfusion after the second bolus; however, this approach is debated. We aimed to determine if requirement of more than one fluid bolus predicts the need for transfusion. METHODS: The 2010 to 2016 highest tier activation patients younger than 15 years from two ACS Level I pediatric trauma centers were identified from prospectively maintained trauma databases. Those with a shock index (heart rate/systolic blood pressure) greater than 0.9 were included. Crystalloid boluses (20 ± 10 mL/kg) and transfusions administered prehospital and within 12 hours of hospital arrival were determined. Univariate and multivariable analyses were conducted to determine association between crystalloid volume and transfusion. RESULTS: Among 208 patients, the mean age was 5 ± 4 years (60% male), 91% sustained blunt injuries, and median (interquartile range) Injury Severity Score was 11 (6,25). Twenty-nine percent received one bolus, 17% received two, and 10% received at least three. Transfusion of any blood product occurred in 50 (24%) patients; mean (range) red blood cells was 23 (0-89) mL/kg, plasma 8 (0-69), and platelets 1 (0-18). The likelihood of transfusion increased logarithmically from 11% to 43% for those requiring 2 or more boluses (Fig. 1). This relationship persisted on multivariable analysis that adjusted for institution, age, and shock index with good discrimination (Area under the Receiver Operating Characteristic, 0.84). Shock index was also strongly associated with transfusion. CONCLUSION: Almost half of pediatric trauma patients with elevated shock index require transfusion following two crystalloid boluses and the odds of requiring a transfusion plateau at this point in resuscitation. This supports consideration of blood with the second bolus in conjunction with shock index though prospective studies are needed to confirm this and its impact on outcomes. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Black Hole Interior in Quantum Gravity.

We discuss the interior of a black hole in quantum gravity, in which black holes form and evaporate unitarily. The interior spacetime appears in the sense of complementarity because of special features revealed by the microscopic degrees of freedom when viewed from a semiclassical standpoint. The relation between quantum mechanics and the equivalence principle is subtle, but they are still consistent.

High affinity binding of an engineered, modular peptide to bone tissue.

Bone grafting procedures have become common due in part to a global trend of population aging. Native bone graft is a popular choice when compared to various synthetic bone graft substitutes, owing to superior biological activity. Nonetheless, the insufficient ability of bone allograft to induce new bone formation and the insufficient remodeling of native bone grafts call for osteoinductive factors during bone repair, exemplified by recombinant human bone morphogenetic protein 2 (rhBMP2). We previously developed a modular bone morphogenetic peptide (mBMP) to address complications associated with the clinical use of rhBMP2 as a bone graft substitute. The mBMP is designed to strongly bind to hydroxyapatite, the main inorganic component of bone and teeth, and to provide pro-osteogenic properties analogous to rhBMP2. Our previous in vivo animal studies showed that mBMP bound to hydroxyapatite-coated orthopedic implants with high affinity and stimulated new bone formation. In this study, we demonstrate specific binding of mBMP to native bone grafts. The results show that mBMP binds with high affinity to both cortical and trabecular bones, and that the binding is dependent on the mBMP concentration and incubation time. Importantly, efficient mBMP binding is also achieved in an ex vivo bone bioreactor where bone tissue is maintained viable for several weeks. In addition, mBMP binding can be localized with spatial control on native bone tissue via simple methods, such as dip-coating, spotting, and direct writing. Taken together with the pro-osteogenic activity of mBMP established in previous bone repair models, these results suggest that mBMP may promote bone healing when coated on native bone grafts in a clinically compatible manner.