Computing the inducibility of B cell lineages under a context-dependent model of affinity maturation: Applications to sequential vaccine design.

A key challenge in B cell lineage-based vaccine design is understanding the inducibility of target neutralizing antibodies. We approach this problem through the use of detailed stochastic modeling of the somatic hypermutation process that occurs during affinity maturation. Under such a model, sequence mutation rates are context-dependent, rendering standard probability calculations for sequence evolution intractable. We develop an algorithmic approach to rapid, accurate approximation of key marginal sequence likelihoods required to inform modern sequential vaccine design strategies. These calculated probabilities are used to define an inducibility index for selecting among potential targets for immunogen design. We apply this approach to the problem of choosing targets for the design of boosting immunogens aimed at elicitation of the HIV broadly-neutralizing antibody DH270min11.

The Impact of Preinjury Antiplatelet and Anticoagulant Use on Elderly Patients with Moderate or Severe Traumatic Brain Injury Following Traumatic Acute Subdural Hematoma.

BACKGROUND: Although it is often assumed that preinjury anticoagulant (AC) or antiplatelet (AP) use is associated with poorer outcomes among those with acute subdural hematoma (aSDH), previous studies have had varied results. This study examines the impact of preinjury AC and AP therapy on aSDH thickness, 30-day mortality, and extended Glasgow Outcome Scale at 6 months in elderly patients (aged ≥65). METHODS: A level 1 trauma center registry was interrogated to identify consecutive elderly patients who presented with moderate or severe traumatic brain injury (TBI) and associated traumatic aSDH between the first of January 2013 and the first of January 2018. Relevant demographic, clinical, and radiological data were retrieved from institutional medical records. The 3 primary outcome measures were aSDH thickness on initial computed tomography scan, 30-day mortality, and unfavorable outcome at 6 months (extended Glasgow Outcome Scale). RESULTS: One hundred thirty-two elderly patients were admitted with moderate or severe TBI and traumatic aSDH. The mean (±SD) age was 78.39 (±7.87) years, and a majority of patients (59.8%, n = 79) were male. There was a statistically significant difference in mean aSDH thickness, but there were no significant differences in 30-day mortality (P = 0.732) and unfavorable outcome between the AP, AC, combined AP and AC, and no antithrombotic exposure groups (P = 0.342). CONCLUSIONS: Further studies with larger sample sizes are necessary to confirm these observations, but our findings do not support the preconceived notion in clinical practice that antithrombotic use is associated with poor outcomes in elderly patients with moderate or severe TBI.

Hyperparathyroidism-jaw Tumor Syndrome: An Overlooked Cause of Severe Hypercalcemia.

Ossifying fibromas of the maxillofacial bones are an uncommon form of benign neoplasm usually treated by surgical excision. Up to 30% of patients with hyperparathyroidism-jaw tumor syndrome, a rare form of multiple endocrine neoplasia resulting from autosomal dominant inactivating mutation of the Hrpt2 tumor suppressor gene, initially present with ossifying fibromas. Coincident hypercalcemia because of the presence of parathyroid adenoma is common in these patients, of whom 15% may have or may develop parathyroid carcinoma. The authors present a case of severe postsurgical hypercalcemia after removal of a large maxillary ossifying fibroma in a patient with previously unrecognized hyperparathyroidism-jaw tumor AU3 syndrome.

Isothermal Oxidation of White Phosphorus Dispersed in Water in a Stirred-Tank Reactor.

A global, first-order kinetic model was found to fit the data for the isothermal wet oxidation of elemental white phosphorus (P4) in a batch, stirred-tank reactor. The initial concentration of white phosphorus solids was held constant at 1 g/L and an air flow of 2.0 standard liters per minute was used to supply the oxygen for the reaction. A CD6-like turbine and an A2 impeller were evaluated at speeds from 1000-2250 rpm. For the CD6-like turbine, mass transfer effects were assumed to be eliminated above 2000 rpm. Thus, the CD6-like turbine with a speed of 2250 rpm was selected for the isothermal studies. Particle size and temperature were varied. For the isothermal conditions, the first order kinetic constant varied from 0.022 min-1 at 46 °C to 0.078 min-1 at 80 °C. The apparent activation energy was 6.78 kcal/mol. Oxygen reacted with the suspended P4 particles forming oxides of phosphorus, primarily phosphorus pentoxide (P4010 or P2 O5). Some of the P2O5 reacted with the water to form PO43- as the primary product of white phosphorus oxidation. The amount of phosphorus pentoxide absorbed in the water increased with temperature. The rate of phosphate formation followed zero order kinetics and was independent of particle size. As the temperature increased, the ratio of PO4/ PO3 increased. This observation and the apparently low activation energy suggest that diffusion effects may not have been eliminated completely.