Distinguishing immunological and behavioral effects of vaccination

The interpretation of vaccine efficacy estimands is subtle, even in randomized trials designed to quantify immunological effects of vaccination. In this article, we introduce terminology to distinguish between different vaccine efficacy estimands and clarify their interpretations. This allows us to explicitly consider immunological and behavioural effects of vaccination, and establish that policy-relevant estimands can differ substantially from those commonly reported in vaccine trials. We further show that a conventional vaccine trial allows identification and estimation of different vaccine estimands under plausible conditions, if one additional post-treatment variable is measured. Specifically, we utilize a ``belief variable'' that indicates the treatment an individual believed they had received. The belief variable is similar to ``blinding assessment'' variables that are occasionally collected in placebo-controlled trials in other fields. We illustrate the relations between the different estimands, and their practical relevance, in numerical examples based on an influenza vaccine trial

Conformal actions of simple Lie groups on compact pseudo-Riemannian manifolds,

Abstract As is well-known, the real rank of a simple Lie group that acts conformally on a pseudo-Riemannian manifold is bounded by means of the signature of the manifold. We give a precise description of the action whenever the real rank of the group reaches that bound, assuming the action is minimal

Monitoring of Cellular Changes in the Bone Marrow following PTH(1-34) Treatment of OVX Rats Using a Portable Stray-Field NMR Scanner

Osteoporosis is characterized by reduction in trabecular bone in conjunction with increased marrow cell adiposity. While these changes occur within weeks, monitoring of treatment efficacy as performed by DEXA is sensitive only to long-term changes. MRI is sensitive to bone marrow changes but is less affordable. In a recent study, we have shown that a stray-field NMR can monitor bone marrow cellular changes that are related to osteoporosis. Objectives. To demonstrate sensitivity of a low-field tabletop NMR scanner to bone marrow dynamics following hormonal treatment in rats. Methods. Two-month-old female rats (n=36) were ovariectomized (OVX) and dosed for the ensuing 3 or 5 weeks with 20 mg/kg of PTH(1-34). Hind limbs femurs and tibiae were isolated and underwent ex vivo microradiography and histology and NMR relaxometry at 6 weeks (preventive experiment) and 11 weeks (therapeutic treatment experiment) after OVX. Results. OVX rats developed osteoporotic changes including adipogenic marrow compared to Sham and PTH treated rats. T2 and ADC NMR relaxation coefficients were found to correlate with marrow composition. Conclusions. This study suggests that stray-field NMR, an affordable method that is sensitive to the rapid cellular changes in bone marrow, may have a clinical value in monitoring hormonal treatment for osteoporosis

A rare brain tumor encountered: Phosphaturic mesenchymal tumor. Case report and review of the literature

Rational: Phosphaturic mesenchymal tumors (PMTs) are rare tumors often causing tumor-induced osteomalacia (TIO), with surgical resection being the first line in the treatment of TIO. There are very few reports of PMTs located in the brain. The authors present one such case, it's management and outcome as well as a review of the literature. Patient concerns: The authors report of a 58 year old male with a background of osteoporosis, bone pain, muscle weakness and gait disturbances for the past several years. He presented to our institution with newly developed absence spells. He underwent imaging which revealed a brain tumor. Interventions: The patient underwent surgery for what was suspected as a meningioma. A gross total resection was done. The pathological diagnosis was that of phosphaturic mesenchymal tumor. Outcomes: Removal of the tumor helped in alleviating the patient's back symptoms immediately after surgery. The patient was discharged home and was followed up by an endocrinologist, with improvement of his bone pain, his muscle weakness and his gait disturbances. Lessons: PMT with involvement of the brain can be treated surgically. Removal of the tumor will alleviate symptoms in patients harboring this rare brain tumor. Keywords: Tumor induced osteomalacia, Phosphaturic mesenchymal tumor, Oncogenic osteomalaci

Artificial neural networks based controller for glucose monitoring during clamp test.

Insulin resistance (IR) is one of the most widespread health problems in modern times. The gold standard for quantification of IR is the hyperinsulinemic-euglycemic glucose clamp technique. During the test, a regulated glucose infusion is delivered intravenously to maintain a constant blood glucose concentration. Current control algorithms for regulating this glucose infusion are based on feedback control. These models require frequent sampling of blood, and can only partly capture the complexity associated with regulation of glucose. Here we present an improved clamp control algorithm which is motivated by the stochastic nature of glucose kinetics, while using the minimal need in blood samples required for evaluation of IR. A glucose pump control algorithm, based on artificial neural networks model was developed. The system was trained with a data base collected from 62 rat model experiments, using a back-propagation Levenberg-Marquardt optimization. Genetic algorithm was used to optimize network topology and learning features. The predictive value of the proposed algorithm during the temporal period of interest was significantly improved relative to a feedback control applied at an equivalent low sampling interval. Robustness to noise analysis demonstrates the applicability of the algorithm in realistic situations