SAT-512 Severe Hypocalcemia Presenting as Status Epilepticus after Denosumab Use in Metastatic Prostate Cancer

Introduction: Denosumab decreases the incidence of skeletal-related events in patients with metastatic bone disease and is used routinely as part of the therapeutic strategy for various cancers. However, it is associated with a high risk of hypocalcemia with incidence of high-grade hypocalcemia (defined as total calcium < 7mg/dl) as high as 5.1% in patients with castrate-resistant prostate cancer. We present a case of severe hypocalcemia presenting with status epilepticus 32 days after administration of denosumab. Case: A 83 year old African American man presented to the emergency room with status epilepticus. Initial labs revealed a critically low calcium (Ca) of <5mg/dl (8.5-10.1) with albumin 2.2 g/dl (3.4-5.0), ionized calcium 1.09 mg/dl (4.6-5.1) and creatinine (Cr) 3.68 mg/dl (0.67-1.17). QTC was prolonged at 544ms (<400ms). He was intubated for airway protection and a continuous infusion of intravenous calcium gluconate was initiated. Three months prior, he had been diagnosed with prostate cancer with diffuse osteoblastic metastases to his ribs, cervical, thoracic, lumbar and sacral vertebrae, right humerus and bilateral iliac bones. He received a first dose of conventional chemotherapy and 120mg denosumab subcutaneously 32 days prior to hospital admission. Lab investigations then were pertinent for Ca of 9 mg/dl, Cr 1.46 mg/dl, and alkaline phosphatase 362 Units/L (25-125). A 25-hydroxy vitamin D (25-D) was not checked. Further evaluation demonstrated intact parathyroid hormone 677.2 pg/ml (18.4-80.1), alkaline phosphatase 397 Units/L, phosphorus 3.6 mg/dl (2.5-4.9) and 25-D 18 ng/ml (30-100). He was also found to have metastatic obstruction of both ureters which had resulted in acute kidney injury. He was slowly weaned off the intravenous calcium and started on calcitriol 2mcg twice daily, 4 gram elemental calcium daily via feeding tube and cholecalciferol 6000 units daily. Calcium levels remained stable at 8.0-8.5mg/dl on this regimen. Given the extensive metastatic disease, the patient’s family elected to pursue hospice care, and he passed away 9 days later. Conclusion: Patients with osteoblastic metastases and renal impairment are at particularly increased risk of hypocalcemia after denosumab, which can be potentially life-threatening. Physicians caring for patients with metastatic prostate cancer should ensure that vitamin D levels are replete and calcium levels are normal prior to administration of denosumab, monitor calcium levels closely, and counsel them about the signs and symptoms of hypocalcemia to allow prompt diagnosis and treatment

Neural networks and support vector machines based bio-activity classification

Classification of various compounds into their respective biological activity classes is important in drug discovery applications from an early phase virtual compound filtering and screening point of view. In this work two types of neural networks, multi layer perceptron (MLP) and radial basis functions (RBF), and support vector machines (SVM) were employed for the classification of three types of biologically active enzyme inhibitors. Both of the networks were trained with back propagation learning method with chemical compounds whose active inhibition properties were previously known. A group of topological indices, selected with the help of principle component analysis (PCA) were used as descriptors. The results of all the three classification methods show that the performance of both the neural networks is better than the SVM

Economic Policies and the Impact of Natural Disasters on Economic Growth: A Threshold Regression Approach

This paper investigates the impact of natural disasters on the long-term macroeconomic performance of a country. More specifically, we want to see whether the impact of natural disasters on economic growth is uniform across countries or it is differentiated according to the macroeconomic policy environment and other structural characteristics of the countries at hand. In order to test this empirically we use the Threshold Regression (TR) approach of Hansen (2000) and data from 90 countries over the period of 1970 to 2001. Our analysis reveals several interesting patterns such as: countries with higher per capita income, higher government spending, higher degree of openness to trade, less fiscal imbalances and greater financial stability are better able to withstand the disaster shock and further prevent its impact on long-term economic growth.Natural Disasters, Economic Policies, Economic Growth, Threshold Regression

Disjointed Service: An English Case Study of Multi-Agency Provision in Tackling Child Trafficking

This paper examines the issue of child trafficking in the United Kingdom and of multi-agency responses in tackling it. The UK, as a signatory to the recent trafficking protocols, is required to implement measures to identify and support potential victims of trafficking - via the National Referral Mechanism. Effective support for child victims is reliant on cooperation between agencies. Our regional case-study contends that fragmented agency understandings of protocols and disjointed partnership approaches in service delivery means the trafficking of vulnerable children continues across the region. This paper asserts that child-trafficking in the UK, previously viewed as an isolated localised phenomenon, maybe far more widespread, revealing deficiencies in child protection services for vulnerable children

Interplay between spin-orbit coupling and Hubbard interaction in SrIrO3 and related Pbnm perovskites

There has been a rapidly growing interest on the interplay between spin-orbit coupling (SOC) and Hubbard interaction U in correlated materials. A current consensus is that the stronger the SOC, the smaller is the critical interaction Uc required for a spin-orbit Mott insulator, because the atomic SOC splits a band into different total angular momentum bands narrowing the effective bandwidth. It was further claimed that at large enough SOC, the stronger the SOC, the weaker the Uc because in general the effective SOC is enhanced with increasing electron-electron interaction strength. Contrary to this expectation, we find that, in orthorhombic perovskite oxides (Pbnm), the stronger the SOC, the bigger the Uc. This is originated from a line of Dirac node in Jeff=1/2 bands near the Fermi level inherited from a combination of the lattice structure and a large SOC. Due to this protected line of nodes, there are small hole and electron pockets in SrIrO3, and such a small density of states makes Hubbard interaction less efficient in building a magnetic insulator. The full phase diagram in U vs. SOC is obtained, where non-magnetic semimetal, magnetic metal, and magnetic insulator are found. Magnetic ordering patterns beyond Uc are also presented. We further discuss implications of our finding in relation to other perovskites such as SrRhO3 and SrRuO3.Comment: 7 pages, 6 figure

SHORT TERM MICROBIAL COLONIZATION OF REPTILE ROADKILL

Little is known about how microbes such as bacteria and fungi in the environment tempo­rally colonize common roadkill reptile carcasses (turtles and snakes). We opportunistically collected and deployed a variety of reptile carcasses often found deceased near roads, including an Eastern Ratsnake (Pantherophis alleghaniensis), an Eastern Box Turtle (Terrapene carolina), and a Snapping Turtle (Chelydra serpentina). We sampled bacteria communities of these carcasses daily for five con­secutive days. We enumerated the number of colony-forming units (CFUs) and characterized microbial distinct colonies using morphology and identification of dominant colonies using 16S rRNA sequencing across carcasses. Several ecologically relevant bacterial phyla were successfully identified colonizing and dominating carcasses differentially, including members of Actinobacteria, Firmicutes, and Proteo­bacteria. We observed higher bacterial colonization (CFUs) for both terrestrial and aquatic turtles, T. carolina and C. serpentina, compared to P. alleghaniensis. This study provides baseline data on the temporal microbiology of deceased reptiles found on roads in the piedmont of North Carolina