Application of Ground Penetrating Radar to the Detection of Subsurface Cavities

Ground Penetrating Radar (GPR) identifies subsurface features by distinguishing materials with different dielectric constants and electrical conductivities. Subsurface cavities can, therefore, be detected by the variation in their electrical properties from the electrical properties of the surrounding material. To test the cavity detection ability of GPR, subsurface cavities of varying size, shape and content were modeled. Radar response to the cavity models was found to be affected by the composition of the surrounding soil material, the depth of the groundwater table, and the radar signal frequency. Based on knowledge gained from the cavity modeling study, a natural subsurface cavity was identified during a GPR field investigation. Limestone features such as bedding planes and fractures were mapped, and a detailed lake bottom profile was obtained by the radar system

Stabilizing Building Foundations Threatened by the Pine Hills, Florida Sinkhole

On June 11, 2002, a 150-foot wide and 60-foot deep sinkhole collapsed in Pine Hills, near Orlando, Florida. The Pine Hills Sinkhole was the largest sinkhole to occur in Central Florida in the past 20 years. The collapse swallowed approximately 10,000 cubic yards of earth, sidewalks, light fixtures, a sanitary sewer and several large oak trees in less than 2 hours. The rim of the sinkhole came within a few feet of the shallow foundations of 2 three-story apartment buildings. Observation and subsequent geotechnical analysis showed that the sinkhole slope supporting the buildings was subject to imminent failure, and if a slope failure were to occur, it would likely result in a complete loss of the structures. The weather forecast predicted heavy rainfall, which could further destabilize the steep sand slope. Immediate action was taken to prevent slope failure, including the rerouting of stormwater roof drains and placement of a 30 mil-thick PVC liner over the slope adjacent to the buildings. A detailed geotechnical investigation including Ground Penetration Radar, electronic Cone Penetration Test soundings and Standard Penetration Test borings was immediately implemented to develop geotechnical parameters for remedial design. Due to critical time constraints, a chemical grouting program was conducted concurrently with the investigation to provide temporary stabilization of the building foundation soils from undermining due to the adjacent sinkhole. Settlement and cracking of the building slab foundations and walls were observed within a few days after the sinkhole collapsed, and the settlement and cracking accelerated with time. The permanent design solution for stabilizing the building foundations, and adjacent sidewalks and utilities, was installation of a Giken Wall using the Press-In installation method. The 200-foot long wall was located between the sinkhole and the buildings. The wall was comprised of 3-foot diameter interlocking steel pipe piles that were 50 feet in length. The combined internal auger and Press-In installation methodology allowed the wall to be constructed adjacent to the sensitive sand slope with negligible ground disturbance. The building movement was arrested by construction of the Giken wall and the building foundation stabilization was complete within 1 month after the sinkhole occurred. The relatively minor damage to the structures was then repaired and tenants have returned to occupy the buildings

P2 receptors in atherosclerosis and postangioplasty restenosis

Atherosclerosis is an immunoinflammatory process that involves complex interactions between the vessel wall and blood components and is thought to be initiated by endothelial dysfunction [Ross (Nature 362:801–09, 1993); Fuster et al. (N Engl J Med 326:242–50, 1992); Davies and Woolf (Br Heart J 69:S3–S11, 1993)]. Extracellular nucleotides that are released from a variety of arterial and blood cells [Di Virgilio and Solini (Br J Pharmacol 135:831–42, 2002)] can bind to P2 receptors and modulate proliferation and migration of smooth muscle cells (SMC), which are known to be involved in intimal hyperplasia that accompanies atherosclerosis and postangioplasty restenosis [Lafont et al. (Circ Res 76:996–002, 1995)]. In addition, P2 receptors mediate many other functions including platelet aggregation, leukocyte adherence, and arterial vasomotricity. A direct pathological role of P2 receptors is reinforced by recent evidence showing that upregulation and activation of P2Y2 receptors in rabbit arteries mediates intimal hyperplasia [Seye et al. (Circulation 106:2720–726, 2002)]. In addition, upregulation of functional P2Y receptors also has been demonstrated in the basilar artery of the rat double-hemorrhage model [Carpenter et al. (Stroke 32:516–22, 2001)] and in coronary artery of diabetic dyslipidemic pigs [Hill et al. (J Vasc Res 38:432–43, 2001)]. It has been proposed that upregulation of P2Y receptors may be a potential diagnostic indicator for the early stages of atherosclerosis [Elmaleh et al. (Proc Natl Acad Sci U S A 95:691–95, 1998)]. Therefore, particular effort must be made to understand the consequences of nucleotide release from cells in the cardiovascular system and the subsequent effects of P2 nucleotide receptor activation in blood vessels, which may reveal novel therapeutic strategies for atherosclerosis and restenosis after angioplasty

A Randomized, Controlled Trial of Interferon Alfa-2b Alone and after Prednisone Withdrawal for the Treatment of Chronic Hepatitis B

Chronic hepatitis B is a serious and often progressive liver disorder for which there is no accepted therapy. Several small clinical trials have suggested that interferon may be helpful in the management of this condition, but most of these studies were uncontrolled, and the interpretation of the data is complicated by variations in dose schedules, major disparities in patient characteristics, and substantial differences in rates of spontaneous seroconversion of hepatitis B e antigen (HBeAg) in untreated controls. 1 , 2 A small, controlled clinical trial showed that 16 weeks of treatment with recombinant interferon alfa-2b resulted in the clearance of HBeAg in approximately . . 

Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome

Objectives To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in ALPK1, is an autoinflammatory disease. Methods This cohort study systematically evaluated 27 patients with ROSAH syndrome for inflammatory features and investigated the effect of ALPK1 mutations on immune signalling. Clinical, immunologic and radiographical examinations were performed, and 10 patients were empirically initiated on anticytokine therapy and monitored. Exome sequencing was used to identify a new pathogenic variant. Cytokine profiling, transcriptomics, immunoblotting and knock-in mice were used to assess the impact of ALPK1 mutations on protein function and immune signalling. Results The majority of the cohort carried the p.Thr237Met mutation but we also identified a new ROSAH-associated mutation, p.Tyr254Cys. Nearly all patients exhibited at least one feature consistent with inflammation including recurrent fever, headaches with meningeal enhancement and premature basal ganglia/brainstem mineralisation on MRI, deforming arthritis and AA amyloidosis. However, there was significant phenotypic variation, even within families and some adults lacked functional visual deficits. While anti-TNF and anti-IL-1 therapies suppressed systemic inflammation and improved quality of life, anti-IL-6 (tocilizumab) was the only anticytokine therapy that improved intraocular inflammation (two of two patients). Patients' primary samples and in vitro assays with mutated ALPK1 constructs showed immune activation with increased NF-κB signalling, STAT1 phosphorylation and interferon gene expression signature. Knock-in mice with the Alpk1 T237M mutation exhibited subclinical inflammation. Clinical features not conventionally attributed to inflammation were also common in the cohort and included short dental roots, enamel defects and decreased salivary flow. Conclusion ROSAH syndrome is an autoinflammatory disease caused by gain-of-function mutations in ALPK1 and some features of disease are amenable to immunomodulatory therapy

Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome

Objectives To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in ALPK1, is an autoinflammatory disease. Methods This cohort study systematically evaluated 27 patients with ROSAH syndrome for inflammatory features and investigated the effect of ALPK1 mutations on immune signalling. Clinical, immunologic and radiographical examinations were performed, and 10 patients were empirically initiated on anticytokine therapy and monitored. Exome sequencing was used to identify a new pathogenic variant. Cytokine profiling, transcriptomics, immunoblotting and knock-in mice were used to assess the impact of ALPK1 mutations on protein function and immune signalling. Results The majority of the cohort carried the p.Thr237Met mutation but we also identified a new ROSAH-associated mutation, p.Tyr254Cys. Nearly all patients exhibited at least one feature consistent with inflammation including recurrent fever, headaches with meningeal enhancement and premature basal ganglia/brainstem mineralisation on MRI, deforming arthritis and AA amyloidosis. However, there was significant phenotypic variation, even within families and some adults lacked functional visual deficits. While anti-TNF and anti-IL-1 therapies suppressed systemic inflammation and improved quality of life, anti-IL-6 (tocilizumab) was the only anticytokine therapy that improved intraocular inflammation (two of two patients). Patients' primary samples and in vitro assays with mutated ALPK1 constructs showed immune activation with increased NF-kappa B signalling, STAT1 phosphorylation and interferon gene expression signature. Knock-in mice with the Alpk1 T237M mutation exhibited subclinical inflammation. Clinical features not conventionally attributed to inflammation were also common in the cohort and included short dental roots, enamel defects and decreased salivary flow. Conclusion ROSAH syndrome is an autoinflammatory disease caused by gain-of-function mutations in ALPK1 and some features of disease are amenable to immunomodulatory therapy