Plummeting Broadcast Storm Problem in Highways by Clustering Vehicles Using Dominating Set and Set Cover.

"Vehicular Ad-hoc Networks" (VANETs): As an active research area in the field of wireless sensor networks, they ensure road safety by exchanging alert messages about unexpected events in a decentralized manner. One of the significant challenges in the design of an efficient dissemination protocol for VANETs is the broadcast storm problem, owing to the large number of rebroadcasts. A generic solution to prevent the broadcast storm problem is to cluster the vehicles based on topology, density, distance, speed, or location in such a manner that only a fewer number of vehicles will rebroadcast the alert message to the next group. However, the selection of cluster heads and gateways of the clusters are the key factors that need to be optimized in order to limit the number of rebroadcasts. Hence, to address the aforementioned issues, this paper presents a novel distributed algorithm CDS_SC: Connected Dominating Set and Set Cover for cluster formation that employs a dominating set to choose cluster heads and set covering to select cluster gateways. The CDS_SC is unique among state-of-the-art algorithms, as it relies on local neighborhood information and constructs clusters incrementally. Hence, the proposed method can be implemented in a distributed manner as an event-triggered protocol. Also, the stability of cluster formation is increased along with a reduction in rebroadcasting by allowing a cluster head to be passive when all its cluster members can receive the message from the gateway vehicles. The simulation was carried out in dense, average, and sparse traffic scenarios by varying the number of vehicles injected per second per lane. Besides, the speed of each individual vehicle in each scenario was varied to test the degree of cohesion between vehicles with different speeds. The simulation results confirmed that the proposed algorithm achieved 99% to 100% reachability of alert messages with only 6% to 10% of rebroadcasting vehicles in average and dense traffic scenarios.

An improved robust heteroscedastic probabilistic neural network based trust prediction approach for cloud service selection.

Trustworthiness is a comprehensive quality metric which is used to assess the quality of the services in service-oriented environments. However, trust prediction of cloud services based on the multi-faceted Quality of Service (QoS) attributes is a challenging task due to the complicated and non-linear relationships between the QoS values and the corresponding trust result. Recent research works reveal the significance of Artificial Neural Network (ANN) and its variants in providing a reasonable degree of success in trust prediction problems. However, the challenges with respect to weight assignment, training time and kernel functions make ANN and its variants under continuous advancements. Hence, this work presents a novel multi-level Hypergraph Coarsening based Robust Heteroscedastic Probabilistic Neural Network (HC-RHRPNN) to predict trustworthiness of cloud services to build high-quality service applications. HC-RHRPNN employs hypergraph coarsening to identify the informative samples, which were then used to train HRPNN to improve its prediction accuracy and minimize the runtime. The performance of HC-RHRPNN was evaluated using Quality of Web Service (QWS) dataset, a public QoS dataset in terms of classifier accuracy, precision, recall, and F-Score.

Rapid synthesis of 125I integrated gold nanoparticles for use in combined neoplasm imaging and targeted radionuclide therapy.

The selective delivery of radionuclides to tissues of interest remains a problematic task during treatment. The lack of tissue specificity for many therapeutics limit their efficacy by putting healthy organs and tissues at risk (e.g., side effects). Therefore, high specificity therapeutic strategies are needed to overcome these risks. The objective of this study was to use a modified citrate reduction technique to synthesize gold nanoparticles (AuNPs) containing 125I in order to combine their unique therapeutic and diagnostic properties. This task was accomplished by varying the insertion time of 125I, which will cause complete aggregation if added too early in the AuNP synthesis process. Even though 125I was utilized in this experiment, studies are underway to see if this approach can be extrapolated to shorter-lived isotopes (e.g., 211At). Characterization of the 125I-AuNPs was carried out using UV-Vis spectrometry and Transmission Electron Microscopy (TEM). The appropriate addition time of 125I was determined to be approximately 50s after the addition of sodium citrate. TEM measured the nanoparticles' diameters to be in the 10-20nm range. The AuNPs were found to be extremely stable, with no observable leaching of radioactivity into the solution. 125I-AuNPs could be beneficial as a contrast agent in CT imaging and therapy since AuNPs enhance the bio-delivery of 125I to neoplasms.

Constrictive Pericarditis Following Correction of Partial Anomalous Pulmonary Venous Drainage.

We report the case of a 23-year-old man who developed constrictive pericarditis within four months after pulmonary valve replacement and repair of partial anomalous pulmonary venous connection. He had previously undergone repair of tetralogy of Fallot in infancy. After an unsuccessful trial of medical management for persistent right heart failure, magnetic resonance imaging was done, which showed a thickened pericardium. He underwent a radical pericardiectomy with a good outcome. The case is presented to illustrate a less well-recognized cause of cardiac failure following congenital cardiac surgery, which may otherwise be attributed to the failure of surgery or residual complications.

Missed case of sinus venosus atrial septal defect post coronary artery bypass grafting.

We report a case of a 41-year-old Indian man who initially underwent an emergency coronary artery bypass grafting surgery (CABG) after presenting with an anterolateral myocardial infarction.Post-operatively he developed progressively worsening symptoms of right heart failure with increasing abdominal distension and lower limb swelling. Clinically, the patient was in NYHA class 4 heart failure.He was admitted multiple times for the treatment of his heart failure, which was recalcitrant to diuretic therapy.He subsequently underwent an MRI scan, which revealed near transmural myocardial infarction involving mainly the left side of the heart. The right atrium and ventricle were grossly dilated, with moderate to severe right ventricular systolic dysfunction. A sinus venosus atrial septal defect with right-sided partial anomalous pulmonary venous drainange (PAPVD) was noted. He subsequently underwent surgery to repair the sinus venosus atrial septal defect (ASD) as well as re-route the PAPVD to the left atrium (LA). He was discharged on post-operative day 19 with oral diuretics.On follow-up at 1 month, the patient's symptoms had resolved and his clinical status corresponded to NYHA class 1-2.

Preliminary production of 211At at the Texas A&M University Cyclotron Institute.

A feasibility study for the production of the alpha particle-emitting radionuclide At was performed at the Texas A&M University Cyclotron Institute as part of the Interdisciplinary Radioisotope Production and Radiochemistry Program. The mission of this program centers upon the production of radionuclides for use in diagnostic and therapeutic nuclear medicine with the primary focus on development of novel therapeutic strategies. As a first step in establishing this program, two goals were outlined: (i) verify production of At and compare results to published data, and (ii) evaluate shielding and radiological safety issues for large-scale implementation using an external target. The radionuclide At was produced via the Bi (α, 2n) At reaction using the K500 cyclotron. Two experiments were conducted, using beam energies of 27.8 MeV and 25.3 MeV, respectively. The resulting yields for At were found to be 36.0 MBq µA h and 12.4 MBq µA h, respectively, which fall within the range of published yield data. Strategies for increasing absolute yield and production efficiency were also evaluated, which focused chiefly on using a new target designed for use with the K150 cyclotron, which will enable the use of a higher beam current. Finally, neutron and gamma dose rates during production were evaluated by using the Monte Carlo code MCNPX. It was determined that a simple structure consisting of 4-in thick borated polyethylene will reduce the neutron dose rate within the cyclotron production vault by approximately a factor of 2, thereby decreasing activation of equipment.

Identifying covariates of population health using extreme bound analysis.

BACKGROUND: The literature is full of lively discussion on the determinants of population health outcomes. However, different papers focus on small and different sets of variables according to their research agenda. Because many of these variables are measures of different aspects of development and are thus correlated, the results for one variable can be sensitive to the inclusion/exclusion of others. METHOD: We tested for the robustness of potential predictors of population health using the extreme bounds analysis. Population health was measured by life expectancy at birth and infant mortality rate. RESULTS: We found that only about half a dozen variables are robust predictors for life expectancy and infant mortality rate. Among them, adolescent fertility rate, improved water sources, and gender equality are the most robust. All institutional variables and environment variables are systematically non-robust predictors of population health. CONCLUSION: The results highlight the importance of robustness tests in identifying predictors or potential determinants of population health, and cast doubts on the findings of previous studies that fail to do so.

Extracorporeal membrane oxygenation for children with fulminant myocarditis.

The purpose of this study was to evaluate the outcomes of children requiring extracorporeal membrane oxygenation for acute myocarditis. The hospital records of 8 patients who underwent membrane oxygenation for myocarditis from January 2002 to October 2008 were reviewed. Ages ranged from 3 to 12 years (median, 6 years). Duration of membrane oxygenation ranged from 89-502 h. Two patients who collapsed and required cardiac massage prior to membrane oxygenation did not survive. Five (62.5%) patients were discharged well, but one developed dilated cardiomyopathy and died 18 months later. One child had severe mitral regurgitation after weaning from membrane oxygenation, and underwent successful mitral valve repair. Another patient had no cardiac contractility for the initial 2 weeks, but regained good cardiac function after 21 days of support. She was weaned off membrane oxygenation and discharged home well. Complications included left hemiparesis in one patient and left hemothorax in 2. Recovery of cardiac function and a good outcome can be anticipated in children with acute myocarditis requiring membrane oxygenation. Initiation of membrane oxygenation before cardiovascular collapse increases the likelihood of survival.

Late complications following tetralogy of Fallot repair: the need for long-term follow-up.

INTRODUCTION: We report a series of operated tetralogy of Fallot (TOF) patients focusing on complications and outcomes. MATERIALS AND METHODS: Data from TOF patients seen at our centre's adult congenital heart disease clinic was analysed. RESULTS: There were 21 patients: the mean age was 32.2 +/- 12.4 years; the age at first operation was 9.0 +/- 7.9 years; the mean postoperative follow-up duration was 23.5 +/- 12.1 years; and the current New York Heart Association (NYHA) status: I, 82%; II, 4%; III, 14%. Fourteen patients had complete operative notes. All these patients underwent total TOF correction; 2 had staged aortopulmonary shunt with total correction at a mean of 3.2 years later, pulmonary artery patch augmentation in 8 patients and pulmonary valvotomy in 8 patients. Three patients required pulmonary valve homograft replacement for severe pulmonary regurgitation (PR) at 13, 28 and 36 years after the initial corrective operation. CURRENT INVESTIGATIONS: RBBB on ECG (91%), QRS duration 137 +/- 29 ms. Echocardiography showed dilated right ventricular end-diastolic (RVED) diameters (3.2 +/- 0.8 cm); severe PR (67%), residual right ventricular outflow tract obstruction (RVOTO) (42%) and VSD patch leakage (9%). Cardiac magnetic resonance (CMR) (8 patients) showed dilated RVED volumes 252.6 +/- 93.8 mL, indexed RV volume 165.7 +/- 34.8 mL; RV systolic function was preserved in most patients with a RV ejection fraction of 49.5 +/- 5.7%. One patient had atrial tachycardia and another had frequent non-sustained ventricular tachycardia that required radiofrequency ablation. CONCLUSION: Patients with TOF who had full corrective surgery during childhood are now surviving into adulthood. Many challenges arising from complications in the postoperative period remain. It is imperative that adult TOF patients should have regular followup to monitor development and subsequent management of these complications.

Molecular imaging of alkylguanine-DNA alkyltransferase: further evaluation of radioiodinated derivatives of O6-benzylguanine.

PURPOSE: An inverse correlation has been established between tumor levels of the DNA repair protein alkylguanine-DNA alkyltransferase (AGT) and a positive outcome after alkylator chemotherapy. Quantitative imaging of AGT could provide important information for patient-specific cancer treatment. Several radiolabeled analogues of O6-benzylguanine (BG), a potent AGT inactivator, have been developed and shown to be capable of labeling pure AGT protein. Herein, two of these analogues--O6-3-[*I]iodobenzylguanine ([*I]IBG) and O6-3-[*I]iodobenzyl-2'-deoxyguanosine ([*I]IBdG)--were further evaluated in two murine xenograft models. (AcO)2-[131I]IBdG, a peracetylated derivative of IBdG, also was investigated as an alternative agent. METHODS: Several biodistribution studies of radioiodinated IBG and IBdG were performed in TE-671 human rhabdomyosarcoma and DAOY human medulloblastoma murine xenograft models. Mice were treated with BG or its nucleoside analogue dBG to deplete the tumor AGT content. The effect of unlabeled IBG and that of 7,8-benzoflavone (BF), an inhibitor of the cytochrome P-450 isozyme CYP1A2, on the tumor uptake of the tracers was determined. The uptake of (AcO)2-[131I]IBdG along with that of [125I]IBdG in DAOY cells in vitro was determined in the presence and absence of a nucleoside transporter inhibitor, dipyridamole. RESULTS: Pretreatment of mice either with BG or dBG failed to reduce tumor levels of [*I]IBG or [*I]IBdG even though such treatments completely depleted tumor AGT content. Treatment of mice with BF increased tumor uptake of [125I]IBG by 56%; however, differentiation of tumors with and without AGT still was not possible. (AcO)2-[131I]IBdG, a peracetylated derivative of IBdG, had a higher uptake in vitro in DAOY tumor cells. However, its uptake, like that of [125I]IBdG, was blocked by dipyridamole. CONCLUSIONS: Taken together, these results suggest that labeled agents that are more specific for cellular AGT and that are more metabolically stable are needed.

Antiepidermal growth factor variant III scFv fragment: effect of radioiodination method on tumor targeting and normal tissue clearance.

INTRODUCTION: MR1-1 is a single-chain Fv (scFv) fragment that binds with high affinity to epidermal growth factor receptor variant III, which is overexpressed on gliomas and other tumors but is not present on normal tissues. The objective of this study was to evaluate four different methods for labeling MR1-1 scFv that had been previously investigated for the radioiodinating of an intact anti-epidermal growth factor receptor variant III (anti-EGFRvIII) monoclonal antibody (mAb) L8A4. METHODS: The MR1-1 scFv was labeled with (125)I/(131)I using the Iodogen method, and was also radiohalogenated with acylation agents bearing substituents that were positively charged--N-succinimidyl-3-[*I]iodo-5-pyridine carboxylate and N-succinimidyl-4-guanidinomethyl-3-[*I]iodobenzoate ([*I]SGMIB)--and negatively charged--N-succinimidyl-3-[*I]iodo-4-phosphonomethylbenzoate ([*I]SIPMB). In vitro internalization assays were performed with the U87MGDeltaEGFR cell line, and the tissue distribution of the radioiodinated scFv fragments was evaluated in athymic mice bearing subcutaneous U87MGDeltaEGFR xenografts. RESULTS AND CONCLUSION: As seen previously with the anti-EGFRvIII IgG mAb, retention of radioiodine activity in U87MGDeltaEGFR cells in the internalization assay was labeling method dependent, with SGMIB and SIPMB yielding the most prolonged retention. However, unlike the case with the intact mAb, the results of the internalization assays were not predictive of in vivo tumor localization capacity of the labeled scFv. Renal activity was dependent on the nature of the labeling method. With MR1-1 labeled using SIPMB, kidney uptake was highest and most prolonged; catabolism studies indicated that this uptake primarily was in the form of epsilon-N-3-[*I]iodo-4-phosphonomethylbenzoyl lysine.

O6-3-[125I]iodobenzyl-2'-deoxyguanosine ([125I]IBdG): synthesis and evaluation of its usefulness as an agent for quantification of alkylguanine-DNA alkyltransferase (AGT).

The development of O(6)-(3-[(125)I]iodobenzyl)-2'-deoxyguanosine ([(125)I]IBdG), the glycosylated analogue of the O(6)-3-iodobenzylguanine (IBG), as an agent for the in vivo mapping of the DNA repair protein alkylguanine-DNA alkyltransferase (AGT) is described. Synthesis of its tin precursor, O(6)-3-trimethylstannylbenzyl-2'-deoxyguanosine (TBdG) was achieved in four steps from deoxyguanosine. Radioiodination of TBdG in a single step gave [(125)I]IBdG in 70-85% isolated radiochemical yield. [(125)I]IBdG bound specifically to pure AGT with an IC(50) of 7.1 microM. From paired-label assays, [(125)I]IBdG showed a 2- to 3-fold higher cellular uptake than [(131)I]IBG in DAOY medulloblastoma, TE-671 rhabdomyosarcoma, SK-Mel-28 melanoma, and HT-29 colon carcinoma human cell lines. Uptake of both labeled compounds in these cell lines decreased with increasing concentrations of unlabeled O(6)-benzylguanine (BG) when BG was present in the medium during incubation with the labeled compounds. Compared to BG, unlabeled IBdG diminished the uptake of [(125)I]IBdG and [(131)I]IBG in DAOY cells more efficiently (IC(50)<1 microM vs >10 microM for BG). There was no significant change in cell-bound activity of [(125)I]IBdG and [(131)I]IBG when BG was removed from the incubation medium before incubating cells with the tracers, suggesting that only a very small portion of radioactivity taken up by the cells is AGT bound. This was corroborated by gel-electrophoresis performed on extracts from cells treated with varying amounts of BG and then incubated with [(125)I]IBdG in the presence of BG. No radiolabeled AGT band was discernable by phosphor-imaging, signifying low cellular AGT binding of the radiotracer. In contrast, when cell extracts were prepared from BG pre-treated cells and aliquots were incubated with [(125)I]IBdG subsequently, the intensity of radiolabeled AGT band decreased linearly as a function of BG concentration. This suggests that the low level of [(125)I]IBdG that binds to AGT does so in a concentration dependent manner. These data suggest that IBdG is transported across the cell membrane to a higher degree than IBG. However, to be a practical tracer for quantifying cellular AGT, considerable localization of such derivatives need to occur within the cell nucleus where AGT is present predominantly.

Radioiodine and 211At-labeled guanidinomethyl halobenzoyl octreotate conjugates: potential peptide radiotherapeutics for somatostatin receptor-positive cancers.

Derivatives of the somatostatin analogues octreotide and octreotate labeled with radioiosotopes are used in the diagnosis and therapy of somatostatin receptor (SSTR)-positive tumors. A method has been devised to synthesize {N-(4-guanidinomethyl-3-iodobenzoyl)-Phe1-octreotate (GMIBO). Receptor binding assay and scatchard analysis yielded a Kd of 4.83 +/- 0.19 nM for this peptide. Derivatives of this peptide labeled with radioiodine ([*I]GMIBO) and the alpha-particle-emitting radiohalogen 211At N-(3-[211At]astato-4-guanidinomethylbenzoyl)-Phe1-octreotate; [211At]AGMBO} were prepared in a single step from a tin precursor in radiochemical yields of 30-35% and 15-20%, respectively. Paired-label internalization assays performed with the SSTR-positive D341 Med human medulloblastoma cell line demonstrated that [125I]GMIBO and [211At]AGMBO were specifically internalized 20-40% more than Nalpha-(1-deoxy-D-fructosyl)-[131I]I-Tyr3-octreotate ([131I]I-Glu-TOCA), the radioiodinated octreotide derivative previously shown to exhibit maximum internalization in this cell line. Uptake of [131I]GMIBO in D341 Med subcutaneous xenografts in a murine model (8.34 +/- 1.82 versus 8.10 +/- 2.23% ID/g at 1h) and SSTR-expressing normal tissues was comparable to that of [125I]I-Glu-TOCA and was shown to be specific. However, the uptake of [131I]GMIBO also was substantially higher in liver (16.9 +/- 3.15 versus 1.39 +/- 0.45% ID/g at 1 h) and in kidneys (44.33 +/- 6.47 versus 3.44 +/- 0.68% ID/g at 1h) compared to that of [125I]I-Glu-TOCA. These data suggest that these novel peptide conjugates retain their specificity for SSTR both in vitro and in vivo; however, because of their higher accumulation in normal tissues they would be best applied in settings amenable to loco-regional administration such as medulloblastoma neoplastic meningitis.

Evaluation of an internalizing monoclonal antibody labeled using N-succinimidyl 3-[131I]iodo-4-phosphonomethylbenzoate ([131I]SIPMB), a negatively charged substituent bearing acylation agent.

Monoclonal antibodies such as L8A4, reactive with the epidermal growth factor receptor variant III, internalize after receptor binding resulting in proteolytic degradation by lysosomes. Labeling internalizing mAbs requires the use of methodologies that result in the trapping of labeled catabolites in tumor cells after intracellular processing. Herein we have investigated the potential utility of N-succinimidyl-3-[131I]iodo-4-phosphonomethylbenzoate ([131I]SIPMB), an acylation agent that couples the corresponding negatively charged acid [131I]IPMBA to the protein, for this purpose. Biodistribution studies demonstrated that [131I]IPMBA cleared rapidly from normal tissues and exhibited thyroid levels < or =0.1% injected dose, consistent with a low degree of dehalogenation. Biodistribution experiments in athymic mice bearing subcutaneous D-256 human glioma xenografts were performed to compare L8A4 labeled using [131I]SIPMB to L8A4 labeled with 125I using both the analogous positively charged acylation agent N-succinimidyl-4-guanidinomethyl-3-[125I]iodobenzoate ([125I]SGMIB) and Iodogen. Tumor uptake of [131I]SIPMB-L8A4 (41.9+/-3.5% ID/g) was nearly threefold that of L8A4 labeled using Iodogen (14.0+/-1.1% ID/g) after 2 days, and tumor to tissue ratios remained uniformly high throughout with [131I]SIPMB-L8A4. Thyroid uptake increased for the Iodogen labeled mAb (3.55+/-0.36 %ID at 5 days) whereas that of [131I]SIPMB labeled mAb remained low (0.21+/-0.04% ID at 5 days). In the second biodistribution, L8A4 labeled using [131I]SIPMB and [125I]SGMIB showed no difference in normal tissue uptake and had nearly identical tumor uptake ([131I]SIPMB, 41.8+/-14.2% ID/g; [125I]SGMIB, 41.6+/-15.8% ID/g, at 4 days). These results suggest that [131I]SIPMB may be a viable acylation agent for the radioiodination of internalizing mAbs.

Primary cardiac paraganglioma.

We report a case of a 29-year-old male, who during workup of hypertension was found to have a malignant primary paraganglioma of the heart. The tumor arose from the site of the aortopulmonary window and right ventricular outflow tract (RVOT) and was removed with the aid of cardiopulmonary bypass. Reconstruction of the RVOT and pulmonary valve was necessary because of involvement by the tumor. The surgical course was uncomplicated, with normalization of catecholamine secretion and blood pressure.

Meta-iodobenzylguanidine derivatives containing a second guanidine moiety.

Radioiodinated meta-iodobenzylguanidine (MIBG) is used in the diagnosis and therapy of various neuroendocrine tumors. To investigate whether an additional guanidine function in the structure of MIBG will yield analogues that may potentially enhance tumor-to-target ratios, two derivatives-one with a guanidine moiety and another with a guanidinomethyl group at the 4-position of MIBG-were prepared. In the absence of any uptake-1 inhibiting conditions, the uptake of 4-guanidinomethyl-3-[(131)I]iodobenzylguanidine ([(131)I]GMIBG) by SK-N-SH cells in vitro was 1.7+/-0.1% of input counts, compared to a value of 40.3+/-1.4% for [(125)I[MIBG suggesting that guanidinomethyl group at the 4-position negated the biological properties of MIBG. On the other hand, 4-guanidino-3-[(131)I]iodobenzylguanidine ([(131)I]GIBG) had an uptake (5.6+/-0.3%) that was 12-13% that of [(125)I]MIBG (46.1+/-2.7%), and the ratio of uptake by control over DMI-treated (nonspecific) cultures was higher for [(131)I]GIBG (20.9+/-0.3) than [(125)I]MIBG itself (15.0+/-2.7). The exocytosis of [(131)I]GIBG and [(125)I]MIBG from SK-N-SH cells was similar. The uptake of [(131)I]GIBG in the mouse target tissues, heart and adrenals, as well as in a number of other tissues was about half that of [(125)I]MIBG. These results suggest that substitution of guanidine functions, especially a guanidinomethyl group, in MIBG structure may not be advantageous.

Atresia of coronary sinus ostium with retrograde drainage via persistent left superior vena cava.

Atesia of the coronary sinus ostium (ACSO) with retrograde drainage of cardiac veins via the left superior vena cava (LSVC) is a very rare abnormality. This condition is usually asymptomatic during life and a majority of the cases were reported as incidental postmortem findings. If there is retrograde venous drainage via persistent LSVC, this communication cannot be ligated irrespective of its size or the presence of a communicating vein because of resultant cardiac congestion and edema. We report herein a 9-month-old Chinese female who underwent repair of a perimembranous ventricular septal defect, patent ductus arteriosus and secundum atrial septal defect. During the operation, ligation of LSVC resulted in myocardial congestion and distension of the heart. The release of ligature decompressed the heart immediately.