Detection of smuggled cocaine in cargo using MDCT.

OBJECTIVE: Smuggling dissolved drugs, especially cocaine, in bottled liquids is an ongoing problem at borders. Common fluoroscopy of packages at the border cannot detect contaminated liquids. The objective of our study was to develop an MDCT screening method to detect cocaine-containing vessels that are hidden between uncontaminated ones in a shipment. MATERIALS AND METHODS: Studies were performed on three wine bottles containing cocaine solutions that were confiscated at the Swiss border. Reference values were obtained by scans of different sorts of commercially available wine and aqueous solutions of dissolved sugar. All bottles were scanned using MDCT, and data evaluation was performed by measuring the mean peak of Hounsfield units. To verify the method, simulated testing was performed. RESULTS: Using measurements of the mean peak of Hounsfield units enables the detection of dissolved cocaine in wine bottles in a noninvasive and rapid fashion. Increasing opacity corresponds well with the concentration of dissolved cocaine. Simulated testing showed that it is possible to distinguish between cocaine-contaminated and uncontaminated wine bottles. CONCLUSION: The described method is an efficacious screening method to detect cocaine-contaminated bottles that are hidden between untreated bottles in cargo. The noninvasive examination of cargo allows a questionable delivery to be tracked without arousing the suspicion of the smugglers.

Mutation in the human homeobox gene NKX5-3 causes an oculo-auricular syndrome.

Several dysmorphic syndromes affect the development of both the eye and the ear, but only a few are restricted to the eye and the external ear. We describe a developmental defect affecting the eye and the external ear in three members of a consanguineous family. This syndrome is characterized by ophthalmic anomalies (microcornea, microphthalmia, anterior-segment dysgenesis, cataract, coloboma of various parts of the eye, abnormalities of the retinal pigment epithelium, and rod-cone dystrophy) and a particular cleft ear lobule. Linkage analysis and mutation screening revealed in the first exon of the NKX5-3 gene a homozygous 26 nucleotide deletion, generating a truncating protein that lacked the complete homeodomain. Morpholino knockdown expression of the zebrafish nkx5-3 induced microphthalmia and disorganization of the developing retina, thus confirming that this gene represents an additional member implicated in axial patterning of the retina.

Silver-base metal epithermal vein and listwaenite types of deposit Crnac, Rogozna Mts., Kosovo. Part I: Ore mineral geochemistry and sulfur isotope study

Pb-Zn-Ag vein and listwaenite types of mineralization in Crnac deposit, Western Vardar zone, were deposited within several stages: (i) the pre-ore stage comprises pyrite, arsenopyrite, pyrrhotite, quartz, kaolinite and is followed by magnetite-pyrite; (ii) the syn-ore stage is composed of galena, sphalerite, tetrahedrite and stefanite; and (iii) the post-ore stage is composed of carbonates, pyrite, arsenopyrite and minor galena. The vein type mineralization is hosted by Jurassic amphibolites and veins terminate within overlying serpentinites. Mineralized listwaenites are developed along the serpentinite-amphibolite interface. The reserves are estimated to 1.7 Mt of ore containing in average 7.6% lead, 2.9% zinc, and 102 g/t silver. Sulfides from the pre- and syn-mineralization assemblage of the vein- and listwaenite-types of mineralization from the Crnac Pb-Zn-Ag deposit have been analyzed using microprobe, crush-leachates and sulfur isotopes. The pre-ore assemblage precipitated under high sulfur fugacities (f(S(2)) = 10(-8)-10(-6) bar) from temperatures ranging between 350 degrees C and 380 degrees C. Most likely water-rock reactions, boiling and/or increase of pH caused an increase of delta(34)S of pyrite toward upper levels within the deposit. The decomposition of pre-ore pyrrhotite to a pyrite-magnetite mixture occurred at a fugacity of sulfur from f(S(2)) = 8.7 x 10(-10) to 9.6 x 10(-9) bar and fugacity of oxygen from f(O(2)) = 2.4 x 10(-30) to 3.1 x 10(-28) bars, indicating a contribution of an oxidizing fluid, i.e. meteoric water during pre-ore stages of hydrothermal activity. The crystallization temperatures obtained by the sphalerite-galena isotope geothermometer range from 230 to 310 degrees C. The delta(34)S values of pre- and syn-ore sulfides (pyrite, galena, sphalerite, delta(34)S = 0.3-5.9 parts per thousand) point to magmatic sulfur. Values of delta(34)S of galena and sphalerite are decreasing upwards due to precipitation of early formed sulfide minerals. Post-ore assemblage precipitated at temperature below 190 degrees C. Based on data presented above, we assume two fluid sources: (i) a magmatic source, supported by sulfur isotopic compositions within pre- and syn-ore minerals and a high mol% of fluorine found within pre- and syn-ore leachates, and (ii) a meteoric source, deduced by coincident pyrite-magnetite intergrowth, sulfur isotopic trends within syn-ore minerals and decrease of crystallization temperatures from the pre-ore stage (380-350 degrees C), towards the syn-ore (310-215 degrees C) and post-ore stages (<190 degrees C). Post-ore fluids are Na-Ca-Mg-K-Li chlorine rich and were modified via water-rock reactions. Simple mineral assemblage and sphalerite composition range from 1.5 to 10.1 mol% of FeS catalog Crnac to a group of intermediate sulfidation epithermal deposit. (C) 2011 Elsevier B.V. All rights reserved.

Differential stress reaction of human colon cells to oleic-acid-stabilized and unstabilized ultrasmall iron oxide nanoparticles.

Therapeutic engineered nanoparticles (NPs), including ultrasmall superparamagnetic iron oxide (USPIO) NPs, may accumulate in the lower digestive tract following ingestion or injection. In order to evaluate the reaction of human colon cells to USPIO NPs, the effects of non-stabilized USPIO NPs (NS-USPIO NPs), oleic-acid-stabilized USPIO NPs (OA-USPIO NPs), and free oleic acid (OA) were compared in human HT29 and CaCo2 colon epithelial cancer cells. First the biophysical characteristics of NS-USPIO NPs and OA-USPIO NPs in water, in cell culture medium supplemented with fetal calf serum, and in cell culture medium preconditioned by HT29 and CaCo₂ cells were determined. Then, stress responses of the cells were evaluated following exposure to NS-USPIO NPs, OA-USPIO NPs, and free OA. No modification of the cytoskeletal actin network was observed. Cell response to stress, including markers of apoptosis and DNA repair, oxidative stress and degradative/autophagic stress, induction of heat shock protein, or lipid metabolism was determined in cells exposed to the two NPs. Induction of an autophagic response was observed in the two cell lines for both NPs but not free OA, while the other stress responses were cell- and NP-specific. The formation of lipid vacuoles/droplets was demonstrated in HT29 and CaCo₂ cells exposed to OA-USPIO NPs but not to NS-USPIO NPs, and to a much lower level in cells exposed to equimolar concentrations of free OA. Therefore, the induction of lipid vacuoles in colon cells exposed to OA utilized as a stabilizer for USPIO NPs is higly amplified compared to free OA, and is not observed in the absence of this lipid in NS-USPIO NPs.

Comparison of microsatellite instability and chromosomal instability in predicting survival of patients with T3N0 colorectal cancer.

BACKGROUND: At least 2 apparently independent mechanisms, microsatellite instability (MSI) and chromosomal instability, are implicated in colorectal tumorigenesis. Their respective roles in predicting clinical outcomes of patients with T3N0 colorectal cancer remain unknown. METHODS: Eighty-eight patients with a sporadic T3N0 colon or rectal adenocarcinoma were followed up for a median of 67 months. For chromosomal instability analysis, Ki-ras mutations were determined by single-strand polymerase chain reaction, and p53 protein staining was studied by immunohistochemistry. For MSI analysis, DNA was amplified by polymerase chain reaction at 7 microsatellite targets (BAT25, BAT26, D17S250, D2S123, D5S346, transforming growth factor receptor II, and BAX). RESULTS: Overall 5-year survival rate was 72%. p53 protein nuclear staining was detected in 39 patients (44%), and MSI was detected in 21 patients (24%). MSI correlated with proximal location (P <.001) and mucinous content (P <.001). In a multivariate analysis, p53 protein expression carried a significant risk of death (relative risk = 4.0, 95% CI = 1.6 to 10.1, P =.004). By comparison, MSI was not a statistically significant prognostic factor for survival in this group (relative risk = 2.2, 95% CI = 0.6 to 7.3, P =.21). CONCLUSIONS: p53 protein overexpression provides better prognostic discrimination than MSI in predicting survival of patients with T3N0 colorectal cancer. Although MSI is associated with specific clinicopathologic parameters, it did not predict overall survival in this group. Assessment of p53 protein expression by immunocytochemistry provides a simple means to identify a subset of T3N0 patients with a 4-times increased risk for death.

Ulnar Nerve Transposition at the Elbow under Local Anesthesia: A Patient Satisfaction Study.

Background Ulnar nerve decompression at the elbow traditionally requires regional or general anesthesia. We wished to assess the feasibility of performing ulnar nerve decompression and transposition at the elbow under local anesthesia. Methods We examined retrospectively the charts of 50 consecutive patients having undergone ulnar nerve entrapment surgery either under general or local anesthesia. Patients were asked to estimate pain on postoperative days 1 and 7 and satisfaction was assessed at 1 year. Results On day 1, pain was comparable among all groups. On day 7, pain scores were twice as high when transposition was performed under general anesthesia when compared with local anesthesia. Patient satisfaction was slightly increased in the local anesthesia group. These patients were significantly more willing to repeat the surgery. Conclusion Ulnar nerve decompression and transposition at the elbow can be performed under local anesthesia without added morbidity when compared with general anesthesia.

Minimization of Nyquist ghosting for echo-planar imaging at ultra-high fields based on a "negative readout gradient" strategy.

PURPOSE: To improve the traditional Nyquist ghost correction approach in echo planar imaging (EPI) at high fields, via schemes based on the reversal of the EPI readout gradient polarity for every other volume throughout a functional magnetic resonance imaging (fMRI) acquisition train. MATERIALS AND METHODS: An EPI sequence in which the readout gradient was inverted every other volume was implemented on two ultrahigh-field systems. Phantom images and fMRI data were acquired to evaluate ghost intensities and the presence of false-positive blood oxygenation level-dependent (BOLD) signal with and without ghost correction. Three different algorithms for ghost correction of alternating readout EPI were compared. RESULTS: Irrespective of the chosen processing approach, ghosting was significantly reduced (up to 70% lower intensity) in both rat brain images acquired on a 9.4T animal scanner and human brain images acquired at 7T, resulting in a reduction of sources of false-positive activation in fMRI data. CONCLUSION: It is concluded that at high B(0) fields, substantial gains in Nyquist ghost correction of echo planar time series are possible by alternating the readout gradient every other volume.

Shikonin-loaded antibody-armed nanoparticles for targeted therapy of ovarian cancer.

Conventional chemotherapy of ovarian cancer often fails because of initiation of drug resistance and/or side effects and trace of untouched remaining cancerous cells. This highlights an urgent need for advanced targeted therapies for effective remediation of the disease using a cytotoxic agent with immunomodulatory effects, such as shikonin (SHK). Based on preliminary experiments, we found SHK to be profoundly toxic in ovarian epithelial cancer cells (OVCAR-5 and ID8 cells) as well as in normal ovarian IOSE-398 cells, endothelial MS1 cells, and lymphocytes. To limit its cytotoxic impact solely to tumor cells within the tumor microenvironment (TME), we aimed to engineer SHK as polymeric nanoparticles (NPs) with targeting moiety toward tumor microvasculature. To this end, using single/double emulsion solvent evaporation/diffusion technique with sonication, we formulated biodegradable NPs of poly(lactic-co-glycolic acid) (PLGA) loaded with SHK. The surface of NPs was further decorated with solubilizing agent polyethylene glycol (PEG) and tumor endothelial marker 1 (TEM1)/endosialin-targeting antibody (Ab) through carbodiimide/N-hydroxysuccinimide chemistry. Having characterized the physicochemical and morphological properties of NPs, we studied their drug-release profiles using various kinetic models. The biological impact of NPs was also evaluated in tumor-associated endothelial MS1 cells, primary lymphocytes, and epithelial ovarian cancer OVCAR-5 cells. Based on particle size analysis and electron microscopy, the engineered NPs showed a smooth spherical shape with size range of 120 to 250 nm and zeta potential value of -30 to -40 mV. Drug entrapment efficiency was ~80%-90%, which was reduced to ~50%-60% upon surface decoration with PEG and Ab. The liberation of SHK from NPs showed a sustained-release profile that was best fitted with Wagner log-probability model. Fluorescence microscopy and flow cytometry analysis showed active interaction of Ab-armed NPs with TEM1-positive MS1 cells, but not with TEM1-negative MS1 cells. While exposure of the PEGylated NPs for 2 hours was not toxic to lymphocytes, long-term exposure of the Ab-armed and PEGylated NPs was significantly toxic to TEM1-positive MS1 cells and OVCAR-5 cells. Based on these findings, we propose SHK-loaded Ab-armed PEGylated PLGA NPs as a novel nanomedicine for targeted therapy of solid tumors.

Tectonomagmatic evolution of Western Amazonia: Geochemical characterization and zircon U-Pb geochronologic constraints from the Peruvian Eastern Cordilleran granitoids

The results of a coupled, in situ laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) U-Pb study on zircon and geochemical characterization of the Eastern Cordilleran intrusives of Peru reveal 1.15 Ga of intermittent magmatism along central Western Amazonia, the Earth's oldest active open continental margin. The eastern Peruvian batholiths are volumetrically dominated by plutonism related to the assembly and breakup of Pangea during the Paleozoic-Mesozoic transition. A Carboniferous-Permian (340-285 Ma) continental arc is identified along the regional orogenic strike from the Ecuadorian border (6 degrees S) to the inferred inboard extension of the Arequipa-Antofalla terrane in southern Peru (14 degrees S). Widespread crustal extension and thinning, which affected western Gondwana throughout the Permian and Triassic resulted in the intrusion of the late- to post-tectonic La Merced-San Ramon-type anatectites dated between 275 and 220 Ma, while the emplacement of the southern Cordillera de Carabaya peraluminous granitoids in the Late Triassic to Early Jurassic (220-190 Ma) represents, temporally and regionally, a separate tectonomagmatic event likely related to resuturing of the Arequipa-Antofalla block. Volcano-plutonic complexes and stocks associated with the onset of the present Andean cycle define a compositionally bimodal alkaline suite and cluster between 180 and 170 Ma. A volumetrically minor intrusive pulse of Oligocene age (ca. 30 Ma) is detected near the southwestern Cordilleran border with the Altiplano. Both post-Gondwanide (30-170 Ma), and Precambrian plutonism (691-1123 Ma) are restricted to isolated occurrences spatially comprising less than 15% of the Eastern Cordillera intrusives. Only one remnant of a Late Ordovician intrusive belt is recognized in the Cuzco batholith (446.5 +/- 9.7 Ma) indicating that the Famatinian arc system previously identified in Peru along the north-central Eastern Cordillera and the coastal Arequipa-Antofalla terrane also existed inboard of this parautochthonous crustal fragment. Hitherto unknown occurrences of late Mesoproterozoic and middle Neoproterozoic granitoids from the south-central cordilleran segment define magmatic events at 691 +/- 13 Ma, 751 +/- 8 Ma, 985 +/- 14 Ma, and 1071-1123 +/- 23 Ma that are broadly coeval with the Braziliano and Grenville-Sunsas orogenies, respectively. Our data suggest the existence of a continuous orogenic belt in excess of 3500 km along Western Amazonia during the formation of Rodinia, its ``early'' fragmentation prior to 690 Ma, and support a model of reaccretion of the Paracas-Arequipa-Antofalla terrane to western Gondwana in the Early Ordovician with subsequent detachment of the Paracas segment in form of the Mexican Oaxaquia microcontinent in Middle Ordovician. A tectonomagmatic model involving slab detachment, followed by underplating of cratonic margin by asthenospheric mantle is proposed for the genesis of the volumetrically dominant Late Paleozoic to early Mesozoic Peruvian Cordilleran batholiths.

Amlodipine and valsartan as components of a rational and effective fixed-dose combination.

Pharmacological treatment of hypertension is effective in preventing cardiovascular and renal complications. Calcium antagonists and blockers of the renin-angiotensin system are widely used today to initiate antihypertensive therapy but, when given as monotherapy, do not suffice in most patients to normalize blood pressure. Combining the two types of agents considerably increases the antihypertensive efficacy, but not at the expense of a deterioration of tolerability. This is exemplified by the experience accumulated with the recently developed fixed dose combination containing the AT(1)-receptor blocker valsartan (160 mg) and the dihydropyridine amlodipine (5 or 10 mg). In a randomized trial, an 8-week treatment normalized blood pressure (<140/90 mmHg) within 8 weeks in a large fraction of hypertensive patients (78.4% and 85.2% using the 5/160 [n = 371] and 10/160 mg [n = 377] dosage, respectively). Like all AT(1)-receptor blockers valsartan has a placebo-like tolerability. Valsartan prevents to a large extent the occurrence amlodipine-induced peripheral edema. Both amlodipine and valsartan have beneficial effects on cardiovascular morbidity and mortality, as well as protective effects on renal function. The co-administration of these two agents is therefore very attractive, as it enables a rapid and sustained blood pressure control in hypertensive patients. The availability of a fixed-dose combination based on amlodipine and valsartan is expected therefore to facilitate the management of hypertension, to improve long-term adherence with antihypertensive therapy and, ultimately, to have a positive impact on cardiovascular and renal outcomes.

Electromyographic, cerebral, and muscle hemodynamic responses during intermittent, isometric contractions of the biceps brachii at three submaximal intensities.

This study examined the electromyographic, cerebral and muscle hemodynamic responses during intermittent isometric contractions of biceps brachii at 20, 40, and 60% of maximal voluntary contraction (MVC). Eleven volunteers completed 2 min of intermittent isometric contractions (12/min) at an elbow angle of 90° interspersed with 3 min rest between intensities in systematic order. Surface electromyography (EMG) was recorded from the right biceps brachii and near infrared spectroscopy (NIRS) was used to simultaneously measure left prefrontal and right biceps brachii oxyhemoglobin (HbO2), deoxyhemoglobin (HHb), and total hemoglobin (Hbtot). Transcranial Doppler ultrasound was used to measure middle cerebral artery velocity (MCAv) bilaterally. Finger photoplethysmography was used to record beat-to-beat blood pressure and heart rate. EMG increased with force output from 20 to 60% MVC (P < 0.05). Cerebral HbO2 and Hbtot increased while HHb decreased during contractions with differences observed between 60% vs. 40% and 20% MVC (P < 0.05). Muscle HbO2 decreased while HHb increased during contractions with differences being observed among intensities (P < 0.05). Muscle Hbtot increased from rest at 20% MVC (P < 0.05), while no further change was observed at 40 and 60% MVC (P > 0.05). MCAv increased from rest to exercise but was not different among intensities (P > 0.05). Force output correlated with the root mean square EMG and changes in muscle HbO2 (P < 0.05), but not changes in cerebral HbO2 (P > 0.05) at all three intensities. Force output declined by 8% from the 1st to the 24th contraction only at 60% MVC and was accompanied by systematic increases in RMS, cerebral HbO2 and Hbtot with a leveling off in muscle HbO2 and Hbtot. These changes were independent of alterations in mean arterial pressure. Since cerebral blood flow and oxygenation were elevated at 60% MVC, we attribute the development of fatigue to reduced muscle oxygen availability rather than impaired central neuronal activation.

Controls on 13C and 14C variability in soil CO2

14C dating of groundwater depends on the isotopic composition of both the solid carbonate and the soil CO2 and requires the use of 14C age correction models. To better assess the variability of the 14C activity of soil CO2 (A14Csoil-CO2) and the δ13C of soil CO2 (δ13Csoil-CO2), which are two parameters used in 14C age correction models, we studied the different processes involving carbon isotopes in the soil. The approach used experimental data from two sites in France (Fontainebleau sands and Astian sands) and a steady-state transport model. In most cases, the 14C activity (A14C) of atmospheric CO2 is directly used in the 14C age correction models as the A14Csoil-CO2. However, we demonstrate that since 1950, the evolution of the A14Csoil-CO2 reflects the competition between the fluxes of root-derived CO2 and organic matter-derived CO2. Therefore, the A14Csoil-CO2 must be used to date groundwater that is younger than 60 years old. Moreover, the δ13C of soil CO2 (δ13Csoil-CO2) showed large seasonal variations that must be taken into account in selecting the δ13Csoil-CO2 for 14C age correction models.

Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters.

Inactivating mutations of the Ten-Eleven Translocation 2 (TET2) gene were first identified in myeloid malignancies and more recently in peripheral T-cell lymphomas (PTCLs). In the present study, we investigated the presence of TET2 coding sequence mutations and their clinical relevance in a large cohort of 190 PTCL patients. TET2 mutations were identified in 40 of 86 (47%) cases of angioimmunoblastic T-cell lymphoma (AITL) and in 22 of 58 (38%) cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), but were absent in all other PTCL entities, with the exception of 2 of 10 cases of enteropathy-associated T-cell lymphoma. Among PTCL-NOS, a heterogeneous group of lymphoma-comprising cases likely to derive from Th follicular (T(FH)) cells similarly to AITL, TET2 mutations were more frequent when PTCL-NOS expressed T(FH) markers and/or had features reminiscent of AITL (58% vs 24%, P = .01). In the AITL and PTCL-NOS subgroups, TET2 mutations were associated with advanced-stage disease, thrombocytopenia, high International Prognostic Index scores, and a shorter progression-free survival.