Phase I evaluation of CycloSam® (Sm-153-DOTMP) bone seeking radiopharmaceutical in dogs with spontaneous appendicular osteosarcoma.

153 Sm-DOTMP (CycloSam® ) is a newly-patented radiopharmaceutical for bone tumor treatment. DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate) is a macrocyclic chelating agent with superior binding properties to 153 Sm when compared with EDTMP (Quadramet™, used for palliative treatment of bone cancer). CycloSam® was administered at 1 mCi/kg (37 MBq/kg) in a prospective pilot study to seven dogs with bone cancer resulting in no myelosuppression. Then, 13 dogs were enrolled in a prospective clinical trial study using traditional 3+3 dose escalation and starting at 1.5 mCi/kg. Baseline evaluation included hematologic and biochemical testing, diagnosis confirmation, thoracic and limb radiographs, technetium-99 m-HDP bone scintigraphy, and 18 F-FDG PET scan (SUVmax). Toxicity (primary endpoint) was assessed through weekly blood counts and adverse events. Dogs received 1.5 mCi/kg (n = 4), 1.75 mCi/kg (n = 6), and 2 mCi/kg (n = 3) of 153 Sm-DOTMP. Dose-limiting neutropenia and thrombocytopenia were seen at 2 mCi/kg. No dose-limiting nonhematologic toxicities occurred. Efficacy (secondary endpoint) was assessed by objective lameness measurement (body-mounted inertial sensors), owner quality-of-life (QoL) questionnaire, and repeat PET scan. Objective lameness measurement improved in four dogs (53%-60% decrease) was equivocal in three dogs, and worsened in four dogs (66%-115% increase); two dogs were not evaluable. Repeat 18 F-FDG PET scan results varied and change in lameness did not consistently correlate with SUVmax changes. QoL score worsened (n = 5) or was improved/stable (n = 7). Carboplatin chemotherapy (300 mg/m2 IV every 3 weeks ×4) started 4 weeks after 153 Sm-DOTMP injection. No dog died of chemotherapy-related complications. All dogs completed study monitoring. The recommended dose for CycloSam® in dogs is 1.75 mCi/kg, which resulted in some pain control with minimal toxicity and was safely combined with chemotherapy.

Electrical and Low Frequency Noise Characterization of Graphene Chemical Sensor Devices Having Different Geometries.

Chemiresistive graphene sensors are promising for chemical sensing applications due to their simple device structure, high sensitivity, potential for miniaturization, low-cost, and fast response. In this work, we investigate the effect of (1) ZnO nanoparticle functionalization and (2) engineered defects onto graphene sensing channel on device resistance and low frequency electrical noise. The engineered defects of interest include 2D patterns of squares, stars, and circles and 1D patterns of slots parallel and transverse to the applied electric potential. The goal of this work is to determine which devices are best suited for chemical sensing applications. We find that, relative to pristine graphene devices, nanoparticle functionalization leads to reduced contact resistance but increased sheet resistance. In addition, functionalization lowers 1/f current noise on all but the uniform mesa device and the two devices with graphene strips parallel to carrier transport. The strongest correlations between noise and engineering defects, where normalized noise amplitude as a function of frequency f is described by a model of AN/fγ, are that γ increases with graphene area and contact area but decreases with device total perimeter, including internal features. We did not find evidence of a correlation between the scalar amplitude, AN, and the device channel geometries. In general, for a given device area, the least noise was observed on the least-etched device. These results will lead to an understanding of what features are needed to obtain the optimal device resistance and how to reduce the 1/f noise which will lead to improved sensor performance.

Functional analysis of a conserved domain in SWITCH1 reveals a role in commitment to female meiocyte differentiation in Arabidopsis.

We have investigated the mechanism of action of SWITCH1/DYAD (SWI1), an important regulator of plant meiosis in Arabidopsis that is required for meiotic chromosome organization including maintenance of sister chromatid cohesion. The central portion of SWI1 contains a domain of unknown function that shows strong conservation between SWI1 and its orthologs in maize and rice and is also found in paralogs including MALE MEIOCYTE DEATH 1 (MMD1). In order to examine the role of this domain we performed domain swap experiments into SWI1 in a swi1 mutant background. Domain swap analysis revealed functional conservation of the central domain between SWI1 and its orthologs but not with the domain from MMD1 suggesting that the domain plays an important role in SWI1 function that has been conserved in orthologs and diverged in paralogs in plant evolution. Analysis of expression of the non-complementing MMD1 domain swap SWI1(DSMMD1)::GFP transgenic lines revealed an altered pattern of expression that suggests a role for SWI1 in commitment to female meiocyte differentiation and meiosis. The results suggest that SWI1 may also play a developmental role as an identity determinant in the female germ cell lineage in addition to its known role in meiotic chromosome organization.

All's Not Well(ens) that Ends Well: Case Study of Significant Thebesian Veins Mimicking Wellens Syndrome.

Thebeisan veins are microfistulous connections between a coronary arterial branch directly to a ventricular or atrial chamber. Extensive thebesian veins that empty into the left ventricle can cause typical chest pain symptoms, troponin elevation, and ischemic EKG changes from coronary steal leading to acute coronary syndrome in extreme cases. Literature review exposed a consistent pattern of EKG findings among patients with extensive thebesian veins involving all three major coronary arteries. We present a case study as an example of this rare anatomic finding of extensive thebesian veins draining into the left ventricle causing acute coronary syndrome in a symptomatic patient with elevated troponin and ischemic changes on EKG. This same EKG pattern that is present in our patient was discovered to be consistent among available case studies reviewed that had included an EKG tracing in their report. A newly proposed association between the ischemic changes on EKG due to extensive thebeisan veins and those of a severe proximal left anterior descending coronary artery stenotic lesion was discovered. The newly discovered consistency in the EKG pattern with acute coronary syndrome caused by extensive thebesian veins is the same pattern as that seen in Wellens Syndrome.