Clinical Best Practices for Radiation Safety During Lutetium-177 Therapy.

IMPORTANCE: 177 Lu therapy as part of theranostic treatment for cancer is expanding but it can be a challenge for sites with limited radiation protection staff to implement the radiation safety program required for therapeutic nuclear medicine. OBJECTIVE: To increase the adoption of 177 Lu therapy, especially in smaller centers and clinics, by providing a collection of radiation safety best practices and operational experience. To provide a resource for radiation safety officers supporting the implementation of a 177 Lu therapy program. METHODS: A panel of 11 radiation safety professionals representing sites across Canada and the United States with experience delivering 177 Lu therapy was assembled and discussed their responses to a list of questions focused on the following radiation safety topics: facility layout and design; radiation safety program; and drug management and patient care. RESULTS: A comprehensive set of best practice guidelines for clinical radiation safety during 177 Lu therapy has been developed based on the collective operational experience of a group of radiation safety professionals. Significant findings included that 177 Lu therapy is often safely administered in unshielded rooms, that staff radiation exposure associated with 177 Lu therapy is minimal relative to other nuclear medicine programs, and that some relatively simple preparation in advance including papering of common surfaces and planning for incontinence can effectively control contamination during therapy. CONCLUSION: The guidance contained in this paper will assist radiation safety professionals in the implementation of safe, effective 177 Lu therapy programs, even at smaller sites with limited to no experience in therapeutic nuclear medicine.

Node-Dependent Photoinduced Electron Transfer in Third-Generation 2D MOFs Containing Earth-Abundant Metal Ions.

Five isostructural 2D metal-organic frameworks (MOFs), based on a photoactive CuI metallolinker and mixed mono-/dinuclear secondary building units (SBUs), are reported. The MOFs 1(M) (M = Mn, Co, Cu, Zn, and Cd) exhibit broad absorption across the visible-light spectrum and emission centered at ca. 730 nm. Upon photoexcitation, the rigidity of the framework hinders the pseudo-Jahn-Teller distortion of the metallolinker's excited state, providing efficient intersystem crossing into the triplet state. Rapid luminescence quenching in 1(Cu) and 1(Co) suggests photoinduced electron transfer (PET) to the SBUs, whereas lifetimes of up to 22.2 ns are observed in 1(Zn). The quantum yields relative to the parent photosensitizer (PS) decrease for metal nodes containing transition metal ions with partially occupied d-orbitals but increase for the d10 systems CdII and ZnII by a factor of up to 6. Importantly, the excited state decay rates directly correlate with the occupancy of the [MII(OH2)]x moieties in the MOFs providing nonradiative decay pathways via O-H oscillators. Cyclovoltammetry reveals minor changes in CuI/II oxidation potential, with excited-state reduction potentials for 1(M) rivalling Ru analogues. These results establish bis(diimine)copper(I) photosensitizers as viable metallolinkers for MOFs and present a rare example of an isostructural series obtained from a photosensitive metallolinker.

Light-harvesting, 3rd generation RuII/CoII MOF with a large, tubular channel aperture.

A photoactive, hetero-metallic CoII/RuII-based metal-organic framework (MOF) with a large channel aperture, ca. 21 Å, is reported. The photophysical properties of the MOF are derived from the RuII nodes giving rise to emission centred at ca. 620 nm and relatively long triplet 3MLCT lifetimes. In addition to the optical attributes, the 1H-imidazo [4,5-f][1,10]-phenanthroline ligand imparts structural functionality to the MOF which is composed of alternating CoII- and RuII-based nodes of Δ and Λ helicity. The framework maintains its integrity upon activation and shows gas sorption behaviour that is characteristic of mesoporous materials promoting high CO2 sorption capacities and selectivities over N2.

Oxide-mediated recovery of field-effect mobility in plasma-treated MoS2.

Precise tunability of electronic properties of two-dimensional (2D) nanomaterials is a key goal of current research in this field of materials science. Chemical modification of layered transition metal dichalcogenides leads to the creation of heterostructures of low-dimensional variants of these materials. In particular, the effect of oxygen-containing plasma treatment on molybdenum disulfide (MoS2) has long been thought to be detrimental to the electrical performance of the material. We show that the mobility and conductivity of MoS2 can be precisely controlled and improved by systematic exposure to oxygen/argon plasma and characterize the material using advanced spectroscopy and microscopy. Through complementary theoretical modeling, which confirms conductivity enhancement, we infer the role of a transient 2D substoichiometric phase of molybdenum trioxide (2D-MoO x ) in modulating the electronic behavior of the material. Deduction of the beneficial role of MoO x will serve to open the field to new approaches with regard to the tunability of 2D semiconductors by their low-dimensional oxides in nano-modified heterostructures.

The risk of unintentional out-of-network encounters with hospital-based physicians at in-network hospitals.

OBJECTIVE: When hospital-based specialists including emergency physicians, anesthesiologists, pathologists and radiologists are not included in the same insurance networks as their parent hospitals, it creates confusion and leads to unexpected costs for patients. This study explored the frequency with which hospital-based physicians at academic medical centers are not included in the network directories for the same insurance networks as their parent teaching hospitals. METHODS: We studied teaching hospitals with residency programs in all four hospital-based specialties. Using insurance plan provider directories, we determined whether each teaching hospital was in-network for randomly selected locally available insurance plans offered through the federal and state marketplace exchanges. For each established hospital-network relationship, we then determined whether hospital-based specialists were included in the provider network directory by searching for the name of each specialty's residency program director and the name of the physician practice group. RESULTS: We identified 79 teaching hospitals participating in 144 locally available insurance plan networks. Hospital-based specialist inclusion in these hospital-network relationships was: emergency physicians: 50.0% (CI: 40%-59%); anesthesiologists: 50.0% (CI: 42%-58%); pathologists: 45.4% (CI: 37%-54%); and radiologists: 55.1% (46%-64%). Inclusion of all four hospital-based specialties occurred in only 45.0% (CI: 36%-54%) of the hospital-network relationships. CONCLUSION: For insurance plans offered through the federal and state marketplace exchanges, hospital-based specialists frequently are not included in the directories for the insurance networks in which their parent teaching hospitals participate. Further research is needed to explore this issue at non-academic hospitals and for off-exchange insurance products, and to determine effective policy solutions.

Ag colloids and arrays for plasmonic non-radiative energy transfer from quantum dots to a quantum well.

Non-radiative energy transfer (NRET) can be an efficient process of benefit to many applications including photovoltaics, sensors, light emitting diodes and photodetectors. Combining the remarkable optical properties of quantum dots (QDs) with the electrical properties of quantum wells (QWs) allows for the formation of hybrid devices which can utilize NRET as a means of transferring absorbed optical energy from the QDs to the QW. Here we report on plasmon-enhanced NRET from semiconductor nanocrystal QDs to a QW. Ag nanoparticles in the form of colloids and ordered arrays are used to demonstrate plasmon-mediated NRET from QDs to QWs with varying top barrier thicknesses. Plasmon-mediated energy transfer (ET) efficiencies of up to ∼25% are observed with the Ag colloids. The distance dependence of the plasmon-mediated ET is found to follow the same d -4 dependence as the direct QD to QW ET. There is also evidence for an increase in the characteristic distance of the interaction, thus indicating that it follows a Förster-like model with the Ag nanoparticle-QD acting as an enhanced donor dipole. Ordered Ag nanoparticle arrays display plasmon-mediated ET efficiencies up to ∼21%. To explore the tunability of the array system, two arrays with different geometries are presented. It is demonstrated that changing the geometry of the array allows a transition from overall quenching of the acceptor QW emission to enhancement, as well as control of the competition between the QD donor quenching and ET rates.

Influence of plasmonic array geometry on energy transfer from a quantum well to a quantum dot layer.

A range of seven different Ag plasmonic arrays formed using nanostructures of varying shape, size and gap were fabricated using helium-ion lithography (HIL) on an InGaN/GaN quantum well (QW) substrate. The influence of the array geometry on plasmon-enhanced Förster resonance energy transfer (FRET) from a single InGaN QW to a ∼80 nm layer of CdSe/ZnS quantum dots (QDs) embedded in a poly(methyl methacrylate) (PMMA) matrix is investigated. It is shown that the energy transfer efficiency is strongly dependent on the array properties and an efficiency of ∼51% is observed for a nanoring array. There were no signatures of FRET in the absence of the arrays. The QD acceptor layer emission is highly sensitive to the array geometry. A model was developed to confirm that the increase in the QD emission on the QW substrate compared with a GaN substrate can be attributed solely to plasmon-enhanced FRET. The individual contributions of direct enhancement of the QD layer emission by the array and the plasmon-enhanced FRET are separated out, with the QD emission described by the product of an array emission factor and an energy transfer factor. It is shown that while the nanoring geometry results in an energy transfer factor of ∼1.7 the competing quenching by the array, with an array emission factor of ∼0.7, results in only an overall gain of ∼14% in the QD emission. The QD emission was enhanced by ∼71% for a nanobox array, resulting from the combination of a more modest energy transfer factor of 1.2 coupled with an array emission factor of ∼1.4.

Uncooled CMOS terahertz imager using a metamaterial absorber and pn diode.

We demonstrate a low-cost uncooled terahertz (THz) imager fabricated in a standard 180 nm CMOS process. The imager is composed of a broadband THz metamaterial absorber coupled with a diode microbolometer sensor where the pn junction is used as a temperature sensitive device. The metamaterial absorber array is integrated in the top metallic layers of a six metal layer process allowing for complete monolithic integration of the metamaterial absorber and sensor. We demonstrate the capability of the detector for stand-off imaging applications by using it to form transmission and reflection images of a metallic object hidden in a manila envelope.

Feedback network models for quantum transport.

Quantum feedback networks have been introduced in quantum optics as a framework for constructing arbitrary networks of quantum mechanical systems connected by unidirectional quantum optical fields, and has allowed for a system theoretic approach to open quantum optics systems. Our aim here is to establish a network theory for quantum transport systems where typically the mediating fields between systems are bidirectional. Mathematically, this leads us to study quantum feedback networks where fields arrive at ports in input-output pairs, making it a special case of the unidirectional theory where inputs and outputs are paired. However, it is conceptually important to develop this theory in the context of quantum transport theory-the resulting theory extends traditional approaches which tend to view the components in quantum transport as scatterers for the various fields, in the process allowing us to consider emission and absorption of field quanta by these components. The quantum feedback network theory is applicable to both Bose and Fermi fields, moreover, it applies to nonlinear dynamics for the component systems. We advance the general theory, but study the case of linear passive quantum components in some detail.

Principles and applications of quantum control engineering.

This is a brief survey of quantum feedback control and specifically follows on from the two-day conference Principles and applications of quantum control engineering, which took place in the Kavli Royal Society International Centre at Chicheley Hall, on 12-13 December 2011. This was the eighth in a series of principles and applications of control to quantum systems workshops.

Single photon quantum filtering using non-Markovian embeddings.

We determine quantum master and filter equations for continuous measurement of systems coupled to input fields in certain non-classical continuous-mode states, specifically single photon states. The quantum filters are shown to be derivable from an embedding into a larger non-Markovian system, and are given by a system of coupled stochastic differential equations.

On structure-preserving transformations of the Ito generator matrix for model reduction of quantum feedback networks.

Two standard operations of model reduction for quantum feedback networks, elimination of internal connections under the instantaneous feedback limit and adiabatic elimination of fast degrees of freedom, are cast as structure-preserving transformations of Ito generator matrices. It is shown that the order in which they are applied is inconsequential.

Non-abelian Weyl commutation relations and the series product of quantum stochastic evolutions.

We show that the series product, which serves as an algebraic rule for connecting state-based input-output systems, is intimately related to the Heisenberg group and the canonical commutation relations. The series product for quantum stochastic models then corresponds to a non-abelian generalization of the Weyl commutation relation. We show that the series product gives the general rule for combining the generators of quantum stochastic evolutions using a Lie-Trotter product formula.

Can peak expiratory flow measurements differentiate chronic obstructive pulmonary disease from congestive heart failure?

Dyspneic patients are commonly encountered by Emergency Medical Service (EMS). Frequent causes include Chronic Obstructive Pulmonary Disease (COPD) and Congestive Heart Failure (CHF). Measurement of peak expiratory flow rate (PEFR) has been proposed to help differentiate COPD from CHF. This prospective, cohort, pilot study was conducted to determine if PEFR in patients with an exacerbation of COPD were significantly different than CHF. Included were patients presenting with dyspnea plus a history of COPD and/or CHF. A PEFR was measured, values were compared to predicted average, and a percentage was calculated. Twenty-one patients were enrolled. Six had a diagnosis of COPD, 12 CHF; 3 had other diagnoses. Mean percentage of predicted PEFR with COPD was 26.36%, CHF 48.9% (P = 0.04). Patients presenting with acute COPD had significantly lower percentage of predicted PEFR than those with CHF. These results suggest that PEFR may be useful in differentiating COPD from CHF. This study should be expanded to the prehospital setting with a larger number of subjects.

Microbial infections in eight genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis.

BACKGROUND: The authors have previously reported genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) based on expression of 88 human genes. AIM: To attempt to reproduce these findings, determine the specificity of this signature to CFS/ME, and test for associations between CFS/ME subtype and infection. METHODS: Expression levels of 88 human genes were determined in blood of 62 new patients with idiopathic CFS/ME (according to Fukuda criteria), six patients with Q-fever-associated CFS/ME from the Birmingham Q-fever outbreak (according to Fukuda criteria), 14 patients with endogenous depression (according to DSM-IV criteria) and 29 normal blood donors. RESULTS: In patients with CFS/ME, differential expression was confirmed for all 88 genes. Q-CFS/ME had similar patterns of gene expression to idiopathic CFS/ME. Gene expression in patients with endogenous depression was similar to that in the normal controls, except for upregulation of five genes (APP, CREBBP, GNAS, PDCD2 and PDCD6). Clustering of combined gene data in CFS/ME patients for this and the authors' previous study (117 CFS/ME patients) revealed genomic subtypes with distinct differences in SF36 scores, clinical phenotypes, severity and geographical distribution. Antibody testing for Epstein-Barr virus, enterovirus, Coxiella burnetii and parvovirus B19 revealed evidence of subtype-specific relationships for Epstein-Barr virus and enterovirus, the two most common infectious triggers of CFS/ME. CONCLUSIONS: This study confirms the involvement of these genes in CFS/ME.

Antibody to parvovirus B19 nonstructural protein is associated with chronic arthralgia in patients with chronic fatigue syndrome/myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a neuro-immune disease of uncertain pathogenesis. Human parvovirus B19 infection has been shown to occur just prior to development of the onset of CFS/ME in several cases, although B19 seroprevalence studies do not show any significant differences between CFS/ME and controls. In this study, we analysed parvovirus B19 markers in CFS/ME patients (n=200), diagnosed according to Fukuda CDC criteria, and normal blood donors (n=200). Serum from each subject was tested for anti-B19 VP2 IgM and IgG (by Biotrin ELISA), anti-B19 NS1 IgM and IgG (by immunofluorescence), and B19 DNA (by real-time PCR). CFS/ME patients and normal blood donors had a similar B19 seroprevalence (75 % versus 78 %, respectively). Eighty-three CFS patients (41.5 %) as compared with fourteen (7 %) normal blood donors tested positive for anti-B19 NS1 IgG (chi(2)=64.8; P<0.0001; odds ratio=9.42, CI 5.11-17.38). Of these 83 patients, 61 complained of chronic joint pain, while 22 did not. Parvovirus B19 DNA was detected in serum of 11 CFS patients and none of the controls by Taqman real-time PCR (chi(2)=9.35, P<0.002). Positivity for anti-B19 NS1 IgG was associated with higher expression levels of the human CFS-associated genes NHLH1 and GABPA. As NS1 antibodies are thought to indicate chronic or severe courses of B19 infection, these findings suggest that although the seroprevalence of B19 in CFS patients is similar to controls, the immune control of the virus in these patients may not be efficient.

Gene expression subtypes in patients with chronic fatigue syndrome/myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. We set out to determine the precise abnormalities of gene expression in the blood of patients with CFS/ME. We analyzed gene expression in peripheral blood from 25 patients with CFS/ME diagnosed according to the Centers for Disease Control and Prevention diagnostic criteria and 50 healthy blood donors, using a microarray with a cutoff fold difference of expression of >or=2.5. Genes showing differential expression were further analyzed in 55 patients with CFS/ME and 75 healthy blood donors, using quantitative polymerase chain reaction. Differential expression was confirmed for 88 genes; 85 were upregulated, and 3 were downregulated. Highly represented functions were hematological disease and function, immunological disease and function, cancer, cell death, immune response, and infection. Clustering of quantitative polymerase chain reaction data from patients with CFS/ME revealed 7 subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes, and severity.

Parathyroid adenoma radiation dose simulator.

INTRODUCTION: As the number of radioisotope localization cases increased at our facility, the pathologists expressed concern regarding radiation exposure from parathyroid specimens. The radiation safety officer was consulted to analyze personnel radiation protection issues. METHODS: Analysis of simulated specimens was performed for a range of activities and masses corresponding to the values that have been observed. The radiation dose rates from these samples were measured using a Ludlum Model 14C survey meter with a Model 44-38 energy compensated GM probe and a Ludlum Model 3 Geiger counter with a Model 44-9 "pancake" style GM probe (Ludlum Measurements, Inc., Sweetwater, Texas). Additionally, 3 consecutive 10-second counts were performed using a USSC Navigator Gamma Guidance System (United States Surgical Corporation, Norwalk, CT). The per-second average readings were recorded. RESULTS: Our sample count-rates ranged from 139 to 2,830 counts/second. The majority of these values fell within the 100 to 1,000 count/second range typically observed during surgery. Based on our sample set, our dose rates at contact with these samples ranged from 0.17 to 4.0 mR/hour depending on the instrument, sample activity, and sample volume. The variation between count rate and dose rate for each observed volume varied linearly with activity. CONCLUSION: Based on these observed radiation doses, we concluded that there is no need to hold parathyroid specimens for 24 to 48 hours after surgical removal for handling because the typical radiation doses are quite low and would not result in significant radiation exposure to pathology personnel.

Recombinant TSH-stimulated, radioguided differentiated thyroid carcinoma surgery.

A novel approach to locating and surgically resecting occult metastatic foci in a 25-year-old female with a history of total thyroidectomy for differentiated thyroid carcinoma was attempted. Two iodine-131 (131I) body scans were performed: one after the patient underwent a 2-3 week thyroxine withdrawal, and another the following week utilizing recombinant TSH-stimulation. Then the patient was treated with 151 mCi of 131I, and 2 weeks later, without further hormonal manipulation, she had radioguided surgery. The two diagnostic 131I body scans were negative, but the post-therapy scan was positive. Two weeks later after pre-operative skin marking, radioguided surgery localized metastatic foci in the central compartment neck just dorsal to the suprasternal notch. No other foci were identified with the probe at surgery. At pathology, 2 of the 12 nodes were positive, as well as a 1 mm metastatic focus in the fat. Provocative imaging protocols, aggressive radioiodine therapy, and the novel use of radioguided surgery to attempt a cure in an 131I image-negative metastatic thyroid carcinoma patient was performed. No other cases using these combined diagnostic and therapeutic efforts have been reported in the literature.