Diagnosis and Management of Paget's Disease of Bone in Adults: A Clinical Guideline.

An evidence-based clinical guideline for the diagnosis and management of Paget's disease of bone (PDB) was developed using GRADE methodology, by a Guideline Development Group (GDG) led by the Paget's Association (UK). A systematic review of diagnostic tests and pharmacological and nonpharmacological treatment options was conducted that sought to address several key questions of clinical relevance. Twelve recommendations and five conditional recommendations were made, but there was insufficient evidence to address eight of the questions posed. The following recommendations were identified as the most important: 1) Radionuclide bone scans, in addition to targeted radiographs, are recommended as a means of fully and accurately defining the extent of metabolically active disease in patients with PDB. 2) Serum total alkaline phosphatase (ALP) is recommended as a first-line biochemical screening test in combination with liver function tests in screening for the presence of metabolically active PDB. 3) Bisphosphonates are recommended for the treatment of bone pain associated with PDB. Zoledronic acid is recommended as the bisphosphonate most likely to give a favorable pain response. 4) Treatment aimed at improving symptoms is recommended over a treat-to-target strategy aimed at normalizing total ALP in PDB. 5) Total hip or knee replacements are recommended for patients with PDB who develop osteoarthritis in whom medical treatment is inadequate. There is insufficient information to recommend one type of surgical approach over another. The guideline was endorsed by the European Calcified Tissues Society, the International Osteoporosis Foundation, the American Society of Bone and Mineral Research, the Bone Research Society (UK), and the British Geriatric Society. The GDG noted that there had been a lack of research on patient-focused clinical outcomes in PDB and identified several areas where further research was needed. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

Zoledronate in the prevention of Paget's (ZiPP): protocol for a randomised trial of genetic testing and targeted zoledronic acid therapy to prevent SQSTM1-mediated Paget's disease of bone.

INTRODUCTION: Paget's disease of bone (PDB) is characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Complications include bone pain, deformity, deafness and pathological fractures. Mutations in sequestosome-1 (SQSTM1) are strongly associated with the development of PDB. Bisphosphonate therapy can improve bone pain in PDB, but there is no evidence that treatment alters the natural history of PDB or prevents complications. The Zoledronate in the Prevention of Paget's disease trial (ZiPP) will determine if prophylactic therapy with the bisphosphonate zoledronic acid (ZA) can delay or prevent the development of PDB in people who carry SQSTM1 mutations. METHODS AND ANALYSIS: People with a family history of PDB aged >30 years who test positive for SQSTM1 mutations are eligible to take part. At the baseline visit, participants will be screened for the presence of bone lesions by radionuclide bone scan. Biochemical markers of bone turnover will be measured and questionnaires completed to assess pain, health-related quality of life (HRQoL), anxiety and depression. Participants will be randomised to receive a single intravenous infusion of 5 mg ZA or placebo and followed up annually for between 4 and 8 years at which point baseline assessments will be repeated. The primary endpoint will be new bone lesions assessed by radionuclide bone scan. Secondary endpoints will include changes in biochemical markers of bone turnover, pain, HRQoL, anxiety, depression and PDB-related skeletal events. ETHICS AND DISSEMINATION: The study was approved by the Fife and Forth Valley Research Ethics Committee on 22 December 2008 (08/S0501/84). Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results of this trial will inform clinical practice by determining if early intervention with ZA in presymptomatic individuals with SQSTM1 mutations can prevent or slow the development of bone lesions with an adverse event profile that is acceptable. TRIAL REGISTRATION NUMBER: ISRCTN11616770.

Acellular comet assay: a tool for assessing variables influencing the alkaline comet assay.

In this study, an acellular modification to the alkaline comet assay to further evaluate key variables within the assay that may influence the outcome of genotoxicity studies is described. This acellular comet assay can detect differences of 0.2 Gy of (60)Co gamma-ray radiation between 0 and 1 Gy and differences of 1 Gy between 0 and 8 Gy; thus, this assay is applicable for a wide range of DNA damage levels. It is also shown that DNA damage from different radiation energies was not significantly different from (60)Co gamma-ray. This assay displayed a statistical increase in DNA damage due to uncontrolled exposure to natural light; however, the slope of the dose-response curve for light-exposed samples was similar to that for samples protected from light. A comparison of the alkaline comet assay with the acellular comet assay allowed for the intrinsic repair capacity of the alkaline comet assay to be quantified.

Excretion of volatile ¹³¹I from rats following administration of Na¹³¹I or MIBG-¹³¹I.

Current practice for radiation protection associated with (131)I therapy mainly focuses on external and internal exposure caused by physical contamination of the hospital staff, other patients and family members. However, if volatile (131)I is excreted by the treated patients, these individuals could also be exposed through inhalation of (131)I. This study quantifies the amount of volatile (131)I excreted by rats after intravenous administration of metaiodobenzylguanidine (MIBG)-(131)I or Na(131)I, the two most common forms of (131)I therapy. The results indicate that in 4 d following administration, the total excretion of volatile (131)I was 0.036 and 0.17 % of the administered activities of MIBG-(131)I and Na(131)I, respectively. As administered activities for (131)I therapy are typically of the order of 1-10 GBq, the overall excretion of volatile (131)I from a patient can be as high as 20 MBq. As a result, a family member can receive up to 0.07 mSv committed effective dose from inhaling the volatile (131)I excreted by the patient.

Metabolism of 210Po in rats: volatile 210Po from faeces.

The metabolic formation of volatile (210)Po species in a rat that was intravenously administered with (210)Po-citrate was investigated in this study. A slurry of the faecal sample was prepared in water and was bubbled with nitrogen gas in a closed system. The discharged gas was passed through a trapping device filled with liquid scintillation cocktail in order to capture any volatile (210)Po species. The amount of (210)Po trapped in the scintillation cocktail was measured by a liquid scintillation analyser that provided evidence of the presence of volatile (210)Po species in the faeces. The presence of volatile (210)Po in the faeces indicates that the metabolic formation of volatile (210)Po is likely to occur in the gut due to bacterial activity. The amount of volatile (210)Po species was compared with the daily faecal excretion of (210)Po. After 2 h of bubbling, the volatile (210)Po collected from the faeces sample was found to be between 1.0 and 1.7 % of the daily faecal excretion for the 4 d following (210)Po-citrate administration.

Biokinetics of ²¹°Po in rats: excretion via urine and faeces and retention in tissues and organs.

Daily excretions of ²¹°Po from rats via urine and faeces following i.v. administration of polonium citrate, from Day 2 to Day 5, were reported, together with retentions in tissues and organs on Day 5. Emphasis is given to the methods of measurement and data quality rather than to the discussion of the observations. The authors aim to contribute data for developing or refining the biokinetic model for ²¹°Po metabolism.

Highly-photoluminescent ZnSe nanocrystals via a non-injection-based approach with precursor reactivity elevated by a secondary phosphine.

Highly-photoluminescent ZnSe quantum dots with 72% quantum yield and 22 nm full width at half maximum were synthesized with more reactive precursors via a non-injection approach with high synthetic reproducibility; (31)P NMR provided insight into the formation mechanisms of ZnSe monomers.

Low-temperature approach to high-yield and reproducible syntheses of high-quality small-sized PbSe colloidal nanocrystals for photovoltaic applications.

Small-sized PbSe nanocrystals (NCs) were synthesized at low temperature such as 50-80 °C with high reaction yield (up to 100%), high quality, and high synthetic reproducibility, via a noninjection-based one-pot approach. These small-sized PbSe NCs with their first excitonic absorption in wavelength shorter than 1200 nm (corresponding to size < ∼3.7 nm) were developed for photovoltaic applications requiring a large quantity of materials. These colloidal PbSe NCs, also called quantum dots, are high-quality, in terms of narrow size distribution with a typical standard deviation of ∼7-9%, excellent optical properties with high quantum yield of ∼50-90% and small full width at half-maximum of ∼130-150 nm of their band-gap photoemission peaks, and high storage stability. Our synthetic design aimed at promotion of the formation of PbSe monomers for fast and sizable nucleation with the presence of a large number of nuclei at low temperature. For formation of the PbSe monomer, our low-temperature approach suggests the existence of two pathways of Pb-Se (route a) and Pb-P (route b) complexes. Either pathway may dominate, depending on the method used and its experimental conditions. Experimentally, a reducing/nucleation agent, diphenylphosphine, was added to enhance route b. The present study addresses two challenging issues in the NC community, the monomer formation mechanism and the reproducible syntheses of small-sized NCs with high yield and high quality and large-scale capability, bringing insight to the fundamental understanding of optimization of the NC yield and quality via control of the precursor complex reactivity and thus nucleation/growth. Such advances in colloidal science should, in turn, promote the development of next-generation low-cost and high-efficiency solar cells. Schottky-type solar cells using our PbSe NCs as the active material have achieved the highest power conversion efficiency of 2.82%, in comparison with the same type of solar cells using other PbSe NCs, under Air Mass 1.5 global (AM 1.5G) irradiation of 100 mW/cm(2).

International workshop on emergency radiobioassay: considerations, gaps and recommendations.

An international workshop on emergency radiobioassay was held in Ottawa, Canada, 1-3 September 2010. Sixty-five scientists and public health officials from five countries attended the workshop and gave 36 presentations. During the workshop, many considerations were raised, gaps identified, and recommendations given for emergency radiobioassay for both preparedness and response in case of a radiological or nuclear incident. In short, some bioassay methods and protocols need to be developed, validated, and exercised; national and international radiobioassay laboratory networks should be established; and communications and collaborations among public health officials, monitoring experts, and medical staff are encouraged. All these activities are required to make us better prepared for an RN emergency.

Low-temperature noninjection approach to homogeneously-alloyed PbSe(x)S(1-x) colloidal nanocrystals for photovoltaic applications.

Homogeneously alloyed PbSe(x)S(1-x) nanocrystals (NCs) with their excitonic absorption peaks in wavelength shorter than 1200 nm were developed for photovoltaic (PV) applications. Schottky-type solar cells fabricated with our PbSe0.3S0.7 NCs as their active materials reached a high power conversion efficiency (PCE) of 3.44%, with an open circuit voltage (V(oc)) of 0.49 V, short circuit photocurrent (J(sc)) of 13.09 mA/cm², and fill factor (FF) of 0.54 under Air Mass 1.5 global (AM 1.5G) irradiation of 100 mW/cm². The syntheses of the small-sized colloidal PbSe(x)S(1-x) NCs were carried out at low temperature (60 °C) with long growth periods (such as 45 min) via a one-pot noninjection-based approach in 1-octadecene (ODE), featuring high reaction yield, high product quality, and high synthetic reproducibility. This low-temperature approach employed Pb(oleate)2 as a Pb precursor and air-stable low-cost thioacetamide (TAA) as a S source instead of air-sensitive high-cost bis(trimethylsilyl)sulfide ((TMS)2S), with n-tributylphosphine selenide (TBPSe) as a Se precursor instead of n-trioctylphosphine selenide (TOPSe). The reactivity difference of TOPSe made from commercial TOP 90% and TBPSe made from commercial TBP 97% and TBP 99% was addressed with in situ observation of the temporal evolution of NC absorption and with ³¹P nuclear magnetic resonance (NMR). Furthermore, the addition of a strong reducing/nucleation agent diphenylphosphine (DPP) promoted the reactivity of the Pb precursor through the formation of a Pb-P complex, which is much more reactive than Pb(oleate)2. Thus, the reactivity of TBPSe was increased more than that of TAA. The larger the DPP-to-Pb feed molar ratio, the more the Pb-P complex, the higher the Se amount in the resulting homogeneously alloyed PbSe(x)S(1-x) NCs. Therefore, the use of DPP allowed reactivity match of the Se and S precursors and led to sizable nucleation at low temperature so that long growth periods became feasible. The present study brings insight into the formation mechanism of monomers, nucleation/growth of colloidal composition-tunable NCs, and materials design and synthesis for next-generation low-cost and high-efficiency solar cells.

MEDECOR--a medical decorporation tool to assist first responders, receivers, and medical reach-back personnel in triage, treatment, and risk assessment after internalization of radionuclides.

After a radiological dispersal device (RDD) event, it is possible for radionuclides to enter the human body through inhalation, ingestion, and skin and wound absorption. From a health physics perspective, it is important to know the magnitude of the intake to perform dosimetric assessments. From a medical perspective, removal of radionuclides leading to dose aversion (hence risk reduction) is of high importance. The efficacy of medical decorporation strategies is extremely dependent upon the time of treatment delivery after intake. The "golden hour," or more realistically 3-4 h, is optimal when attempting to increase removal of radionuclides from extracellular fluids prior to cellular incorporation. To assist medical first response personnel in making timely decisions regarding appropriate treatment delivery modes, it is desirable to have a software tool that compiles existing radionuclide decorporation therapy data and allows a user to perform simple diagnosis leading to optimized decorporation treatment strategies. In its most simple application, the software is a large database of radionuclide decorporation strategies and treatments. The software can also be used in clinical interactive mode, in which the user inputs the radionuclide, estimated activity, route of intake and time since exposure. The software makes suggestions as to the urgency of treatment (i.e., triage) and the suggested therapy. Current developments include risk assessment which impacts the potential risk of delivered therapy and resource allocation of therapeutic agents. The software, developed for the Canadian Department of National Defence (DND), is titled MEDECOR (MEdical DECORporation). The MEDECOR tool was designed for use on both personal digital assistant and laptop computer environments. The tool was designed using HTML/Jscript, to allow for ease of portability amongst different computing platforms. This paper presents the features of MEDECOR, results of testing at a major NATO exercise, and future development of this tool into MEDECOR2.

Metabolism of 210Po in rats: volatile 210Po in excreta.

Polonium-210 ((210)Po) is one of the most toxic radionuclides and was used as a poison in the Alexander Litvinenko case. In this study of the metabolism of (210)Po in rats, volatile (210)Po in excreta was measured, filling a knowledge gap of the previous studies. Five rats were intravenously administrated with 2 kBq and another five with 10 kBq of (210)Po (citrate form). They were housed in a glass Metabowl system for 4 d following the administration. Volatile (210)Po from the excreta was collected in a trapping system filled with liquid scintillation cocktail and was measured by liquid scintillation counting. Results showed that the daily excretion of volatile (210)Po by the rats is in a very small percentage (0.002-0.009 %) of the administered amounts. However, if the administered amount is large, the excretion of volatile (210)Po can be significant.

Medical preparedness for chemical, biological, radiological, nuclear, and explosives (CBRNE) events: gaps and recommendations.

The Workshop on Medical Preparedness for Chemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) events: national scan was held on 20 and 21 May 2010 at the Diefenbunker Museum in Ottawa, Canada. The purpose of the workshop was to provide the CBRNE Research and Technology Initiative with a Canadian national profile of existing capabilities and anticipated gaps in casualty management consistent with the community emergency response requirements. The workshop was organised to enable extensive round-table discussions and provide a summary of key gaps and recommendations for emergency response planners.

Dealing with at-risk populations in radiological/nuclear emergencies.

In a mass casualty event, there will be at-risk populations that will require unique triage, treatment and consequence management to minimise immediate and long-term health effects. This statement is particularly true for radiological/nuclear (R/N) disasters where individuals exhibit a broad range of physiological responses to radiation exposure. For example, immunocompromised individuals will experience more detrimental radiation health effects; however, it is not always possible to definitively identify these individuals at the time of triage. Immediate and long-term consequence management for these individuals may require unique and potentially limited resources. Thus, at the time of an R/N event, it is crucial to assist community planners by: (a) rapidly identifying at-risk individuals who may have been exposed; (b) determining the dose and individual-specific health risks associated with radiation exposure; (c) identifying additional resources needed to deal with unique, population-specific requirements; and (d) developing treatment strategies in keeping with the rules of 'supply and demand'. A comprehensive approach to identifying issues relevant to the R/N emergency preparedness for dealing with at-risk populations will be discussed with the aim of defining future research objectives.

Issues, considerations and recommendations on emergency preparedness for vulnerable population groups.

The Workshop on Emergency Preparedness for Vulnerable Population Groups was held on 2 and 3 March 2009 in Ottawa, ON, Canada. The purpose of the workshop was to enhance communications within the emergency community response network and to identify the needs and gaps of emergency preparedness against chemical, biological, radiological, nuclear and explosives events for vulnerable population groups. The workshop was organised to enable extensive round-table discussions and provide a summary of key issues, considerations and recommendations for emergency response planners.