A Randomized, Double-Blind, Dose-Finding, Multicenter, Phase 2 Study of Radium Chloride (Ra 223) in Patients with Bone Metastases and Castration-Resistant Prostate Cancer

BACKGROUND: Patients with castration-resistant prostate cancer (CRPC) and bone metastases have an unmet clinical need for effective treatments that improve quality of life and survival with a favorable safety profile. OBJECTIVE: To prospectively evaluate the efficacy and safety of three different doses of radium chloride (Ra 223) in patients with CRPC and bone metastases. DESIGN, SETTING, AND PARTICIPANTS: In this phase 2 double-blind multicenter study, 122 patients were randomized to receive three injections of Ra 223 at 6-wk intervals, at doses of 25 kBq/kg (n=41), 50 kBq/kg (n=39), or 80 kBq/kg (n=42). The study compared the proportion of patients in each dose group who had a confirmed decrease of =50% in baseline prostate-specific antigen (PSA) levels. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Efficacy was evaluated using blood samples to measure PSA and other tumor markers, recorded skeletal-related events, and pain assessments. Safety was evaluated using adverse events (AEs), physical examination, and clinical laboratory tests. The Jonckheere-Terpstra test assessed trends between groups. RESULTS AND LIMITATIONS: The study met its primary end point with a statistically significant dose-response relationship in confirmed =50% PSA declines for no patients (0%) in the 25-kBq/kg dose group, two patients (6%) in the 50-kBq/kg dose group, and five patients (13%) in the 80-kBq/kg dose group (p=0.0297). A =50% decrease in bone alkaline phosphatase levels was identified in six patients (16%), 24 patients (67%), and 25 patients (66%) in the 25-, 50-, and 80-kBq/kg dose groups, respectively (p

Isotopic, trace element and nutrient characterization of coastal waters from Ubatuba inner shelf area, south-eastern Brazil

Stable isotopes, tritium, radium isotopes, radon, trace elements and nutrients data were collected during two sampling campaigns in the Ubatuba coastal area (south-eastern Brazil) with the aim of investigating submarine groundwater discharge (SGD) in the region. The isotopic composition (delta D, delta(18)O, (3)H) of submarine waters was characterised by significant variability and heavy isotope enrichment. The stable isotopes and tritium data showed good separation of groundwater and seawater groups. The contribution of groundwater in submarine waters varied from a few % to 17%. Spatial distribution of (222)Rn activity concentration in surface seawater revealed changes between 50 and 200 Bq m(-3) which were in opposite relationship with observed salinities. Time series measurements of (222)Rn activity concentration in Flamengo Bay (from 1 to 5 kBq m(-3)), obtained by in situ underwater gamma-spectrometry showed a negative correlation between the (222)Rn activity concentration and tide/salinity. This may be caused by sea level changes as tide effects induce variations of hydraulic gradients, which increase (222)Rn concentration during lower sea level, and opposite, during high tides where the (222)Rn activity concentration is smaller. The estimated SGD fluxes varied during 22-26 November between 8 and 40 cm d(-1), with an average value of 21 cm d(-1) (the unit is cm(3)/cm(2) per day). The radium isotopes and nutrient data showed scattered distributions with offshore distance and salinity. which implies that in a complex coast with many small bays and islands, the area has been influenced by local currents and groundwater-seawater mixing. SGD in the Ubatuba area is fed by coastal contaminated groundwater and re-circulated seawater (with small admixtures of groundwater). which claims for potential environmental concern with implications on the management of freshwater resources in the region. (C) 2007 Elsevier Ltd. All rights reserved.

(223)Ra and other bone-targeting radiopharmaceuticals-the translation of radiation biology into clinical practice

Osseous metastases are a source of significant morbidity for patients with a variety of cancers. Radiotherapy is well established as an effective means of palliating symptoms associated with such metastases. The role of external beam radiotherapy is limited where sites of metastases are numerous and widespread. Low linear energy transfer (LET) radionuclides have been utilized to allow targeted delivery of radiotherapy to disparate sites of disease, with evidence of palliative benefit. More recently, the bone targeting, high LET radionuclide (223)Ra has been shown to not only have a palliative effect but also a survival prolonging effect in metastatic, castration-resistant prostate cancer with bone metastases. This article reviews the different radionuclide-based approaches for targeting bone metastases, with an emphasis on (223)Ra, and key elements of the underlying radiobiology of these that will impact their clinical effectiveness. Consideration is given to the remaining unknowns of both the basic radiobiological and applied clinical effects of (223)Ra as targets for future research.

Bone-targeting radiopharmaceuticals including radium-223

ABSTRACT: Bone-seeking radionuclides including samarium-153 ethylene diamine tetramethylene phosphonate and strontium-89 have been used for decades in the palliation of pain from bone metastases especially from prostate cancer. Emerging evidence of improved survival in metastatic castration-resistant prostate cancer (CRPC) with the first-in-class a-radionuclide, radium-223 (Ra) has rekindled interest in the role of bone-seeking radionuclide therapy.We review the literature for randomized controlled trials of bone-seeking radionuclides and explore some of the issues regarding the optimal use of these agents. In particular, we discuss dose, dose rate, radiobiology, and quality of radiation and postulate on potential future directions in particular combination schedules. ß-Emitting, bone-seeking radionuclides have proven ability to control pain in prostate cancer metastatic to bone with pain response rates in the order of 60% to 70% when used as single agents. Most of the published trials were underpowered to detect differences in survival; however, there is evidence of the potential for disease modification when these agents are used in combination with chemotherapy or in multiple cycles.Data from the recent phase III ALSYMPCA trial that compared Ra to placebo in symptomatic CRPC demonstrate a significant improvement in median overall survival of 3.6 months for patients with symptomatic CRPC metastatic to bone treated with 6 cycles of the a-emitting radionuclide Ra compared with placebo. The success of Ra in improving survival in CRPC will lead this agent to become part of the treatment paradigm for this disease, and with such an excellent safety profile, Ra has huge potential in combination strategies as well as for use earlier in the natural history of metastatic prostate cancer.

Quadrupole moments of radium isotopes from the 7p^2P_3/2 hyperfine structure in Ra II

The hyperfine structure and isotope shift of ^{221- 226}Ra and ^{212, 214}Ra have been measured in the ionic (Ra 11) transition 7s^2 S_{1/2} - 7p ^2 P_{3/2} (\lamda = 381.4 nm). The method of on-line collinear fast-beam laser spectroscopy has been applied using frequency-doubling of cw dye laser radiation in an external ring cavity. The magnetic hyperfine fields are compared with semi-empirical and ab initio calculations. The analysis of the quadrupole splitting by the same method yields the following, improved values of spectroscopic quadrupole moments: Q_s(^221 Ra)= 1.978(7)b, Q_s (^223 Ra)= 1.254(3)b and the reanalyzed values Q_s(^209 Ra) = 0.40(2)b, Q_s(^211 Ra) = 0.48(2)b, Q_s(^227 Ra)= 1.58(3)b, Q_s (^229 Ra) = 3.09(4)b with an additional scaling uncertainty of ±5%. Furthermore, the J-dependence of the isotope shift is analyzed in both Ra II transitions connecting the 7s^2 S_{1/2} ground state with the first excited doublet 7p^ P_{1/2} and 7p^ P_{3/2}.

Poster abstract : Energy-efficient rate adaptive MAC Protocol (RA-MAC) for long-lived sensor networks

This paper introduces an energy-efficient Rate Adaptive MAC (RA-MAC) protocol for long-lived Wireless Sensor Networks (WSN). Previous research shows that the dynamic and lossy nature of wireless communication is one of the major challenges to reliable data delivery in a WSN. RA-MAC achieves high link reliability in such situations by dynamically trading off radio bit rate for signal processing gain. This extra gain reduces the packet loss rate which results in lower energy expenditure by reducing the number of retransmissions. RA-MAC selects the optimal data rate based on channel conditions with the aim of minimizing energy consumption. We have implemented RA-MAC in TinyOS on an off-the-shelf sensor platform (TinyNode), and evaluated its performance by comparing RA-MAC with state-ofthe- art WSN MAC protocol (SCP-MAC) by experiments.

Validation of the Drinking Refusal Self-Efficacy Questionnaire - Revised in an Adolescent Sample (DRSEQ-RA)

Adolescent drinking is a significant issue yet valid psychometric tools designed for this group are scarce. The Drinking Refusal Self-Efficacy Questionnaire—Revised Adolescent Version (DRSEQ-RA) is designed to assess an individual's belief in their ability to resist drinking alcohol. The original DRSEQ-R consists of three factors reflecting social pressure refusal self-efficacy, opportunistic refusal self-efficacy and emotional relief refusal self-efficacy. A large sample of 2020 adolescents aged between 12 and 19 years completed the DRSEQ and measures of alcohol consumption in small groups. Using confirmatory factor analysis, the three factor structure was confirmed. All three factors were negatively correlated with both frequency and volume of alcohol consumption. Drinkers reported lower drinking refusal self-efficacy than non-drinkers. Taken together, these results suggest that the adolescent version of the Drinking Refusal Self-Efficacy Questionnaire (DRSEQ-RA) is a reliable and valid measure of drinking refusal self-efficacy.

Remembering the Peel Island Lazaret through re-imagining the Teerk Roo Ra forest

This paper discusses my current research which aims to re-member the site of the Peel Island Lazaret through re-imagining the Teerk Roo Ra forest as a series of animated artworks. Teerk Roo Ra National Park (formally known as Peel Island) is a small island in Moreton Bay, Queensland and is visible on the ferry journey from Cleveland to Stradbroke Island. The island has an intriguing history, and is the site of a former Lazaret and quarantine station. The Lazaret treated patients diagnosed with Hansen’s disease (or Leprosy), and operated between 1907 and 1959. In this paper I will discuss conceptions of the non-indigenous historical context of the Peel Island Lazaret and the notion of the liminal state (Turner,1967). Through this discussion conceptions of place from Australian cultural theorist Ross Gibson are also examined. The concept of two overlapping realms is then explored through the clues and shared stories about the people who inhabited the site. There is then an explanation of my own approach to re-member this place through re-imagining the forest that witnessed the events of the Lazaret. I then draw on theories of the uncanny from German Psychiatrist Ernst Jentsch, Austrian Neurologist Sigmund Freud and South African animation theorist Meg Rickards to argue that my experience of the forest of Teerk Roo Ra was an uncanny experience where two worlds or states of mind existed simultaneously and overlapped, causing a viscerally unsettling uncanny experience. Through an analysis of Czech Surrealist Animator Jan Švankmajer’s cinematic narrative Down to the cellar (1982), my creative work Structure #24(2011), and Australian Artist Patricia Piccinini’s cinematic artwork The Gathering (2007), I discuss the situation of the inanimate and the animate co-existing simultaneously. Using this approach I propose an understanding of the uncanny as an intellectual uncertainty as outlined by Jentsch (1906). I also develop the notion of the familiar being concealed and becoming unfamiliar through mimicry (Freud, 1919). These discussions form an introduction to my creative work Nocturne #5(2014) which re-members the forests of Teerk Roo Ra as an uncanny place primarily expressed through animation.

Zapys zemelʹnyĭ Na pravo korystovanni︠a︡ zemli︠u︡, shcho znakhoditʹsi︠a︡ v Odeskoï guberni Peryletravenʹsʹkyĭ okruzi Kantakuzenʹsʹy raʹoni pid nazvoi︠u︡ Trudovyshyĭ artilʹ Slava

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Zapys zemelʹnyĭ Na pravo korystovanni︠a︡ zemli︠u︡, shcho znakhoditʹsi︠a︡ v Odeskoï guberni Peryletravenʹsʹkyĭ okruzi Kantakuzenʹsʹy raʹoni pid nazvoi︠u︡ Trudovyshyĭ artilʹ Slava

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Sobre as alterações no crédito imobiliário e outras referentes à política habitacional contidas na MP 2.212 de 30/8/01 e nas MPs 2.221 e 2.223 de 4/9/01

Consultoria Legislativa - Área VII - Finanças, Direito Comercial, Direito Econômico, Defesa do Consumidor - Área XI - Meio Ambiente, Geografia, Urbanismo, Arquitetura.

Diário da Constituinte [gravação de vídeo] : [programa n. 223]

Continua o impasse na Assembleia Nacional Constituinte sobre o sistema de governo. O Relator da Comissão de Sistematização da Assembleia Nacional Constituinte (ANC), Deputado Bernardo Cabral (PMDB-AM) ainda não se decidiu entre o presidencialismo, parlamentarismo puro e híbrido. O Deputado Manoel Moreira (PMDB-SP) declara que a preocupação é encontrar um sistema que tenha condições de governabilidade ao país. Cidadãos opinam sobre o tema. O Relator Bernardo Cabral declara sua opinião sobre o parlamentarismo. O Deputado Theodoro Mendes (PMDB-SP) apresenta proposta mantendo o presidencialismo, mas com o fortalecimento do Legislativo. A emenda do Senador Nelson Carneiro (PMDB-RJ) adota o parlamentarismo, mas dá ao presidente o poder de exonerar o primeiro-ministro. O Deputado Cid Carvalho (PMDB-MA) tenta o consenso, com a proposta do parlamentarismo adotado de forma gradual e mandato de seis anos para o Presidente José Sarney. O Senador Fernando Henrique Cardoso (PMDB-SP) admite a necessidade de um período de adaptação, mas não de dois ou três anos. O Deputado Victor Faccioni (PDS-RS) defende o parlamentarismo.

Hizkuntza idatziaren i(ra)kaskuntza Urtxintxa metodoari jarraituz

Lan hau, Ikastolen Elkarteak sortutako Urtxintxa metodoaren 5 urteko irakaslearen gidaliburuen idazten eta irakurtzen irakasteko atalaren analisian oinarritzen da. Proiektu hau ikuspegi konstruktibista batetik eratu da, beraz, honetan idazten eta irakurtzen irakasteko erabiltzen den materialek teoria konstruktibistari jarraitzen diote. Material hau aztertu da Haur Hezkuntzako 5 urteko gelan idazketa eta irakurketa lantzeko zein neurritan erabilgarria den ezagutzeko helburuarekin. Ikerketaren ondorioek agerian utzi dute Urtxintxa modu eraikitzailean eta globalizatuan hizkuntza idatzia lantzeko gida erabilgarria dela. Idazketa-irakurketaren inguruan proposatzen diren jarduerek hizkuntza idatziaren erabilera funtzionala sustatzen dute eta horrela, haurren ikasketa esanguratsua ziurtatzen dute.