Study of the impact of tissue density heterogeneities on 3-dimensional abdominal dosimetry: comparison between dose kernel convolution and direct monte carlo methods.

Dose kernel convolution (DK) methods have been proposed to speed up absorbed dose calculations in molecular radionuclide therapy. Our aim was to evaluate the impact of tissue density heterogeneities (TDH) on dosimetry when using a DK method and to propose a simple density-correction method. METHODS: This study has been conducted on 3 clinical cases: case 1, non-Hodgkin lymphoma treated with (131)I-tositumomab; case 2, a neuroendocrine tumor treatment simulated with (177)Lu-peptides; and case 3, hepatocellular carcinoma treated with (90)Y-microspheres. Absorbed dose calculations were performed using a direct Monte Carlo approach accounting for TDH (3D-RD), and a DK approach (VoxelDose, or VD). For each individual voxel, the VD absorbed dose, D(VD), calculated assuming uniform density, was corrected for density, giving D(VDd). The average 3D-RD absorbed dose values, D(3DRD), were compared with D(VD) and D(VDd), using the relative difference Δ(VD/3DRD). At the voxel level, density-binned Δ(VD/3DRD) and Δ(VDd/3DRD) were plotted against ρ and fitted with a linear regression. RESULTS: The D(VD) calculations showed a good agreement with D(3DRD). Δ(VD/3DRD) was less than 3.5%, except for the tumor of case 1 (5.9%) and the renal cortex of case 2 (5.6%). At the voxel level, the Δ(VD/3DRD) range was 0%-14% for cases 1 and 2, and -3% to 7% for case 3. All 3 cases showed a linear relationship between voxel bin-averaged Δ(VD/3DRD) and density, ρ: case 1 (Δ = -0.56ρ + 0.62, R(2) = 0.93), case 2 (Δ = -0.91ρ + 0.96, R(2) = 0.99), and case 3 (Δ = -0.69ρ + 0.72, R(2) = 0.91). The density correction improved the agreement of the DK method with the Monte Carlo approach (Δ(VDd/3DRD) < 1.1%), but with a lesser extent for the tumor of case 1 (3.1%). At the voxel level, the Δ(VDd/3DRD) range decreased for the 3 clinical cases (case 1, -1% to 4%; case 2, -0.5% to 1.5%, and -1.5% to 2%). No more linear regression existed for cases 2 and 3, contrary to case 1 (Δ = 0.41ρ - 0.38, R(2) = 0.88) although the slope in case 1 was less pronounced. CONCLUSION: This study shows a small influence of TDH in the abdominal region for 3 representative clinical cases. A simple density-correction method was proposed and improved the comparison in the absorbed dose calculations when using our voxel S value implementation.

El programa de cooperación interuniversitària de la AECID: 18 años de historia interrumpidos por la crisis econòmica

Nota on es vol fer constar la cancel·lació del “Programa de Cooperación Interuniversitaria” conegut per l'acrònim “PCI” de l' “Agencia Española de Cooperación Internacional para el Desarrollo” (AECID), un dels programes més exitosos y de més llarga tradició de la cooperació espanyola

Viabilidade econômica da produção de novilhas leiteiras a pasto em sistema de integração lavoura-pecuária

O objetivo deste trabalho foi avaliar a rentabilidade do sistema de integração lavoura-pecuária (ILP), em comparação ao cultivo de cereais de inverno e de plantas de cobertura para o plantio direto de soja e milho no verão. Foram comparados dados simulados de sistema agrícola tradicional com produção de grãos de milho e soja, no verão, e cultivo de trigo e plantas de cobertura do solo, no inverno; e dados de um trabalho publicado em que foram avaliadas combinações de pastagens (diversificadas ou puras) e categorias de animais (leves ou pesados), com produção de grãos de milho e soja, no verão, e pastejo no inverno. A análise econômica foi realizada com base nos resultados experimentais e simulada para uma propriedade de 100 ha. A ILP com recria de novilhas leiteiras em pastagens anuais de inverno, em substituição ao sistema convencional com cultivo de cereais de inverno e plantas de cobertura de solo para o plantio direto, é a alternativa mais rentável aos produtores.

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.

Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer.

INTRODUCTION: To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years. RESULTS: Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V(120) (urethral volume receiving &gt; or =120% of the prescribed HDR-B dose) was associated with acute (P=.047) and late &gt; or = grade 2 GU toxicities (P=.049). CONCLUSIONS: Late grades 3 and 4GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V(120) on GU toxicity should be validated in further studies.

Étude des biais sur la dose parentérale d'un nouveau médicament lors d'un essai clinique avec profil cinétique

Introduction et objectif: Lors d'essais cliniques, le pharmacien est responsable de la préparation et de la dispensation des médicaments à évaluer. Un article récent a toutefois montré que les aspects pharmaceutiques liés au contrôle de la dose administrée in fine étaient souvent mal contrôlés. Il peut exister une différence entre la dose nominale fournie par le certificat d'analyse du fabricant et la dose réellement administrée au sujet, biais qui se reporte en cascade sur l'estimation des paramètres pharmacocinétiques (PK), comme la clairance ou le volume de distribution. Ce travail visait à évaluer les biais entachant la quantité de médicament réellement injectée (iv/sc) aux volontaires d'un essai clinique étudiant la PK et la relation dose-réponse d'un nouveau produit biotechnologique. Méthode: La dose de médicament administrée lors de l'essai clinique (D) a été calculée de la manière suivante: D = C * V - pertes. La concentration du produit (C; titre nominal du fabricant) a été vérifiée par immuno-essai. Le volume de médicament injecté (V) a été déterminé pour chaque injection par pesée (n=72), en utilisant la masse de la seringue avant et après injection et la densité du produit. Enfin, une analyse in vitro a permis d'évaluer les pertes liées à l'adsorption du produit dans les lignes de perfusion et de choisir le dispositif adéquat in vivo. Résultats: La concentration du médicament s'est révélée proche du titre nominal (96 ± 7%), et a été utilisée comme référence. Le volume injecté était quant à lui entaché d'un biais systématique par rapport à la valeur théorique correspondant à 0.03 mL pour la dose minimale (i.e. 75% du volume à injecter à cette dose). Une analyse complémentaire a montré que cela s'expliquait par une réaspiration partielle de la solution médica-menteuse avant le retrait de la seringue après injection sc, due à l'élasticité du piston. En iv, le biais était par contre provoqué par une réaspiration du soluté de perfusion co-administré. Enfin, la mesure des quantités de médicament récupérées après injection dans le dispositif de perfusion a démontré des pertes minimales par adsorption. Discussion-conclusion: Cette étude confirme l'existence de biais inversement corrélés au volume et à la concentration du médicament administré, pouvant provoquer des erreurs importantes sur les paramètres PK. Ce problème est négligé ou insuffisamment considéré dans les protocoles de Phase I et nécessiterait une planification rigoureuse. Les procédures opératoires devraient attirer l'attention sur ce point crucial.

Adubação potássica em arroz irrigado conforme a capacidade de troca catiônica do solo

O objetivo deste trabalho foi avaliar a resposta do arroz irrigado por inundação à aplicação de doses de potássio, conforme a capacidade de troca catiônica (CTC) do solo. Foram utilizados 16 solos com diferentes valores de CTC a pH 7,0 (CTCpH7), divididos em duas classes: solos com CTCpH7 até 15 cmol c dm-3 e com CTCpH7 maior que esse valor. O experimento foi realizado nas safras agrícolas de 2005/2006 e 2006/2007, em oito locais por ano agrícola, com uso de diferentes cultivares de arroz, conforme o local ou o ano. Foram calculados os incrementos médios da produtividade de arroz pela aplicação das doses de K, em função da razão K/CTCpH7. A dose de máxima eficiência econômica (DMEE) de potássio foi calculada de acordo com os preços do fertilizante e do arroz, praticados de 2003 a 2012. O arroz respondeu de forma econômica à aplicação de potássio, em ambas as classes de CTCpH7 utilizadas, com maior incremento de produtividade nos solos com menor relação K/CTCpH7. Na média dos dez anos, a DMEE foi sempre superior a U$ 100,00 e maior nos solos com CTCpH7>15,0 cmol c dm-3.

Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial.

BACKGROUND: Three small trials suggest that intravenous immunoglobulin can affect biomarkers and symptoms of mild-to-moderate Alzheimer's disease. We tested the safety, effective dose, and infusion interval of intravenous immunoglobulin in such patients. METHODS: We did a multicentre, placebo-controlled phase 2 trial at seven sites in the USA and five in Germany. Participants with probable Alzheimer's disease aged 50-85 years were randomly assigned (by a computer-generated randomisation sequence, with block sizes of eight) to infusions every 4 weeks (0·2, 0·5, or 0·8 g intravenous immunoglobulin per kg bodyweight, or placebo) or infusions every 2 weeks (0·1, 0·25, or 0·4 g/kg, or placebo). Patients, caregivers, investigators assessing outcomes, and staff at imaging facilities and the clinical research organisation were masked to treatment allocation, but dispensing pharmacists, the statistician, and the person responsible for final PET analyses were not. Treatment was masked with opaque pouches and infusion lines. The primary endpoint was median area under the curve (AUC) of plasma amyloid β (Aβ)(1-40) between the last infusion and the final visit (2 weeks or 4 weeks depending on infusion interval) in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). FINDINGS: 89 patients were assessed for eligibility, of whom 58 were enrolled and 55 included in the primary analysis. Median AUC of plasma Aβ(1-40) was not significantly different for intravenous immunoglobulin compared with placebo for five of the six intervention groups (-18·0 [range -1347·0 to 1068·5] for 0·2 g/kg, -364·3 [-5834·5 to 1953·5] for 0·5 g/kg, and -351·8 [-1084·0 to 936·5] for 0·8 g/kg every 4 weeks vs -116·3 [-1379·0 to 5266·0] for placebo; and -13·8 [-1729·0 to 307·0] for 0·1 g/kg, and -32·5 [-1102·5 to 451·5] for 0·25 g/kg every 2 weeks vs 159·5 [51·5 to 303·0] for placebo; p>0·05 for all). The difference in median AUC of plasma Aβ(1-40) between the 0·4 g/kg every 2 weeks group (47·0 [range -341·0 to 72·5]) and the placebo group was significant (p=0·0216). 25 of 42 (60%) patients in the intervention group versus nine of 14 (64%) receiving placebo had an adverse event. Four of 42 (10%) patients in the intravenous immunoglobulin group versus four of 14 (29%) receiving placebo had a serious adverse event, including one stroke in the intervention group. INTERPRETATION: Intravenous immunoglobulin may have an acceptable safety profile. Our results did not accord with those from previous studies. Longer trials with greater power are needed to assess the cognitive and functional effects of intravenous immunoglobulin in patients with Alzheimer's disease.

Canakinumab Relieves Symptoms of Acute Flares and Improves Health-Related Quality Of Life (HRQoL) in Difficult-To-Treat Gouty Arthritis Patients by Suppressing Inflammation: Results of a Randomized, Dose-Ranging Study

RATIONALE:We investigated the impact of canakinumab, a fully human anti-interleukin-1b monoclonal antibody on inflammation and HRQoL in gouty arthritis patients.METHODS: In this 8-week, single-blind, dose-ranging study, patients with acute gouty arthritis flares, unresponsive/intolerant or contraindicated to NSAIDs and/or colchicine were randomized to single subcutaneous canakinumab (10, 25, 50, 90, or 150mg, N5143) or single intramuscular triamcinolone acetonide (TA, 40mg, N557). Patients assessed pain (Likert scale), physicians assessed clinical signs of joint inflammation, and HRQoL was recorded using SF-36.RESULTS: At baseline, 98% patients had moderate-to-extreme pain, 85% had moderate/severe joint swelling, 64-79% had elevated inflammatory markers and HRQoL scores indicated impaired physical function. Percentage of patients with no/mild pain was numerically greater in most canakinumab groups vs. TA, 24-72h post-dose; difference significant for 150mg group at these time-points (P<0.05). Canakinumab 150mg was associated with significantly lower Likert scores for tenderness [OR, 3.2; 95% CI, 1.27-7.89; P50.014] and swelling (OR, 2.7; 95% CI, 1.09-6.50, P50.032) at 72h vs. TA; erythema was not different. Median CRP and SAA levels normalized by 7 days post-dose in most canakinumab groups, but remained elevated in TA. Physical function improved at 7 days postdose in all groups, highest improvement for canakinumab 150mg. SF-36 scores for physical functioning and bodily pain with canakinumab 150mg approached US general population scores by 7 days post-dose and exceeded normal values by 8 weeks post-dose.CONCLUSION: Canakinumab 150mg produced significantly greater and rapid pain-relief and improvements in HRQoL vs. TAin acute gouty arthritis patients.

La Situació econòmica i turística a la Costa Brava

Visió de la realitat econòmica de la Costa Brava 20 anys després del Debat Costa Brava de 1976, sobretot centrat en l’activitat turística

Concentração eficiente e econômica de caulim para a proteção de algodoeiro contra o bicudo

Resumo:O objetivo deste trabalho foi determinar a concentração de caulim mais eficiente e econômica para a proteção de algodoeiro contra os danos causados pelo bicudo-do-algodoeiro (Anthonomus grandis). Utilizou-se o delineamento experimental de blocos ao acaso, com cinco tratamentos de pulverizações com caulim nas concentrações: 20, 40, 60, 80 e 100 g L-1. Determinaram-se os seguintes parâmetros: percentagem de botões florais com orifícios de oviposição por fêmeas do bicudo; resíduos de caulim depositados sobre as folhas e as brácteas do algodoeiro; média da produção; e receita líquida do algodão, por hectare, a partir da pesagem da pluma de algodão com caroço. As percentagens de botões florais com orifício de oviposição variaram de 13,6 a 30,8%; o resíduo médio de caulim depositado nas folhas, de 0,0010 a 0,0034 mg mm-2, e nas brácteas, de 0,0010 a 0,0034 mg mm-2; a produção variou de 348,1 a 717,8 kg ha-1; e a receita líquida de algodão de R$ 1.033,88 a R$ 2.098,86 por hectare. As concentrações de caulim mais eficientes para a proteção de algodoeiro contra o bicudo são as de 60, 80 e 100 g L-1; no entanto, a de 60 g L-1foi a mais econômica.

Frações ótimas da adubação com fósforo no pré-plantio e na fertirrigação por gotejamento de tomateiro

Resumo:O objetivo deste trabalho foi estabelecer frações ótimas da dosagem total de fósforo, a serem aplicadas no pré-plantio e na fertirrigação do tomateiro de crescimento determinado, bem como determinar o efeito das diferentes formas de aplicação do nutriente sobre sua distribuição espacial no solo. Os tratamentos consistiram de cinco esquemas de aplicação do fertilizante: 100, 75, 50, 25 e 0% da dose total de P, dividida entre o pré-plantio (superfosfato triplo incorporado ao solo) e a fertirrigação (ácido fosfórico). O experimento foi realizado em Latossolo Vermelho argiloso com duas classes de disponibilidade de P - 7,5 e 32,9 mg dm-3 (Mehlich-1). Os tratamentos não apresentaram efeito sobre as variáveis de produção do tomateiro cultivado no solo com alta disponibilidade de P. Entretanto, no solo com menor disponibilidade do nutriente, a fertirrigação com P apresentou efeito quadrático sobre a produtividade de frutos, a receita líquida e a taxa líquida de retorno. Os melhores resultados foram obtidos com a aplicação de metade da dose total de P pela fertirrigação. A fertirrigação possibilitou movimento vertical do nutriente no solo para até 30 cm de profundidade, e movimento horizontal de até 15 cm.