An investigation of dose calculation accuracy in intensity-modulated radiotherapy of sites in the head & neck

Knowledge of the accuracy of dose calculations in intensity-modulated radiotherapy of the head and neck is essential for clinical confidence in these highly conformal treatments. High dose gradients are frequently placed very close to critical structures, such as the spinal cord, and good coverage of complex shaped nodal target volumes is important for long term-local control. A phantom study is presented comparing the performance of standard clinical pencil-beam and collapsed-cone dose algorithms to Monte Carlo calculation and three-dimensional gel dosimetry measurement. All calculations and measurements are normalized to the median dose in the primary planning target volume, making this a purely relative study. The phantom simulates tissue, air and bone for a typical neck section and is treated using an inverse-planned 5-field IMRT treatment, similar in character to clinically used class solutions. Results indicate that the pencil-beam algorithm fails to correctly model the relative dose distribution surrounding the air cavity, leading to an overestimate of the target coverage. The collapsed-cone and Monte Carlo results are very similar, indicating that the clinical collapsed-cone algorithm is perfectly sufficient for routine clinical use. The gel measurement shows generally good agreement with the collapsed-cone and Monte Carlo calculated dose, particularly in the spinal cord dose and nodal target coverage, thus giving greater confidence in the use of this class solution.

Association of a vitamin D receptor polymorphism with sporadic breast cancer development

Breast cancer is the leading cause of cancer death among Australian women and its incidence is annually increasing. Genetic factors are involved in the complex etiology of breast cancer. The seco-steroid hormone, 1.25 dihydroxy vitamin D3 can influence breast cancer cell growth in vitro. A number of studies have reported correlations between vitamin D receptor (VDR) gene polymorphisms and several diseases including prostate cancer and osteoporosis. In breast cancer, low vitamin D levels in serum are correlated with disease progression and bone metastases, a situation also noted in prostate cancer and suggesting the involvement of the VDR. In our study, 2 restriction fragment length polymorphisms (RFLP) in the 3' region (detected by Apa1 and Taq1) and an initiation codon variant in the 5' end of the VDR gene (detected by Fok1) were tested for association with breast cancer risk in 135 females with sporadic breast cancer and 110 cancer-free female controls. Allele frequencies of the 3' Apa1 polymorphism showed a significant association (p = 0.016; OR = 1.56, 95% CI = 1.09-2.24) while the Taq1 RFLP showed a similar trend (p = 0.053; OR = 1.45, 95% CI = 1.00-2.00). Allele frequencies of the Fok1 polymorphism were not significantly different (p = 0.97; OR = 0.99, 95% CI = 0.69-1.43) in the study population. Our results suggest that specific alleles of the VDR gene located near the 3' region may identify an increased risk for breast cancer and justify further investigation of the role of VDR in breast cancer.

The silent and apparent neurological injury in transcatheter aortic valve implantation study (SANITY) : concept, design and rationale

Background The incidence of clinically apparent stroke in transcatheter aortic valve implantation (TAVI) exceeds that of any other procedure performed by interventional cardiologists and, in the index admission, occurs more than twice as frequently with TAVI than with surgical aortic valve replacement (SAVR). However, this represents only a small component of the vast burden of neurological injury that occurs during TAVI, with recent evidence suggesting that many strokes are clinically silent or only subtly apparent. Additionally, insult may manifest as slight neurocognitive dysfunction rather than overt neurological deficits. Characterisation of the incidence and underlying aetiology of these neurological events may lead to identification of currently unrecognised neuroprotective strategies. Methods The Silent and Apparent Neurological Injury in TAVI (SANITY) Study is a prospective, multicentre, observational study comparing the incidence of neurological injury after TAVI versus SAVR. It introduces an intensive, standardised, formal neurologic and neurocognitive disease assessment for all aortic valve recipients, regardless of intervention (SAVR, TAVI), valve-type (bioprosthetic, Edwards SAPIEN-XT) or access route (sternotomy, transfemoral, transapical or transaortic). Comprehensive monitoring of neurological insult will also be recorded to more fully define and compare the neurological burden of the procedures and identify targets for harm minimisation strategies. Discussion The SANITY study undertakes the most rigorous assessment of neurological injury reported in the literature to date. It attempts to accurately characterise the insult and sustained injury associated with both TAVI and SAVR in an attempt to advance understanding of this complication and associations thus allowing for improved patient selection and procedural modification.

Acid-catalysed cyclisations: structures of novel products isolated in the reaction of 2-[3-(2,6-dimethoxyphenyl)but-2-enyl]-2-methylcyclopentane-1,3-dione with MeOH-HCl

Reaction of the title compound (1a) with anhydrous MeOH-HCl gave 2-endo-(2,6-dimethoxyphenyl)-2-exo-methyl-5-methylbicyclo[3.2.1]octane-6,8-dione (3a), 1,5,14-timethoxy-5,8-seco-6,7-dinorestra-1,3,5(10),9(11)-tetraen-17-one (4), 1,5-dimethoxy-5,8-seco-6,7-dinorestra-1,3,5(10),8,14-pentaen-17-one (5), and 3,4,5,6-tetrahydro-2,7-dimethoxy-3,6-dimethyl-3,2,6-(13-oxopropan[1]yI[3]ylidene)-2H-1-benzoxocin (6). Structures assigned to compounds (3a), (4), and (6) are based on spectral data. The exo-tricyclic acetal structure (6) was further confirmed by the analysis of the 1H n.m.r. spectra of the isomeric alcohols (11) and (12), obtained by sodium borohydride reduction of (6).

Asymmetric total synthesis of erythromycin. 2. Synthesis of an erythronolide A lactone system

In reporting a total synthesis of erythromycin (la) we described in the preceding paper1 the synthesis of the erythronolide A seco acid derivative 2 in optically active form. In this paper we wish to report a successful transformation of 2 to 12 (synthetically equivalent to erythronolide A) via lactonization and also demonstrate that the proper functionalization of a substrate is critical for the successful lactonization.

Structural flexibility in the biocatalyst-mediated functionalization of ring `A' in salannin, a tetranortriterpene from Azadirachta indica

Nocardia sp. quantitatively converts salannin 1 and 3-de-O-acetylsalannin 2 (C-seco limonoids) into 3-deacetoxy-1-de[(E)-2-methylbut-2-enoyloxy]salannin-1-en-3-one 10, a novel and potentially bioactive compound with an alpha,beta-unsaturated ketone moiety in ring `A'. In order to establish the sequence of events involved in this transformation and the structural specificity of this bacterial system, several new derivatives of salannin 1 have been prepared. These studies have indicated that the transformation is initiated by deacetylation at C-3, followed by oxidation of the secondary hydroxy group to 3-keto, which appears to facilitate the elimination of the tigloyloxy/acetoxy group at C-1 with the formation of an olefinic linkage between C-1 and C-2. The organism very efficiently transforms some of the derivatives of salannin into their corresponding compounds possessing an enone systemin ring `A', an essential pre-requisite for various biological activities. Some of the C-seco limonoids prepared in the present study, viz. 10, 1,2-didehydro-1,3-dideoxy-3-oxosalannic acid 18, 3-deacetoxy-1-de[(E)-2-methylbut-2-enoyloxy]-20,21,22,23-tetrahydrosal annin-1-en-3-one 15 and 1,2-didehydro-1,3-dideoxy-3-oxosalannol 23 were hitherto not known.

[n]peristylanes and [n]oxa[n]peristylanes (n = 3-6): A theoretical study

Theoretical studies at the HF and Becke3LYP levels using 6-31G* basis sets were carried out on a series of [n]peristylanes and [n]oxa[n]peristylanes (n = 3-6) to understand their structure and energetics. The structures of the [3]- and [4]peristylanes (1, 2) and their era-derivatives (5, 6) were calculated to have the anticipated high symmetry, C-nv. In contrast, a C-s structure (9) at HF/6-31G* and another (25) at the Becke3LYP/6-31G* level were calculated for the [5]oxa[5]peristylane. The energy difference between them is extremely small even though there are major differences in the structures indicating every soft potential energy surface: On the other hand, the potential energy surface of [6]oxa[6]peristylane is not as soft. Similar structures were also calculated for the top rings. Calculations on the seco-compounds 11-14 and 15-19 (Table 4) indicate that there is no unusual strain involved in the formation of 27 from 19. The Li+ interaction energies of the [n]oxa[n]peristylanes are 61.7 (n = 3), 72.8 (n = 4), 84.2 (n = 5) and 91.7 (n = 6) kcal mol(-1) at the Becke3LYP/6-3IG* level. Dramatic differences between the C-C bond lengths obtained from the solid state X-ray diffraction studies and those from the calculations for the [n]oxa[n]peristylanes were also observed.

Sistematización de la información sobre dendroenergía existente en la región del Pacífico y Central de Nicaragua, período 1993-2012

La leña es la forma más simple de biomasa utilizada en los hogares del mundo. En Nicaragua, casi el cincuenta por ciento de los nicaragüenses cocinan con leña y carbón. Esta demanda de leña ha provocado sobre explotación del bosque seco del Pacifico de Nicaragua, ocasionando degradación progresiva del bosque. La información dendroenergética de los focos de producción de leña se encuentra dispersa y desorganizada, esto justifica la realización del presente estudio de sistematización, que servirá para establecer lineamientos básicos sobre las pautas a seguir al momento de la planificación, seguimiento y evaluación de proyectos y/o programas dendroenergéticos. La información se recolectó a través de entrevistas dirigidas a responsables administrativos o técnicos de cada entidad relevante del sector dendroenerg ético. Adicionalmente se recolectó información bibliográfica de documentos físicos y electrónicos. La información se organizó en cuatro tópicos: Leyes/políticas: se identificó la necesidad de la formulación y adición de leyes y/o políticas que promuevan y faciliten la inversión en proyectos de generación eléctrica renovable; Investigaciones/estudios/publicaciones: se observa buena cantidad de investigaciones y documentos educativos, sin embargo, están desactualizados y sin contenido ambiental completo; Organización, poca vinculación de las instancias gubernamentales del sector con los actores locales como las asociaciones, cooperativas y productores individuales; Producción/comercialización, limitada a actividades de plantación y producción de plántulas con fines energéticos. En conclusión, el sector dendroenergético en Nicaragua es poco atractivo a la inversión por los procedimientos administrativos, las normas jurídicas y la falta de mecanismos de incentivos y créditos. Las cooperativas y asociaciones no están bien vinculadas entre ellas, lo que no les permite incidir en políticas a favor del sector. Sin embargo, se detectan aspectos positivos, como La Estrategia de Leña y Carbón y la inserción en muchos hogares de las estufas mejoradas como mecanismo de ahorro dendroenergético.