Endocavitary contact radiation therapy for ultrasonographically staged T1 N0 and T2 N0 rectal cancer.

BACKGROUND: The purpose of this study was to determine the long-term outcomes of patients undergoing endocavitary contact radiation therapy (ECR) for stage I rectal cancer. METHODS: A database of patients treated with ECR for biopsy-proven rectal adenocarcinoma from July 1986 to June 2006 was reviewed retrospectively. Only patients with primary, non-metastatic, ultrasonographically staged T1 N0 and T2 N0 cancer who had no adjuvant treatment were included. Patients received a median of 90 (range 60-190) Gy contact radiation, delivered transanally by a 50-kV X-ray tube in two to five fractions. RESULTS: Of 149 patients, 77 (40 T1, 37 T2) met the inclusion criteria. Median age was 74 (range 38-104) years, and median follow-up 69 (range 10-219) months. ECR failed in 21 patients (27 per cent) (persistent disease, four; recurrence, 17), of whom ten remained disease free after salvage therapy. The estimated 5-year disease-free survival rate was 74 (95 per cent confidence interval 63 to 83) per cent after ECR alone, and 87 (76 to 93) per cent when survival after salvage therapy for recurrence was included. CONCLUSION: ECR is a minimally invasive treatment option for early-stage rectal cancer. However, similar to other local therapies, ECR has a worse oncological outcome than radical surgery.

Donor site morbidity of the posterior conchal region.

BACKGROUND: The perichondral cutaneous graft (PCCG) from the posterior conchal region is an elegant solution for the coverage of facial defects with particular stability requirements. The donor defect can easily be covered with a transposition flap from the postauricular region. Although this region is a common donor site for skin grafts and has an important supporting function for glasses or hearing aids, little is known about long-term morbidity after graft harvest. OBJECTIVE: To assess the morbidity of the posterior concha and the postauricular region in terms of pain, scar formation, and patient satisfaction. MATERIALS AND METHODS: A retrospective study of 16 patients who had a PCCG harvested from the posterior concha. RESULTS: Two patients presented with a postoperative wound dehiscence on the postauricular region and one with a keloid scar on the posterior concha. One case of transitory hyperesthesia and pain when sleeping on the operated site was observed. None had complaints related to wearing glasses or hearing aids. CONCLUSION: Donor site morbidity of the postauricular and posterior conchal region is minimal and associated with high patient satisfaction, excellent aesthetic results, and emotional detachment from the hidden donor site.

Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis. Results of a 2-year study.

A Strontium ranelate appears to influence more than alendronate distal tibia bone microstructure as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and biomechanically relevant parameters as assessed by micro-finite element analysis (mu FEA), over 2 years, in postmenopausal osteoporotic women.Introduction Bone microstructure changes are a target in osteoporosis treatment to increase bone strength and reduce fracture risk.Methods Using HR-pQCT, we investigated the effects on distal tibia and radius microstructure of strontium ranelate (SrRan; 2 g/day) or alendronate (70 mg/week) for 2 years in postmenopausal osteoporotic women. This exploratory randomized, double-blind trial evaluated HR-pQCT and FEA parameters, areal bone mineral density (BMD), and bone turnover markers.Results In the intention-to-treat population (n = 83, age: 64 +/- 8 years; lumbar T-score: -2.8 +/- 0.8 [DXA]), distal tibia Cortical Thickness (CTh) and Density (DCort), and cancellous BV/TV increased by 6.3%, 1.4%, and 2.5%, respectively (all P < 0.005), with SrRan, but not with alendronate (0.9%, 0.4%, and 0.8%, NS) (P < 0.05 for all above between-group differences). Difference for CTh evaluated with a distance transformation method was close to significance (P = 0.06). The estimated failure load increased with SrRan (+2.1%, P < 0.005), not with alendronate (-0.6%, NS) (between-group difference, P < 0.01). Cortical stress was lower with SrRan (P < 0.05); both treatments decreased trabecular stress. At distal radius, there was no between-group difference other than DCort (P < 0.05). Bone turnover markers decreased with alendronate; bALP increased (+21%) and serum-CTX-I decreased (-1%) after 2 years of SrRan (between-group difference at each time point for both markers, P < 0.0001). Both treatments were well tolerated.Conclusions Within the constraints of HR-pQCT method, and while a possible artefactual contribution of strontium cannot be quantified, SrRan appeared to influence distal tibia bone microstructure and FEA-determined biomechanical parameters more than alendronate. However, the magnitude of the differences is unclear and requires confirmation with another method.

Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial.

BACKGROUND: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. METHODS: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. RESULTS: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. CONCLUSIONS: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.

Upregulation of the GABA transporter GAT-1 in the gracile nucleus in the spared nerve injury model of neuropathic pain.

Neuropathic pain is a major health issue and is frequently accompanied by allodynia (painful sensations in response to normally non-painful stimulations), and unpleasant paresthesia/dysesthesia, pointing to alterations in sensory pathways normally dedicated to the processing of non-nociceptive information. Interestingly, mounting evidence indicate that central glial cells are key players in allodynia, partly due to changes in the astrocytic capacity to scavenge extracellular glutamate and gamma-aminobutyric acid (GABA), through changes in their respective transporters (EAAT and GAT). In the present study, we investigated the glial changes occurring in the dorsal column nuclei, the major target of normally innocuous sensory information, in the rat spared nerve injury (SNI) model of neuropathic pain. We report that together with a robust microglial and astrocytic reaction in the ipsilateral gracile nucleus, the GABA transporter GAT-1 is upregulated with no change in GAT-3 or glutamate transporters. Furthermore, [(3)H] GABA reuptake on crude synaptosome preparation shows that transporter activity is functionally increased ipsilaterally in SNI rats. This GAT-1 upregulation appears evenly distributed in the gracile nucleus and colocalizes with astrocytic activation. Neither glial activation nor GAT-1 modulation was detected in the cuneate nucleus. Together, the present results point to GABA transport in the gracile nucleus as a putative therapeutic target against abnormal sensory perceptions related to neuropathic pain.

Biosafety assessment of probiotics used for human consumption: recommendations from the EU-PROSAFE project

On June 26-27, 2006, 60 academic and industry scientists gathered during the PROSAFE workshop to discuss recommendations on taxonomy, antibiotic resistance, in vitro assessment of virulence and in vivo assessment of safety of probiotics used for human consumption. For identification of lactic acid bacteria (LAB) intended for probiotic use, it was recommended that conventional biochemical methods should be complemented with molecular methods and that these should be performed by an expert lab. Using the newly developed LAB Susceptibility test Medium (LSM), tentative epidemiological cut-off values were proposed. It was recommended that potentially probiotic strains not belonging to the wildtype distributions of relevant antimicrobials should not be developed as future products for human or animal consumption. Furthermore, it was recommended that the use of strains harbouring known and confirmed virulence genes should be avoided. Finally, for in vivo assessment of safety by investigating strain pathogenicity in animal models, the rat endocarditis model appeared to be the most reliable model tested in the PROSAFE project. Moreover, consensus was reached for approving the necessity of a human colonisation study in a randomised placebo-controlled double-blind design; however, further discussions are needed on the details of such as study.

Polymorphisms in fibronectin binding protein A of Staphylococcus aureus are associated with infection of cardiovascular devices.

Medical implants, like cardiovascular devices, improve the quality of life for countless individuals but may become infected with bacteria like Staphylococcus aureus. Such infections take the form of a biofilm, a structured community of bacterial cells adherent to the surface of a solid substrate. Every biofilm begins with an attractive force or bond between bacterium and substratum. We used atomic force microscopy to probe experimentally forces between a fibronectin-coated surface (i.e., proxy for an implanted cardiac device) and fibronectin-binding receptors on the surface of individual living bacteria from each of 80 clinical isolates of S. aureus. These isolates originated from humans with infected cardiac devices (CDI; n = 26), uninfected cardiac devices (n = 20), and the anterior nares of asymptomatic subjects (n = 34). CDI isolates exhibited a distinct binding-force signature and had specific single amino acid polymorphisms in fibronectin-binding protein A corresponding to E652D, H782Q, and K786N. In silico molecular dynamics simulations demonstrate that residues D652, Q782, and N786 in fibronectin-binding protein A form extra hydrogen bonds with fibronectin, complementing the higher binding force and energy measured by atomic force microscopy for the CDI isolates. This study is significant, because it links pathogenic bacteria biofilms from the length scale of bonds acting across a nanometer-scale space to the clinical presentation of disease at the human dimension.

Aprenentatge per a la comprensió en entorns virtuals als centres de secundà ria: La Xarxa School plus

[cat] Aquest projecte és una continuació del programa de recerca iniciat amb el projecte de R+D "School+ more than a platform to build the school of tomorrow" (IST-2000-25162) parcialment finançat per la Unió Europea a través de la convocatòria L'Escola del Demà, del Programa de Tecnologies de la Societat de la Informació del 5è Programa Marc. Aquesta iniciativa va ser seguida i aprofundida amb el projecte "Aprenentatge per a la comprensió en entorns virtuals als centres de secundària: la Xarxa School+", parcialment finançat pel DURSI a través de la convocatòria ARIE 2004. En aquest sentit, s'inscriu sota el mateix paraigües epistemològic (sociocultural) i metodològic (construccionista) dels projectes anteriors, i es basa en la utilització de diferents tipus d'evidències,en aquest cas però prestant especial atenció a la qüestió de l'avaluació de l'aprenentatge per a la comprensió i la dotació de sentit. En aquest context adquireix especial rellevància la idea del portafoli -o e-portafoli, webfoli, portafoli electrònic o digital- com a estratègia avaluadora de la comprensió i afavoridora de formes més complexes d'aprenentatge. En aquest informe, i d¿acord amb allò manifestat al projecte de recerca, es donen respostes a les següents qüestions: (a) quines són les possibilitats i les limitacions del portafoli electrònic com a sistema per avaluar processos d'aprenentatge de caràcter complex, orientats a la comprensió i la dotació de sentit; (b) com tenen lloc els processos d'innovació i millora a l'ensenyament secundari quan es fan servir entorns virtuals d'informació i comunicació, i es persegueix el desenvolupament d'un model pedagògic i curricular de caràcter interdisciplinari;(c) quins processos pedagògics, organitzatius, cognitius i emocionals estan implicats en les situacions d'aprenentatge orientades a la comprensió i la dotació de sentit, i no en la memorització i repetició de continguts; (d) com es desenvolupen experiències de col·laboració entre professors, estudiants i centres de secundària.

Advances in Near-surface Seismology and Ground-penetrating Radar

Advances in Near-surface Seismology and Ground-penetrating Radar (SEG Geophysical Developments Series No. 15) is a collection of original papers by renowned and respected authors from around the world. Technologies used in the application of near-surface seismology and ground-penetrating radar have seen significant advances in the last several years. Both methods have benefited from new processing tools, increased computer speeds, and an expanded variety of applications. This book, divided into four sections ? ?Reviews,? ?Methodology,? ?Integrative Approaches,? and ?Case Studies? ? captures the most significant cutting-edge issues in active areas of research, unveiling truly pertinent studies that address fundamental applied problems. This collection of manuscripts grew from a core group of papers presented at a postconvention workshop, ?Advances in Near-surface Seismology and Ground-penetrating Radar,? held during the 2009 SEG Annual Meeting in Houston, Texas. This is the first cooperative publication effort between the near-surface communities of SEG, AGU, and EEGS. It will appeal to a large and diverse audience that includes researchers and practitioners inside and outside the near-surface geophysics community.

Subgroup-specific structural variation across 1,000 medulloblastoma genomes.

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy.

Whole anterior segment proton beam radiotherapy for diffuse iris melanoma.

AIM: To report the results of whole anterior segment proton beam radiotherapy (PBR) for diffuse iris melanoma. METHODS: Between 2000 and 2011, 12 patients with iris melanoma received PBR to the entire iris and ciliary body. RESULTS: Patients had a mean age of 57 years and a median follow-up of 3.5 years (range 1-11.6 years). Tumour iris involvement was 1-4 h in five patients, 5-8 h in four and 9-12 h in three. Angle involvement was 6-8 h in five patients and 9-12 h in seven. The visual acuity (VA) before treatment was 6/5-6/6 in six patients, 6/8-6/9 in three and 6/18-6/38 in three. No tumour recurrence occurred during the follow-up period. Glaucoma treatment was required in 11 of 12 patients. The visual acuity at the last follow-up was 6/5-6/9 in five patients, 6/18-6/24 in three, 6/60-1/60 in two and no light perception in two. Four patients developed varying non-severe degrees of limbal stem cell deficiency, which was treatable with conservative measures. CONCLUSIONS: Whole anterior segment PBR is a useful alternative to enucleation for diffuse iris melanoma. Most patients will need treatment for glaucoma and some may require treatment for tear-film instability and/or stem cell failure.

Aprenentatge per a la comprensió en entorns virtuals als centres de secundà ria: La Xarxa School plus

[cat] Aquest projecte és una continuació del programa de recerca iniciat amb el projecte de R+D "School+ more than a platform to build the school of tomorrow" (IST-2000-25162) parcialment finançat per la Unió Europea a través de la convocatòria L'Escola del Demà, del Programa de Tecnologies de la Societat de la Informació del 5è Programa Marc. Aquesta iniciativa va ser seguida i aprofundida amb el projecte "Aprenentatge per a la comprensió en entorns virtuals als centres de secundària: la Xarxa School+", parcialment finançat pel DURSI a través de la convocatòria ARIE 2004. En aquest sentit, s'inscriu sota el mateix paraigües epistemològic (sociocultural) i metodològic (construccionista) dels projectes anteriors, i es basa en la utilització de diferents tipus d'evidències,en aquest cas però prestant especial atenció a la qüestió de l'avaluació de l'aprenentatge per a la comprensió i la dotació de sentit. En aquest context adquireix especial rellevància la idea del portafoli -o e-portafoli, webfoli, portafoli electrònic o digital- com a estratègia avaluadora de la comprensió i afavoridora de formes més complexes d'aprenentatge. En aquest informe, i d¿acord amb allò manifestat al projecte de recerca, es donen respostes a les següents qüestions: (a) quines són les possibilitats i les limitacions del portafoli electrònic com a sistema per avaluar processos d'aprenentatge de caràcter complex, orientats a la comprensió i la dotació de sentit; (b) com tenen lloc els processos d'innovació i millora a l'ensenyament secundari quan es fan servir entorns virtuals d'informació i comunicació, i es persegueix el desenvolupament d'un model pedagògic i curricular de caràcter interdisciplinari;(c) quins processos pedagògics, organitzatius, cognitius i emocionals estan implicats en les situacions d'aprenentatge orientades a la comprensió i la dotació de sentit, i no en la memorització i repetició de continguts; (d) com es desenvolupen experiències de col·laboració entre professors, estudiants i centres de secundària.