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Objective: To determine the inter-rater reliability of the 13-point manual muscle test (MMT) in two upper limb muscle groups of people with tetraplegiaSetting: The study was conducted at three spinal cord injury (SCI) units.Participants: Sixty people with complete or incomplete tetraplegia.Methods: The inter-rater reliability of the 13-point MMT was investigated. Strength of the elbow flexors and/or wrist extensors in people with tetraplegia was measured by two physiotherapists on the same day.Results: The weighted kappa coefficient (95% confidence interval) reflecting the agreement between the two strength assessments by two different assessors for the wrist extensors and elbow flexors were 0.96 (0.93 to 0.99) and 0.94 (0.89 to 0.99), respectively. Repeat measurements by different physiotherapists were within 1 of 13 points of each other 82% of the time for wrist extensors and 87% of the time for the elbow flexors.Conclusion: The 13-point MMT is a reliable measure of strength in the wrist extensors and elbow flexors of people with tetraplegia.

AIDS Clinical Trial Group study A5202 (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT00118898","term_id":"NCT00118898"}}NCT00118898) was a phase 3b, randomized, partially blinded equivalence study of open-label atazanavir/ritonavir or efavirenz, plus either placebo-controlled tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine, in treatment-naive adults living with HIV-1, evaluating efficacy, safety, and tolerability. We report an analysis of the contribution of participant characteristics to the disposition of tenofovir plasma concentrations. Tenofovir concentration data from a total of 817 individuals (88% of the total number of eligible patients randomly assigned to receive treatment in the TDF-containing arms of A5202) were available for analysis. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. One- and two-compartment models with first-order absorption and first-order elimination were evaluated. An exponential error model was used for examination of interindividual variability (IIV), and a proportional and mixed-error model was assessed for residual variability. The final structural model contained two compartments with first-order absorption and elimination. IIV was estimated for apparent clearance (CL/F) and the first-order absorption rate constant (ka), and a proportional residual variability model was selected. The final mean parameter estimates were as follows: ka = 2.87 h−1, CL/F = 37.2 liters/h, apparent volumes of the central and peripheral compartments = 127 and 646 liters, respectively, and apparent intercompartmental clearance = 107 liters/h. In addition to race/ethnicity, creatinine clearance and assignment to atazanavir/ritonavir or efavirenz were significantly associated with CL/F (P < 0.001). In conclusion, race/ethnicity is associated with tenofovir oral CL in HIV-1 positive, treatment-naive adults. This covariate relationship raises questions about the possibility of differences in efficacy and risk of adverse events in different patient populations and suggests that examining preexposure prophylaxis regimens and tenofovir exposure in different race/ethnicity groups be considered.

Aims: The treatment of prostate cancer has evolved markedly over the last 40 years, including radiotherapy, notably with escalated dose and targeting. However, the optimal treatment for localised disease has not been established in comparative randomised trials. The aim of this article is to describe the history ofprostate radiotherapy trials, including their quality assurance processes, and to compare these with the ProtecT trial.Materials and methods: The UK ProtecT randomised trial compares external beam conformal radiotherapy, surgery and active monitoring for clinically localized prostate cancer and will report on the primary outcome (disease-specific mortality) in 2016 following recruitment between 1999 and 2009. The embedded quality assurance programme consists of on-site machine dosimetry at the nine trial centres, a retrospective review of outlining and adherence to dose constraints based on the trial protocol in 54 participants (randomly selected, around 10% of the total randomised to radiotherapy, n ¼ 545). These quality assurance processes and results were compared with prostate radiotherapy trials of a comparable era.Results: There has been an increasingly sophisticated quality assurance programme in UK prostate radiotherapy trials over the last 15 years, reflecting dose escalation and treatment complexity. In ProtecT, machine dosimetry results were comparable between trial centres and with the UK RT01 trial. The outliningreview showed that most deviations were clinically acceptable, although three (1.4%) may have been of clinical significance and were related to outlining of theprostate. Seminal vesicle outlining varied, possibly due to several prostate trials running concurrently with different protocols. Adherence to dose constraints inProtecT was considered acceptable, with 80% of randomised participants having two or less deviations and planning target volume coverage was excellent.Conclusion: The ProtecT trial quality assurance results were satisfactory and comparable with trials of its era. Future trials should aim to standardise treatment protocols and quality assurance programmes where possible to reduce complexities for centres involved in multiple trials. 2016 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.

BACKGROUND: Patient-reported outcomes (PROs) might detect more toxic effects of radiotherapy than do clinician-reported outcomes. We did a quality of life (QoL) substudy to assess PROs up to 24 months after conventionally fractionated or hypofractionated radiotherapy in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP) trial.METHODS: The CHHiP trial is a randomised, non-inferiority phase 3 trial done in 71 centres, of which 57 UK hospitals took part in the QoL substudy. Men with localised prostate cancer who were undergoing radiotherapy were eligible for trial entry if they had histologically confirmed T1b-T3aN0M0 prostate cancer, an estimated risk of seminal vesicle involvement less than 30%, prostate-specific antigen concentration less than 30 ng/mL, and a WHO performance status of 0 or 1. Participants were randomly assigned (1:1:1) to receive a standard fractionation schedule of 74 Gy in 37 fractions or one of two hypofractionated schedules: 60 Gy in 20 fractions or 57 Gy in 19 fractions. Randomisation was done with computer-generated permuted block sizes of six and nine, stratified by centre and National Comprehensive Cancer Network (NCCN) risk group. Treatment allocation was not masked. UCLA Prostate Cancer Index (UCLA-PCI), including Short Form (SF)-36 and Functional Assessment of Cancer Therapy-Prostate (FACT-P), or Expanded Prostate Cancer Index Composite (EPIC) and SF-12 quality-of-life questionnaires were completed at baseline, pre-radiotherapy, 10 weeks post-radiotherapy, and 6, 12, 18, and 24 months post-radiotherapy. The CHHiP trial completed accrual on June 16, 2011, and the QoL substudy was closed to further recruitment on Nov 1, 2009. Analysis was on an intention-to-treat basis. The primary endpoint of the QoL substudy was overall bowel bother and comparisons between fractionation groups were done at 24 months post-radiotherapy. The CHHiP trial is registered with ISRCTN registry, number ISRCTN97182923.FINDINGS: 2100 participants in the CHHiP trial consented to be included in the QoL substudy: 696 assigned to the 74 Gy schedule, 698 assigned to the 60 Gy schedule, and 706 assigned to the 57 Gy schedule. Of these individuals, 1659 (79%) provided data pre-radiotherapy and 1444 (69%) provided data at 24 months after radiotherapy. Median follow-up was 50·0 months (IQR 38·4-64·2) on April 9, 2014, which was the most recent follow-up measurement of all data collected before the QoL data were analysed in September, 2014. Comparison of 74 Gy in 37 fractions, 60 Gy in 20 fractions, and 57 Gy in 19 fractions groups at 2 years showed no overall bowel bother in 269 (66%), 266 (65%), and 282 (65%) men; very small bother in 92 (22%), 91 (22%), and 93 (21%) men; small bother in 26 (6%), 28 (7%), and 38 (9%) men; moderate bother in 19 (5%), 23 (6%), and 21 (5%) men, and severe bother in four (INTERPRETATION: The incidence of patient-reported bowel symptoms was low and similar between patients in the 74 Gy control group and the hypofractionated groups up to 24 months after radiotherapy. If efficacy outcomes from CHHiP show non-inferiority for hypofractionated treatments, these findings will add to the growing evidence for moderately hypofractionated radiotherapy schedules becoming the standard treatment for localised prostate cancer.FUNDING: Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.

Introduction The Voice Clinic is a multidisciplinary specialist voice clinic. Our aim is to review patient demographics, subjective symptoms both at presentation and 16 months post clinic and patient satisfaction. Methods A retrospective review of all pre treatment voice clinic questionnaires for all new patients who attended the voice clinic over a 3-month period. A telephone interview was conducted 16 months after first presentation to determine patient satisfaction and whether patient’s symptoms had improved. Results A total of 25 patients who had completed a pre clinic questionnaire were identified, 17/25 completed the follow up interview. 88% of patients reported symptoms of ≥ 6 months duration. 41% underwent Speech and Language Therapy (SALT), 24% had medical management, 6% surgery, and 30% were given advice only. On a severity scale of 1- 10 (10 most severe) 40% rated their voice severity to be ≥5/10 at presentation, 16 months later this was 11% of patients. 56% rated the impact of their voice on their life to be ≥ 5/10 at presentation, 16 months later this was 6%. Conclusion Although limited the review shows that for the majority of patients their symptoms and quality of life improved after review at the multidisciplinary clinic.

BACKGROUND: Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment. We present a pre-planned analysis of the efficacy and side-effects of a randomised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up.METHODS: CHHiP is a randomised, phase 3, non-inferiority trial that recruited men with localised prostate cancer (pT1b-T3aN0M0). Patients were randomly assigned (1:1:1) to conventional (74 Gy delivered in 37 fractions over 7·4 weeks) or one of two hypofractionated schedules (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks) all delivered with intensity-modulated techniques. Most patients were given radiotherapy with 3-6 months of neoadjuvant and concurrent androgen suppression. Randomisation was by computer-generated random permuted blocks, stratified by National Comprehensive Cancer Network (NCCN) risk group and radiotherapy treatment centre, and treatment allocation was not masked. The primary endpoint was time to biochemical or clinical failure; the critical hazard ratio (HR) for non-inferiority was 1·208. Analysis was by intention to treat. Long-term follow-up continues. The CHHiP trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN97182923.FINDINGS: Between Oct 18, 2002, and June 17, 2011, 3216 men were enrolled from 71 centres and randomly assigned (74 Gy group, 1065 patients; 60 Gy group, 1074 patients; 57 Gy group, 1077 patients). Median follow-up was 62·4 months (IQR 53·9-77·0). The proportion of patients who were biochemical or clinical failure free at 5 years was 88·3% (95% CI 86·0-90·2) in the 74 Gy group, 90·6% (88·5-92·3) in the 60 Gy group, and 85·9% (83·4-88·0) in the 57 Gy group. 60 Gy was non-inferior to 74 Gy (HR 0·84 [90% CI 0·68-1·03], pNI=0·0018) but non-inferiority could not be claimed for 57 Gy compared with 74 Gy (HR 1·20 [0·99-1·46], pNI=0·48). Long-term side-effects were similar in the hypofractionated groups compared with the conventional group. There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures. The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group (RTOG) grade 2 or worse bowel and bladder adverse events was 13·7% (111 events) and 9·1% (66 events) in the 74 Gy group, 11·9% (105 events) and 11·7% (88 events) in the 60 Gy group, 11·3% (95 events) and 6·6% (57 events) in the 57 Gy group, respectively. No treatment-related deaths were reported.INTERPRETATION: Hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions and is recommended as a new standard of care for external-beam radiotherapy of localised prostate cancer.FUNDING: Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.

Summary Background Prostate cancer might have high radiation-fraction sensitivity, implying a therapeutic advantage of hypofractionated treatment. We present a pre-planned preliminary safety analysis of side-effects in stages 1 and 2 of a randomised trial comparing standard and hypofractionated radiotherapy. Methods We did a multicentre, randomised study and recruited men with localised prostate cancer between Oct 18, 2002, and Aug 12, 2006, at 11 UK centres. Patients were randomly assigned in a 1:1:1 ratio to receive conventional or hypofractionated high-dose intensity-modulated radiotherapy, and all were given with 3–6 months of neoadjuvant androgen suppression. Computer-generated random permuted blocks were used, with risk of seminal vesicle involvement and radiotherapy-treatment centre as stratification factors. The conventional schedule was 37 fractions of 2 Gy to a total of 74 Gy. The two hypofractionated schedules involved 3 Gy treatments given in either 20 fractions to a total of 60 Gy, or 19 fractions to a total of 57 Gy. The primary endpoint was proportion of patients with grade 2 or worse toxicity at 2 years on the Radiation Therapy Oncology Group (RTOG) scale. The primary analysis included all patients who had received at least one fraction of radiotherapy and completed a 2 year assessment. Treatment allocation was not masked and clinicians were not blinded. Stage 3 of this trial completed the planned recruitment in June, 2011. This study is registered, number ISRCTN97182923. Findings 153 men recruited to stages 1 and 2 were randomly assigned to receive conventional treatment of 74 Gy, 153 to receive 60 Gy, and 151 to receive 57 Gy. With 50·5 months median follow-up (IQR 43·5–61·3), six (4·3%; 95% CI 1·6–9·2) of 138 men in the 74 Gy group had bowel toxicity of grade 2 or worse on the RTOG scale at 2 years, as did five (3·6%; 1·2–8·3) of 137 men in the 60 Gy group, and two (1·4%; 0·2–5·0) of 143 men in the 57 Gy group. For bladder toxicities, three (2·2%; 0·5–6·2) of 138 men, three (2·2%; 0·5–6·3) of 137, and none (0·0%; 97·5% CI 0·0–2·6) of 143 had scores of grade 2 or worse on the RTOG scale at 2 years. Interpretation Hypofractionated high-dose radiotherapy seems equally well tolerated as conventionally fractionated treatment at 2 years. Funding Stage 1 was funded by the Academic Radiotherapy Unit, Cancer Research UK programme grant; stage 2 was funded by the Department of Health and Cancer Research UK.

La relazione presenta i risultati degli scavi condotti tra il 1977 e il 1981 presso le imponenti rovine note come Le Mura di Santo Stefano, situate vicino Anguillara Sabazia, appena 3 km a sud del Lago di Bracciano. La fase più antica di occupazione era relativa ad una fattoria di I secolo d.C. Intorno al 200 d.C. viene costruita una serie di strutture, compreso un edificio a pianta rettangolare su tre piani copiosamente decorato con diciannove tipi di marmo, suggerendo così che il complesso avesse un carattere lussuoso, possibilmente parte di un latifundium. Si hanno evidenze di ulteriori attività nel III o inizi IV secolo d.C. Nel IX secolo, dopo un periodo di abbandono, parte del complesso fu convertito nella chiesa di Santo Stefano. L'aula rettangolare fu rioccupata e le restanti rovine usate come cimitero. Si è dedotto che il sito possa aver funzionato come centro di una proprietà medievale, parte della domusculta papale, o in alternativa come un fundus di una struttura monastica. Nell'XI secolo il sito fu abbandonato, dopo ehe i resti di scheletri appartenenti ad almeno 90 individui, e le ossa di tre cani, furono interrati in un pozzo tappato con pezzi di sculture marmoree romane.

This article summarises the progress made in implementing the recommendations in the review of Measurement of Government Output and Productivity for the National Accounts led by Sir Tony Atkinson which reported in January 2005. The review recommended changes to the way output was then directly measured in the National Accounts for particular services, as well as making proposals for measuring the output of services which were not directly measured. Resulting improvements in measuring government output have led to an estimated 5.1 percentage point addition to the cumulative growth in government output between 1995 and 2005. Economic & Labour Market Review (2009) 3, 39–44; doi:10.1057/elmr.2009.142

Fin dal 2005 la British School at Rome con l'Università di Perugia e la Soprintendenza per i Beni Archeologici del Lazio sta conducendo uno studio sistematico del territorio di Cittareale, situato sulle montagne appenniniche a nord-est di Rieti, lungo la Via Salaria, sul confine tra le regioni Lazio, Umbria e Marche. Il progetto è parte di una serie più ampia di eventi programmati per il 2009 per ricordare il bimillenario della nascita di Vespasiano, ed è focalizzato principalmente sulla localizzazione e lo scavo del vicus di Falacrinae, dove Svetonio riporta che nacque l'imperatore. Il progetto ha comportato come prima cosa un programma di indagine di superficie, quindi l'analisi di una serie di siti attraverso la ricognizione geofisica, e lo scavo. Questo contributo presenta i risultati delle ricognizioni geofisiche e li compara con le evidenze emerse dallo scavo.

LE TRE ‘CRISI’ DELL'ETRURIA MERIDIONALE: RISULTATI PRELIMINARI DEL PROGETTO VALLE DEL TEVERECon questo articolo si intende fornire un resoconto preliminare su alcuni dei risultati principali del progetto Valle del Tevere condotto dalla British School at Rome. Il lavoro si concentra sui risultati attenuti dal riesame dei materiali raccolti in occasione della South Etruria Survey e illustra come questi consentano di rivedere le precedenti interpretazioni proposte. Sono stati scelti tre casi-studio al fine di dimostrare come il progetto stia consentendo di ripensare i cambiamenti dei paesaggi della Media Valle del Tevere e, in particolare, di collocarli nel contesto del continuo e mutevole rapporto con Roma, durante i periodi storici di supposta ‘crisi’: il V–IV secolo a.C, il II secolo a.C. e il tardoantico–alto medioevo. Ogni periodo mostra differenti gradi di continuità e cambiamenti. Si è preferito pertanto adottare un termine neutrale come ‘trasformazione’, piuttosto che ‘crisi’ e situare ognuno di questi cambiamenti all'interno di una più lunga prospettiva storica e di una più ampia struttura interpretativa.

A Roman marketplace and town called the Forum Novum, initially began construction in the [Formula: see text] century BC and flourished well into the [Formula: see text] century AD. At present most of the town remains is below ground. The site is situated next to a completely restored [Formula: see text] century AD church and a partially reconstructed marketplace. Ground penetrating radar surveys have been conducted at the Forum Novum during 1998 through 2001 field seasons to remotely detect buildings of this ancient town. Using 300 and [Formula: see text] radar antennas and closely spaced radar profiles, time slice and 3-D volume analysis of the reflection data were computed. GPR surveys in the area detected a large oval-shaped structure [Formula: see text] along its major axis. This structure is from a [Formula: see text] century AD Roman amphitheater. Subsequent excavations from one of the eight entrances reveal that the internal amphitheater oval is nearly a meter thick and is composed of a cemented stone wall buried [Formula: see text] below the ground surface. The time slices revealed completely different top layer reflections from structures associated with a destroyed mausoleum, which could also be seen by the naked eye as crop marks. Archaeologists often reconstruct subsurface archaeology based on crop marks. In this case however, radar was able to detect structures near the surface—and a much different set of structures lying deeper using time slice analysis. Other structures detected in the GPR surveys include a large building complex found next to a reconstructed marketplace, and believed to be living quarters adjacent to the central market area. A large Roman villa was also imaged in one area and later excavated to reveal internal walls that include a garden atrium.

This study aimed to evaluate whether the use of preoperative ultrasound (US)-guided wire localization of metastatic axillary lymph nodes (LN) assessed previously by core needle biopsy (CNB) and clip placement in breast cancer patients improves successful surgical removal.A retrospective review examined breast cancer patients who underwent US-guided CNB of an axillary LN and biopsy clip placement as well as axillary lymph node dissection (ALND) or sentinel node lymph node biopsy (SLNB) from 1 January 2010 to 30 September 2013. Preoperative needle localization status, neoadjuvant chemotherapy, and type of axillary LN surgery were reviewed. Confirmation that the metastatic LN had been surgically removed was determined on the specimen image, by pathologic report confirmation, or by pre-radiation therapy computed tomography (CT) scan.Preoperative US-guided needle localization was performed for 68.2 % (73/107) of the patients, with 97.3 % (n = 71) demonstrating confirmation of biopsy clip and LN removal versus 79.4 % (n = 27) of the 34 patients showing no performance of needle localization (p = 0.0043). Subgroup analysis showed a significant difference in removal of metastatic LN between the patients who received neoadjuvant chemotherapy [97 % of LNs removed with wire localization (n = 65/67) vs. 83.3 % of LNs removed without wire localization (n = 20/24; p = 0.04)] and the patients who had ALND, [96.3 % of LNs removed with wire localization (n = 52/54) vs. 77.8 % of LNs removed without wire localization (n = 21/27; p = 0.015)].US-guided wire localization of metastatic axillary LNs that have had biopsy with clip placement significantly improves the success rate of surgical removal, allowing more accurate staging and decreasing the false-negative rates of SLNB after neoadjuvant therapy.

The Roman town of Forum Novum lies in the Sabine hills to the northeast of Rome. Its study forms part of the British School at Rome's Tiber Valley Project, a collaborative research initiative which studies the Tiber valley as the hinterland of Rome, tracing the impact of Rome's development on the history of its settlement, economy, and cultural identity from 1000 B.C. to A.D. 1300 (Patterson and Millett 1999; Pattersonet al.2000) (fig. 1). The project draws on the extensive work carried out in this area to produce a new, material-based history of the valley. While the project seeks to re-evaluate past survey material, a vital contrast is provided by the development of new field projects to fill the gaps in settlement knowledge. Three main lacunae have been identified: the study of urban centres; the dearth of data from the E bank of the Tiber; and the poor understanding of the late-antique and early Mediaeval landscape. Forum Novum offers an opportunity to address all these lacunae.Urbanism forms a key research theme for the Tiber Valley Project. In marked contrast to the intensity of archaeological work on rural settlement in this area, there has been little systematic research on towns. Study has tended to concentrate on the excavation of monumental structures or, more rarely, the investigation of single and exceptional towns such as Ostia and Rome itself. Surprisingly little is known of the organization of the smaller towns and knowledge of their history is based largely on the epigraphic and documentary evidence.

In 1997 a new collaborative research project was initiated by the British School at Rome. This project draws on a variety of sources of archaeological information to explore the regional impact of the City of Rome throughout the period from 1000 BC to AD 1300. The project provides a common collaborative research framework which brings together a range of archaeologists and historians working in various institutions. In this paper those involved in different aspects of this new project outline their work and its overall objectives.

IL PROGETTO ‘LA VALLE DEL TEVERE’Questo articolo tratta gli obiettivi e struttura del nuovo progetto di ricerca della British School at Rome, il progetto ‘la Valle del Tevere’ e presenta alcuni dei primi risultati, anche se preliminari. L'obiettivo principale di questo progetto è di studiare il mutevole paesaggio della valle dal 1000 a.C. al 1300 d.C., indagando sull'impatto di crescita, successo e declinio di Roma sul suo entroterra e sui conseguenti effetti della città e flume sull'insediamento, economia e identità culturale. Questa iniziativa raduna molti studiosi con interessi di ricerca in questo campo ed in effetti include una serie di progetti connessi, ciascuno con i suoi specifici obiettivi di ricerca, ma allo stesso tempo parte di un progetto più ampio. La storia dell'insediamento è studiata tramite un riesame dei dati rilevati dai progetti britannici, in particolare quelli della ‘South Etruria Survey’, diretta da John Ward-Perkins, oltre ai dati pubblicati di progetti italiani. Allo stesso tempo, nuove ricerche sul campo sono in programma con l'intento di riempire le lacune esistenti. Due nuovi progetti iniziarono nel 1997 concentrandosi sul tema dell'urbanismo. Le ricognizioni a Falerii Novi e a Forum Novum hanno esaminato l'organizzazione interna delle citta tramite sistematiche ricognizioni in superficie e indagini geofisiche. I primi risultati chiaramente dimostrano il potenziale di questo approccio. Queste tecniche verranno applicate ad una gamma di centri urbani nella media valle del Tevere. La comprensione dell'interazione della città e della valle implica il mettere insieme l'informazione esistente relativa l'insediamento, le reti di comunicazione, l'economia e l'ambiente, oltre all'integrazione dei nuovi dati. Un elemento chiave del progetto è l'uso di un sistema GIS per l'integrazione ed analisi dei diversi livelli di informazione.

Purpose/Method.Transfection experiments have been used to identify activated oncogenes in a wide variety of tumour types. Here we describe the use of transfection experiments utilizing DNA from a human pleomorphic liposarcoma to identify a novel gene, designatedlipwhich maps to chromosome 19.Results. lipwas expressed in all sarcoma cell lines examined and a wide variety of normal tissues. Sequencing of cDNAs prepared from transcripts of the normallipgene indicates thatlipis predicted to encode a 966 amino acid protein with a region of homology to proteins such asvav, dbl, lbcandect-2which act as GDP–GTP exchange factors for the RAS superfamily of small GTP-binding proteins, and the N-terminal 830 amino acids are identical to the recently identified gene p115-RhoGEF, an exchange factor for RHOA. In transfectants,liphas undergone a rearrangement which results in C-terminal truncation of the predicted LIP protein. However, we failed to detect this alteration in the primary liposarcoma used in the original transfection experiments, or in other sarcoma specimens examined.Discussion.When considered together, these observations suggest that transforminglipsequences represent an alternatively spliced form of p115-RhoGEF that is activated for transformation by C-terminal truncation during transfection, and is not widely involved in sarcoma development.

Purpose. Amplification of genetic sequences on chromosome 12q13 is frequently found in soft tissue tumours. However, for theMDM2gene, over-expression of the MDM2 protein has not always been shown to accompany gene amplification, raising the possibility that amplification of genetic sequences targets alternative genes on chromosome 12q13 for over-expression. To investigate this discrepancy, we have examined 129 soft tissue tumours for amplification of theMDM2gene using Southern analysis, and 39 of these tumours were also examined by immunohistochemical staining for MDM2 over-expression.Results. Gene amplification was identified in 14/114 (12.3%) of the malignant tumours, but was not identified in any of the benign tumours; 21/39 (54%) of the malignant tumours also demonstrated MDM2 over-expression. Within this group theMDM2gene was over-expressed in every tumour in which the gene amplification was found, and over-expression in the absence of gene amplification was also found in an additional 10 tumours.Discussion. These data demonstrate a clear correlation between the presence ofMDM2amplification and MDM2 over-expression, and provide persuasive evidence therefore that the amplification of genetic sequences on chromosome 12q13 in soft tissue sarcomas targets theMDM2gene for over-expression. These data also indicate that alternative mechanisms may contribute to MDM2 over-expression within some tumours.

2 Background: We aimed to explore the dose response relationship for two 3 Gray (Gy) hypofractionated radiotherapy (hRT) schedules for localised prostate cancer (PCa). Methods: hRT schedules of 60Gy/20 fractions (f) and 57Gy/19f were compared with conventional RT (cRT) 74Gy/37f; iso-effective for alpha-beta ratios of 2.5Gy and 1.5Gy respectively. The trial was powered to demonstrate non-inferiority between each hRT schedule and cRT, with 3,213 patients (pt) needed to rule out 5% inferiority (80% power, 1-sided alpha 5%) assuming 70% event-free rate in cRT, corresponding to a critical hazard ratio (HR) of 1.21. The trial was not formally powered to directly compare the two hRT schedules. Pt with N0 T1b-T3a localised PCa were randomized (1:1:1 ratio). The primary endpoint was PCa progression (freedom from biochemical failure by Phoenix consensus guidelines or PCa recurrence). Acute toxicity was assessed up to 18 weeks post treatment and late side effects to 5 years (yr) by RTOG, LENT-SOM and patient reported outcomes (PROs). Results: 3,216 pts were randomized between 2002 and 2011; 1,065 (74Gy), 1,074 (60Gy), 1,077 (57Gy). Baseline characteristics were well balanced across groups: median age 69 yr; NCCN risk group 15% low, 73% intermediate, 12% high. With median follow up 5.2yr, 5yr progression-free rate (95% CI) was 74Gy: 88.3% (86.0%, 90.2%); 60Gy: 90.6% (88.5%, 92.3%), 57Gy: 85.9 (83.4, 88.0); HR60/74: 0.83, 90% CI (0.68, 1.03), HR57/74: 1.20, 90% CI (0.99, 1.45). Significantly more events were observed with 57Gy compared to 60Gy; HR57/60: 1.44, 90% CI (1.18, 1.75), log-rank p=0.003. No significant difference in acute RTOG bladder or bowel toxicity was observed between hRT schedules. Late toxicity profile was favorable; with grade 2+ RTOG bladder (60Gy: 16/960 (1.7%); 57Gy: 11/962 (1.1%), p=0.34) and bowel (60Gy: 28/960 (2.9%); 57Gy: 17/962 (1.8%), p=0.10) toxicity at 2yr. Analysis of LENT-SOM and PROs supported these results. Conclusions: With 5 yr follow-up treatment with a 3Gy schedule of 60Gy/20f shows improved treatment efficacy compared to 57Gy/19f and is non-inferior to 74Gy/37f with a similar low level of acute and late normal tissue damage. Clinical trial information: ISRCTN97182923.

In this study we have screened a series of 29 primary leiomyosarcomas for abnormalities of both the p53 gene and the MDM2 gene, which encodes a p53-associated protein. SSCP (single-strand conformation polymorphism) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA were used to establish that 6/29 tumours possessed point mutations of the p53 gene. Using a monoclonal antibody that recognises the p53 protein in immunohistochemical staining experiments, we observed overexpression of the p53 protein in five of the six tumours containing point mutations in the p53 gene. Southern analysis of tumour DNA revealed that 2/29 tumours demonstrated amplification of the MDM2 gene. When considered together, these results indicate that alterations in both the p53 gene and MDM2 gene are important in the development of a significant minority of leiomyosarcomas. In addition, we have demonstrated a significant association between the presence of abnormalities of the p53 gene or MDM2 genes in leiomyosarcomas and a more advanced clinicopathological stage (P = 0.03). We have also examined the role of the DCC tumour-suppressor gene in the development of human soft-tissue tumours in a variety of histological types. Except for evidence of a rearrangement in a single leiomyosarcoma cell line, SK-UT-1, we have found no direct evidence to support a role for mutation of the gene in the development of human soft-tissue tumours. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 6

The paper presents the results of an on-going study of the Roman town and early medieval bishopric of Forum Novum at Vescovio in the middle Tiber valley to the north of Rome. The work forms part of the British School at Rome's Tiber Valley Project, which studies the changing landscapes of the middle Tiber valley as the hinterland of Rome through two millennia, from 1000 BC to AD 1000. At Forum Novum a range of remote sensing techniques are being combined with excavation to examine the extent and organization of a Roman town and its development through time. From 1997 to 2001 a series of topographic and high-resolution ground-based remote sensing surveys took place at Forum Novum, which provide a basic map of the ancient centre. The integrated remote sensing surveys were carried out using the magnetic, geoelectric and ground-penetrating radar (GPR) methods. The analysis of the gradiometric, resistivity and GPR time-slice maps indicate that many structural foundations and walls of the buildings are still well preserved below the surface. The results, which are presented and discussed in this paper, demonstrate the potential of remote sensing techniques for our understanding of the extent and organization of urban centres. In the case of Forum Novum, where much of the ancient centre lies under modern structures, GPR survey, in particular, proved fundamental. Further, the results of the georadar surveys permitted archaeologists to select key areas of the town for more detailed investigation through excavation. Copyright © 2004 John Wiley & Sons, Ltd.

Linkage analysis in cancer families and the observation of rare cytogenetic abnormalities in the germline DNA of affected individuals can be used to identify the chromosomal location of the genetic defect associated with a familial cancer trait, as described in Chapter 2. The resolution of genetic mapping involving large consortium studies and multiple highly polymorphic marker probes is of the order of 1–2 cM, which corresponds to approximately 1–2 megabases (Mb). This compares to the size of whole chromosomes, which is of the order of 50 to 300 Mb.

BackgroundAntiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and findings1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; pConclusionEFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial registrationwww.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary.

Nel'articolo si ricostruiscono i caratteri della cultura materiale e della circolazione dei reperti nel territorio Decimano, area rurale a sud di Ravenna, basandosi sui dati di ricognizioni di superficie effettuate dall'Università di Bologna.

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