Dosimetry of 90Y-ibritumomab tiuxetan as consolidation of first remission in advanced-stage follicular lymphoma: results from the international phase 3 first-line indolent trial.

The objective of this analysis was to assess the radiation exposure associated with (90)Y-ibritumomab tiuxetan when used as consolidation therapy in adults with low or minimal tumor burden after first-line therapy of advanced follicular lymphoma (FL). METHODS: The patients who were enrolled in the phase 3 first-line indolent trial were 18 y or older, with CD20(+) grade 1 or 2 stage III or IV FL, and a partial response, complete response, or unconfirmed complete response to first-line chemotherapy. The patients were allocated randomly to receive a single infusion of unlabeled rituximab 250 mg/m(2) on day -7 and consolidation on day 0 with a single dose of (90)Y-ibritumomab tiuxetan, 14.8 MBq/kg, immediately after unlabeled rituximab, 250 mg/m(2), or no further treatment. On day -7, a subset of patients received an injection of 185 MBq of (111)In-ibritumomab tiuxetan immediately after unlabeled rituximab, 250 mg/m(2), for central dosimetry analysis. Correlations were assessed between organ radiation absorbed dose and toxicity, body weight, body mass index, and progression-free survival. RESULTS: Central dosimetry evaluations were available from 57 of 70 patients. Median radiation absorbed doses were 100 cGy (range, 28-327 cGy) for the red marrow and 72 cGy (range, 46-106 cGy) for the whole body. Radiation absorbed doses did not differ significantly between patients who had a partial response or complete response to initial therapy. Progression-free survival correlated significantly with the whole-body (r = 0.4401; P = 0.0006) and bone marrow (r = 0.2976; P = 0.0246) radiation dose. Body weight was significantly negatively correlated with whole-body radiation dose (r = -0.4971; P < 0.0001). Neither the whole-body radiation dose nor the bone marrow radiation dose correlated with hematologic toxicity. CONCLUSION: In patients with low or minimal residual tumor burden after first-line chemotherapy of advanced FL, whole-body and bone marrow exposure after (90)Y-ibritumomab tiuxetan consolidation showed a significant positive correlation with progression-free survival, whereas dosimetric data could not predict hematologic toxicity.

Missouri River Flood Coordination Task Force Report, September 25, 2011

The Missouri River floods of 2011 will go down in history as the longest duration flooding event this state has seen to date. The combination of above normal snowfall in the upper Missouri River basin followed by the equivalent of nearly one year’s worth of rainfall in May created an above normal runoff situation which filled the Missouri River and the six main reservoirs within the basin. Compounding this problem was colder than normal temperatures which kept much of the snowpack in the upper basin on the ground longer into the spring, setting the stage for this historic event. The U.S. Army Corps of Engineers (USACE) began increasing the outflow at Gavin’s Point, near Yankton, South Dakota in May. On June 14, 2011, the outflow reached a record rate of over 160,000 cubic feet per second (cfs), over twice the previous record outflow set in 1997. This increased output from Gavin’s Point caused the Missouri River to flow out of its banks covering over 283,000 acres of land in Iowa, forcing hundreds of evacuations, damaging 255,000 acres of cropland and significantly impacting the levee system on the Missouri River basin. Over the course of the summer, approximately 64 miles of primary roads closed due to Missouri River flooding, including 54 miles of Interstate Highway. Many county secondary roads were closed by high water or overburdened due to the numerous detours and road closures in this area. As the Missouri River levels began to increase, municipalities and counties aided by State and Federal agencies began preparing for a sustained flood event. Citizens, businesses, state agencies, local governments and non‐profits made substantial preparations, in some cases expending millions of dollars on emergency protective measures to protect their facilities from the impending flood. Levee monitors detected weak spots in the levee system in all affected counties, with several levees being identified as at risk levees that could potentially fail. Of particular concern was the 28 miles of levees protecting Council Bluffs. Based on this concern, Council Bluffs prepared an evacuation plan for the approximately 30,000 residents that resided in the protected area. On May 25, 2011, Governor Branstad directed the execution of the Iowa Emergency Response Plan in accordance with Section 401 of the Stafford Act. On May 31, 2011, HSEMD Administrator, Brigadier General J. Derek Hill, formally requested the USACE to provide technical assistance and advanced measures for the communities along the Missouri River basin. On June 2, 2011 Governor Branstad issued a State of Iowa Proclamation of Disaster Emergency for Fremont, Harrison, Mills, Monona, Pottawattamie, and Woodbury counties. The length of this flood event created a unique set of challenges for Federal, State and local entities. In many cases, these organizations were conducting response and recovery operations simultaneously. Due to the length of this entire event, the State Emergency Operations Center and the local Emergency Operations Centers remained open for an extended period of time, putting additional strain on many organizations and resources. In response to this disaster, Governor Branstad created the Missouri River Recovery Coordination Task Force to oversee the State’s recovery efforts. The Governor announced the creation of this Task Force on October 17, 2011 and appointed Brigadier General J. Derek Hill, HSEMD Administrator as the chairman. This Task Force would be a temporary group of State agency representatives and interested stakeholders brought together to support the recovery efforts of the Iowa communities impacted by the Missouri River Flood. Collectively, this group would analyze and share damage assessment data, coordinate assistance across various stakeholders, monitor progress, capture best practices and identify lessons learned.

Phase II study of imatinib in advanced chordoma.

PURPOSE: To explore the antitumor activity of imatinib in patients with advanced platelet-derived growth factor β (PDGFB)/PDGF receptor β (PDGFRB)-positive chordomas.¦PATIENTS AND METHODS: In a collaborative Italian-Swiss, prospective, phase II clinical study conducted from November 2004 through April 2006, 56 patients with advanced PDGFB and/or PDGFRB chordoma received 800 mg/d of imatinib until progression. The primary end point was the overall tumor response rate (ORR), defined by RECIST. Secondary, exploratory end points included tissue response (ie, changes in tumor density or signal intensity/contrast enhancement, and/or [18F]-fluorodeoxyglucose positron emission tomography [PET] uptake), overall survival, progression-free survival (PFS), and pain score.¦RESULTS: Among 50 patients evaluable by RECIST, the best response was one partial response (PR) obtained at 6 months (ORR, 2%). There were 35 patients with stable disease (SD, 70%) and a 64% clinical benefit rate (ie, RECIST complete response + PR + SD ≥ 6 months). A minor dimensional response (< 20%) was detected in nine patients. A maximum standard uptake value decrease ≥ 25% was observed in 10 (39%) of 26 patients evaluable for PET response at 3 months. Changes in the Brief Pain Inventory score were consistent with the response assessment. Median PFS (intention-to-treat population, 56 patients) was 9 months. No unexpected toxicities were observed.¦CONCLUSION: This is the largest phase II study in chordoma to date. It confirms anecdotal evidence that imatinib has antitumor activity in this orphan disease, and therefore, it is worth further investigation.

Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib.

Patients diagnosed with advanced gastrointestinal stromal tumours (GISTs) who are resistant or intolerant to both imatinib and second-line sunitinib have a poor prognosis and few therapeutic options. We evaluated the efficacy of nilotinib, a novel tyrosine kinase inhibitor (TKI) in patients pretreated with imatinib and sunitinib. Fifty-two consecutive patients treated with oral nilotinib, 400mg twice daily, within the nilotinib compassionate use programme in 12 European cancer centres, were included in this retrospective analysis. Median age was 59 years (range 24-80), and all patients had WHO performance score better than 3. All patients had failed both imatinib and sunitinib pretreatment, either due to progressing GIST (96%) or intolerance (4%). Five patients (10%; 95% confidence interval (CI) 2-18) responded to nilotinib and 19 patients (37%; 95% CI 24-50) achieved a disease stabilisation. Nilotinib was generally well tolerated, but six patients (12%) discontinued treatment due to intolerance. Median progression-free survival of nilotinib treatment was 12 weeks (95% CI 9-15; range 0-104) and median overall survival was 34 weeks (95% CI 3-65; range 2-135). Nilotinib is active in GIST resistant to both imatinib and sunitinib. These results warrant further investigation of nilotinib in GIST.

Report on the Iowa Department of Agriculture and Land Stewardship for the year ended June 30, 2012

Report on the Iowa Department of Agriculture and Land Stewardship for the year ended June 30, 2012

Climatic and land use changes in the NW of Iberian Peninsula recorded in a 1,500-year record from Lake Sanabria

L'estudi de diversos descriptors paleoambientals com ara el pol·len, les diatomees i la sedimentologia, realitzat en sediments procedents del llac de Sanabria (NO de la península Ibèrica), ha aportat informació sobre les oscil·lacions climàtiques atribuïdes als períodes càlids tardoromà i medieval, així com a la petita edat del gel. Entre els anys 440 i 950 dC, el clima es caracteritzà per temperatures suaus i un règim de precipitacions mediterrani, malgrat l¿existència de pulsacions més fredes vers els anys 530 i 700 dC. Les evidències pol·líniques dels usos del sòl indiquen l'extensió d¿activitats ramaderes i agrícoles. Aquesta fase correspon al final del període càlid romà i al període càlid medieval. El canvi de condicions climàtiques es produeix entre els anys 950 i 1100 dC, moment en què els valors mínims de matèria orgànica, pol·len arbori, concentració de diatomees, nitrogen total (TN) i mida del gra indiquen temperatures més baixes i un règim de precipitacions més regular. Aquest període correspon a

Thymostimulin versus placebo for palliative treatment of locally advanced or metastasised hepatocellular carcinoma: a phase III clinical trial.

BACKGROUND: Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC) in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. METHODS: The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky >or=60%/Child-Pugh <or= 12) were randomised to receive thymostimulin 75 mg s.c. 5x/week or placebo stratified according to liver function. Primary endpoint was twelve-month survival, secondary endpoints overall survival (OS), time to progression (TTP), tumor response, safety and quality of life. A subgroup analysis according to liver function, KPS and tumor stage (Okuda, CLIP and BCLC) formed part of the protocol. RESULTS: Twelve-month survival was 28% [95%CI 17-41; treatment] and 32% [95%CI 19-44; control] with no significant differences in median OS (5.0 [95% CI 3.7-6.3] vs. 5.2 [95% CI 3.5-6.9] months; p = 0.87, HR = 1.04 [95% CI 0.7-1.6]) or TTP (5.3 [95%CI 2.0-8.6] vs. 2.9 [95%CI 2.6-3.1] months; p = 0.60, HR = 1.13 [95% CI 0.7-1.8]). Adjustment for liver function, Karnofsky status or tumor stage did not affect results. While quality of life was similar in both groups, fewer patients on thymostimulin suffered from accumulating ascites and renal failure. CONCLUSIONS: In our phase III trial, we found no evidence of any benefit to thymostimulin in the treatment of advanced HCC and there is therefore no justification for its use as single-agent treatment. The effect of thymostimulin on hepato-renal function requires further confirmation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN64487365.

Advanced geostatistical and machine-learning models for spatial data analysis of radioactively contaminated regions

Radioactive soil-contamination mapping and risk assessment is a vital issue for decision makers. Traditional approaches for mapping the spatial concentration of radionuclides employ various regression-based models, which usually provide a single-value prediction realization accompanied (in some cases) by estimation error. Such approaches do not provide the capability for rigorous uncertainty quantification or probabilistic mapping. Machine learning is a recent and fast-developing approach based on learning patterns and information from data. Artificial neural networks for prediction mapping have been especially powerful in combination with spatial statistics. A data-driven approach provides the opportunity to integrate additional relevant information about spatial phenomena into a prediction model for more accurate spatial estimates and associated uncertainty. Machine-learning algorithms can also be used for a wider spectrum of problems than before: classification, probability density estimation, and so forth. Stochastic simulations are used to model spatial variability and uncertainty. Unlike regression models, they provide multiple realizations of a particular spatial pattern that allow uncertainty and risk quantification. This paper reviews the most recent methods of spatial data analysis, prediction, and risk mapping, based on machine learning and stochastic simulations in comparison with more traditional regression models. The radioactive fallout from the Chernobyl Nuclear Power Plant accident is used to illustrate the application of the models for prediction and classification problems. This fallout is a unique case study that provides the challenging task of analyzing huge amounts of data ('hard' direct measurements, as well as supplementary information and expert estimates) and solving particular decision-oriented problems.

Novel Chemotherapy Combinations in Advanced Gastric Cancer: an Updated Meta-Analysis

Combination chemotherapy is widely accepted for patients with advanced gastric cancer, but uncertainty remains regarding the choice of the regimen. Objectives: To assess the effect of: Comparison 1) irinotecan versus non-irinotecancontaining regimens, comparison 2) docetaxel versus non-docetaxel-containing regimens, comparison 3) regimens including oral 5-FU prodrugs versus intravenous fluoropyrimidines, comparison 4) oxaliplatin versus cisplatin-containing regimens on overall survival. Search Strategy: We searched: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, proceedings from ECCO, ESMO, ASCO until December 2009. Selection Criteria: Randomised controlled trials on the above mentioned chemotherapy regimens in advanced or metastatic denocarcinoma of the stomach or GE-junction. Results: The meta-analysis of overall survival for comparison 1) included 4 trials, 640 patients, and results in a HR of 0.86 (95% CI 0.73-1.02) in favour of the irinotecancontaining regimens. For comparison 2) 4 trials with a total of 924 patients have been included in the analysis of overall survival. The resulting HR is 0.93 (95% CI 0.79-1.09) in favour of the docetaxel-containing regimens, with moderate heterogeneity (I2 =7%). For comparison 3 and 4, one major relevant study (Cunningham 2008) could not be included in this meta-analysis after discussion because it included patients with squamous cell cancer of the esophagus as well. Thus, for comparison 3) one relevant study (Kang 2009; 316 patients) comparing capecitabine versus 5-FU in combination with cisplatin is eligible. The resulting HR is 0.85 (95%CI 0.65-1.11) in favour of the oral regimen. For comparison 4) two eligible trials were identified (Al Batran 2008, Popov 2008; 292 patients) with a resulting HR of 0.82 (95% CI 0.47-1.45) in favour of the oxaliplatin-based regimens. For three further trials data is incomplete at present. Conclusions: Chemotherapy combinations including irinotecan, oxaliplatin, docetaxel or oral 5-FU prodrugs are alternative treatment options to cisplatin/5-FU or cisplatin/ 5-FU/anthracycline-combinations, but do not provide significant advantages in overall survival. Supported by: KKS Halle, grant number [BMBF/FKZ 01GH01GH0105]. Disclosure: All authors have declared no conflicts of interest.

A phase I pharmacokinetic study of hypoxic abdominal stop-flow perfusion with gemcitabine in patients with advanced pancreatic cancer and refractory malignant ascites

PURPOSE: As no curative treatment for advanced pancreatic and biliary cancer with malignant ascites exists, new modalities possibly improving the response to available chemotherapies must be explored. This phase I study assesses the feasibility, tolerability and pharmacokinetics of a regional treatment of gemcitabine administered in escalating doses by the stop-flow approach to patients with advanced abdominal malignancies (adenocarcinoma of the pancreas, n = 8, and cholangiocarcinoma of the liver, n = 1). EXPERIMENTAL DESIGN: Gemcitabine at 500, 750 and 1,125 mg/m(2) was administered to three patients at each dose level by loco-regional chemotherapy, using hypoxic abdominal stop-flow perfusion. This was achieved by an aorto-caval occlusion by balloon catheters connected to an extracorporeal circuit. Gemcitabine and its main metabolite 2',2'-difluorodeoxyuridine (dFdU) concentrations were measured by high performance liquid chromatography with UV detection in the extracorporeal circuit during the 20 min of stop-flow perfusion, and in peripheral plasma for 420 min. Blood gases were monitored during the stop-flow perfusion and hypoxia was considered stringent if two of the following endpoints were met: pH </= 7.2, pO(2) nadir ratio </=0.70 or pCO(2) peak ratio >/=1.35. The tolerability of this procedure was also assessed. RESULTS: Stringent hypoxia was achieved in four patients. Very high levels of gemcitabine were rapidly reached in the extracorporeal circuit during the 20 min of stop-flow perfusion, with C (max) levels in the abdominal circuit of 246 (+/-37%), 2,039 (+/-77%) and 4,780 (+/-7.3%) mug/ml for the three dose levels 500, 750 and 1,125 mg/m(2), respectively. These C (max) were between 13 (+/-51%) and 290 (+/-12%) times higher than those measured in the peripheral plasma. Similarly, the abdominal exposure to gemcitabine, calculated as AUC(t0-20), was between 5.5 (+/-43%) and 200 (+/-66%)-fold higher than the systemic exposure. Loco-regional exposure to gemcitabine was statistically higher in presence of stringent hypoxia (P < 0.01 for C (max) and AUC(t0-20), both normalised to the gemcitabine dose). Toxicities were acceptable considering the complexity of the procedure and were mostly hepatic; it was not possible to differentiate the respective contributions of systemic and regional exposures. A significant correlation (P < 0.05) was found between systemic C (max) of gemcitabine and the nadir of both leucocytes and neutrophils. CONCLUSIONS: Regional exposure to gemcitabine-the current standard drug for advanced adenocarcinoma of the pancreas-can be markedly enhanced using an optimised hypoxic stop-flow perfusion technique, with acceptable toxicities up to a dose of 1,125 mg/m(2). However, the activity of gemcitabine under hypoxic conditions is not as firmly established as that of other drugs such as mitomycin C, melphalan or tirapazamine. Further studies of this investigational modality, but with bioreductive drugs, are therefore warranted first to evaluate the tolerance in a phase I study and later on to assess whether it does improve the response to chemotherapy.

The emergence of forensic nursing and advanced nursing practice in Switzerland: an innovative case study consultation.

BACKGROUND AND METHODS: The objectives of this article were to systematically describe and examine the novel roles and responsibilities assumed by nurses in a forensic consultation for victims of violence at a University Hospital in French-speaking Switzerland. Utilizing a case study methodology, information was collected from two main sources: (a) discussion groups with nurses and forensic pathologists and (b) a review of procedures and protocols. Following a critical content analysis, the roles and responsibilities of the forensic nurses were described and compared with the seven core competencies of advanced nursing practice as outlined by Hamric, Spross, and Hanson (2009). RESULTS: Advanced nursing practice competencies noted in the analysis included "direct clinical practice," "coaching and guidance," and "collaboration." The role of the nurse in terms of "consultation," "leadership," "ethics," and "research" was less evident in the analysis. DISCUSSION AND CONCLUSION: New forms of nursing are indeed practiced in the forensic clinical setting, and our findings suggest that nursing practice in this domain is following the footprints of an advanced nursing practice model. Further reflections are required to determine whether the role of the forensic nurse in Switzerland should be developed as a clinical nurse specialist or that of a nurse practitioner.

Anatomical distribution of areas of preserved cartilage in advanced femorotibial osteoarthritis using CT arthrography (Part 1).

OBJECTIVE: To determine subregions of normal and abnormal cartilage in advanced stages of femorotibial osteoarthritis (OA) by mapping the entire femorotibial joint in a cohort of pre-total knee replacement (TKR) OA knees. DESIGN: We defined an areal subdivision of the femorotibial articular cartilage surface on CT arthrography (CTA), allowing the division of the femorotibial articular surface into multiple (up to n = 204 per knee) subregions and the comparison of the same areas between different knees. Two readers independently classified each cartilage area as normal, abnormal or non-assessable in 41 consecutive pre-TKR OA knees. RESULTS: A total of 6447 cartilage areas (from 41 knees) were considered assessable by both readers. The average proportion of preserved cartilage was lower in the medial femorotibial joint than in the lateral femorotibial joint for both readers (32.0/69.8% and 33.9/68.5% (medial/lateral) for reader 1 and 2 respectively, all P < 0.001). High frequencies of normal cartilage were observed at the posterior aspect of the medial condyle (up to 89%), and the anterior aspect of the lateral femorotibial compartment (up to 100%). The posterior aspect of the medial condyle was the area that most frequently exhibited preserved cartilage in the medial femorotibial joint, contrasting with the high frequency of cartilage lesions in the rest of that compartment. CONCLUSIONS: Cartilage at the posterior aspect of the medial condyle, and at the anterior aspect of the lateral femorotibial compartment, may be frequently preserved in advanced grades of OA.

La pratique infirmière avancée [Advanced practice nursing].

Dans les sociétés contemporaines axées sur le savoir, plus grande sera la proportion de leur population détentrice d'une formation supérieure et engagée en recherche, plus avancé sera leur développement économique et social.1,2 Par contre, dans ces sociétés, le vieillissement de la population, l'importance ccordée aux soins de santé axés sur les maladies chroniques et les coûts financiers de ceux-ci exercent une forte pression sur les systèmes de santé. Les nterventions doivent donc être les plus efficaces possible, avec un rapport coût/efficacité optimal. Cela requiert que les infirmières soient capables d'oeuvrer en pratique avancée, c'est-à-dire capables de développer, implémenter et évaluer des approches cliniques infirmières basées sur des preuves, de tester de nouvelles interventions potentiellement plus efficientes et de promouvoir un programme de recherche portant explicitement sur l'amélioration de la qualité et sécurité des soins en contexte d'interdisciplinarité.