Floods in Iowa : stage and discharge,1976.

This report presents station descriptions and tables of peak stages and discharges for 259 continuous and partial-record gaging stations all of which are located at or within the boundaries of Iowa. contained in this report are not only the data for the annual flood series for each gaging station but also for the partial-duration series at those stations for which they could be obtained. This report has been designed to present a summary of the recorded data concerning floods in Iowa.

Morbidity and outcome after sentinel lymph node dissection in patients with early-stage malignant cutaneous melanoma.

OBJECTIVE: Prospective analysis of the morbidity and outcome of the sentinel lymph node (SLN) technique in a consecutive series of patients with early-stage melanoma. METHODS: Between 1997 and 1998, 60 patients with stage IB-II malignant melanoma underwent SLN dissection. Preoperative dynamic lymphoscintigraphy with mapping of the lymph vessels and lymph nodes and location of the sentinel node was performed the day before SLN dissection. SLN was identified by use of the blue dye technique. SLN was assessed for histopathological and immunohistochemical examination. Postoperative morbidity and mortality were recorded. Follow-up consisted of repetitive clinical examination with lymph nodes status, laboratory and radiologic findings. RESULTS: Tumor-positive SLN was observed in 18% of the patients and stage II disease was found in 91% of the patients with positive SLN. Breslow thickness was the only significant factor predicting involvement of a SLN (p = 0.02). In 36% of the positive SLN, metastases could be assessed only by immunohistochemical examination. Postoperative complications after SLN dissection were observed in 5% in comparison with 36% after elective lymph node dissection. After a mean follow-up of 32 months, recurrence was observed in 3% with a mean disease-free survival of 8 months. Overall survival was 82% and 90% in patients with positive and negative SLN, respectively. Overall mortality was 15%, due to distant metastases in 78% of the cases. CONCLUSIONS: Staging of early-stage melanoma with the SLN dissection by use of the blue dye technique combined to lymphoscintigraphy and immunohistochemistry is reliable and safe, with less morbidity than elective lymphadenectomy. Long-term follow-up is mandatory to establish the exact reliability of SLN dissection.

Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial.

PURPOSE: Mutations within the KRAS proto-oncogene have predictive value but are of uncertain prognostic value in the treatment of advanced colorectal cancer. We took advantage of PETACC-3, an adjuvant trial with 3,278 patients with stage II to III colon cancer, to evaluate the prognostic value of KRAS and BRAF tumor mutation status in this setting. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tissue blocks (n = 1,564) were prospectively collected and DNA was extracted from tissue sections from 1,404 cases. Planned analysis of KRAS exon 2 and BRAF exon 15 mutations was performed by allele-specific real-time polymerase chain reaction. Survival analyses were based on univariate and multivariate proportional hazard regression models. RESULTS: KRAS and BRAF tumor mutation rates were 37.0% and 7.9%, respectively, and were not significantly different according to tumor stage. In a multivariate analysis containing stage, tumor site, nodal status, sex, age, grade, and microsatellite instability (MSI) status, KRAS mutation was associated with grade (P = .0016), while BRAF mutation was significantly associated with female sex (P = .017), and highly significantly associated with right-sided tumors, older age, high grade, and MSI-high tumors (all P < 10(-4)). In univariate and multivariate analysis, KRAS mutations did not have a major prognostic value regarding relapse-free survival (RFS) or overall survival (OS). BRAF mutation was not prognostic for RFS, but was for OS, particularly in patients with MSI-low (MSI-L) and stable (MSI-S) tumors (hazard ratio, 2.2; 95% CI, 1.4 to 3.4; P = .0003). CONCLUSION: In stage II-III colon cancer, the KRAS mutation status does not have major prognostic value. BRAF is prognostic for OS in MS-L/S tumors.

Early Stage Primary Bone Lymphoma: A Retrospective, Multicenter Rare Cancer Network Study

PURPOSE/OBJECTIVE(S): Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas, and 4-5% of all extranodal lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with stage I and II PBL. MATERIALS/METHODS: Between 1987 and 2008, 116 consecutive patients with PBL treated in 13 RCNinstitutions were included in this study. Inclusion criteriawere: age.17 yrs, PBLin stage I and II, andminimum6months follow-up. The median agewas 51 yrs (range: 17-93).Diagnosticwork-up included plain boneXray (74%of patients), scintigraphy (62%), CT-scan (65%),MRI (58%), PET (18%), and bone-marrow biopsy (84%).All patients had biopsy-proven confirmation of non-Hodgkin's lymphoma (NHL). The histopathological type was predominantly diffuse large B-cell lymphoma (78%) and follicular lymphoma (6%), according to theWHOclassification. One hundred patients had a high-grade, 7 intermediate and 9 low-gradeNHL. Ninety-three patients had anAnn-Arbor stage I, and 23 had a stage II. Seventy-seven patients underwent chemoradiotherapy (CXRT), 12 radiotherapy (RT) alone, 10 chemotherapy alone (CXT), 9 surgery followed by CXRT, 5 surgery followed by CXT, and 2 surgery followed by RT. One patient died before treatment.Median RT dosewas 40Gy (range: 4-60).Themedian number ofCXTcycleswas 6 (range, : 2-8).Median follow-upwas 41months (range: 6-242). RESULTS: Following treatment, the overall response rate was 91% (CR 74%, PR 17%). Local recurrence was observed in 12 (10%) patients, and systemic recurrence in 17 (15%) patients. Causes of death included disease progression in 16, unrelated disease in 6, CXT-related toxicity in 1, and secondary cancer in 2 patients. The 5-yr overall survival (OS), disease-free survival (DFS), lymphoma- specific survival (LSS), and local control (LC) were 76%, 69%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for survival were: age\50 years (p = 0.008), IPI score #1 (p = 0.009), complete response (p\0.001), CXT (p = 0.008), number of CXT cycles $6 (p = 0.007), and RT dose . 40 Gy (p = 0.005). In multivariate analysis age, RT dose, complete response, and absence of B symptoms were independent factors influencing the outcome. There were 3 patients developing grade 3 or more (CTCAE.V3.0) toxicities. CONCLUSIONS: This large multicenter study, confirms the relatively good prognosis of early stage PBL, treated with combined CXRT. Local control was excellent, and systemic failure occurred infrequently. A sufficient dose of RT (. 40 Gy) and complete CXT regime (. 6 cycles) were associated with a better outcome. Combined modality appears to be the treatment of choice.

Copeptin as a diagnostic biomarker for sepsis-related deaths.

Copeptin has been shown to increase in patients with sepsis, severe sepsis and septic shock. In the study herein described, copeptin was measured in a series of sepsis-related fatalities and control cases that underwent medico-legal investigations. No age-dependent differences in copeptin levels in either sepsis or control cases were observed. No correlation between copeptin concentrations and postmortem interval was identified in either group. Copeptin levels were significantly higher in sepsis cases. Moreover, copeptin concentrations in septic cases correlated with procalcitonin, C-reactive protein and interleukin 6 values. These preliminary findings seem to indicate that copeptin can be reliably measured in biological samples collected during postmortem investigations. These results also suggest that hemodynamic instability associated with sepsis and septic shock can be characterized by copeptin measurement also in the forensic casework.

gp100(209-2M) peptide immunization of human lymphocyte antigen-A2+ stage I-III melanoma patients induces significant increase in antigen-specific effector and long-term memory CD8+ T cells.

Thirty-five HLA-A2(+) patients with completely resected stage I-III melanoma were vaccinated multiple times over 6 months with a modified melanoma peptide, gp100(209-2M), emulsified in Montanide adjuvant. Direct ex vivo gp100(209-2M) tetramer analysis of pre- and postvaccine peripheral blood mononuclear cells (PBMCs) demonstrated significant increases in the frequency of tetramer(+) CD8(+) T cells after immunization for 33 of 35 evaluable patients (median, 0.36%; range, 0.05-8.9%). Ex vivo IFN-gamma cytokine flow cytometry analysis of postvaccine PBMCs after brief gp100(209-2M) in vitro activation showed that for all of the patients studied tetramer(+) CD8(+) T cells produced IFN-gamma; however, some patients had significant numbers of tetramer(+) IFN-gamma(-) CD8(+)T cells suggesting functional anergy. Additionally, 8 day gp100(209-2M) in vitro stimulation (IVS) of pre- and postvaccine PBMCs resulted in significant expansion of tetramer(+) CD8(+) T cells from postvaccine cells for 34 patients, and these IVS tetramer(+) CD8(+) T cells were functionally responsive by IFN-gamma cytokine flow cytometry analysis after restimulation with either native or modified gp100 peptide. However, correlated functional and phenotype analysis of IVS-expanded postvaccine CD8(+) T cells demonstrated the proliferation of functionally anergic gp100(209-2M)- tetramer(+) CD8(+) T cells in several patients and also indicated interpatient variability of gp100(209-2M) stimulated T-cell proliferation. Flow cytometry analysis of cryopreserved postvaccine PBMCs from representative patients showed that the majority of tetramer(+) CD8+ T cells (78.1 +/- 4.2%) had either an "effector" (CD45 RA(+)/CCR7(-)) or an "effector-memory" phenotype (CD45RA(-)/CCR7(-)). Notably, analysis of PBMCs collected 12-24 months after vaccine therapy demonstrated the durable presence of gp100(209-2M)-specific memory CD8(+) T cells with high proliferation potential. Overall, this report demonstrates that after vaccination with a MHC class I-restricted melanoma peptide, resected nonmetastatic melanoma patients can mount a significant antigen-specific CD8(+) T-cell immune response with a functionally intact memory component. The data further support the combined use of tetramer binding and functional assays in correlated ex vivo and IVS settings as a standard for immunomonitoring of cancer vaccine patients.

Endocan measurement for the postmortem diagnosis of sepsis

The vascular endothelium has been shown to play a pivotal role in the pathophysiology of sepsis through the expression of surface proteins and secretion of soluble mediators. Endocan (endothelial cell-specific molecule-1), a 50-kDa dermatan sulfate proteoglycan, is expressed by endothelial cells in lung and kidney and can be detected at low levels in the serum of healthy subjects. Increased concentrations were described in patients with sepsis, severe sepsis and septic shock compared to healthy individuals, with serum concentrations related to the severity of illness. In the present study, we investigated endocan, procalcitonin and C-reactive protein in postmortem serum from femoral blood in a series of sepsis-related fatalities and control individuals who underwent medicolegal investigations. Endocan was also measured in pericardial fluid. Two study groups were prospectively formed, a sepsis-related fatalities group and a control group. The sepsis-related fatalities group consisted of sixteen forensic autopsy cases with documented clinical diagnosis of sepsis in vivo. The control group consisted of sixteen forensic autopsy cases with various noninfectious causes of death. Postmortem serum endocan concentrations were significantly higher in the sepsis group, with values ranging from 0.519ng/ml to 6.756ng/ml. In the control group, endocan levels were undetectable in eleven out of sixteen cases. The results of the data analysis revealed similar endocan concentrations in the pericardial fluid of both studied groups. Endocan can be considered a suitable biological parameter for the detection of sepsis-related deaths in forensic pathology routine.

Evolution of gene expression in fire ants: the effects of developmental stage, caste, and species.

Ants provide remarkable examples of equivalent genotypes developing into divergent and discrete phenotypes. Diploid eggs can develop either into queens, which specialize in reproduction, or workers, which participate in cooperative tasks such as building the nest, collecting food, and rearing the young. In contrast, the differentiation between males and females generally depends upon whether eggs are fertilized, with fertilized (diploid) eggs giving rise to females and unfertilized (haploid) eggs giving rise to males. To obtain a comprehensive picture of the relative contributions of gender (sex), caste, developmental stage, and species divergence to gene expression evolution, we investigated gene expression patterns in pupal and adult queens, workers, and males of two species of fire ants, Solenopsis invicta and S. richteri. Microarray hybridizations revealed that variation in gene expression profiles is influenced more by developmental stage than by caste membership, sex, or species identity. The second major contributor to variation in gene expression was the combination of sex and caste. Although workers and queens share equivalent diploid nuclear genomes, they have highly distinctive patterns of gene expression in both the pupal and the adult stages, as might be expected given their extraordinary level of phenotypic differentiation. Overall, the difference in the proportion of differentially expressed genes was greater between workers and males than between workers and queens or queens and males, consistent with the fact that workers and males share neither gender nor reproductive capability. Moreover, between-species comparisons revealed that the greatest difference in gene expression patterns occurred in adult workers, a finding consistent with the fact that adult workers most directly experience the distinct external environments characterizing the different habitats occupied by the two species. Thus, much of the evolution of gene expression in ants may occur in the worker caste, despite the fact that these individuals are largely or completely sterile. Analyses of gene expression evolution revealed a combination of positive selection and relaxation of stabilizing selection as important factors driving the evolution of such genes.

Assessment of early-stage optic nerve invasion in retinoblastoma using high-resolution 1.5 Tesla MRI with surface coils: a multicentre, prospective accuracy study with histopathological correlation.

OBJECTIVES: To assess the accuracy of high-resolution (HR) magnetic resonance imaging (MRI) in diagnosing early-stage optic nerve (ON) invasion in a retinoblastoma cohort. METHODS: This IRB-approved, prospective multicenter study included 95 patients (55 boys, 40 girls; mean age, 29 months). 1.5-T MRI was performed using surface coils before enucleation, including spin-echo unenhanced and contrast-enhanced (CE) T1-weighted sequences (slice thickness, 2 mm; pixel size <0.3 × 0.3 mm(2)). Images were read by five neuroradiologists blinded to histopathologic findings. ROC curves were constructed with AUC assessment using a bootstrap method. RESULTS: Histopathology identified 41 eyes without ON invasion and 25 with prelaminar, 18 with intralaminar and 12 with postlaminar invasion. All but one were postoperatively classified as stage I by the International Retinoblastoma Staging System. The accuracy of CE-T1 sequences in identifying ON invasion was limited (AUC = 0.64; 95 % CI, 0.55 - 0.72) and not confirmed for postlaminar invasion diagnosis (AUC = 0.64; 95 % CI, 0.47 - 0.82); high specificities (range, 0.64 - 1) and negative predictive values (range, 0.81 - 0.97) were confirmed. CONCLUSION: HR-MRI with surface coils is recommended to appropriately select retinoblastoma patients eligible for primary enucleation without the risk of IRSS stage II but cannot substitute for pathology in differentiating the first degrees of ON invasion. KEY POINTS: • HR-MRI excludes advanced optic nerve invasion with high negative predictive value. • HR-MRI accurately selects patients eligible for primary enucleation. • Diagnosis of early stages of optic nerve invasion still relies on pathology. • Several physiological MR patterns may mimic optic nerve invasion.

Stage of change of cigarette smoking in alcohol-dependent patients.

Despite the heavy burden of tobacco-related problems in alcohol-dependent patients, little effort has been directed toward reducing the prevalence of smoking in these patients. It seems reasonable to develop nicotine addiction treatments for alcohol-dependent patients based on the smoker's stage of change. To assess the stage of change for tobacco consumption and possible quitting barriers in alcohol-dependent patients, 88 consecutively admitted inpatients of a Swiss university-affiliated alcohol withdrawal clinic were interviewed with a semistructured schedule. More than half of the alcohol-dependent smokers (50.7%) considered the possibility of smoking cessation or had already decided to stop, although the majority (83.1%) were highly dependent smokers. Positive reinforcers were factors influencing motivation both to stop smoking as well as to continue smoking, whereas negative reinforcers had no influence. As recovering alcoholic patients are often interested in smoking cessation and the introduction of nicotine treatment interventions has been shown not to jeopardize the outcome of alcohol treatment, alcohol treatment programs should include counseling for smoking cessation. Education and training for staff is essential, as their beliefs and habits remain an important barrier.

La cohorte sepsis lausannoise: une opportunité de développer la recherche dans le Réseau latin de médecine intensive [Lausanne Cohort of septic patients as an opportunity to develop multidisciplinary research within the Swiss Latin Network of Intensive Care Medicine]

Despite recent medical progresses in patient support, the mortality of sepsis remains high. Recently, new supporting strategies were proposed to improve outcome. Whereas such strategies are currently considered as standard of care, their real impact on mortality, morbidity, length of stay, and hence, health care resources utilization has been only weakly evaluated so far. Obviously, there is a critical need for epidemiologic surveys of sepsis to better address these major issues. The Lausanne Cohort of septic patients aims at building a large clinical, biological and microbiological database that will be used as a multidisciplinary research platform to study the various pathogenic mechanisms of sepsis in collaboration with the various specialists. This could be an opportunity to strengthen the collaboration within the Swiss Latin network of Intensive Care Medicine.

Artificial muscle for end-stage heart failure.

We describe a device made of artificial muscle for the treatment of end-stage heart failure as an alternative to current heart assist devices. The key component is a matrix of nitinol wires and aramidic fibers called Biometal muscle (BM). When heated electrically, it produces a motorless, smooth, and lifelike motion. The BM is connected to a carbon fiber scaffold, tightening the heart and providing simultaneous assistance to the left and right ventricles. A pacemaker-like microprocessor drives the contraction of the BM. We tested the device in a dedicated bench model of diseased heart. It generated a systolic pressure of 75 mm Hg and ejected a maximum of 330 ml/min, with an ejection fraction of 12%. The device required a power supply of 6 V, 250 mA. This could be the beginning of an era in which BMs integrate or replace the mechanical function of natural muscles.

Automatic Tracer-Dilution Method Used for Stage-Discharge Ratings and Streamflow Hydrographs on Small Iowa Streams, HR-285, 1990

An automatic system was designed to concurrently measure stage and discharge for the purpose of developing stage-discharge ratings and high flow hydrographs on small streams. Stage, or gage height, is recorded by an analog-to-digital recorder and discharge is determined by the constant-rate tracer-dilution method. The system measures flow above a base stage set by the user. To test the effectiveness of the system and its components, eight systems, with a variety of equipment, were installed at crest-stage gaging stations across Iowa. A fluorescent dye, rhodamine-WT, was used as the tracer. Tracer-dilution discharge measurements were made during 14 flow periods at six stations from 1986 through 1988 water years. Ratings were developed at three stations with the aid of these measurements. A loop rating was identified at one station during rapidly-changing flow conditions. Incomplete mixing and dye loss to sediment apparently were problems at some stations. Stage hydrographs were recorded for 38 flows at seven stations. Limited data on background fluorescence during high flows were also obtained.

bHLH class transcription factors take centre stage in phytochrome signalling.

The phytochrome family of photoreceptors (there are five phytochromes in Arabidopsis, named phyA to phyE) maximally absorbs red and far-red light and plays important functions throughout the life cycle of plants. Several recent studies have shown that multiple related bHLH (basic helix-loop-helix) class transcription factors play key roles in phytochrome signal transduction. Somewhat surprisingly these transcription factors primarily act as negative regulators of phytochrome signalling. Moreover, in some cases, the phytochromes inhibit those negative regulators.

Protection from lethal Gram-negative bacterial sepsis by targeting Toll-like receptor 4

Rapport de synthèse : L'immunité innée regroupe les mécanismes moléculaires et cellulaires formant la première ligne de défense contre les infections microbiennes. La détection des micro-organismes pathogènes est assurée par des cellules sentinelles (cellules dendritiques et macrophages) qui jouent un rôle fondamental dans l'initiation des mécanismes de défense de l'hôte. Au contact de produits microbiens, ces cellules produisent un large échantillonnage de molécules, dont des cytokines, impliquées dans le développement de la réponse inflammatoire. La régulation de cette réponse relève d'un équilibre délicat, son insuffisance tant que son excès pouvant compromettre le devenir des patients infectés. La sepsis sévère et le choc septique représentent les formes les plus sévères d'infection, et leur mortalité demeure élevée (25 à 30% pour la sepsis sévère et 50 à 60% pour le choc septique). De plus, l'incidence de la sepsis tend à augmenter, atteignant en 2000 plus de 240 cas pour 100'000 personnes en Grande-Bretagne. La sepsis est caractérisée dans sa phase aiguë par une réponse inflammatoire exubérante. La plupart des thérapies visant à la bloquer ont toutefois montré des bénéfices incertains lors de leur application clinique. Il est donc impératif d'identifier de nouvelles cibles thérapeutiques. Les "Toll-like receptors" (TLRs) sont une famille de récepteurs qui jouent un rôle fondamental dans la détection des micro-organismes par les cellules du système immunitaire inné. Parmi eux, TLR4 est indispensable à la reconnaissance du lipopolysaccharide (LPS) des bactéries Gram-négatives. L'interaction entre TLR4 et le LPS représentant un élément précoce de la réponse de l'hôte à l'infection, nous avons émit l'hypothèse que TLR4 pourrait représenter une cible de choix en vue du développement de nouvelles thérapies contre la sepsis. Dans l'objectif de valider ce concept, nous avons, dans un premier temps, démontré que des souris génétiquement déficientes en TLR4 étaient totalement résistantes au choc septique induit par Escherichia coli (E. coli), une bactérie Gram-négative fréquemment responsable de sepsis. Forts de cette observation, nous avons développé une molécule recombinante composée du domaine extracellulaire de TLR4 fusionné à la partie IgGi-Fc. Cette molécule soluble, qui inhibait la réponse des macrophages au LPS in vitro, a été utilisée pour générer des anticorps anti-TLR4 chez le lapin. La spécificité et l'efficacité de ces anticorps ont été prouvées en démontrant que les anti-TLR4 bloquaient les signaux d'activation intracellulaire et la production de TNF et d'IL-6 en réponse au LPS et aux bactéries Gram-négatives in vitro et in vivo. Enfin, l'efficacité des ces anticorps a été testée dans des modèles de sepsis chez la souris. Ainsi, l'injection prophylactique (-lh) ou thérapeutique (+3h) d'anticorps anti-TLR4 réduisait la production de TNF et protégeait les animaux de la mort. De manière spectaculaire, ces anticorps réduisaient également la production de TNF et protégeaient de la sepsis à E. coli lorsqu'ils étaient administrés de manière prophylactique (-4h) et thérapeutique, jusqu'à 13 heures après l'initiation de l'infection. Ces résultats indiquent donc qu'il est possible de bloquer le développement de la réponse inflammatoire et de protéger du choc septique à bactéries Gram-négatives en utilisant des thérapies ciblant TLR4. Par ailleurs, ils suggèrent qu'une fenêtre d'opportunité de plusieurs heures pourrait être mise à profit pour initier un traitement chez les patients septiques. Ces résultats devraient encourager la poursuite des essais cliniques en cours qui visent à tester l'efficacité de thérapies dirigées contre TLR4 comme traitement complémentaire de la sepsis.