Quadrivalent versus trivalent influenza vaccine: clinical outcomes in two influenza seasons, historical cohort study.

OBJECTIVES: The quadrivalent influenza vaccine (QIV) contains two influenza B antigens (one of each B lineage), while the trivalent vaccine (TIV) contains solely one. As a result, a mismatch between the circulating B lineage and the lineage in the TIV occurs frequently. We aimed to compare the frequency of clinically significant outcomes in a large cohort of vaccinees receiving either TIV or QIV. METHODS: Historical cohort study of all inactivated influenza vaccinees (aged 3 years and older) in a Health Maintenance Organization insuring 1.2 million individuals, over two influenza seasons in which both vaccines were provided non-selectively. Primary outcome was hospital admissions during the influenza season. Multivariate analysis was performed using logistic regression to adjust for relevant covariates. RESULTS: Our cohort included 150 518 and 168 296 vaccinees in the first (S1) and second season (S2), respectively. The two influenza seasons were characterized by high Influenza B activity. Of those vaccinated with QIV, 2074 of 49 726 (4.2%) and 6563 of 121 741 (5.4%) were hospitalized compared with 7378 of 100 792 (7.3%) and 3372 of 46 555 (7.2%) of those vaccinated with TIV (S1 and S2, respectively). After multivariate analysis adjusting for several covariates (gender, age, socioeconomic status, chronic morbidity, timing of vaccination), compared with TIV recipients, QIV vaccinees had lower odds for hospitalization (OR = 0.92, 95% CI 0.87-0.98 and OR = 0.89, 95% CI 0.85-0.93) or emergency department visit (OR = 0.91, 95% CI 0.87-0.95 and OR = 0.84, 95% CI 0.81-0.87) in S1 and S2, respectively (p < 0.001). Lower odds of mortality and influenza-like illness were also observed in S2 (OR = 0.61, 95% CI 0.50-0.75 and OR = 0.92, 95% CI 0.90-0.95, respectively). CONCLUSIONS: In seasons with relatively high influenza B activity, QIV appeared more protective than TIV in Israel.

miRò: a miRNA knowledge base.

miRò is a web-based knowledge base that provides users with miRNA-phenotype associations in humans. It integrates data from various online sources, such as databases of miRNAs, ontologies, diseases and targets, into a unified database equipped with an intuitive and flexible query interface and data mining facilities. The main goal of miRò is the establishment of a knowledge base which allows non-trivial analysis through sophisticated mining techniques and the introduction of a new layer of associations between genes and phenotypes inferred based on miRNAs annotations. Furthermore, a specificity function applied to validated data highlights the most significant associations. The miRò web site is available at: http://ferrolab.dmi.unict.it/miro.Database URL:http://ferrolab.dmi.unict.it/miro.

NetMatch: a Cytoscape plugin for searching biological networks.

UNLABELLED: NetMatch is a Cytoscape plugin which allows searching biological networks for subcomponents matching a given query. Queries may be approximate in the sense that certain parts of the subgraph-query may be left unspecified. To make the query creation process easy, a drawing tool is provided. Cytoscape is a bioinformatics software platform for the visualization and analysis of biological networks. AVAILABILITY: The full package, a tutorial and associated examples are available at the following web sites: http://alpha.dmi.unict.it/~ctnyu/netmatch.html, http://baderlab.org/Software/NetMatch.

Adaptive combinatorial design to explore large experimental spaces: approach and validation.

Systems biology requires mathematical tools not only to analyse large genomic datasets, but also to explore large experimental spaces in a systematic yet economical way. We demonstrate that two-factor combinatorial design (CD), shown to be useful in software testing, can be used to design a small set of experiments that would allow biologists to explore larger experimental spaces. Further, the results of an initial set of experiments can be used to seed further 'Adaptive' CD experimental designs. As a proof of principle, we demonstrate the usefulness of this Adaptive CD approach by analysing data from the effects of six binary inputs on the regulation of genes in the N-assimilation pathway of Arabidopsis. This CD approach identified the more important regulatory signals previously discovered by traditional experiments using far fewer experiments, and also identified examples of input interactions previously unknown. Tests using simulated data show that Adaptive CD suffers from fewer false positives than traditional experimental designs in determining decisive inputs, and succeeds far more often than traditional or random experimental designs in determining when genes are regulated by input interactions. We conclude that Adaptive CD offers an economical framework for discovering dominant inputs and interactions that affect different aspects of genomic outputs and organismal responses.

AntiClustal: Multiple Sequence Alignment by antipole clustering and linear approximate 1-median computation.

In this paper we present a new Multiple Sequence Alignment (MSA) algorithm called AntiClusAl. The method makes use of the commonly use idea of aligning homologous sequences belonging to classes generated by some clustering algorithm, and then continue the alignment process ina bottom-up way along a suitable tree structure. The final result is then read at the root of the tree. Multiple sequence alignment in each cluster makes use of the progressive alignment with the 1-median (center) of the cluster. The 1-median of set S of sequences is the element of S which minimizes the average distance from any other sequence in S. Its exact computation requires quadratic time. The basic idea of our proposed algorithm is to make use of a simple and natural algorithmic technique based on randomized tournaments which has been successfully applied to large size search problems in general metric spaces. In particular a clustering algorithm called Antipole tree and an approximate linear 1-median computation are used. Our algorithm compared with Clustal W, a widely used tool to MSA, shows a better running time results with fully comparable alignment quality. A successful biological application showing high aminoacid conservation during evolution of Xenopus laevis SOD2 is also cited.

Thermoluminescent dosimetry of the Symmetra 125I model I25.S06 interstitial brachytherapy seed.

As the efficacy of brachytherapy prostate treatment is becoming realized, new models of 125I seeds are being introduced. In this article we present thermoluminescent dosimetry (TLD) in a solid water phantom for a new design of 125I seed (UroMed/Bebig Symmetra, Model I25.S06). TLD cubes, LiF TLD-100, from Bicron (Solon, OH) with dimension 1 x 1 x 1 mm3 were irradiated at various distances from the seed at angles ranging from 0 degrees to 90 degrees in 10 degrees increments. The TLD detectors were calibrated by irradiation in a 60Co teletherapy beam. Monte Carlo simulation was used to account for TLD energy dependence and the deviation of solid water composition (as determined by chemical analysis of a sample) from liquid water. Dose rates per unit air kerma strength were determined based on calibrations traceable to the 1999 NIST standard (corrected for NIST measurement errors made in 1999) for the Symmetra seed. Dose data is presented in TG-43 format as a function of distance and angle. Values for lambda, F(r, theta), g(r), and the anisotropy constant are obtained for use in radiation treatment planning (RTP) software. The dose rate constant was determined to be 1.033+/-6.4% cGy h(-1) U(-1), which is comparable to model 6702 and higher than model 6711. We find the relative dose distributions of the Symmetra seed are similar to model 6702, and less anisotropic than model 6711. After accounting for deviation of measured solid water composition from the manufacturer's specification, good agreement between TLD results and Monte-Carlo-aided values was found.

cis element/transcription factor analysis (cis/TF): a method for discovering transcription factor/cis element relationships.

We report a simple new algorithm, cis/TF, that uses genomewide expression data and the full genomic sequence to match transcription factors to their binding sites. Most previous computational methods discovered binding sites by clustering genes having similar expression patterns and then identifying over-represented subsequences in the promoter regions of those genes. By contrast, cis/TF asserts that B is a likely binding site of a transcription factor T if the expression pattern of T is correlated to the composite expression patterns of all genes containing B, even when those genes are not mutually correlated. Thus, our method focuses on binding sites rather than genes. The algorithm has successfully identified experimentally-supported transcription factor binding relationships in tests on several data sets from Saccharomyces cerevisiae.

The negative impact of anemia on radiotherapy and chemoradiation outcomes.

In cancer patients, anemia is common and has been found to impair quality of life and reduce locoregional disease control conferred by radiotherapy. The prognostic importance of anemia in the radiation oncology setting may be related to a reduction of molecular oxygen levels, thereby attenuating radiation-induced damage and ultimate cell death. Substantially higher doses of radiation are required to eradicate malignant cells under the hypoxic conditions commonly identified in solid tumors. Consistent with this, patients with hypoxic solid tumors have been found to have shorter postradiation disease-free survival rates relative to patients with well-oxygenated tumors. An attempt to enhance intratumoral oxygenation via correction of anemia, a highly prevalent but modifiable condition, is therefore a reasonable approach to optimize radiotherapy and chemoradiation outcomes. Clinical studies investigating recombinant human erythropoietin (epoetin alfa) as an adjunct to radiotherapy have demonstrated its ability to increase and maintain hemoglobin (Hb) levels during the course of radiotherapy. In a study involving anemic patients undergoing chemoradiation for head and neck cancer, epoetin alfa extended locoregional control and survival to rates reported for patients with normal pretreatment Hb levels. Given the high prevalence and prognostic significance of anemia during radiotherapy, strategies that safely and effectively increase Hb levels may be of value for optimizing radiotherapy and chemoradiation outcomes.

Prevalence of anemia in cancer patients undergoing radiation therapy.

Anemia is associated with reduced local tumor control and impaired quality of life in patients with several types of solid tumors. The prevalence of anemia in patients who present at radiation oncology departments has not been well documented, and the impact of anemia on the outcome of radiation therapy is not widely appreciated in the radiation oncology setting. In an ongoing study, we are retrospectively reviewing the medical charts of patients before and after radiation therapy at our institutions to determine the magnitude of the anemia problem in this population. Preliminary data are available for 574 randomly selected patients (52% female) seen between December 1996 and June 1999. At presentation, 41% of all patients were anemic (hemoglobin < 12 g/dL); by the end of radiation therapy, this percentage increased to 54%. The most common tumor types were prostate (16%), breast (14%), head and neck (12%), colorectal (11%), lung/bronchus (11%), and uterine-cervix (9%). Anemia was most prevalent in patients with uterine-cervical tumors (75%), increasing to 79% by the end of radiation therapy. The prevalence of lung/bronchus and colorectal cancer was 55% and 44%, respectively, at baseline and increased to 77% and 63%, respectively, after radiation therapy. For nearly all tumor types, the majority of patients had or developed mild to moderate anemia (hemoglobin 10.0 to 11.9 g/dL). These data show that anemia is widespread among patients seen in radiation oncology practices. However, the anemia is usually mild and readily correctable. Because anemia and hypoxia possibly associated with anemia are obstacles to local tumor control and maintenance of quality of life, strategies to reverse anemia should receive greater attention.

The American Brachytherapy Society recommendations for brachytherapy of soft tissue sarcomas.

PURPOSE: This report presents the American Brachytherapy Society (ABS) guidelines for the use of brachytherapy for patients with soft tissue sarcoma. METHODS AND MATERIALS: Members of the ABS with expertise in soft tissue sarcoma formulated brachytherapy guidelines based upon their clinical experience and a review of the literature. The Board of Directors of the ABS approved the final report. RESULTS: Brachytherapy used alone or in combination with external beam irradiation is an established means of safely providing adjuvant local treatment after resection for soft tissue sarcomas in adults and in children. Brachytherapy options include low dose rate techniques with iridium 192 or iodine 125, fractionated high dose rate brachytherapy, or intraoperative high dose rate therapy. Recommendations are made for patient selection, techniques, dose rates, and dosages. Complications and possible interventions to minimize their occurrence and severity are reviewed. CONCLUSION: Brachytherapy represents an effective means of enhancing the therapeutic ratio, offering both biologic and dosimetric advantage in the treatment of patients with soft tissue sarcoma. The treatment approach used depends upon the institution, physician expertise, and the clinical situation. Guidelines are established for the use of brachytherapy in the treatment of soft tissue sarcomas in adults and in children. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies. These guidelines will be modified, as further clinical results become available.

Anemia treatment and the radiation oncologist: optimizing patient outcomes.

Anemia is a frequent complication of cancer and its associated treatment. Although its occurrence is well documented in the chemotherapy setting, the prevalence and nature of anemia in the radiation oncology setting have been inadequately characterized. Preliminary findings from an ongoing retrospective study at Beth Israel Medical Center in New York indicate that mild-to-moderate anemia (ie, hemoglobin levels of 10 to 12 g/dL) is common at presentation for radiation therapy and increases in prevalence and severity during the course of radiation treatment. The symptoms of mild-to-moderate anemia, particularly fatigue, can substantially impair the quality of life of cancer patients. Furthermore, an extensive body of literature has documented an association between low hemoglobin levels and poor locoregional tumor control and survival following curative-intent radiation therapy. Greater efforts by radiation oncologists to document and treat anemia in patients undergoing radiation therapy may provide an opportunity to improve postradiation outcomes and well-being.

The role of brachytherapy for palliation.

The goal of palliative radiation is to alleviate symptoms in a short amount of time and maintain an optimal functional and quality-of-life level while minimizing toxicity and patient inconvenience. Despite advances in multimodality antineoplastic therapies, failure to control the tumor at its primary site frustratingly remains the predominant source of morbidity and mortality in many patients with cancer. Escalation of doses of radiation using external beam irradiation has been shown to improve local tumor control, but limits are imposed by the tolerance of normal surrounding structures. The highly conformal nature of brachytherapy enables the radiation oncologist to accomplish safe escalation of radiation doses to the tumor while minimizing doses to normal surrounding structures. Thus, by enhancing the potential for local control, brachytherapy used alone or as a supplement to external beam radiation therapy retains a significant and important role in achieving the goals of palliation. Proper patient selection, excellent technique, and adherence to implant rules will minimize the risk of complications. The advantages realized with the use of brachytherapy include good patient tolerance, short treatment time, and high rates of sustained palliation. This article reviews various aspects of palliative brachytherapy, including patient selection criteria, implant techniques, treatment planning, dose and fractionation schedules, results, and complications of treatment. Tumors of the head and neck, trachea and bronchi, esophagus, biliary tract, and brain, all in which local failure represents the predominant cause of morbidity and mortality, are highlighted.

Radiotherapy-associated anemia: the scope of the problem.

The impact of anemia on cancer patients undergoing chemotherapy is well established, but only recently has the prevalence of anemia in patients receiving radiotherapy received much attention. Many cancer patients present with anemia prior to radiotherapy, and even more experience anemia or a worsening of anemia at some point during treatment. However, the problem of anemia is often ignored because patients may experience only functional anemia, defined as a hemoglobin level less than 12 g/dl. Unless physiologic anemia (hemoglobin = 8 g/dl) is discovered, efforts to correct anemia are often not made. Because hemoglobin levels <12 g/dl seem to be associated with tumor hypoxia and poorer outcomes of radiotherapy in a number of patient populations, ignoring even modest anemia can result in decreased locoregional control, overall survival, and quality of life (QOL). Because increasing hemoglobin levels 1-2 g/dl is usually easily accomplished, there exists the potential for improving outcomes by paying greater attention to this problem. This article focuses on the prevalence of anemia, particularly functional anemia, and discusses the impact of anemia on locoregional control, overall survival, and QOL.

Radiotherapy-Associated Anemia: The Scope of the Problem.

The impact of anemia on cancer patients undergoing chemotherapy is well established, but only recently has the prevalence of anemia in patients receiving radiotherapy received much attention. Many cancer patients present with anemia prior to radiotherapy, and even more experience anemia or a worsening of anemia at some point during treatment. However, the problem of anemia is often ignored because patients may experience only functional anemia, defined as a hemoglobin level less than 12 g/dl. Unless physiologic anemia (hemoglobin = 8 g/dl) is discovered, efforts to correct anemia are often not made. Because hemoglobin levels <12 g/dl seem to be associated with tumor hypoxia and poorer outcomes of radiotherapy in a number of patient populations, ignoring even modest anemia can result in decreased locoregional control, overall survival, and quality of life (QOL). Because increasing hemoglobin levels 1-2 g/dl is usually easily accomplished, there exists the potential for improving outcomes by paying greater attention to this problem. This article focuses on the prevalence of anemia, particularly functional anemia, and discusses the impact of anemia on locoregional control, overall survival, and QOL.

Conjunctival fibroblasts enhance the survival and functional activity of peripheral blood eosinophils in vitro.

PURPOSE: To examine the effect of human conjunctival fibroblasts on the survival and functional activity of human peripheral blood eosinophils. METHODS: Eosinophils were purified by negative immunoselection [magnetic activated cell sorter (MACS), purity > 97%] from volunteers with mild atopia. Fibroblasts were cultured from conjunctival specimens of healthy donors. Eosinophils were cultured on confluent monolayers of conjunctival fibroblasts or in culture medium alone. Eosinophil survival was evaluated by the trypan blue exclusion test. Eosinophil adherence was assessed by counting the attached cells after washing the cultures. Eosinophil viability and adherence in coculture were also assessed in the presence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF), anti-interleukin (IL)-3, and anti-IL-5 neutralizing antibodies. Cocultured eosinophils were activated by lipopolysaccharide (LPS) after 4 days in culture, and eosinophil peroxidase (EPO) release was determined as a marker of their activation. RESULTS: Eosinophils cocultured with conjunctival fibroblasts had a significantly increased viability of 35.9% (P = 0.004) and 12.8% (P = 0.003) on days 4 and 8, respectively. Fibroblast-conditioned medium did not enhance the survival of eosinophils. The increase in eosinophil survival in coculture was partially inhibited by anti-GM-CSF (P = 0.019), anti-IL-3 (P = 0.033), or anti-IL-5 (P = 0.011), whereas eosinophil adherence was reduced by anti-GM-CSF alone (P = 0.034). LPS activation of eosinophils cultured for 4 days with conjunctival fibroblasts induced higher EPO release than in freshly isolated eosinophils (P = 0.01). CONCLUSIONS: Human conjunctival fibroblasts induced prolonged survival and increased secretory function of human peripheral blood eosinophils. Increased survival is partially mediated by IL-3, IL-5, and GM-CSF. The coculture of conjunctival fibroblasts with eosinophils can serve as an in vitro system for the study of eosinophil behavior in the ocular surface and of cellular interactions in allergic eye diseases.

Brachytherapy in the treatment of colorectal malignancies.

By precisely delivering a single, high dose fraction of intraoperative radiation under direct visualization while excluding surrounding normal dose-limiting tissues, IORT has improved the therapeutic ratio of tumor control to morbidity. Both IOERT and HDR-IORT represent effective means of delivering this therapy, and either may be chosen with equal confidence, depending upon the facilities available, physician preference, and the clinical situation. The extraordinary efforts often required in the management of these highly selected patients is justified by the improvement achieved in the enhanced local control rates and increased cure rates. Preoperative chemoradiation therapy followed by gross total resection and IORT affords the patient the highest likelihood of local control and survival. The importance of aggressive surgery in achieving gross total resection with pathologically negative margins is reflected by the dramatic correlation reported between margin status and local control. The high complication rate associated with this multidisciplinary therapy is, no doubt, multifactorial and may be attributed to the advanced disease state at presentation and the intensive multidisciplinary treatments administered. In an effort to eradicate disease and prolong survival, many consider these elevated complication rates acceptable, particularly in light of the complexity of these cases, as well as the morbidity and mortality associated with persistent disease in the pelvis.

New techniques for DNA sequence classification.

DNA sequence classification is the activity of determining whether or not an unlabeled sequence S belongs to an existing class C. This paper proposes two new techniques for DNA sequence classification. The first technique works by comparing the unlabeled sequence S with a group of active motifs discovered from the elements of C and by distinction with elements outside of C. The second technique generates and matches gapped fingerprints of S with elements of C. Experimental results obtained by running these algorithms on long and well conserved Alu sequences demonstrate the good performance of the presented methods compared with FASTA. When applied to less conserved and relatively short functional sites such as splice-junctions, a variation of the second technique combining fingerprinting with consensus sequence analysis gives better results than the current classifiers employing text compression and machine learning algorithms.

Elective irradiation of the N0 neck in squamous cell carcinoma of the upper aerodigestive tract.

The decision of how to optimally manage the clinically negative neck is based on the likelihood of clinically inapparent disease and the efficacy of salvage therapy. The criteria of decision for elective management of the neck takes into account the site, size, depth of infiltration, grading of the primary lesion, clinical and radiologic evaluation, and patient wishes. Diagnostic procedures currently used in evaluating head and neck cancer patients with nodal disease are reviewed. Elective irradiation of the N0 neck in patients with squamous cell carcinoma of the head and neck is an effective means of maintaining locoregional control. The impact of elective nodal treatment on disease free survival and overall survival is discussed.