Molecular profiling of individual tumor cells by hyperspectral microscopic imaging.

We developed a hyperspectral microscopic imaging (HMI) platform that can precisely identify and quantify 10 molecular markers in individual cancer cells in a single pass. The exploitation of an improved separation of circulating tumor cells and the application of HMI provided an opportunity (1) to identify molecular changes in these cells, (2) to recognize the coexpression of these markers, (3) to pose an important opportunity for noninvasive diagnosis, and (4) to use targeted therapy. We balanced the intensity of 10 fluorochromes bound to 10 different antibodies, each specific to a particular tumor marker, so that the intensity of each fluorochrome can be discerned from overlapping emissions. Using 2 touch preps from each primary breast cancer, the average molecular marker intensities of 25 tumor cells gave a representative molecular signature for the tumor despite some cellular heterogeneity. The intensities determined by the HMI correlate well with the conventional 0-3+ analysis by experts in cellular pathology. Because additional multiplexes can be developed using the same fluorochromes but different antibodies, this analysis allows quantification of many molecular markers on a population of tumor cells. HMI can be automated completely, and eventually, it could allow the standardization of protein biomarkers and improve reproducibility among clinical pathology laboratories.

Is the true 'wisdom of the crowd' to copy successful individuals?

Diversity of expertise at an individual level can increase intelligence at a collective level-a type of swarm intelligence (SI) popularly known as the 'wisdom of the crowd'. However, this requires independent estimates (rare in the real world owing to the availability of public information) and contradicts people's bias for copying successful individuals. To explain these inconsistencies, 429 people took part in a 'guess the number of sweets' exercise. Guesses made with no public information were diverse, resulting in highly accurate SI. Individuals with access to the previous guess, mean guess or a randomly chosen guess, tended to over-estimate the number of sweets and this undermined SI. However, when people were provided with the current best guess, this prevented very large (inaccurate) guesses, resulting in convergence of guesses towards the true value and accurate SI across a range of group sizes. Thus, contrary to previous work, we show that social influence need not undermine SI, especially where individual decisions are made sequentially and then aggregated. Furthermore, we offer an explanation for why people have a bias to recruit and follow experts in team settings: copying successful individuals can enable accuracy at both the individual and group level, even at small group sizes.

Phylogenetic analysis of WNV in North American blood donors during the 2003-2004 epidemic seasons.

West Nile Virus (WNV) collected from 179 human blood donors in 25 US states and three Canadian provinces during the 2003 and 2004 epidemic seasons were genetically analyzed. The evolution of WNV during its Western spread was examined by envelope (E) gene sequencing of all 179 cases and full open reading frame sequencing of a subset of 20 WNV to determine if geographic and temporal segregation of distinct viral variants had occurred. Median joining network analysis was used to examine the genetic relationship between E gene variants and identified four large genetic clusters showing the gradual accumulation of mutations during the virus' western expansion. Two related WNV variants and their descendents, undetected in prior years, expanded in frequency. Apparent founder effects were observed in some regional outbreaks possibly due to local WNV colonization by a limited number of viruses. Amino acid mutations associated with newly expanding genetic variants reflect either selectively neutral mutational drift and/or mutations providing replicative advantages over the previously dominant forms of WNV.

Improvement of local control of T3 and T4 nasopharyngeal carcinoma by hyperfractionated radiotherapy and concomitant chemotherapy.

PURPOSE: When the primary tumor of nasopharyngeal carcinoma (NPC) is treated at the base of skull and intracranium with conventional radiotherapy, the result is generally poor. In this report, we investigated whether hyperfractionated radiotherapy (HFRT) and concomitant chemotherapy (CCT) could achieve better local control and survival in NPC patients with T3 and T4 lesions. PATIENTS AND METHODS: Forty-eight patients (11 T3 and 37 T4 NPC) were treated with HFRT and CCT. HFRT was administered at 1.2 Gy per fraction, two fractions per day, Monday-Friday for 62 fractions for a total dose of 74.4 Gy. Concomitant chemotherapy consisting of cis-diamino-dichloroplatinum (CDDP) alone or CDDP and 5-fluorouracil was delivered simultaneously with radiotherapy during Weeks 1 and 6. Adjuvant chemotherapy consisted of CDDP and 5-fluorouracil for 2 to 3 cycles and was given monthly beginning 1 month after completion of radiation. RESULTS: With a median follow-up of 57 months (range: 28-94 months), the 3-year locoregional control rate was 93%, the disease-free survival rate was 71%, and the overall survival rate was 72%. For T4 patients, the 3-year locoregional control rate was 91%, disease-free survival was 62%, and overall survival was 63%. The major acute toxicity was Grade 3 mucositis in 73% and Grade 2 weight loss in 31% of patients. Fifty percent of patients were tube fed. Most patients tolerated the combined modality treatments relatively well; 88% of patients completed their radiation treatment within 8 weeks. CONCLUSION: HFRT and CCT for T3 and T4 NPC were associated with excellent local control and improved survival. The treatment-related toxicity was acceptable and reversible. We would recommend using HFRT with CCT for advanced T-stage NPC if the three-dimensional conformal radiation planning shows a significant portion of the brainstem to be inside the treatment field.