NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality.

PURPOSE: NovoTTF-100A is a portable device delivering low-intensity, intermediate frequency electric fields via non-invasive, transducer arrays. Tumour Treatment Fields (TTF), a completely new therapeutic modality in cancer treatment, physically interfere with cell division. METHODS: Phase III trial of chemotherapy-free treatment of NovoTTF (20-24h/day) versus active chemotherapy in the treatment of patients with recurrent glioblastoma. Primary end-point was improvement of overall survival. RESULTS: Patients (median age 54years (range 23-80), Karnofsky performance status 80% (range 50-100) were randomised to TTF alone (n=120) or active chemotherapy control (n=117). Number of prior treatments was two (range 1-6). Median survival was 6.6 versus 6.0months (hazard ratio 0.86 [95% CI 0.66-1.12]; p=0.27), 1-year survival rate was 20% and 20%, progression-free survival rate at 6months was 21.4% and 15.1% (p=0.13), respectively in TTF and active control patients. Responses were more common in the TTF arm (14% versus 9.6%, p=0.19). The TTF-related adverse events were mild (14%) to moderate (2%) skin rash beneath the transducer arrays. Severe adverse events occurred in 6% and 16% (p=0.022) of patients treated with TTF and chemotherapy, respectively. Quality of life analyses favoured TTF therapy in most domains. CONCLUSIONS: This is the first controlled trial evaluating an entirely novel cancer treatment modality delivering electric fields rather than chemotherapy. No improvement in overall survival was demonstrated, however efficacy and activity with this chemotherapy-free treatment device appears comparable to chemotherapy regimens that are commonly used for recurrent glioblastoma. Toxicity and quality of life clearly favoured TTF.

Singling out individual inventors from patent data

An increasing number of studies have sprung up in recent years seeking to identify individual inventors from patent data. Different heuristics have been suggested to use their names and other information disclosed in patent documents in order to find out “who is who” in patents. This paper contributes to this literature by setting forth a methodology to identify them using patents applied to the European Patent Office (EPO hereafter). As in the large part of this literature, we basically follow a three-steps procedure: (1) the parsing stage, aimed at reducing the noise in the inventor’s name and other fields of the patent; (2) the matching stage, where name matching algorithms are used to group possible similar names; (3) the filtering stage, where additional information and different scoring schemes are used to filter out these potential same inventors. The paper includes some figures resulting of applying the algorithms to the set of European inventors applying to the EPO for a large period of time.

Periprocedural Hemodynamic Depression Is Associated With a Higher Number of New Ischemic Brain Lesions After Stenting in the International Carotid Stenting Study-MRI Substudy.

BACKGROUND AND PURPOSE: Carotid artery stenting (CAS) is associated with a higher risk of both hemodynamic depression and new ischemic brain lesions on diffusion-weighted imaging than carotid endarterectomy (CEA). We assessed whether the occurrence of hemodynamic depression is associated with these lesions in patients with symptomatic carotid stenosis treated by CAS or CEA in the randomized International Carotid Stenting Study (ICSS)-MRI substudy. METHODS: The number and total volume of new ischemic lesions on diffusion-weighted imaging 1 to 3 days after CAS or CEA was measured in the ICSS-MRI substudy. Hemodynamic depression was defined as periprocedural bradycardia, asystole, or hypotension requiring treatment. The number of new ischemic lesions was the primary outcome measure. We calculated risk ratios and 95% confidence intervals per treatment with Poisson regression comparing the number of lesions in patients with or without hemodynamic depression. RESULTS: A total of 229 patients were included (122 allocated CAS; 107 CEA). After CAS, patients with hemodynamic depression had a mean of 13 new diffusion-weighted imaging lesions, compared with a mean of 4 in those without hemodynamic depression (risk ratio, 3.36; 95% confidence interval, 1.73-6.50). The number of lesions after CEA was too small for reliable analysis. Lesion volumes did not differ between patients with or without hemodynamic depression. CONCLUSIONS: In patients treated by CAS, periprocedural hemodynamic depression is associated with an excess of new ischemic lesions on diffusion-weighted imaging. The findings support the hypothesis that hypoperfusion increases the susceptibility of the brain to embolism. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25337470.

Segmental copy number variation shapes tissue transcriptomes

Abstract : Copy number variation (CNV) of DNA segments has recently gained considerable interest as a source of genetic variation likely to play a role in phenotypic diversity and evolution. Much effort has been put into the identification and mapping of regions that vary in copy number among seemingly normal individuals, both in humans and in a number of model organisms, using both bioinformatic and hybridization-based methods. Synteny studies suggest the existence of CNV hotspots in mammalian genomes, often in connection with regions of segmental duplication. CNV alleles can be in equilibrium within a population, but can also arise de novo between generations, illustrating the highly dynamic nature of these regions. A small number of studies have assessed the effect of CNV on single loci, however, at the genome-wide scale, the functional impact of CNV remains poorly studied. We have explored the influence of CNV on gene expression, first using the Williams-Beuren syndrome (WBS) associated deletion as a model, and second at the genome-wide scale in inbred mouse strains. We found that the WBS deletion influences the expression levels not only of the hemizygous genes, but also affects the euploid genes mapping nearby. Consistently, on a genome wide scale we observe that CNV genes are expressed at more variable levels than genes that do not vary in copy number. Likewise, CNVs influence the relative expression levels of genes that map to the flank of the genome rearrangements, thus globally influencing tissue transcriptomes. Further studies are warranted to complete cataloguing and fine mapping of CNV regions, as well as to elucidate the different mechanisms by which CNVs influence gene expression. Résumé : La variation en nombre de copies (copy number variation ou CNV) de segments d'ADN suscite un intérêt en tant que variation génétique susceptible de jouer un r81e dans la diversité phénotypique et l'évolution. Les régions variables en nombre de copies parmi des individus apparemment normaux ont été cartographiées et cataloguées au moyen de puces à ADN et d'analyse bioinformatique. L'étude de la synténie entre plusieurs espèces de mammifères laisse supposer l'existence de régions à haut taux de variation, souvent liées à des duplications segmentaires. Les allèles CNV peuvent être en équilibre au sein d'une population ou peuvent apparaître de novo. Ces faits illustrent la nature hautement dynamique de ces régions. Quelques études se sont penchées sur l'effet de la variation en nombre de copies de loci isolés, cependant l'impact de ce phénomène n'a pas été étudié à l'échelle génomique. Nous avons examiné l'influence des CNV sur l'expression des gènes. Dans un premier temps nous avons utilisé la délétion associée au syndrome de Williams-Beuren (WBS), puis, dans un second temps, nous avons poursuivi notre étude à l'échelle du génome, dans des lignées consanguines de souris. Nous avons établi que la délétion WBS influence l'expression non seulement des gènes hémizygotes, mais également celle des gènes euploïdes voisins. A l'échelle génomique, nous observons des phénomènes concordants. En effet, l'expression des gènes variant en nombre de copies est plus variable que celles des gènes ne variant pas. De plus, à l'instar de la délétion WBS, les CNV influencent l'expression des gènes adjacents, exerçant ainsi un impact global sur les profils d'expression dans les tissus. Résumé pour un large public : De nombreuses maladies ont pour cause un défaut génétique. Parmi les types de mutations, on compte la disparition (délétion) d'une partie de notre génome ou sa duplication. Bien que l'on connaisse les anomalies associées à certaines maladies, les mécanismes moléculaires par lesquels ces réarrangements de notre matériel génétique induisent les maladies sont encore méconnus. C'est pourquoi nous nous sommes intéressés à la régulation des gènes dans les régions susceptibles à délétion ou duplication. Dans ce travail, nous avons démontré que les délétions et les duplications influencent la régulation des gènes situés à proximité, et que ces changements interviennent dans plusieurs organes.

Mitotic figure counts are significantly overestimated in resection specimens of invasive breast carcinomas.

Several authors have demonstrated an increased number of mitotic figures in breast cancer resection specimen when compared with biopsy material. This has been ascribed to a sampling artifact where biopsies are (i) either too small to allow formal mitotic figure counting or (ii) not necessarily taken form the proliferating tumor periphery. Herein, we propose a different explanation for this phenomenon. Biopsy and resection material of 52 invasive ductal carcinomas was studied. We counted mitotic figures in 10 representative high power fields and quantified MIB-1 immunohistochemistry by visual estimation, counting and image analysis. We found that mitotic figures were elevated by more than three-fold on average in resection specimen over biopsy material from the same tumors (20±6 vs 6±2 mitoses per 10 high power fields, P=0.008), and that this resulted in a relative diminution of post-metaphase figures (anaphase/telophase), which made up 7% of all mitotic figures in biopsies but only 3% in resection specimen (P<0.005). At the same time, the percentages of MIB-1 immunostained tumor cells among total tumor cells were comparable in biopsy and resection material, irrespective of the mode of MIB-1 quantification. Finally, we found no association between the size of the biopsy material and the relative increase of mitotic figures in resection specimen. We propose that the increase in mitotic figures in resection specimen and the significant shift towards metaphase figures is not due to a sampling artifact, but reflects ongoing cell cycle activity in the resected tumor tissue due to fixation delay. The dwindling energy supply will eventually arrest tumor cells in metaphase, where they are readily identified by the diagnostic pathologist. Taken together, we suggest that the rapidly fixed biopsy material better represents true tumor biology and should be privileged as predictive marker of putative response to cytotoxic chemotherapy.

Number of X-ray examinations performed on paediatric and geriatric patients compared with adult patients.

The age of the patient is of prime importance when assessing the radiological risk to patients due to medical X-ray exposures and the total detriment to the population due to radiodiagnostics. In order to take into account the age-specific radiosensitivity, three age groups are considered: children, adults and the elderly. In this work, the relative number of examinations carried out on paediatric and geriatric patients is established, compared with adult patients, for radiodiagnostics as a whole, for dental and medical radiology, for 8 radiological modalities as well as for 40 types of X-ray examinations. The relative numbers of X-ray examinations are determined based on the corresponding age distributions of patients and that of the general population. Two broad groups of X-ray examinations may be defined. Group A comprises conventional radiography, fluoroscopy and computed tomography; for this group a paediatric patient undergoes half the number of examinations as that of an adult, and a geriatric patient undergoes 2.5 times more. Group B comprises angiography and interventional procedures; for this group a paediatric patient undergoes a one-fourth of the number of examinations carried out on an adult, and a geriatric patient undergoes five times more.

Concurrent and simultaneous polydrug use among young Swiss males: use patterns and associations of number of substances used with health issues.

Background: Simultaneous polydrug use (SPU) may represent a greater incremental risk factor for human health than concurrent polydrug use (CPU). However, few studies have examined these patterns of use in relation to health issues, particularly with regard to the number of drugs used. Methods: In the present study, we have analyzed data from a representative sample of 5734 young Swiss males from the Cohort Study on Substance Use Risk Factors. Exposure to drugs (i.e., alcohol, tobacco, cannabis, and 15 other illicit drugs), as well as mental, social and physical factors, were studied through regression analysis. Results: We found that individuals engaging in CPU and SPU followed the known stages of drug use, involving initial experiences with licit drugs (e.g., alcohol and tobacco), followed by use of cannabis and then other illicit drugs. In this regard, two classes of illicit drugs were identified, including first uppers, hallucinogens and sniffed drugs; and then "harder" drugs (ketamine, heroin, and crystal meth), which were only consumed by polydrug users who were already taking numerous drugs. Moreover, we observed an association between the number of drugs used simultaneously and social issues (i.e., social consequences and aggressiveness). In fact, the more often the participants simultaneously used substances, the more likely they were to experience social problems. In contrast, we did not find any relationship between SPU and depression, anxiety, health consequences, or health. Conclusions: We identified some associations with SPU that were independent of CPU. Moreover, we found that the number of concurrently used drugs can be a strong factor associated with mental and physical health, although their simultaneous use may not significantly contribute to this association. Finally, the negative effects related to the use of one substance might be counteracted by the use of an additional substance.

A comparative study on the different staining methods and number of specimens for the detection of acid fast bacilli

The presence of acid fast bacilli in multiple specimens was investigated comparatively with Ziehl-Neelsen (ZN) and fluorescence microscopy (FM) staining in order to determine sensitivity in detecting tuberculosis (TB). A total of 465 specimens obtained from 295 patients were analysed at Harran University Medical School Hospital between March 1998 and March 2000. The culture was employed as the reference method. Sixty-eight patients (23.1%) were diagnosed as having TB by culture. The ZN and FM staining sensitivities were 67.6% (46/68) and 85.2% (58/68) respectively. Two hundred and one patients (68.1%) submitted one specimen to the laboratory. TB positivity was detected in 42 (20.9%) of these patients by culture. The sensitivities of ZN and FM stains were found to be 61% and 83% in these patients. However, in 18 patients (6.1%) who submitted two specimens to the laboratory, the TB was positive in six of them (33.3%) and ZN and FM sensitivities were 66% and 83% respectively. When three specimens or more were collected from the patients (76 patients, 25.8%), TB positivity was determined in 20 of them (26.3%) and the sensitivities were 80% and 92% in the ZN- and FM-stained smears, respectively. Our data indicate that in the diagnosis of TB, FM has greater sensitivity than ZN. In particular, in the case of a single specimen, the diagnostic value of FM is quite significant. It is, therefore, possible to conclude that both ZN and FM staining can be used for the diagnosis of TB when there are more than two specimens. However, if only one or two specimens are available, FM staining is preferable.

Determinants of high-growth firms:why do some countries have more high-growth firms than others?

High-growth firms have been shown to be a key factor for economic growth and structural change. This paper analyses the determinants of the number of high-growth firms in a country for 17 OECD countries between 1999 and 2005, using the Amadeus data set, the GEM data set, and others. The first contribution of this paper is that it is – as far as we know – the first empirical analysis of high-growth firms at the country level on the basis of actual measured growth. Second, we find indicative empirical evidence for three driving forces of high growth, viz. entrepreneurship, institutional settings, and opportunities for growth, all in accordance with theory and empirical findings in related fields of research. Third, the paper gives a tentative explanation of the differences in the average percentage of high-growth firms between countries. Finally, the paper gives some clues for policy makers how to promote high-growth firms. Keywords: high-growth firms, fast growing firms, entrepreneurship, institutional obstacles, opportunities for growth

Random mating with a finite number of matings.

Random mating is the null model central to population genetics. One assumption behind random mating is that individuals mate an infinite number of times. This is obviously unrealistic. Here we show that when each female mates a finite number of times, the effective size of the population is substantially decreased.

Using the Number of Pores on Fingerprint Images to Detect Spoofing Attacks

Abstract-Due to the growing use of biometric technologies inour modern society, spoofing attacks are becoming a seriousconcern. Many solutions have been proposed to detect the use offake "fingerprints" on an acquisition device. In this paper, wepropose to take advantage of intrinsic features of friction ridgeskin: pores. The aim of this study is to investigate the potential ofusing pores to detect spoofing attacks.Results show that the use of pores is a promising approach. Fourmajor observations were made: First, results confirmed that thereproduction of pores on fake "fingerprints" is possible. Second,the distribution of the total number of pores between fake andgenuine fingerprints cannot be discriminated. Third, thedifference in pore quantities between a query image and areference image (genuine or fake) can be used as a discriminatingfactor in a linear discriminant analysis. In our sample, theobserved error rates were as follows: 45.5% of false positive (thefake passed the test) and 3.8% of false negative (a genuine printhas been rejected). Finally, the performance is improved byusing the difference of pore quantity obtained between adistorted query fingerprint and a non-distorted referencefingerprint. By using this approach, the error rates improved to21.2% of false acceptation rate and 8.3% of false rejection rate.

Seasonal analysis of the number of aeropiles in Anocentor nitens (Neumann, 1897) (Acari: Ixodidae) from the State of Rio de Janeiro, Brazil

Variation between aeropile numbers of the right and left peritrematic plate in male and female Anocentor nitens (Neumann, 1897) is reported from a site in Brazil. From January to December 1998, 146 males and 247 females of A. nitens were recovered from Equus caballus L. in Silva Jardim District, State of Rio de Janeiro. Asymmetry of numbers of aeropiles between right and left plates occurred in 83.6% of the males and 82.2% of the females. Differences in the number of aeropiles between the sexes were not significant. Quantitative variation of aeropiles was correlated to the period of recovery, with significant asymmetry detected in August-September and November-December, mainly in males. Results suggest an adaptation, especially in the male ticks, that expresses itself as greater variation in the number of aeropiles in some periods of the year.