bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical implementation of a digital tomosynthesis‐based seed reconstruction algorithm for intraoperative postimplant dose evaluation in low dose rate prostate brachytherapy
Authors: Brunet‐Benkhoucha Malik , Verhaegen Frank , Lassalle Stéphanie , Béliveau‐Nadeau Dominic , Reniers Brigitte , Donath David , Taussky Daniel , Carrier Jean‐François
Published: October 2009

Purpose:

The low dose rate brachytherapy procedure would benefit from an intraoperative postimplant dosimetry verification technique to identify possible suboptimal dose coverage and suggest a potential reimplantation. The main objective of this project is to develop an efficient, operator‐free, intraoperative seed detection technique using the imaging modalities available in a low dose rate brachytherapy treatment room.

Methods:

This intraoperative detection allows a complete dosimetry calculation that can be performed right after an I‐125 prostate seed implantation, while the patient is still under anesthesia. To accomplish this, a digital tomosynthesis‐based algorithm was developed. This automatic filtered reconstruction of the 3D volume requires seven projections acquired over a total angle of 60° with an isocentric imaging system.

Results:

A phantom study was performed to validate the technique that was used in a retrospective clinical study involving 23 patients. In the patient study, the automatic tomosynthesis‐based reconstruction yielded seed detection rates of 96.7% and 2.6% false positives. The seed localization error obtained with a phantom study is. The average time needed for reconstruction is below 1 min. The reconstruction algorithm also provides the seed orientation with an uncertainty of . The seed detection algorithm presented here is reliable and was efficiently used in the clinic.

Conclusions:

When combined with an appropriate coregistration technique to identify the organs in the seed coordinate system, this algorithm will offer new possibilities for a next generation of clinical brachytherapy systems.
Characterization of free breathing patterns with 5D lung motion model
Authors: Zhao Tianyu , Lu Wei , Yang Deshan , Mutic Sasa , Noel Camille E. , Parikh Parag J. , Bradley Jeffrey D. , Low Daniel A.
Published: October 2009

Purpose:

To determine the quiet respiration breathing motion model parameters for lung cancer and nonlung cancer patients.

Methods:

49 free breathing patient 4DCT image datasets (25 scans, cine mode) were collected with simultaneous quantitative spirometry. A cross‐correlation registration technique was employed to track the lung tissue motion between scans. The registration results were applied to a lung motion model: , where is the position of a piece of tissue located at reference position during a reference breathing phase (zero tidal volume , zero airflow ). is a parameter that characterizes the motion due to air filling (motion as a function of tidal volume ) and is the parameter that accounts for the motion due to the imbalance of dynamical stress distributions during inspiration and exhalation that causes lung motion hysteresis (motion as a function of airflow ). The parameters and together provide a quantitative characterization of breathing motion that inherently includes the complex hysteresis interplay. The and distributions were examined for each patient to determine overall general patterns and interpatient pattern variations.

Results:

For 44 patients, the greatest values of were observed in the inferior and posterior lungs. For the rest of the patients, reached its maximum in the anterior lung in three patients and the lateral lung in two patients. The hysteresis motion had greater variability, but for the majority of patients, was largest in the lateral lungs.

Conclusions:

This is the first report of the three‐dimensional breathing motion model parameters for a large cohort of patients. The model has the potential for noninvasively predicting lung motion. The majority of patients exhibited similar maps and the maps showed greater interpatient variability. The motion parameter interpatient variability will inform our need for custom radiation therapy motion models. The utility of this model depends on the parameter stability over time, which is still under investigation.
Implementation and characterization of a 320‐slice volumetric CT scanner for simulation in radiation oncology
Authors: Coolens C. , Breen S. , Purdie T. G. , Owrangi A. , Publicover J. , Bartolac S. , Jaffray D. A.
Published: October 2009

Purpose:

Effective target definition and broad employment of treatment response assessment with dynamic contrast‐enhanced CT in radiation oncology requires increased speed and coverage for use within a single bolus injection. To this end, a novel volumetric CT scanner (Aquilion One, Toshiba, Tochigi Pref., Japan) has been installed at the Princess Margaret Hospital for implementation into routine CT simulation. This technology offers great advantages for anatomical and functional imaging in both scan speed and coverage. The aim of this work is to investigate the system's imaging performance and quality as well as CT quantification accuracy which is important for radiotherapy dose calculations.

Methods:

The 320‐slice CT scanner uses a wide‐area (2D) solid‐state detector design which provides the possibility to acquire a volumetric axial length of without moving the CT couch. This is referred to as “volume” and can be scanned with a rotation speed of . The scanner can also be used as a 64‐slice CT scanner and perform conventional (axial) and helical acquisitions with collimation ranges of 1–32 and , respectively. Commissioning was performed according to AAPM Reports TG 66 and 39 for both helical and volumetric imaging. Defrise and other cone‐beam image analysis tests were performed.

Results:

Overall, the imaging spatial resolution and geometric efficiency (GE) were found to be very good (, spatial integrity and ) and within the AAPM guidelines as well as IEC recommendations. Although there is evidence of some cone‐beam artifacts when scanning the Defrise phantom, image quality was found to be good and sufficient for treatment planning (soft tissue noise ). Measurements of CT number stability and contrast‐to‐noise values across the volume indicate clinically acceptable scan accuracy even at the field edge.

Conclusions:

Initial experience with this exciting new technology confirms its accuracy for routine CT simulation within radiation oncology and allows for future investigations into specialized dynamic volumetric imaging applications.
Medical Imaging Principles, Detectors, and Electronics
Authors: Davros William
Published: October 2009

Medical Imaging Principles, Detectors, and Electronics Iniewski Krysztof Wiley, New Jersey, 2009. 305 pp. Price: $110.00. ISBN: 978‐0‐470‐39164‐8 (hardcover).
Time dependence of energy spectra of brachytherapy sources and its impact on the half and the tenth value layers
Authors: Yue Ning J. , Chen Zhe , Hearn Robert A. , Rodgers Joseph J. , Nath Ravinder
Published: October 2009

Purpose:

Several factors including radionuclide purity influence the photon energy spectra from sealed brachytherapy sources. The existence of impurities and trace elements in radioactive materials as well as the substrate and encapsulation may not only alter the spectrum at a given time but also cause change in the spectra as a function of time. The purpose of this study is to utilize a semiempirical formalism, which quantitatively incorporates this time dependence, to calculate and evaluate the shielding requirement impacts introduced by this time dependence for a source.

Methods:

The formalism was used to calculate the thicknesses in lead for a model 200 seed. Prior to 2005, the in this source was purified to a level better than 0.006% of the total activity, the key trace impurity consisting of . Because emits higher energy photons and has a much longer half‐life of compared to , its presence in seeds led to a time dependence of the photon spectrum and other related physical quantities. This study focuses on the time dependence of the NthVL and the analysis of the corresponding shielding requirements.

Results:

The results indicate that the first HVL and the first TVL in lead steadily increased with time for about and then reached a plateau. The increases at plateau were more than 1000 times compared to the corresponding values on the zeroth day. The second and third TVLs in lead reached their plateaus in about 100 and , respectively, and the increases were about 19 and 2.33 times the corresponding values on the zeroth day, respectively. All the TVLs demonstrated a similar time dependence pattern, with substantial increases and eventual approach to a plateau.

Conclusions:

The authors conclude that the time dependence of the emitted photon spectra from brachytherapy sources can introduce substantial variations in the values of the with time if certain impurities are present. The contribution of to the dose rate constant was less than 0.03% in the earlier seeds, and because of the use of new processing technologies since 2005, this impurity has been essentially eliminated, as demonstrated in the measured spectra of current model 200 seeds. This study illustrates the importance of performing photon spectroscopy of the manufactured radioactive sources as a quality assurance test for an assessment over time of both the radiation protection and the dosimetric properties.
Pretreatment of Epithelial Cells with Rifaximin Alters Bacterial Attachment and Internalization Profiles
Authors: Brown Eric L. , Xue Qiong , Jiang Zhi-Dong , Xu Yi , DuPont Herbert L.
Published: October 2009

Rifaximin is a poorly absorbed semisynthetic antibiotic derivative of rifampin licensed for use in the treatment of traveler's diarrhea. Rifaximin reduces the symptoms of enteric infection, often without pathogen eradication and with limited effects on intestinal flora. Epithelial cells (HEp-2 [laryngeal], HCT-8 [ileocecal], A549 [lung], and HeLa [cervical]) were pretreated with rifaximin (or control antibiotics) prior to the addition of enteroaggregative
Escherichia coli
(EAEC). EAEC adherence was significantly reduced following rifaximin pretreatment compared to pretreatment with rifampin or doxycycline for three of the four cell lines tested. The rifaximin-mediated changes to epithelial cells were explored further by testing the attachment and internalization of either
Bacillus anthracis
or
Shigella sonnei
into A549 or HeLa cells, respectively. The attachment and internalization of
B. anthracis
were significantly reduced following rifaximin pretreatment. In contrast, neither the attachment nor the internalization of
S. sonnei
was affected by rifaximin pretreatment of HeLa cells, suggesting that rifaximin-mediated modulation of host cell physiology affected bacteria utilizing distinct attachment/internalization mechanisms differently. In addition, rifaximin pretreatment of HEp-2 cells led to reduced concentrations of inflammatory cytokines from uninfected cells. The study provides evidence that rifaximin-mediated changes in epithelial cell physiology are associated with changes in bacterial attachment/internalization and reduced inflammatory cytokine release.
Pharmacokinetic Properties of Azithromycin in Pregnancy
Authors: Salman Sam , Rogerson Stephen J. , Kose Kay , Griffin Susan , Gomorai Servina , Baiwog Francesca , Winmai Josephine , Kandai Josin , Karunajeewa Harin A. , O'Halloran Sean J. , Siba Peter , Ilett Kenneth F. , Mueller Ivo , Davis Timothy M. E.
Published: October 2009

Azithromycin (AZI) is an azalide antibiotic with antimalarial activity that is considered safe in pregnancy. To assess its pharmacokinetic properties when administered as intermittent preventive treatment in pregnancy (IPTp), two 2-g doses were given 24 h apart to 31 pregnant and 29 age-matched nonpregnant Papua New Guinean women. All subjects also received single-dose sulfadoxine-pyrimethamine (SP) (1,500 mg or 75 mg) or chloroquine (450-mg base daily for 3 days). Blood samples were taken at 0, 1, 2, 3, 6, 12, 24, 32, 40, 48, and 72 h and on days 4, 5, 7, 10, and 14 for AZI assay by ultra-high-performance liquid chromatography-tandem mass spectrometry. The treatments were well tolerated. Using population pharmacokinetic modeling, a three-compartment model with zero-order followed by first-order absorption and no lag time provided the best fit. The areas under the plasma concentration-time curve (AUC
0-∞
) (28.7 and 31.8 mg·h liter
−1
for pregnant and nonpregnant subjects, respectively) were consistent with the results of previous studies, but the estimated terminal elimination half-lives (78 and 77 h, respectively) were generally longer. The only significant relationship for a range of potential covariates, including malarial parasitemia, was with pregnancy, which accounted for an 86% increase in the volume of distribution of the central compartment relative to bioavailability without a significant change in the AUC
0-∞
. These data suggest that AZI can be combined with compounds with longer half-lives, such as SP, in combination IPTp without the need for dose adjustment.
Mapping Simocyclinone D8 Interaction with DNA Gyrase: Evidence for a New Binding Site on GyrB
Authors: Sissi C. , Vazquez E. , Chemello A. , Mitchenall L. A. , Maxwell A. , Palumbo M.
Published: October 2009

Simocyclinone D8, a coumarin derivative isolated from
Streptomyces antibioticus
Tü 6040, represents an interesting new antiproliferative agent. It was originally suggested that this drug recognizes the GyrA subunit and interferes with the gyrase catalytic cycle by preventing its binding to DNA. To further characterize the mode of action of this antibiotic, we investigated its binding to the reconstituted DNA gyrase (A
2
B
2
) as well as to its GyrA and GyrB subunits and the individual domains of these proteins, by performing protein melting and proteolytic digestion studies as well as inhibition assays. Two binding sites were identified, one (anticipated) in the N-terminal domain of GyrA (GyrA59) and the other (unexpected) at the C-terminal domain of GyrB (GyrB47). Stabilization of the A subunit appears to be considerably more effective than stabilization of the B subunit. Our data suggest that these two distinct sites could cooperate in the reconstituted enzyme.
Factors Influencing Pharmacokinetics of Prophylactic Posaconazole in Patients Undergoing Allogeneic Stem Cell Transplantation
Authors: Kohl V. , Müller C. , Cornely O. A. , Abduljalil K. , Fuhr U. , Vehreschild J. J. , Scheid C. , Hallek M. , Rüping M. J. G. T.
Published: October 2009

The objectives of the present study were to elucidate the factors influencing the pharmacokinetics of prophylactically administered posaconazole in allogeneic hematopoietic stem cell transplant (SCT) recipients. Between May 2007 and November 2008, clinical data were obtained from all SCT recipients at the University Hospital of Cologne undergoing therapeutic drug monitoring (TDM) of serum prophylactic posaconazole concentrations. The posaconazole concentrations were determined by high-performance liquid chromatography. We developed a population pharmacokinetic model using nonlinear mixed-effect modeling (NONMEM). The list of covariates tested included age; body weight; body height; gender; posaconazole dose; race; coadministration of antineoplastic chemotherapy; day of stem cell transplantation; concomitant ranitidine, pantoprazole, cyclosporine, or tacrolimus administration; coincident fever; diarrhea; and plasma gamma-glutamyltransferase activity. A total of 149 serum posaconazole concentrations from 32 patients were obtained. A one-compartment model with first-order absorption and elimination as the basic structural model appropriately described the data, with the apparent clearance being 75.8 liters/h (95% confidence interval [CI], 65.2 to 86.4 liters/h) and the apparent volume being distribution of 835 liters (95% CI, 559 to 1,111 liters). Among the covariates tested, significant effects were found for age (decrease in the volume of distribution of 123 liters per year of age) and the presence of diarrhea (59% loss of bioavailability). A basis for prediction of the mean posaconazole concentrations in allogeneic SCT recipients with hematological malignancies is provided for a given dose. Corresponding adjustments of the starting dose according to the presence of diarrhea and according to age appear to be justified before TDM results are available.
Major Surface Protease of Trypanosomatids: One Size Fits All?
Authors: Yao Chaoqun
Published: October 2009

Major surface protease (MSP or GP63) is the most abundant glycoprotein localized to the plasma membrane ofLeishmaniapromastigotes. MSP plays several important roles in the pathogenesis of leishmaniasis, including but not limited to (i) evasion of complement-mediated lysis, (ii) facilitation of macrophage (Mø) phagocytosis of promastigotes, (iii) interaction with the extracellular matrix, (iv) inhibition of natural killer cellular functions, (v) resistance to antimicrobial peptide killing, (vi) degradation of Mø and fibroblast cytosolic proteins, and (vii) promotion of survival of intracellular amastigotes. MSP homologues have been found in all other trypanosomatids studied to date including heteroxenous members ofTrypanosoma cruzi, the extracellularTrypanosoma brucei, unusual intraerythrocyticEndotrypanumspp., phytoparasiticPhytomonasspp., and numerous monoxenous species. These proteins are likely to perform roles different from those described forLeishmaniaspp. Multiple MSPs in individual cells may play distinct roles at some time points in trypanosomatid life cycles and collaborative or redundant roles at others. The cellular locations and the extracellular release of MSPs are also discussed in connection with MSP functions in leishmanial promastigotes.
Helicobacter pylori
Lipopolysaccharides Upregulate Toll-Like Receptor 4 Expression and Proliferation of Gastric Epithelial Cells via the MEK1/2-ERK1/2 Mitogen-Activated Protein Kinase Pathway
Authors: Yokota Shin-ichi , Okabayashi Tamaki , Rehli Michael , Fujii Nobuhiro , Amano Ken-ichi
Published: October 2009

Helicobacter pylori
is recognized as an etiological agent of gastroduodenal diseases.
H. pylori
produces various toxic substances, including lipopolysaccharide (LPS). However,
H. pylori
LPS exhibits extremely weakly endotoxic activity compared to the typical LPS, such as that produced by
Escherichia coli
, which acts through Toll-like receptor 4 (TLR4) to induce inflammatory molecules. The gastric epithelial cell lines MKN28 and MKN45 express TLR4 at very low levels, so they show very weak interleukin-8 (IL-8) production in response to
E. coli
LPS, but pretreatment with
H. pylori
LPS markedly enhanced IL-8 production induced by
E. coli
LPS by upregulating TLR4 via TLR2 and the MEK1/2-ERK1/2 pathway. The transcription factor NF-Y was activated by this signal and promoted transcription of the
tlr4
gene. These MEK1/2-ERK1/2 signal-mediated activities were more potently activated by LPS carrying a weakly antigenic epitope, which is frequently found in gastric cancers, than by LPS carrying a highly antigenic epitope, which is associated with chronic gastritis.
H. pylori
LPS also augmented the proliferation rate of gastric epithelial cells via the MEK1/2-ERK1/2 pathway.
H. pylori
LPS may be a pathogenic factor causing gastric tumors by enhancing cell proliferation and inflammation via the MEK1/2-ERK1/2 mitogen-activated protein kinase cascade in gastric epithelial cells.
The Stability of Cytadherence Proteins in
Mycoplasma pneumoniae
Requires Activity of the Protein Kinase PrkC
Authors: Schmidl Sebastian R. , Gronau Katrin , Hames Claudine , Busse Julia , Becher Dörte , Hecker Michael , Stülke Jörg
Published: October 2009

Mycoplasma pneumoniae
belongs to the mollicutes, a group of bacteria that have strongly reduced genomes but that are nevertheless capable of independent life. With only three transcription factors, the regulatory features of these bacteria are very limited. Thus, posttranslational regulation might be important for
M. pneumoniae
. In addition to the highly specific HPr kinase, the
M. pneumoniae prkC
gene encodes the serine/threonine protein kinase C. In order to study the function(s) of this kinase, we isolated an
M. pneumoniae
mutant affected in PrkC. This mutation resulted in nonadherent growth and loss of cytotoxicity. Examination of the phosphorylation profile of the
prkC
mutant suggested that phosphorylation of cytadherence proteins was affected by the loss of this kinase. In contrast, inactivation of the
prpC
gene affecting the protein phosphatase that antagonizes PrkC-dependent phosphorylation resulted in more intensive phosphorylation of the cytadherence proteins HMW1 and HMW3 of the major adhesin P1 and of the surface protein MPN474. Moreover, loss of PrkC affects not only the phosphorylation state of the cytadherence proteins but also their intracellular accumulation. However, the expression of the corresponding genes was not affected by PrkC, suggesting that PrkC-dependent phosphorylation results in stabilization of the cytadherence proteins. The HMW proteins and P1 are part of the so-called terminal organelle of
M. pneumoniae
that is involved in gliding motility, cell division, and adhesion to host epithelial tissues. Our observations suggest that the posttranslational modification of cytadherence proteins by PrkC is essential for the development and function of the
M. pneumoniae
terminal organelle.
Candida albicans
Releases Soluble Factors That Potentiate Cytokine Production by Human Cells through a Protease-Activated Receptor 1- and 2-Independent Pathway
Authors: Cheng Shih-Chin , Chai Louis Y. A. , Joosten Leo A. B. , Vecchiarelli Anna , Hube Bernhard , Van Der Meer Jos W. , Kullberg Bart Jan , Netea Mihai G.
Published: October 2009

The innate immune system recognizes pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRR) and transduces downstream signaling to activate the host defense. Here we report that in addition to direct PAMP-PRR interactions, live
Candida albicans
cells can release soluble factors to actively potentiate interleukin-6 (IL-6) and IL-8 production induced in human mononuclear cells by the fungi. Although protease-activated receptor 1 (PAR1) and PAR2 ligation can moderately upregulate Toll-like receptor 4 (TLR4)-mediated IL-8 production, no effect on the
C. albicans
-induced cytokine was apparent. Similarly, the blockade of PAR signaling did not reverse the potentiation of cytokine production induced by soluble factors released by
C. albicans
. In conclusion,
C. albicans
releases soluble factors that potentiate cytokine release in a PAR1/2-independent manner. Thus, human PAR1 and PAR2 have a redundant role in the activation of human cells by
C. albicans
.
ECG as a part of the preparticipation screening programme: an old and still present international dilemma
Authors: Hevia A Carro , Fernández M M , Palacio J M A , Martín E H , Castro M G , Reguero J J Rodríguez
Published: October 2009

Introduction

Long-term Italian experience has provided evidence that preparticipation screening in competitive athletes with 12-lead ECG, history and physical examination is effective in identifying potentially lethal cardiovascular diseases. However, it is not being routinely practised in other countries.

Objectives

To evaluate the usefulness of a preparticipation screening programme in a sample of players belonging to different disciplines.

Material and methods

From September 2006 to June 2008, 1220 young athletes from different sports disciplines underwent a cardiovascular examination that included personal and family history, physical examination and a resting 12-lead ECG. Those with abnormal findings were referred for additional tests.

Results

1220 Athletes were screened: 96% males; mean age 23 (4) years. 90 (7.4%) players were referred for additional tests because of abnormal findings on baseline examination: 11 (0.9%) personal or family history, 4 (0.08%) physical examination and 75 (6.14%) 12-lead ECG. Echocardiographic assessment fulfilled left ventricular hypertrophy criteria in 8 of the 90 players. Of those, one case was considered an athlete's heart and one case was diagnosed with hypertrophic cardiomyopathy (septal thickness 23 mm). Further tests were needed in the remaining six, included in the “grey area”, with one additional case of hypertrophic cardiomyopathy (apical variant) suggested by cardiac MRI.

Conclusion

Given the ability of 12-lead ECG to detect individuals with structural heart disease, we suggest its inclusion as a part of preparticipation screening programmes.
Heat injury in youth sport: Table 1
Authors: Marshall S W
Published: October 2009

Heat injury is a potentially lethal condition that is considered to be completely preventable. Fatal heat injury is relatively rare (0.20 per 100 000 player-seasons in US high school football) and there are very limited data on non-fatal incidence. Expert recommendations for prevention include gradual acclimatisation of youth athletes to hot conditions, reductions in activity in hot and humid conditions, wearing light and light-coloured clothing, careful monitoring of athletes for signs of heat injury to facilitate immediate detection, having the resources to immediately and rapidly cool affected athletes, and education of athletes, care givers, and coaches about heat injury. Although a base of observational case data, physiological information, and expert opinion exists, the science surrounding this field is devoid of health communication and health behaviour research, and there is a pressing need for analytical studies to evaluate intervention programmes and/or identify new risk factors. There is also a need for ongoing data collection on heat injury incidence and on the knowledge, attitudes and behaviours towards heat injury among youth athletes, their care givers and their coaches.
Recent advances in understanding the molecular basis of Paget disease of bone
Authors: Goode A , Layfield R
Published: October 2009

Paget disease of bone (PDB) is a relatively common disorder characterised by increased bone turnover within discrete lesions throughout the skeleton. The condition has a strong genetic component, with mutations affecting theSQSTM1gene that encodes the p62 protein often found in PDB patients, although environmental factors also play an important role in disease aetiology. The precise disease mechanism(s) in familial forms and sporadic forms of PDB is unclear, although defective RANK-NF-κB signalling has been suggested to contribute to the increased activity of pagetic osteoclasts in the former. Here, there is a review of recent advances in the understanding of the molecular basis of PDB with particular emphasis on findings since 2008, and focus on newly defined functions of the p62 protein upon whichSQSTM1mutations may impact in the development of the pagetic phenotype.
The significance of tumour cell immunophenotype in myeloma and its impact on clinical outcome
Authors: Ngo N-T , Brodie C , Giles C , Horncastle D , Klammer M , Lampert I A , Rahemtulla A , Naresh K N
Published: October 2009

Background and aims:

Antigen expression of multiple myeloma (MM) cells is heterogeneous. We have investigated the clinical impact of expression of some of the commonly used immunohistochemical markers in the diagnostic work-up of bone marrow trephine biopsy (BMTB) samples in MM.

Patients and methods:

BMTB samples from 107 MM patients who had received an autologous stem cell transplant (ASCT) following chemotherapy were evaluated. In 75 cases, the immunophenotype had been evaluated on two or more occasions on further follow-up.

Results:

In the cases evaluated, 32%, 79%, 73%, 39% and 60% of cases had been scored positive for CD20, CD79a, CD56, cyclin D1 and epithelial membrane antigen (EMA) respectively. Absence of CD79a was predictive of poor overall survival (OS) from the time of transplant (p = 0.029) and poor event-free survival (EFS) from the time of transplant (p = 0.003). Absence of EMA (p = 0.02) was predictive of poor EFS from the time of diagnosis. Presence of CD56 was predictive of poor EFS from the time of diagnosis (p = 0.026). On multivariate analysis, only CD79a expression (OS and EFS from the time of transplant) and EMA expression (EFS from the time of diagnosis) maintained their significance. 13 of 75 patients showed an immunophenotypic drift during the disease course. Loss of CD20 (four cases) during the disease course in cases that were previously scored positive correlated with significant worsening both, of OS (p = 0.02) and EFS (p = 0.009) from the time of diagnosis.

Conclusion:

Immunophenotype impacts on clinical outcome in MM.
APPROXIMATING SMALLEST ENCLOSING BALLS WITH APPLICATIONS TO MACHINE LEARNING
Authors: NIELSEN FRANK , NOCK RICHARD
Published: October 2009

In this paper, we first survey prior work for computing exactly or approximately the smallest enclosing balls of point or ball sets in Euclidean spaces. We classify previous work into three categories: (1) purely combinatorial, (2) purely numerical, and (3) recent mixed hybrid algorithms based on coresets. We then describe two novel tailored algorithms for computing arbitrary close approximations of the smallest enclosing Euclidean ball. These deterministic heuristics are based on solving relaxed decision problems using a primal-dual method. The primal-dual method is interpreted geometrically as solving for a minimum covering set, or dually as seeking for a minimum piercing set. Finally, we present some applications in machine learning of the exact and approximate smallest enclosing ball procedure, and discuss about its extension to non-Euclidean information-theoretic spaces.
REDUCING THE TIME COMPLEXITY AND IDENTIFYING ILL-POSED PROBLEM INSTANCES OF MINKOWSKI SUM BASED SIMILARITY CALCULATIONS
Authors: BEKKER HENK , BRINK AXEL A. , ROERDINK JOS B. T. M.
Published: October 2009

To calculate the Minkowski-sum based similarity measure of two convex polyhedra, many relative orientations have to be considered. These relative orientations are characterized by the fact that some faces and edges of the polyhedra are parallel. For every relative orientation of the polyhedra, the volume or mixed volume of their Minkowski sum is evaluated. From the minimum of this volume, the similarity measure is calculated. In this article two issues are addressed. First, we propose and test a method to reduce the set of relative orientations to be considered by using geometric inequalities in the slope diagrams of the polyhedra. In this way, the time complexity of O(n6) is reduced to O(n4.5). Secondly, we determine which relative orientation problems are ill-posed and may be skipped because they do not maximize the similarity measure.
SEARCH FOR STEADY AND TRANSIENT POINT-LIKE SOURCES OF NEUTRINOS WITH ANTARES
Authors:   on behalf of the ANTARES Collaboration, BIGONGIARI CIRO
Published: October 2009

The ANTARES underwater neutrino telescope has been completed in May 2008 and is now taking data continuously. Thanks to its very good angular resolution (better than 0.3° for neutrinos with energy above 10 TeV) ANTARES is especially suited for the search of astrophysical point-like sources of high energy neutrinos. Data taken with a limited detector (5 out of 12 lines) between January and December 2007 have been analyzed to look for a possible neutrino excess from a list of prospective neutrino sources. In the case of transient sources, like GRBs, the short duration of the expected neutrino signal can be exploited to enhance the signal to noise ratio. ANTARES strategy for both steady and transient point-like sources is discussed. The methodology adopted and the results obtained are shown.
SEARCHES FOR A DIFFUSE FLUX OF EXTRATERRESTRIAL MUON NEUTRINOS WITH THE ICECUBE OBSERVATORY
Authors:   for the ICECUBE Collaboration (See for a full list of authors.), DEMIRÖRS LEVENT
Published: October 2009

The IceCube observatory is currently being contructed at the South Pole. Scheduled to be completed in 2011, it already offers a large increase in sensitivity over its predecessor, the AMANDA detector. This increase is expected to improve significantly the search for extraterrestrial neutrinos which are currently under way. One of the key searches at the IceCube observatory is for a diffuse flux of high energy extraterrestrial muon neutrinos, in excess of that observed from cosmic-ray induced atmospheric neutrinos. In this paper, we will review results obtained with the AMANDA and early IceCube detectors as well as give an outlook on upcoming analyses.
THE PROMPT AND HIGH ENERGY EMISSION OF GAMMA RAY BURSTS
Authors: MÉSZÁROS PETER
Published: October 2009

I discuss some recent results on the prompt emission of gamma-ray bursts, in particular the jet and radiation properties of the naked-eye burst GRB 080319b, based on Swift and related observations. I then discuss the recent observations by the Fermi satellite of GRB 080916C, the resulting constraints for the bulk Lorentz factor determinations, and the highest lower limit on the quantum gravity energy scale obtained so far.
PHYSICS INSIGHTS FROM RECENT MAGIC AGN OBSERVATIONS
Authors:   on behalf of the MAGIC Collaboration, WAGNER ROBERT
Published: October 2009

The total set of the 14 active galactic nuclei detected by MAGIC so far includes well-studied bright blazars like Mkn 501, the giant radio galaxy M 87, but also the distant flat-spectrum radio quasar 3C 279, and an intriguing gamma-ray source in the 3C 66A/B region, whose energy spectrum is not compatible with the expectations from 3C 66A. Besides scheduled observations, so far MAGIC succeeded in discovering TeV gamma rays from three blazars following triggers from high optical states. I report selected highlights from recent MAGIC observations of extragalactic TeV gamma-ray sources, emphasizing and discussing the new physics insights the MAGIC observations were able to contribute.
MODIFICATION OF HIGH ENERGY γ-RAY SPECTRUM OF BLAZARS DUE TO INTERNAL AND INTERGALACTIC ABSORPTION
Authors: ZACHAROPOULOU OLGA , KHANGULYAN DMITRY , AHARONIAN FELIX
Published: October 2009

Blazars are effective emitters of γ-rays with spectra extending to GeV and TeV energies. In the case of distant TeV blazars, γ-rays undergo severe absorption due to interactions with diffuse intergalactic radiation fields resulting in significant deformations of the initial (source) spectra. Even for the lowest possible level of the Extragalactic Background Light (EBL), the absorption-corrected γ-ray spectra from some TeV blazars appear unusually hard, which cannot be explained within the standard particle acceleration models of blazars. The simplest and most natural solution of this problem seems to us the realization of internal absorption of γ-rays in narrow (e.g. Planckian type) radiation fields in the immediate vicinity of the γ-ray production region.
INNOVATION AND STRATEGIC TYPES OF FAMILY SMEs: A TEST AND EXTENSION OF MILES AND SNOW'S CONFIGURATIONAL MODEL
Authors: PITTINO DANIEL , VISINTIN FRANCESCA
Published: October 2009

In this paper is we attempt to construct and validate a typology of innovation strategies among family SMEs applying the Miles and Snow's configurational model. We also try to extend the scope of the model testing the fit between entrepreneurial, managerial and governance characteristics and innovative posture of the firm. Research has been carried out on a representative sample of small and medium family firms of the Italian region Friuli Venezia Giulia. Results indicate that significant differences in the mentioned contextual variables exist among different strategic typologies of family firms, however some questions remain unanswered and more effort is needed to develop the configurational approach in the field of family business.
CASE STUDIES ON WHAT ENTREPRENEURS ACTUALLY DO TO ATTRACT RESOURCES: A TWO-ROUTE FRAMEWORK
Authors: LOPES MIGUEL PEREIRA , PINA E. CUNHA MIGUEL , DA PALMA PATRICIA JARDIM
Published: October 2009

Taking a grounded approach, we devised a framework to explain how entrepreneurs attract critical resources to venture creation and development. The study was based on qualitative data from a series of interviews with thirteen entrepreneurs conducted in a sample of six case studies. The framework distinguishes two routes that entrepreneurs use to attract resources for their ventures: idea selling, referring to how the entrepreneurs seek to engage others within the venture and to persuade them to support their entrepreneurial efforts; and network building, concerning the attraction effects of the entrepreneurs' social network positions and venture legitimacy. The framework adds to entrepreneurship theory by proposing a conceptual model of resource gathering strategies in new venture creation and development.
PROJECTIVE SPECTRUM IN BANACH ALGEBRAS
Authors: YANG RONGWEI
Published: October 2009

For a tuple A = (A1, A2, …, An) of elements in a unital algebra [Formula: see text] over ℂ, its projective spectrumP(A) or p(A) is the collection of z ∈ ℂn, or respectively z ∈ ℙn-1 such that A(z) = z1A1 + z2A2 + ⋯ + znAn is not invertible in [Formula: see text]. In finite dimensional case, projective spectrum is a projective hypersurface. When A is commuting, P(A) looks like a bundle over the Taylor spectrum of A. In the case [Formula: see text] is reflexive or is a C*-algebra, the projective resolvent setPc(A) := ℂn \ P(A) is shown to be a disjoint union of domains of holomorphy. [Formula: see text]-valued 1-form A-1(z)dA(z) reveals the topology of Pc(A), and a Chern–Weil type homomorphism from invariant multilinear functionals to the de Rham cohomology [Formula: see text] is established.
NONLINEARITY OF MATRIX GROUPS
Authors: KASSABOV MARTIN , SAPIR MARK V.
Published: October 2009

Answering a question of G. Yu, we show that the group EL3(ℤ 〈 x, y 〉) is not linear over any field. We also prove that for every unitary associative ring R, the group ELk(R) (k ≥ 3) is linear over ℂ if and only if R has a finite index ideal that is linear over ℂ.
ViewpointOn public service and computer science
Authors: Smith Jonathan M.
Published: October 2009

Members of the computer science community should become more involved in public service by becoming program managers at federal agencies, the opportunities and benefits of which are outlined here.
Scratch
Authors: Resnick Mitchel , Maloney John , Monroy-Hernández Andrés , Rusk Natalie , Eastmond Evelyn , Brennan Karen , Millner Amon , Rosenbaum Eric , Silver Jay , Silverman Brian , Kafai Yasmin
Published: October 2009

"Digital fluency" should mean designing, creating, and remixing, not just browsing, chatting, and interacting.
PuzzledCovering the plane
Authors: Winkler Peter
Published: October 2009

Welcome to three new puzzles. Solutions to the first two will be published next month; the third is (as yet) unsolved. In each, the issue is how your intuition matches up with the mathematics.
Energy-efficient register caching with compiler assistance
Authors: Jones Timothy M. , O'Boyle Michael F. P. , Abella Jaume , González Antonio , Ergin Oğuz
Published: October 2009

The register file is a critical component in a modern superscalar processor. It must be large enough to accommodate the results of all in-flight instructions. It must also have enough ports to allow simultaneous issue and writeback of many values each cycle. However, this makes it one of the most energy-consuming structures within the processor with a high access latency. As technology scales, there comes a point where register accesses are the bottleneck to performance and so must be pipelined over several cycles. This increases the pipeline depth, lowering performance.

To overcome these challenges, we propose a novel use of compiler analysis to aid register caching. Adding a register cache allows us to preserve single-cycle register accesses, maintaining performance and reducing energy consumption. We do this by passing information to the processor using free bits in a real ISA, allowing us to cache only the most important registers. Evaluating the register cache over a variety of sizes and associativities and varying the read ports into the cache, our best scheme achieves an energy-delay-squared (EDD) product of 0.81, with a performance increase of 11%. Another configuration saves 13% of register system energy. Using four register cache read ports brings both performance gains and energy savings, consistently outperforming two state-of-the-art hardware approaches.
Towards update-conscious compilation for energy-efficient code dissemination in WSNs
Authors: Li Weijia , Zhang Youtao , Yang Jun , Zheng Jiang
Published: October 2009

Postdeployment code dissemination in wireless sensor networks (WSN) is challenging, as the code has to be transmitted via energy-expensive wireless communication. In this article, we propose novel update-conscious compilation (UCC) techniques to achieve energy efficiency. By integrating the compilation decisions in generating the old binary, an update-conscious compiler strives to match the old decisions, which improves the binary code similarity, reduces the amount of transmitted data to remote sensors, and thus, consumes less energy. In this article, we develop update-conscious register allocation and data layout algorithms. Our experimental results show great improvements over the traditional, update-oblivious approaches.
Design and optimization of the store vectors memory dependence predictor
Authors: Subramaniam Samantika , Loh Gabriel H.
Published: October 2009

Allowing loads that do not violate memory ordering to issue out of order with respect to earlier unresolved store addresses is very important for extracting parallelism in large-window superscalar processors. Previous research has proposed memory dependence prediction algorithms to prevent only loads with true memory dependencies from issuing in the presence of unresolved stores. Techniques such as load-store pair identification and store sets have been very successful in achieving performance levels close to that attained by an oracle-dependence predictor, but have relatively complex or power-hungry designs. In this article, we use the idea of dependency vectors from matrix schedulers for nonmemory instructions and adapt them to implement a new dependence prediction algorithm. We show that for conservatively sized processors, a simple PC-indexed table that tracks misordered loads is sufficient to provide most of the performance benefits achieved by more sophisticated predictors. On more aggressive processor configurations, however, our “Store Vector” algorithm provides better performance than the state-of-the-art store sets predictor while maintaining a simpler and more scalable design.
Application development with the FlexWAFE real-time stream processing architecture for FPGAs
Authors: Lucas Amilcar Do Carmo , Sahlbach Henning , Whitty Sean , Heithecker Sven , Ernst Rolf
Published: October 2009

The challenges posed by complex real-time digital image processing at high resolutions cannot be met by current state-of-the-art general-purpose or DSP processors, due to the lack of processing power. On the other hand, large arrays of FPGA-based accelerators are too inefficient to cover the needs of cost sensitive professional markets. We present a new architecture composed of a network of configurable flexible weakly programmable processing elements, Flexible Weakly programmable Advanced Film Engine (FlexWAFE). This architecture delivers both programmability and high efficiency when implemented on an FPGA basis. We demonstrate these claims using a professional next-generation noise reducer with more than 170G image operations/s at 80% FPGA area utilization on four Virtex II-Pro FPGAs. This article will focus on the FlexWAFE architecture principle and implementation on a PCI-Express board.
A packet-switched network architecture for reconfigurable computing
Authors: Lloyd Scott , Snell Quinn
Published: October 2009

A packet-switched network architecture named Qnet and programming interface is presented that simplifies the integration of reconfigurable computing modules within a Field-Programmable Gate Array (FPGA). Qnet provides an abstraction layer to the designer of FPGA accelerator modules that hides the complexities of the system, while supporting a high degree of parallelism and performance. The architecture facilitates system design with pluggable, reusable modules. A network protocol is described that supports a three-party communication scheme between an initiator, a sender and a receiver. This protocol allows a master device to manage the state of other devices and the data flow within the system. An example using a high-level language is given. The Qnet architecture opens the computational power of FPGAs to computer scientists and software developers.
ReconOS
Authors: Lübbers Enno , Platzner Marco
Published: October 2009

Rising logic densities together with the inclusion of dedicated processor cores push reconfigurable devices from being applied for glue logic and prototyping towards implementing complete reconfigurable systems-on-chip. The mix of fast CPU cores and fine-grained reconfigurable logic allows to map both sequential, control-dominated code and highly parallel data-centric computations onto one platform. However, traditional design techniques that view specialized hardware circuits as passive coprocessors are ill-suited for programming these reconfigurable computers. In particular, the programming models for software—running on an embedded operating system—and digital hardware—synthesized to an FPGA—lack commonalities, which hinders design space exploration and severely impairs the potential for code reuse.

In this article, we present ReconOS, an execution environment based on existing embedded operating systems that extends the multithreaded programming model established in the software domain to reconfigurable hardware. Using threads and common synchronization and communication services as an abstraction layer, ReconOS allows for the creation of portable and flexible multithreaded applications targeting CPU/FPGA systems. This article discusses the ReconOS programming model and its execution environment, presents implementations based on modern platform FPGAs and the operating systems eCos and Linux, evaluates time and area overheads of the proposed mechanisms and, finally, demonstrates the feasibility of the multithreading design approach on several case studies.
FPGA placement using space-filling curves
Authors: Banerjee Pritha , Sur-Kolay Susmita , Bishnu Arijit , Das Sandip , Nandy Subhas C. , Bhattacharjee Subhasis
Published: October 2009

Research in VLSI placement, an NP-hard problem, has branched in two different directions. The first one employs iterative heuristics with many tunable parameters to produce a near-optimal solution but without theoretical guarantee on its quality. The other one considers placement as a graph-embedding problem and designs approximation algorithms with provable bounds on the quality of the solution. In this article, we aim at unifying the above two directions. First, we extend the existing approximation algorithms for graph embedding in 1D and 2D grid to those for hypergraphs, which typically model circuits to be placed on a FPGA. We prove an approximation bound of
O
(
d
√log
n
log log
n
) for 1D, that is, linear arrangement and
O
(
d
log
n
log log
n
) for the 2D grid, where
d
is the maximum degree of hyperedges and
n
, the number of vertices in the hypergraph. Next, we propose an efficient method based on linear arrangement of the CLBs and the notion of space-filling curves for placing the configurable logic blocks (CLBs) of a netlist on island-style FPGAs with an approximation guarantee of
O
(
4
√log
n
√
kd
log log
n
), where
k
is the number of nets. For the set of FPGA placement benchmarks, the running time is near linear in the number of CLBs thus allowing for scalability towards large circuits. We obtained a 33× speed-up, on average, with only 1.31× degradation in the quality of the solution compared to that produced by the popular FPGA tool VPR, thereby demonstrating the suitability of this very fast method for FPGA placement, with a provable performance guarantee.