Advanced head and neck cancer: Long-term results of chemo-radiotherapy, complications and induction of second malignancies

Background: Chemo-radiotherapy is superior to radiotherapy alone in the treatment of advanced, inoperable head and neck cancer. The long-term treatment results, the induction of second malignant tumors, and other long-term toxicities are not well defined. Patients and Methods: 100 consecutive patients with advanced head and neck cancer who were treated at our center were studied. Treatment results, survival, the occurrence of late complications, and second malignant tumors (SMT) were investigated. 78 patients were treated with a protocol combining cisplatinum, 5-fluorouracil, folinic acid and hyper-fractionated irradiation. 22 patients were treated with other chemo-radiotherapy protocols. The relative risk of developing an SMT was compared with that within the normal population. Results: The cumulative total probability of survival was 51.1% at 2 years and 38.7% at 4 years. The probability of relapse-free survival was 39.9% at 2 years and 36.7% at 4 years. A total of 7 patients developed SMT (4 cases of lung cancer, 2 colon cancers, 1 skin cancer). After 6 years, a cumulative risk of SMT of 8.7% was observed. The relative risk of developing an SMT was significantly increased (4.45-fold in males) compared with a normal population. 13 of 38 evaluable patients (34.2%) had severe late complications like fibrosis of soft tissues, nerve lesions, or were dependent on tracheal cannulas. Conclusions: The treatment results and long-term prognoses in our population of unselected high-risk patients are unsatisfactory, but comparable to those from multicenter studies. About 35% of patients become long-term (> 4 years) survivors. SMT generally occur early, have a poor prognosis and, most likely, are not treatment-related. Approximately 30% of long-term survivors have severe, often incapacitating late effects. The treatment and - if possible - prevention of these late effects is important for the quality of life of patients who survived advanced head and neck cancer

Performance of compressed sensing for fluorine-19 magnetic resonance imaging at low signal-to-noise ratio conditions

PURPOSE: To examine the performance of compressed sensing (CS) in reconstructing low signal-to-noise ratio (SNR) (19)F MR signals that are close to the detection threshold and originate from small signal sources with no a priori known location. METHODS: Regularization strength was adjusted automatically based on noise level. As performance metrics, root-mean-square deviations, true positive rates (TPRs), and false discovery rates were computed. CS and conventional reconstructions were compared at equal measurement time and evaluated in relation to high-SNR reference data. (19)F MR data were generated from a purpose-built phantom and benchmarked against simulations, as well as from the experimental autoimmune encephalomyelitis mouse model. We quantified the signal intensity bias and introduced an intensity calibration for in vivo data using high-SNR ex vivo data. RESULTS: Low-SNR (19)F MR data could be reliably reconstructed. Detection sensitivity was consistently improved and data fidelity was preserved for undersampling and averaging factors of α = 2 or = 3. Higher α led to signal blurring in the mouse model. The improved TPRs at α = 3 were comparable to a 2.5-fold increase in measurement time. Whereas CS resulted in a downward bias of the (19)F MR signal, Fourier reconstructions resulted in an unexpected upward bias of similar magnitude. The calibration corrected signal-intensity deviations for all reconstructions. CONCLUSION: CS is advantageous whenever image features are close to the detection threshold. It is a powerful tool, even for low-SNR data with sparsely distributed (19)F signals, to improve spatial and temporal resolution in (19)F MR applications

UniPROBE, update 2011: expanded content and search tools in the online database of protein-binding microarray data on protein–DNA interactions

The Universal PBM Resource for Oligonucleotide-Binding Evaluation (UniPROBE) database is a centralized repository of information on the DNA-binding preferences of proteins as determined by universal protein-binding microarray (PBM) technology. Each entry for a protein (or protein complex) in UniPROBE provides the quantitative preferences for all possible nucleotide sequence variants (‘words’) of length k (‘k-mers’), as well as position weight matrix (PWM) and graphical sequence logo representations of the k-mer data. In this update, we describe >130% expansion of the database content, incorporation of a protein BLAST (blastp) tool for finding protein sequence matches in UniPROBE, the introduction of UniPROBE accession numbers and additional database enhancements. The UniPROBE database is available at http://uniprobe.org.National Institutes of Health (U.S.) (grant number R01 HG003985

UniPROBE, update 2011: expanded content and search tools in the online database of protein-binding microarray data on protein–DNA interactions

The Universal PBM Resource for Oligonucleotide-Binding Evaluation (UniPROBE) database is a centralized repository of information on the DNA-binding preferences of proteins as determined by universal protein-binding microarray (PBM) technology. Each entry for a protein (or protein complex) in UniPROBE provides the quantitative preferences for all possible nucleotide sequence variants (‘words’) of length k (‘k-mers’), as well as position weight matrix (PWM) and graphical sequence logo representations of the k-mer data. In this update, we describe >130% expansion of the database content, incorporation of a protein BLAST (blastp) tool for finding protein sequence matches in UniPROBE, the introduction of UniPROBE accession numbers and additional database enhancements. The UniPROBE database is available at http://uniprobe.org.National Institutes of Health (U.S.) (grant number R01 HG003985

The materiality of digital media: The hard disk drive, phonograph, magnetic tape and optical media in technical close-up

Popular discourses surrounding contemporary digital media often misrepresent it as immaterial and ephemeral, overlooking the material devices that store and generate our media objects. This article materially ‘descends’ into a selection of prior media forms that make up the genealogy of the hard disk drive (HDD) to challenge our reliance on conceptual misrepresentations. This material analysis is used to situate digital media in a genealogy of prior media forms, to enrich our understanding of how media’s affordances arise from the interplay of both formal and forensic materiality and to demonstrate the value of reintegrating materiality back into the study of media

HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants

The resolution of genome-wide association studies (GWAS) is limited by the linkage disequilibrium (LD) structure of the population being studied. Selecting the most likely causal variants within an LD block is relatively straightforward within coding sequence, but is more difficult when all variants are intergenic. Predicting functional non-coding sequence has been recently facilitated by the availability of conservation and epigenomic information. We present HaploReg, a tool for exploring annotations of the non-coding genome among the results of published GWAS or novel sets of variants. Using LD information from the 1000 Genomes Project, linked SNPs and small indels can be visualized along with their predicted chromatin state in nine cell types, conservation across mammals and their effect on regulatory motifs. Sets of SNPs, such as those resulting from GWAS, are analyzed for an enrichment of cell type-specific enhancers. HaploReg will be useful to researchers developing mechanistic hypotheses of the impact of non-coding variants on clinical phenotypes and normal variation. The HaploReg database is available at http://compbio.mit.edu/HaploReg.National Institutes of Health (U.S.) (R01-HG004037)National Institutes of Health (U.S.) (RC1-HG005334)National Science Foundation (U.S.) (HG005334

A Paper-Based Multiplexed Transaminase Test for Low-Cost, Point-of-Care Liver Function Testing

In developed nations, monitoring for drug-induced liver injury through serial measurements of serum transaminases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] in at-risk individuals is the standard of care. Despite the need, monitoring for drug-related hepatotoxicity in resource-limited settings is often limited by expense and logistics, even for patients at highest risk. This article describes the development and clinical testing of a paper-based, multiplexed microfluidic assay designed for rapid, semiquantitative measurement of AST and ALT in a fingerstick specimen. Using 223 clinical specimens obtained by venipuncture and 10 fingerstick specimens from healthy volunteers, we have shown that our assay can, in 15 min, provide visual measurements of AST and ALT in whole blood or serum, which allow the user to place those values into one of three readout “bins” [5× ULN, corresponding to tuberculosis/HIV treatment guidelines] with >90% accuracy. These data suggest that the ultimate point-of-care fingerstick device will have high impact on patient care in low-resource settings.Chemistry and Chemical Biolog

Quantitative comparison of the magnetic proximity effect in Pt detected by XRMR and XMCD

X-ray resonant magnetic reflectivity (XRMR) allows for the simultaneous measurement of structural, optical and magnetooptic properties and depth profiles of a variety of thin film samples. However, a same-beamtime same-sample systematic quantitative comparison of the magnetic properties observed with XRMR and x-ray magnetic circular dichroism (XMCD) is still pending. Here, the XRMR results (Pt L$_{3}$ absorption edge) for the magnetic proximity effect in Pt deposited on the two different ferromagnetic materials Fe and Co$_{33}$Fe$_{67}$ are compared with quantitatively analyzed XMCD results. The obtained results are in very good quantitative agreement between the absorption-based (XMCD) and reflectivity-based (XRMR) techniques taking into account an ab initio calculated magnetooptic conversion factor for the XRMR analysis. Thus, it is shown that XRMR provides quantitative reliable spin depth profiles important for spintronic and spin caloritronic transport phenomena at this type of magnetic interfaces.Comment: This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in Appl. Phys. Lett. 118, 012407 (2021) and may be found at https://aip.scitation.org/doi/abs/10.1063/5.003258

Fluorine-19 MRI at 21.1 T: enhanced spin-lattice relaxation of perfluoro-15-crown-5-ether and sensitivity as demonstrated in ex vivo murine neuroinflammation

OBJECTIVE: Fluorine MR would benefit greatly from enhancements in signal-to-noise ratio (SNR). This study examines the sensitivity gain of (19)F MR that can be practically achieved when moving from 9.4 to 21.1 T. MATERIALS AND METHODS: We studied perfluoro-15-crown-5-ether (PFCE) at both field strengths (B(0)), as a pure compound, in the form of nanoparticles (NP) as employed to study inflammation in vivo, as well as in inflamed tissue. Brains, lymph nodes (LNs) and spleens were obtained from mice with experimental autoimmune encephalomyelitis (EAE) that had been administered PFCE NPs. All samples were measured at both B(0) with 2D-RARE and 2D-FLASH using (19)F volume radiofrequency resonators together. T(1) and T(2) of PFCE were measured at both B(0) strengths. RESULTS: Compared to 9.4 T, an SNR gain of > 3 was observed for pure PFCE and > 2 for PFCE NPs at 21.1 T using 2D-FLASH. A dependency of (19)F T(1) and T(2) relaxation on B(0) was demonstrated. High spatially resolved (19)F MRI of EAE brains and LNs at 21.1 T revealed signals not seen at 9.4 T. DISCUSSION: Enhanced SNR and T(1) shortening indicate the potential benefit of in vivo (19)F MR at higher B(0) to study inflammatory processes with greater detail