International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017).

In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography or bidimensional tumor measurements on computerized tomography scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single-dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47 828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.

Transcultural adaptation of the Breast Cancer Awareness Measure.

AIM: To overcome the lack of a validated and robust Arabic instrument to measure breast cancer awareness. BACKGROUND: Currently, there is no validated Arabic instrument for measuring breast cancer awareness levels. We adapted, translated and validated the Breast Cancer Awareness Measure developed by Cancer Research UK. METHODS: The instrument was translated into Arabic and back-translated for validation. Validation and reliability tests were conducted using purposively sampled 972 Arab women older than 20 years, living in Oman. The adapted content was validated by a panel of medical, linguistic and cultural experts, followed by cognitive interviews (n = 10), behavioural coding (n = 30) and criterion validation (n = 646). The instrument was tested for acceptability and its subscales for internal consistency. Inter-rater reliability was estimated between two similar groups (n = 144 and n = 142) to test homogeneity. RESULTS: The adapted and translated instrument had a high acceptability (98.7% completed). The validation process shaped the adaptation, and resulted in strong criterion validity (R = 0.58, P < 0.01). The instrument subscales for risk factors and warning signs had high internal consistency (Cronbach's alpha 0.856 and 0.890, respectively), with all floor and ceiling effects less than 15%. The correlation measure for inter-rater reliability was 0.97 (P < 0.01). DISCUSSION: Through the incorporation of contextual characteristics and prevalent beliefs among Arab populations, the adapted Best Cancer Awareness Measure is a robust Arabic instrument for the measurement of breast cancer awareness and early detection practices among Arab women. LIMITATIONS: The purposively selected sample may not be representative of the population. CONCLUSION AND IMPLICATIONS FOR HEALTH POLICY: Improvement of awareness and early detection of breast cancer can contribute towards reducing mortality from the disease. The adapted instrument has policy implications, since measurement of awareness levels is essential towards breast health promotion policies in Arab countries.

Pick-up and drop transfer of diamond nanosheets.

Nanocrystalline diamond (NCD) is a promising material for electronic and mechanical micro- and nanodevices. Here we introduce a versatile pick-up and drop technique that makes it possible to investigate the electrical, optical and mechanical properties of as-grown NCD films. Using this technique, NCD nanosheets, as thin as 55 nm, can be picked-up from a growth substrate and positioned on another substrate. As a proof of concept, electronic devices and mechanical resonators are fabricated and their properties are characterized. In addition, the versatility of the method is further explored by transferring NCD nanosheets onto an optical fiber, which allows measuring its optical absorption. Finally, we show that NCD nanosheets can also be transferred onto two-dimensional crystals, such as MoS2, to fabricate heterostructures. Pick-up and drop transfer enables the fabrication of a variety of NCD-based devices without requiring lithography or wet processing.

Hydrogen termination of CVD diamond films by high-temperature annealing at atmospheric pressure.

A high-temperature procedure to hydrogenate diamond films using molecular hydrogen at atmospheric pressure was explored. Undoped and doped chemical vapour deposited (CVD) polycrystalline diamond films were treated according to our annealing method using a H2 gas flow down to ~50 ml∕min (STP) at ~850 °C. The films were extensively evaluated by surface wettability, electron affinity, elemental composition, photoconductivity, and redox studies. In addition, electrografting experiments were performed. The surface characteristics as well as the optoelectronic and redox properties of the annealed films were found to be very similar to hydrogen plasma-treated films. Moreover, the presented method is compatible with atmospheric pressure and provides a low-cost solution to hydrogenate CVD diamond, which makes it interesting for industrial applications. The plausible mechanism for the hydrogen termination of CVD diamond films is based on the formation of surface carbon dangling bonds and carbon-carbon unsaturated bonds at the applied tempera-ture, which react with molecular hydrogen to produce a hydrogen-terminated surface.

An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors.

To address the biological heterogeneity of lung cancer, we studied 199 lung adenocarcinomas by integrating genome-wide data on copy number alterations and gene expression with full annotation for major known somatic mutations in this cancer. This showed non-random patterns of copy number alterations significantly linked to EGFR and KRAS mutation status and to distinct clinical outcomes, and led to the discovery of a striking association of EGFR mutations with underexpression of DUSP4, a gene within a broad region of frequent single-copy loss on 8p. DUSP4 is involved in negative feedback control of EGFR signaling, and we provide functional validation for its role as a growth suppressor in EGFR-mutant lung adenocarcinoma. DUSP4 loss also associates with p16/CDKN2A deletion and defines a distinct clinical subset of lung cancer patients. Another novel observation is that of a reciprocal relationship between EGFR and LKB1 mutations. These results highlight the power of integrated genomics to identify candidate driver genes within recurrent broad regions of copy number alteration and to delineate distinct oncogenetic pathways in genetically complex common epithelial cancers.

Quantitation of intracellular [Na+] in vivo by using TmDOTP5- as an NMR shift reagent and extracellular marker.

A method is presented to measure the absolute concentration of intracellular Na+ ([Na+]i) in vivo by using interleaved 23Na- and 31P-nuclear magnetic resonance (NMR) spectroscopy and TmDOTP5- as shift reagent and chemical marker of tissue extracellular space (ECS). The technique was used to determine [Na+]i and relative ECS in livers of control rats (21 +/- 3 and 0.11 +/- 0.02 mM, respectively) and in rats exposed to carbon tetrachloride (103 +/- 29 and 0.23 +/- 0.03 mM, respectively). The NMR measurements were confirmed independently on excised tissue samples by using atomic absorption spectroscopy. The results confirm that TmDOTP5- can be used as a combined cation shift reagent and ECS marker, thereby allowing quantitation of [Na+]i in vivo by NMR.

Three-dimensional triple-quantum-filtered 23Na imaging of the dog head in vivo.

Multiple-quantum (MQ) -filtered 23Na NMR has been proposed as a means to partially discriminate between intracellular and extracellular sodium. However, low signal-to-noise ratio (SNR) has been a major obstacle to MQ-filtered 23Na imaging becoming an important technique for biological and clinical applications. We compared the various MQ-filtered 23Na imaging pulse sequences to select the optimum sequence that provides the best SNR. The results of phantom experiments show that the gradient-echo MQ-filtered 23Na imaging sequence produces the best SNR. We also report, for the first time, three-dimensional single-quantum (SQ) and triple-quantum (TQ) -filtered 23Na images of the live dog brain and demonstrate the sensitivity of these images to ischemia produced by euthanizing the animal. The SQ images showed a 10% to 15% decrease in signal intensity from the brain post-mortem, whereas the TQ-filtered images showed a 40% to 50% increase. These changes in signal intensities are consistent with the influx of Na+ into the cells upon death. The feasibility of obtaining TQ-filtered 23Na images of in situ dog brain encourages us to apply this technique to humans.

Evaluation of triple quantum-filtered 23Na NMR spectroscopy in the in situ rat liver.

Triple quantum (TQ)-filtered 23Na NMR spectroscopy and the shift reagent, TmDOTP5-, have been used to evaluate the contributions of intra- (Na+i) and extracellular (Na+e) sodium to the TQ-filtered signal in the rat liver, in situ. Na+e contributed significantly to the total TQ-filtered signal in live animals, and the intensity of this signal did not change postmortem. The TQ-filtered Na+i signal increased by approximately 380% over a period of 1 h postmortem, whereas the single quantum (SQ) Na+i increased by 90%. The constancy of the TQ-filtered Na+i signal indicates that changes in total TQ-filtered 23Na signal intensity in liver (without a shift reagent) may accurately reflect changes in TQ-filtered Na+i signal intensity. The large percent increase in the TQ-filtered Na+i signal as compared to the SQ signal suggests that the fraction of Na+i interacting with macromolecules increases after death.

Three-dimensional triple quantum-filtered 23Na imaging of rabbit kidney with weighted signal averaging.

Low signal-to-noise ratio (SNR) has been the main obstacle to multiple quantum-filtered 23Na imaging becoming an important technique for biologic and clinical applications. Through computer simulations and phantom experiments, we show that the SNR in 23Na imaging can be substantially improved by weighted signal averaging. Three-dimensional single quantum and triple quantum (TQ)-filtered 23Na images of an externalized rabbit kidney were collected with this technique. The TQ-filtered image did not show any signal when the animal was alive. However, upon sacrificing the animal, the renal cortex became clearly visible without any significant increase in signal from the medullary region. This increase in TQ-filtered signal in the renal cortex may be caused by an increased concentration of intracellular Na+ in the large intracellular space present herein, compared with the medulla. To our knowledge, this study represents the first example of three-dimensional TQ-filtered 23Na image of a biological sample.

TmDOTP5- as a 23Na shift reagent for the in vivo rat kidney.

Since transmembrane sodium gradient is essential to many cell functions, there is continuing interest in methods that differentiate intracellular and extracellular Na+. In the kidney, shift reagent (SR) aided 23Na magnetic resonance spectroscopy (MRS) has been successfully used only in isolated cells, tubules, and the perfused organ. In this report, we demonstrate for the first time that TmDOTP5- can be used to distinguish Na+ compartments in kidneys in vivo. Infusion of 80 mM TmDOTP5- without added Ca2+ produced three resolved 23Na resonances, which we have assigned to intracellular Na+, vascular Na+, and intraluminal Na+. In comparison, infusion of 400 mM DyTTHA3- produced two broad and unresolved resonances. The 31P spectra of the cellular high energy phosphate metabolites indicate that TmDOTP5- is safe for in vivo applications. Washout studies suggest that this SR displays renal clearance similar to that of MR imaging contrast agents. However, the glomerular filtration rate (GFR) in animals infused with TmDOTP5- was reduced by 49% compared with the GFR in control animals, perhaps due to the hypotensive effects of the SR. We conclude that TmDOTP5- is effectively cleared from the blood of live animals but that a different formulation will be required for clinical application.

[AIDS complicated with disseminated toxoplasmosis: a pathological study of 9 autopsy cases].

Nine autopsy cases of disseminated toxoplasmosis in New York are reported. Brain were involved in 9 cases, heart in 8, lung in 4, and pancreas, GI tract, thyroid, lymph nodes and urogenital organs were also involved. There were toxoplasma encephalitis in 9 cases, myocarditis in 4, pneumonia in 3 and pancreatitis in 2. Only toxoplasma encephalitis and pneumonia produced signs and symptoms leading to diagnosis by CT scan of brain, toxoplasma antibody titer and confirmed by smears, bone marrow biopsy and autopsy based on recognition of encysted toxoplasma. The authors classified the lesions as static (latent), necrotic, infiltrative and proliferative status, with the emphasis on the diagnostic significance of identification of toxoplasma, especially its encysted form.

Thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate) as a 23Na shift reagent for the in vivo rat liver.

The use of thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate (TmDOTP5-) as an in vivo 23Na NMR shift reagent for rat liver was evaluated by collecting interleaved 23Na and 31P spectra. Infusion of 80 mM TmDOTP5- without added Ca2+ produced baseline-resolved peaks from intra- and extracellular sodium without producing any changes in phosphate metabolite resonances or intracellular pH. Several key physiological parameters measured in parallel groups of animals confirmed that liver physiology is largely unaffected by this shift reagent. A direct comparison of TmDOTP5- versus DyTTHA3- showed that after infusion of 5-8 times more DyTTHA3-, the extracellular sodium peak shifted by the same amount as with TmDOTP5-, but the two 23Na resonances were very broad and not resolved. The baseline-resolved peaks with TmDOTP5- allowed us to measure the in vivo T1 and T2 relaxation characteristics of intra- and extracellular Na+. The measured T1, T2s, and T2f values and the relative contributions from the slow and fast T2 components for intracellular Na+ in liver did not differ significantly from the values reported for perfused frog heart. The T1 and T2 relaxation curves of the extracellular Na+ resonances fit a monoexponential function. Analysis of the relative contribution of the fast- and slow-relaxing T2 components from intracellular Na+ resulted in a calculated visibility factor of 69 +/- 4% and the intracellular Na+ concentration calculated from the NMR peak intensity ratio, the measured visibility factor, and literature values of intra- and extracellular volume was 19 mM. These results indicate that TmDOTP5- promises to be quite useful as an in vivo shift reagent for liver and other organs.