Isatuximab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients with renal impairment: ICARIA-MM subgroup analysis

The randomized, phase 3 ICARIA-MM study investigated isatuximab (Isa) with pomalidomide and dexamethasone (Pd) versus Pd in patients with relapsed/refractory multiple myeloma and ?2 prior lines. This prespecified subgroup analysis examined efficacy in patients with renal impairment (RI; estimated glomerular filtration rate <60 mL/min/1.73 m²). Isa 10 mg/kg was given intravenously once weekly in cycle 1, and every 2 weeks in subsequent 28-day cycles. Patients received standard doses of Pd. Median progression-free survival (PFS) for patients with RI was 9.5 months with Isa-Pd (n = 55) and 3.7 months with Pd (n = 49; hazard ratio [HR] 0.50; 95% confidence interval [CI], 0.30-0.85). Without RI, median PFS was 12.7 months with Isa-Pd (n = 87) and 7.9 months with Pd (n = 96; HR 0.58; 95% CI, 0.38-0.88). The overall response rate (ORR) with and without RI was higher with Isa-Pd (56 and 68%) than Pd (25 and 43%). Complete renal response rates were 71.9% (23/32) with Isa-Pd and 38.1% (8/21) with Pd; these lasted ?60 days in 31.3% (10/32) and 19.0% (4/21) of patients, respectively. Isa pharmacokinetics were comparable between the subgroups, suggesting no need for dose adjustment in patients with RI. In summary, the addition of Isa to Pd improved PFS, ORR and renal response rates

Wavelet Cycle Spinning Denoising of NDE Ultrasonic Signals Using a Random Selection of Shifts

Wavelets are a powerful tool for signal and image denoising. Most of the denoising applications in different fields were based on the thresholding of the discrete wavelet transform (DWT) coefficients. Nevertheless, DWT transform is not a time or shift invariant transform and results depend on the selected shift. Improvements on the denoising performance can be obtained using the stationary wavelet transform (SWT) (also called shift-invariant or undecimated wavelet transform). Denoising using SWT has previously shown a robust and usually better performance than denoising using DWT but with a higher computational cost. In this paper, wavelet shrinkage schemes are applied for reducing noise in synthetic and experimental non-destructive evaluation ultrasonic A-scans, using DWT and a cycle-spinning implementation of SWT. A new denoising procedure, which we call random partial cycle spinning (RPCS), is presented. It is based on a cycle-spinning over a limited number of shifts that are selected in a random way. Wavelet denoising based on DWT, SWT and RPCS have been applied to the same sets of ultrasonic A-scans and their performances in terms of SNR are compared. In all cases three well known threshold selection rules (Universal, Minimax and Sure), with decomposition level dependent selection, have been used. It is shown that the new procedure provides a good robust denoising performance, without the DWT fluctuating performance, and close to SWT but with a much lower computational cost.This work was partially supported by Spanish MCI Project DPI2011-22438San Emeterio Prieto, JL.; Rodríguez-Hernández, MA. (2015). Wavelet Cycle Spinning Denoising of NDE Ultrasonic Signals Using a Random Selection of Shifts. Journal of Nondestructive Evaluation. 34(1):1-8. https://doi.org/10.1007/s10921-014-0270-8S18341Galloway, R.L., McDermott, B.A., Thurstone, F.L.: A frequency diversity process for speckle reduction in real-time ultrasonic images. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 35, 45–49 (1988)Newhouse, V.L., Bilgutay, N.M., Saniie, J., Furgason, E.S.: Flaw-to-grain echo enhancement by split spectrum processing. Ultrasonics 20, 59–68 (1982)Karpur, P., Canelones, O.J.: Split spectrum processing: a new filtering approach for improved signal-to-noise ratio enhancement of ultrasonic signals. Ultrasonics 30, 351–357 (1992)Donoho, D.L., Johnstone, I.M.: Ideal spatial adaptation by wavelet shrinkage. Biometrika 81, 425–455 (1994)Donoho, D.L., Johnstone, I.M., Kerkyacharian, G., Picard, D.: Wavelet shrinkage: asymptotia? J. R Stat. Soc. Ser. B 57, 301–369 (1995)Donoho, D.L., Johnstone, I.M.: Adapting to unknown smoothness via wavelet shrinkage. J. Am. Stat. Assoc. 90, 1200–1224 (1995)Johnstone, I.M., Silverman, B.W.: Wavelet threshold estimators for data with correlated noise. J. R Stat. Soc. 59, 319–351 (1997)Jansen, M.: Noise Reduction by Wavelet Thresholding. Lecture Notes in Statistics 161. Springer, New York (2001). doi: 10.1007/978-1-4613-0145-5Nason, G.P., Silverman, B.W.:The stationary wavelet transform and some statistical applications. In: Antoniadis, A., Oppenheim, G. (eds.) Wavelets and Statistics. Lecture Notes in Statistics, Vol. 103, pp 281–299. Springer, New York (1995)Lang, M., Guo, H., Odegard, J.E., Burrus, C.S.: Noise reduction using an undecimated discrete wavelet transform. IEEE Signal Proc. Lett. 3, 10–12 (1996)Coifman, R.R., Donoho, D.L.: Translation-invariant de-noising. In: Antoniadis, A., Oppenheim, G. (eds.) Wavelets and Statistics. Lecture Notes in Statistics, vol. 103, pp 125–150, Springer, New York (1995) .Abbate, A., Koay, J., Frankel, J., Schroeder, S.C., Das, P.: Signal detection and noise suppression using a wavelet transform signal processor: application to ultrasonic flaw detection. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 44, 14–26 (1997)Lázaro, J.C., San Emeterio, J.L., Ramos, A., Fernandez, J.L.: Influence of thresholding procedures in ultrasonic grain noise reduction using wavelets. Ultrasonics 40, 263–267 (2002)Matz, V., Smid, R., Starman, S., Kreidl, M.: Signal-to-noise ratio enhancement based on wavelet filtering in ultrasonic testing. Ultrasonics 49, 752–759 (2009)Kubinyi, M., Kreibich, O., Neuzil, J., Smid, R.: EMAT noise suppression using information fusion in stationary wavelet packets. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 58, 1027–1036 (2011)Shi, G.M., Chen, X.Y., Song, X.X., Qui, F., Ding, A.L.: Signal matching wavelet for ultrasonic flaw detection in high background noise. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 58, 776–787 (2011)Song, S.P., Que, P.W.: Wavelet based noise suppression technique and its application to ultrasonic flaw detection. Ultrasonics 44, 188–193 (2006)Rodriguez, M.A., San Emeterio, J.L., Lázaro, J.C., Ramos, A.: Ultrasonic flaw detection in NDE of highly scattering materials using wavelet and Wigner-Ville transform processing. Ultrasonics 42, 847–851 (2004)Zhang, G.M., Zhang, S.Y., Wang, Y.W.: Application of adaptive time-frequency decomposition in ultrasonic NDE of highly-scattering materials. Ultrasonics 38, 961–964 (2000)Drai, R., Khelil, M., Benchaala, A.: Time frequency and wavelet transform applied to selected problems in ultrasonics NDE. NDT & E Int. 35, 567–572 (2002)Pardo, E., San Emeterio, J.L.: Noise reduction in ultrasonic NDT using undecimated wavelet transforms. Ultrasonics 44, e1063–e1067 (2006)Kechida, A., Drai, R., Guessoum, A.: Texture analysis for flaw detection in ultrasonic images. J. Nondestruct. Eval. 31, 108–116 (2012). doi: 10.1007/s10921-011-0126-4Rucka, M., Wilde, K.: Experimental study on ultrasonic monitoring of splitting failure in reinforced concrete. J. Nondestruct. Eval. 32, 372–383 (2013). doi: 10.1007/s10921-013-0191-yHosseini, S.M.H., Duczek, S., Gabbert, U.: Damage localization in plates using mode conversion characteristics of ultrasonic guided waves. J. Nondestruct. Eval. 33, 152–165 (2014). doi: 10.1007/s10921-013-0211-yMohammed, M.S., Ki-Seong, K.: Shift-invariant wavelet packet for signal de-noising in ultrasonic testing. Insight 54, 366–370 (2012)San Emeterio, J.L., Rodriguez-Hernandez, M.A.: Wavelet denoising of ultrasonic A-scans by random partial cycle spinning. 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Gingival Fibroblasts Display Reduced Adhesion and Spreading on Extracellular Matrix: A Possible Basis for Scarless Tissue Repair?

Unlike skin, oral gingiva do not scar in response to injury. The basis of this difference is likely to be revealed by comparing the responses of dermal and gingival fibroblasts to fibrogenic stimuli. Previously, we showed that, compared to dermal fibroblasts, gingival fibroblasts are less responsive to the potent pro-fibrotic cytokine TGFβ, due to a reduced production of endothelin-1 (ET-1). In this report, we show that, compared to dermal fibroblasts, human gingival fibroblasts show reduced expression of pro-adhesive mRNAs and proteins including integrins α2 and α4 and focal adhesion kinase (FAK). Consistent with these observations, gingival fibroblasts are less able to adhere to and spread on both fibronectin and type I collagen. Moreover, the enhanced production of ET-1 mRNA and protein in dermal fibroblasts is reduced by the FAK/src inhibitor PP2. Given our previous observations suggesting that fibrotic fibroblasts display elevated adhesive properties, our data suggest that scarring potential may be based, at least in part, on differences in adhesive properties among fibroblasts resident in connective tissue. Controlling adhesive properties may be of benefit in controlling scarring in response to tissue injury

Provision of artificial warrens as a means to enhance native wild rabbit populations: what type of warren and where should they be sited?

In Spain, wild rabbits are essential for some highly endangered species, and, therefore, many actions have been undertaken to increase their populations. In the present study, artificial warrens are provided as a means to increase shelter for native wild rabbit populations in a given area. We evaluate the use of three types of warrens by rabbits and the effect on that use of five habitat characteristics at two spatial scales (500 × 500-m grids and 25-m plots). To evaluate that use, we identified pre-established signs at the entrances to each warren, and based on this, we calculated occupancy rate and activity. Our results indicate that rabbit abundance within a grid is the only variable which simultaneously explains both the greater occupancy and the higher activity in the artificial warrens located in that grid. Some 73.2% of the grids showed signs of rabbit use at the time of the evaluation. However, the pre-existing rabbit populations within the grids were not quantified and, hence, we cannot state that the warrens contributed to an increase in the rabbit abundance. Regarding the habitat, our results reveal that warrens should be situated in grids with food coverage of less than 50%, while the use of each individual refuge is greater where food availability in the immediate surroundings is at least 20% and shelter at least 50%. The tube warrens showed significantly greater rabbit use than the other types while there was little difference between the stone and pallet warrens in terms of use

Physics and Applications of Laser Diode Chaos

An overview of chaos in laser diodes is provided which surveys experimental achievements in the area and explains the theory behind the phenomenon. The fundamental physics underpinning this behaviour and also the opportunities for harnessing laser diode chaos for potential applications are discussed. The availability and ease of operation of laser diodes, in a wide range of configurations, make them a convenient test-bed for exploring basic aspects of nonlinear and chaotic dynamics. It also makes them attractive for practical tasks, such as chaos-based secure communications and random number generation. Avenues for future research and development of chaotic laser diodes are also identified.Comment: Published in Nature Photonic

Eliciting health state utilities for Dupuytren's contracture using a discrete choice experiment

Background and purpose An internet-based discrete choice experiment (DCE) was conducted to elicit preferences for a wide range of Dupuytren’s contracture (DC)-related health states. An algorithm was subsequently developed to convert these preferences into health state utilities that can be used to assess DC’s impact on quality of life and the value of its treatments. Methods Health state preferences for varying levels of DC hand severity were elicited via an internet survey from a sample of the UK adult population. Severity levels were deined using a combination of contractures (0, 45, or 90 degrees) in 8 proximal interphalangeal and metacarpophalangeal joints of the index, middle, ring, and little ingers. Right-handed, left-handed, and ambidextrous respondents indicated which hand was preferable in each of the 10 randomly-selected hand-pairings comparing different DC severity levels. For consistency across comparisons, anatomically precise digital hand drawings were used. To anchor preferences onto the traditional 0–1 utility scale used in health economic evaluations, unaffected hands were assigned a utility of 1.0 whereas the utility for a maximally affected hand (i.e., all 8 joints set at 90 degrees of contracture) was derived by asking respondents to indicate what combination of attributes and levels of the EQ-5D-5L proile most accurately relects the impact of living with such hand. Conditional logistic models were used to estimate indirect utilities, then rescaled to the anchor points on the EQ-5D-5L. Results Estimated utilities based on the responses of 1,745 qualiied respondents were 0.49, 0.57, and 0.63 for completely affected dominant hands, non-dominant hands, or ambidextrous hands, respectively. Utility for a dominant hand with 90-degree contracture in t h e metacarpophalangeal joints of the ring and little ingers was estimated to be 0.89. Separately, reducing the contracture of metacarpophalangeal joint for a little inger from 50 to 12 degrees would improve utility by 0.02. Interpretation DC is associated with substantial utility decrements. The algorithms presented herein provide a robust and lexible framework to assess utility for varying degrees of DC severity