Sensorineural hearing loss enhances auditory sensitivity and temporal integration for amplitude modulation.

Amplitude-modulation detection thresholds (AMDTs) were measured at 40 dB sensation level for listeners with mild-to-moderate sensorineural hearing loss (age: 50-64 yr) for a carrier frequency of 500 Hz and rates of 2 and 20 Hz. The number of modulation cycles, N, varied between two and nine. The data were compared with AMDTs measured for young and older normal-hearing listeners [Wallaert, Moore, and Lorenzi (2016). J. Acoust. Soc. Am. 139, 3088-3096]. As for normal-hearing listeners, AMDTs were lower for the 2-Hz than for the 20-Hz rate, and AMDTs decreased with increasing N. AMDTs were lower for hearing-impaired listeners than for normal-hearing listeners, and the effect of increasing N was greater for hearing-impaired listeners. A computational model based on the modulation-filterbank concept and a template-matching decision strategy was developed to account for the data. The psychophysical and simulation data suggest that the loss of amplitude compression in the impaired cochlea is mainly responsible for the enhanced sensitivity and temporal integration of temporal envelope cues found for hearing-impaired listeners. The data also suggest that, for AM detection, cochlear damage is associated with increased internal noise, but preserved short-term memory and decision mechanisms.N.W. was supported by a grant from Neurelec Oticon Medical. C.L. was supported by two grants from ANR (HEARFIN and HEART projects). S.D.E. was supported by Deutsche Forschungsgemeinschaft (DFG) FOR 1732 (TPE). B.C.J.M. was supported by the EPSRC (UK, grant RG78536). This work was also supported by ANR-11-0001-02 PSL* and ANR-10-LABX-0087. We thank Nihaad Paraouty and two anonymous reviewers for helpful comments and suggestions relating to this study

Recombination from polar InGaN/GaN quantum well structures at high excitation carrier densities

In this paper we report on the emergence of a high energy band at high optically excited carrier densities in the low temperature photoluminescence spectra from polar InGaN/GaN single quantum well structures. This high energy band emerges at carrier densities when the emission from the localized ground states begins to saturate. We attribute this high energy band to recombination involving higher energy less strongly localized electron and hole states that are populated once the localized ground states become saturated; this assignment is supported by the results from an atomistic tight-binding model. A particular characteristic of the recombination at the high carrier densities is that the overall forms of the photoluminescence decay curves bear great similarity to those from semiconductor quantum dots. The decay curves consist of plateaus where the photoluminescence intensity is constant with time as a result of Pauli state blocking in the high energy localized states followed by a rapid decrease in intensity once the carrier density is sufficiently low that the states involved are no longer saturated

Atom gravimeters and gravitational redshift

In a recent paper, H. Mueller, A. Peters and S. Chu [A precision measurement of the gravitational redshift by the interference of matter waves, Nature 463, 926-929 (2010)] argued that atom interferometry experiments published a decade ago did in fact measure the gravitational redshift on the quantum clock operating at the very high Compton frequency associated with the rest mass of the Caesium atom. In the present Communication we show that this interpretation is incorrect.Comment: 2 pages, Brief Communication appeared in Nature (2 September 2010

Optical properties of c-Plane InGaN/GaN single quantum wells as a function of total electric field strength

We present low temperature photoluminescence spectra from four InGaN/GaN single quantum well structures where the total electric field across the quantum wells was varied by the manipulation of the surface polarization field, which is of opposite sign to the electrostatic built-in field originating from spontaneous and piezoelectric polarization intrinsic to the material. We find that, overall, the photoluminescence peak emission energy increases and its full width at half maximum decreases with decreasing total internal electric field. Using an atomistic tight-binding model of a quantum well with different total internal electric fields, we find that the calculated mean and standard deviation ground state transition energies follow the same trends with field as our experimentally determined spectral peak energies and widths. Overall, we attribute this behavior to a reduction in the quantum confined Stark effect and a connected reduction in the variation of ground state transition energies with decreasing electric field, respectively

Comparing the effects of age on amplitude modulation and frequency modulation detection.

Frequency modulation (FM) and amplitude modulation (AM) detection thresholds were measured at 40 dB sensation level for young (22-28 yrs) and older (44-66 yrs) listeners with normal audiograms for a carrier frequency of 500 Hz and modulation rates of 2 and 20 Hz. The number of modulation cycles, N, varied between 2 and 9. For FM detection, uninformative AM at the same rate as the FM was superimposed to disrupt excitation-pattern cues. For both groups, AM and FM detection thresholds were lower for the 2-Hz than for the 20-Hz rate, and AM and FM detection thresholds decreased with increasing N. Thresholds were higher for older than for younger listeners, especially for FM detection at 2 Hz, possibly reflecting the effect of age on the use of temporal-fine-structure cues for 2-Hz FM detection. The effect of increasing N was similar across groups for both AM and FM. However, at 20 Hz, older listeners showed a greater effect of increasing N than younger listeners for both AM and FM. The results suggest that ageing reduces sensitivity to both excitation-pattern and temporal-fine-structure cues for modulation detection, but more so for the latter, while sparing temporal integration of these cues at low modulation rates.N.W. was supported by a grant from Neurelec Oticon Medical. C.L. was supported by two grants from ANR (HEARFIN and HEART projects). This work was also supported by ANR-11-0001-02 PSL* and ANR-10-LABX-0087

Optimising use of electronic health records to describe the presentation of rheumatoid arthritis in primary care: a strategy for developing code lists

Background Research using electronic health records (EHRs) relies heavily on coded clinical data. Due to variation in coding practices, it can be difficult to aggregate the codes for a condition in order to define cases. This paper describes a methodology to develop ‘indicator markers’ found in patients with early rheumatoid arthritis (RA); these are a broader range of codes which may allow a probabilistic case definition to use in cases where no diagnostic code is yet recorded. Methods We examined EHRs of 5,843 patients in the General Practice Research Database, aged ≥30y, with a first coded diagnosis of RA between 2005 and 2008. Lists of indicator markers for RA were developed initially by panels of clinicians drawing up code-lists and then modified based on scrutiny of available data. The prevalence of indicator markers, and their temporal relationship to RA codes, was examined in patients from 3y before to 14d after recorded RA diagnosis. Findings Indicator markers were common throughout EHRs of RA patients, with 83.5% having 2 or more markers. 34% of patients received a disease-specific prescription before RA was coded; 42% had a referral to rheumatology, and 63% had a test for rheumatoid factor. 65% had at least one joint symptom or sign recorded and in 44% this was at least 6-months before recorded RA diagnosis. Conclusion Indicator markers of RA may be valuable for case definition in cases which do not yet have a diagnostic code. The clinical diagnosis of RA is likely to occur some months before it is coded, shown by markers frequently occurring ≥6 months before recorded diagnosis. It is difficult to differentiate delay in diagnosis from delay in recording. Information concealed in free text may be required for the accurate identification of patients and to assess the quality of care in general practice

The Plasmodium falciparum, Nima-related kinase Pfnek-4: a marker for asexual parasites committed to sexual differentiation

<b>Background</b> Malaria parasites undergo, in the vertebrate host, a developmental switch from asexual replication to sexual differentiation leading to the formation of gametocytes, the only form able to survive in the mosquito vector. Regulation of the onset of the sexual phase remains largely unknown and represents an important gap in the understanding of the parasite's complex biology. <b>Methods:</b> The expression and function of the Nima-related kinase Pfnek-4 during the early sexual development of the human malaria parasite Plasmodium falciparum were investigated, using three types of transgenic Plasmodium falciparum 3D7 lines: (i) episomally expressing a Pfnek-4-GFP fusion protein under the control of its cognate pfnek-4 promoter; (ii) episomally expressing negative or positive selectable markers, yeast cytosine deaminase-uridyl phosphoribosyl transferase, or human dihydrofolate reductase, under the control of the pfnek-4 promoter; and (iii) lacking a functional pfnek-4 gene. Parasite transfectants were analysed by fluorescence microscopy and flow cytometry. In vitro growth rate and gametocyte formation were determined by Giemsa-stained blood smears. <b>Results:</b> The Pfnek-4-GFP protein was found to be expressed in stage II to V gametocytes and, unexpectedly, in a subset of asexual-stage parasites undergoing schizogony. Culture conditions stimulating gametocyte formation resulted in significant increase of this schizont subpopulation. Moreover, sorted asexual parasites expressing the Pfnek-4-GFP protein displayed elevated gametocyte formation when returned to in vitro culture in presence of fresh red blood cells, when compared to GFP- parasites from the same initial population. Negative selection of asexual parasites expressing pfnek-4 showed a marginal reduction in growth rate, whereas positive selection caused a marked reduction in parasitaemia, but was not sufficient to completely abolish proliferation. Pfnek-4- clones are not affected in their asexual growth and produced normal numbers of stage V gametocytes. <b>Conclusions:</b> The results indicate that Pfnek-4 is not strictly gametocyte-specific, and is expressed in a small subset of asexual parasites displaying high rate conversion to sexual development. Pfnek-4 is not required for erythrocytic schizogony and gametocytogenesis. This is the first study to report the use of a molecular marker for the sorting of sexually-committed schizont stage P. falciparum parasites, which opens the way to molecular characterization of this pre-differentiated subpopulation

A meta-analysis of controlled trials of recombinant human activated protein C therapy in patients with sepsis

BACKGROUND: Meta-analysis of two randomised controlled trials in severe sepsis performed with recombinant human activated protein C may provide further insight as to the therapeutic utility of targeting the clotting cascade in this syndrome. METHODS: In search for relevant studies published, two randomized clinical trials were found eligible. RESULTS: The studies, PROWESS and ADDRESS, enrolled a total of 4329 patients with risk ratio (RR) and 95% confidence interval (CI) data for effect on 28-day mortality relative to control treatment of 0.92 (0.83–1.02) suggesting that recombinant human activated protein C is not beneficial in severe sepsis. In PROWESS, 873 of 1690 patients presented with low risk, and 2315 of 2639 patients in ADDRESS as defined by APACHE II score < 25. In this low-risk stratum, no effect of recombinant human activated protein C administration on 28-day mortality was observed. This observation appears to be consistent and homogenous. Heterogeneity between the two studies, however, was seen in patients with APACHE II score ≥ 25 in whom recombinant activated protein C was effective in PROWESS (n = 817; RR 0.71, CI 0.59–0.85) whereas a tendency toward harm was present in ADDRESS (n = 324; RR 1.21, CI 0.85–1.74). Even though the overall treatment effect in this high-risk population was still in favour of treatment with recombinant activated protein C (n = 1141; RR 0.80, CI 0.68–0.94), the observed heterogeneity suggests that the efficacy of recombinant human activated protein C is not robust. Not unlikely, the adverse tendency observed could have become significant with higher statistical power would ADDRESS not have been terminated prematurely. CONCLUSION: This meta-analysis, therefore, raises doubts about the clinical usefulness of recombinant activated protein C in patients with severe sepsis and an APACHE II score ≥ 25 which can only be resolved by another properly designed clinical trial