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Objectives This study aimed to develop a patient-centred approach to the burden of acute type A aortic dissection (ATAAD) through modelling. The main objective was to identify potential improvements in managing this life-threatening cardiovascular condition and to provide evidence-based recommendations to optimise outcomes.Design We developed a predictive model along patient pathways to estimate the burden of ATAAD through the years of life lost (YLLs) metric. The model was created based on a systematic review of the literature and was parameterised using demographic data from the German healthcare environment. The model was designed to allow interactive simulation of different scenarios resulting from changes in key impact factors.Setting The study was conducted using data from the German healthcare environment and results from the literature review.Participants The study included a comprehensive modelling of ATAAD cases in Germany but did not directly involve participants.Interventions There were no specific interventions applied in this study based on the modelling design.Primary and secondary outcome measures The single outcome measure was the estimation of YLL due to ATAAD in Germany.Results Our model estimated 102 791 YLL per year for ATAAD in Germany, with 62 432 and 40 359 YLL for men and women, respectively. Modelling an improved care setting yielded 93 191 YLL or 9.3% less YLL compared with the current standard while a worst-case scenario resulted in 113 023 or 10.0% more YLL. The model is accessible at https://acuteaorticdissection.com/ to estimate custom scenarios.Conclusions Our study provides an evidence-based approach to estimating the burden of ATAAD and identifying potential improvements in the management of pathways. This approach can be used by healthcare decision-makers to inform policy changes aimed at optimising patient outcomes. By considering patient-centred approaches in any healthcare environment, the model has the potential to improve efficient care for patients suffering from ATAAD.

Advancements in cochlear implants (CIs) have led to a significant increase in bilateral CI users, especially among children. Yet, most bilateral CI users do not fully achieve the intended binaural benefit due to potential limitations in signal processing and/or surgical implant positioning. One crucial auditory cue that normal hearing (NH) listeners can benefit from is the interaural time difference (ITD), i.e., the time difference between the arrival of a sound at two ears. The ITD sensitivity is thought to be heavily relying on the effective utilization of temporal fine structure (very rapid oscillations in sound). Unfortunately, most current CIs do not transmit such true fine structure. Nevertheless, bilateral CI users have demonstrated sensitivity to ITD cues delivered through envelope or interaural pulse time differences, i.e., the time gap between the pulses delivered to the two implants. However, their ITD sensitivity is significantly poorer compared to NH individuals, and it further degrades at higher CI stimulation rates, especially when the rate exceeds 300 pulse per second. The overall purpose of this research thread is to improve spatial hearing abilities in bilateral CI users. This study aims to develop electroencephalography (EEG) paradigms that can be used with clinical settings to assess and optimize the delivery of ITD cues, which are crucial for spatial hearing in everyday life. The research objective of this article was to determine the effect of CI stimulation pulse rate on the ITD sensitivity, and to characterize the rate-dependent degradation in ITD perception using EEG measures. To develop protocols for bilateral CI studies, EEG responses were obtained from NH listeners using sinusoidal-amplitude-modulated (SAM) tones and filtered clicks with changes in either fine structure ITD (ITDFS) or envelope ITD (ITDENV). Multiple EEG responses were analyzed, which included the subcortical auditory steady-state responses (ASSRs) and cortical auditory evoked potentials (CAEPs) elicited by stimuli onset, offset, and changes. Results indicated that acoustic change complex (ACC) responses elicited by ITDENV changes were significantly smaller or absent compared to those elicited by ITDFS changes. The ACC morphologies evoked by ITDFS changes were similar to onset and offset CAEPs, although the peak latencies were longest for ACC responses and shortest for offset CAEPs. The high-frequency stimuli clearly elicited subcortical ASSRs, but smaller than those evoked by lower carrier frequency SAM tones. The 40-Hz ASSRs decreased with increasing carrier frequencies. Filtered clicks elicited larger ASSRs compared to high-frequency SAM tones, with the order being 40 > 160 > 80> 320 Hz ASSR for both stimulus types. Wavelet analysis revealed a clear interaction between detectable transient CAEPs and 40-Hz ASSRs in the time-frequency domain for SAM tones with a low carrier frequency.

Abstract The recently observed FLASH effect describes the observation of normal tissue protection by ultra-high dose rates (UHDR), or dose delivery in a fraction of a second, at similar tumor-killing efficacy of conventional dose delivery and promises great benefits for radiotherapy patients. Dedicated studies are now necessary to define a robust set of dose application parameters for FLASH radiotherapy and to identify underlying mechanisms. These studies require particle accelerators with variable temporal dose application characteristics for numerous radiation qualities, equipped for preclinical radiobiological research. Here we present the dresden platform, a research hub for ultra-high dose rate radiobiology. By uniting clinical and research accelerators with radiobiology infrastructure and know-how, the dresden platform offers a unique environment for studying the FLASH effect. We introduce its experimental capabilities and demonstrate the platform’s suitability for systematic investigation of FLASH by presenting results from a concerted in vivo radiobiology study with zebrafish embryos. The comparative pre-clinical study was conducted across one electron and two proton accelerator facilities, including an advanced laser-driven proton source applied for FLASH-relevant in vivo irradiations for the first time. The data show a protective effect of UHDR irradiation up to $$10^{5}\text{Gy}/\text{s}$$ 10 5 Gy / s and suggests consistency of the protective effect even at escalated dose rates of $$10^9\text{Gy}/\text{s}$$ 10 9 Gy / s . With the first clinical FLASH studies underway, research facilities like the dresden platform, addressing the open questions surrounding FLASH, are essential to accelerate FLASH’s translation into clinical practice.

Coagulopathy is common in patients undergoing thoracic aortic repair for Stanford type A aortic dissection. Non-critical administration of blood products may adversely affect the outcome. It is therefore important to be familiar with the pathologic conditions that lead to coagulopathy in complex cardiac surgery. Adequate care of these patients includes the collection of the medical history regarding the use of antithrombotic and anticoagulant drugs, and a sophisticated diagnosis of the coagulopathy with viscoelastic testing and subsequently adapted coagulation therapy with labile and stable blood products. In addition to the above-mentioned measures, intraoperative blood conservation measures as well as good interdisciplinary coordination and communication contribute to a successful hemostatic management strategy.

Abstract Application experiments with laser plasma-based accelerators (LPA) for protons have to cope with the inherent fluctuations of the proton source. This creates a demand for non-destructive and online spectral characterization of the proton pulses, which are for application experiments mostly spectrally filtered and transported by a beamline. Here, we present a scintillator-based time-of-flight (ToF) beam monitoring system (BMS) for the recording of single-pulse proton energy spectra. The setup’s capabilities are showcased by characterizing the spectral stability for the transport of LPA protons for two beamline application cases. For the two beamline settings monitored, data of 122 and 144 proton pulses collected over multiple days were evaluated, respectively. A relative energy uncertainty of 5.5% (1 $$\upsigma$$ σ ) is reached for the ToF BMS, allowing for a Monte-Carlo based prediction of depth dose distributions, also used for the calibration of the device. Finally, online spectral monitoring combined with the prediction of the corresponding depth dose distribution in the irradiated samples is demonstrated to enhance applicability of plasma sources in dose-critical scenarios.

BackgroundAfter admission to hospital, COVID-19 progresses in a substantial proportion of patients to critical disease that requires intensive care unit (ICU) admission.MethodsIn a pragmatic, non-blinded trial, 387 patients aged 40-90 years were randomised to receive treatment with SoC plus doxycycline (n = 192) or SoC only (n = 195). The primary outcome was the need for ICU admission as judged by the attending physicians. Three types of analyses were carried out for the primary outcome: "Intention to treat" (ITT) based on randomisation; "Per protocol" (PP), excluding patients not treated according to randomisation; and "As treated" (AT), based on actual treatment received. The trial was undertaken in six hospitals in India with high-quality ICU facilities. An online application serving as the electronic case report form was developed to enable screening, randomisation and collection of outcomes data.ResultsAdherence to treatment per protocol was 95.1%. Among all 387 participants, 77 (19.9%) developed critical disease needing ICU admission. In all three primary outcome analyses, doxycycline was associated with a relative risk reduction (RRR) and absolute risk reduction (ARR): ITT 31.6% RRR, 7.4% ARR (P = 0.063); PP 40.7% RRR, 9.6% ARR (P = 0.017); AT 43.2% RRR, 10.8% ARR (P = 0.007), with numbers needed to treat (NTT) of 13.4 (ITT), 10.4 (PP), and 9.3 (AT), respectively. Doxycycline was well tolerated with not a single patient stopping treatment due to adverse events.ConclusionsIn hospitalized COVID-19 patients, doxycycline, a safe, inexpensive, and widely available antibiotic with anti-inflammatory properties, reduces the need for ICU admission when added to SoC.

Every-day acoustical environments are often complex, typically comprising one attended target sound in the presence of interfering sounds (e.g., disturbing conversations) and reverberation. Here we assessed binaural detection thresholds and (supra-threshold) binaural audio quality ratings of four distortions types: spectral ripples, non-linear saturation, intensity and spatial modifications applied to speech, guitar, and noise targets in such complex acoustic environments (CAEs). The target and (up to) two masker sounds were either co-located as if contained in a common audio stream, or were spatially separated as if originating from different sound sources. The amount of reverberation was systematically varied. Masker and reverberation had a significant effect on the distortion-detection thresholds of speech signals. Quality ratings were affected by reverberation, whereas the effect of maskers depended on the distortion. The results suggest that detection thresholds and quality ratings for distorted speech in anechoic conditions are also valid for rooms with mild reverberation, but not for moderate reverberation. Furthermore, for spectral ripples, a significant relationship between the listeners’ individual detection thresholds and quality ratings was found. The current results provide baseline data for detection thresholds and audio quality ratings of different distortions of a target sound in CAEs, supporting the future development of binaural auditory models.

Recent studies on loudness perception of binaural broadband signals in hearing impaired listeners found large individual differences, suggesting the use of such signals in hearing aid fitting. Likewise, clinical cochlear implant (CI) fitting with narrowband/single-electrode signals might cause suboptimal loudness perception in bilateral and bimodal CI listeners. Here spectral and binaural loudness summation in normal hearing (NH) listeners, bilateral CI (biCI) users, and unilateral CI (uCI) users with normal hearing in the unaided ear was investigated to assess the relevance of binaural/bilateral fitting in CI users. To compare the three groups, categorical loudness scaling was performed for an equal categorical loudness noise (ECLN) consisting of the sum of six spectrally separated third-octave noises at equal loudness. The acoustical ECLN procedure was adapted to an equivalent procedure in the electrical domain using direct stimulation. To ensure the same broadband loudness in binaural measurements with simultaneous electrical and acoustical stimulation, a modified binaural ECLN was introduced and cross validated with self-adjusted loudness in a loudness balancing experiment. Results showed a higher (spectral) loudness summation of the six equally loud narrowband signals in the ECLN in CI compared to NH. Binaural loudness summation was found for all three listener groups (NH, uCI, and biCI). No increased binaural loudness summation could be found for the current uCI and biCI listeners compared to the NH group. In uCI loudness balancing between narrowband signals and single electrodes did not automatically result in a balanced loudness perception across ears, emphasizing the importance of binaural/bilateral fitting.

Abstract Introduction: Cocaine use is known to be associated with an increased risk for vascular diseases. It is likely to trigger or increase the risk for an aortic dissection. We conducted an analysis of 45 cases of cocaine-related aortic dissection to further characterize the clinical features and outcomes of this patient cohort. Methods: Our study cohort of 45 patients consisted of 11 cases from our institutional database and 34 published case reports. Results: The observed cases of acute aortic dissection related to cocaine use showed a high proportion of young (41.3±8.67 years) and male (88.9%) patients. Most of the cases (75%) were classified as Stanford type A. Also, in 75% of the cases, cocaine use was prevalent for more than one year. Median time from last cocaine use to onset of symptoms was one hour. In-hospital mortality was 21.4%, while additional 11.9% of the cases died before arriving at the hospital. Conclusion: Acute aortic dissection related to cocaine use occurs in predominantly young male patients and has a dismal outcome when compared to all comer series.

The individual loudness perception of a patient plays an important role in hearing aid satisfaction and use in daily life. Hearing aid fitting and development might benefit from individualized loudness models (ILMs), enabling better adaptation of the processing to individual needs. The central question is whether additional parameters are required for ILMs beyond non-linear cochlear gain loss and linear attenuation common to existing loudness models for the hearing impaired (HI). Here, loudness perception in eight normal hearing (NH) and eight HI listeners was measured in conditions ranging from monaural narrowband to binaural broadband, to systematically assess spectral and binaural loudness summation and their interdependence. A binaural summation stage was devised with empirical monaural loudness judgments serving as input. While NH showed binaural inhibition in line with the literature, binaural summation and its inter-subject variability were increased in HI, indicating the necessity for individualized binaural summation. Toward ILMs, a recent monaural loudness model was extended with the suggested binaural stage, and the number and type of additional parameters required to describe and to predict individual loudness were assessed. In addition to one parameter for the individual amount of binaural summation, a bandwidth-dependent monaural parameter was required to successfully account for individual spectral summation.

Abstract The shape of a wave carries all information about the spatial and temporal structure of its source, given that the medium and its properties are known. Most modern imaging methods seek to utilize this nature of waves originating from Huygens’ principle. We discuss the retrieval of the complete kinetic energy distribution from the acoustic trace that is recorded when a short ion bunch deposits its energy in water. This novel method, which we refer to as Ion-Bunch Energy Acoustic Tracing (I-BEAT), is a refinement of the ionoacoustic approach. With its capability of completely monitoring a single, focused proton bunch with prompt readout and high repetition rate, I-BEAT is a promising approach to meet future requirements of experiments and applications in the field of laser-based ion acceleration. We demonstrate its functionality at two laser-driven ion sources for quantitative online determination of the kinetic energy distribution in the focus of single proton bunches.

Shaping particle beams generated from laser-plasma accelerators is challenging. Here the authors demonstrate an all-optical method to structure the accelerated proton beam by modulating and imprinting the spatial laser profile onto the proton beam.

AimsThe aim of this study was to compare discrepancies between diagnosed and autopsied causes of death in 1,112 hospital autopsies and to determine the factors causing this discrepancies.Methods1,112 hospital autopsies between 2010 and 2013 were retrospectively studied. Ante-mortem diagnoses were compared to causes of death as determined by autopsy. Clinical diagnoses were extracted from the autopsy request form, and post-mortem diagnoses were assessed from respective autopsy reports. Variables, such as sex, age, Body Mass Index, category of disease, duration of hospital stay and new-borns were studied in comparison to discrepancy. P-values were derived from the Mann-Whitney U test for the constant features and chi-2 test, p-values < 0,05 were considered significant.Results73.9% (n = 822) patients showed no discrepancy between autopsy and clinical diagnosis. The duration of hospitalisation (6 vs. 9 days) and diseases of the cardiovascular system (61.7%) had a significant impact on discrepancies.ConclusionAge, cardiovascular diseases and duration of hospital stay significantly affect discrepancies in ante- and post-mortem diagnoses.

Abstract PET/CT plays an important role in the diagnosis, staging and management of many pediatric malignancies. The techniques for performing PET/CT examinations in children have evolved, with increasing attention focused on reducing patient exposure to ionizing radiation dose whenever possible and minimizing scan duration and sedation times, with a goal toward optimizing the overall patient experience. This review outlines our approach to performing PET/CT, including a discussion of the indications for a PET/CT exam, approaches for optimizing the exam protocol, and a review of different approaches for acquiring the CT portion of the PET/CT exam. Strategies for PACS integration, image display, interpretation and reporting are also provided. Most practices will develop a strategy for performing PET/CT that best meets their respective needs. The purpose of this article is to provide a comprehensive overview for radiologists who are new to pediatric PET/CT, and also to provide experienced PET/CT practitioners with an update on state-of-the art CT techniques that we have incorporated into our protocols and that have enabled us to make considerable improvements to our PET/CT practice.

Serial-section electron microscopy such as FIB-SEM (focused ion beam scanning electron microscopy) has become an important tool for neuroscientists to trace the trajectories and global architecture of neural circuits in the brain, as well as to visualize the 3D ultrastructure of cellular organelles in neurons. In this study, we examined 3D features of mitochondria in electron microscope images generated from serial sections of four regions of mouse brains: nucleus accumbens (NA), hippocampal CA1, somatosensory cortex and dorsal cochlear nucleus (DCN). We compared mitochondria in the presynaptic terminals to those in the postsynaptic/dendritic compartments, and we focused on the shape and size of mitochondria. A common feature of mitochondria among the four brain regions is that presynaptic mitochondria generally are small and short, and most of them do not extend beyond presynaptic terminals. In contrast, the majority of postsynaptic/dendritic mitochondria are large and many of them spread through significant portions of the dendrites. Comparing among the brain areas, the cerebral cortex and DCN have even larger postsynaptic/dendritic mitochondria than the NA and CA1. Our analysis reveals that mitochondria in neurons are differentially sized and arranged according to their subcellular locations, suggesting a spatial organizing principle of mitochondria at the synapse.

Objectives: There has been an increase in the number of women Veterans with service connected disabilities, which are illnesses or injuries incurred or aggravated during military service. We compared military service and disability characteristics in women and men ≤50 years of age. Methods: This study included 4,029,672 living Veterans who had at least 1 service connected condition and an active award status as of October 1, 2016. The date of last award as well as demographic, military service, and disability characteristics were obtained from the Veterans Benefits Administration (VBA) VETSNET file. Results: Among 388,947 women Veterans with service connected conditions, almost 60% (n = 231,364) were ≤50 years of age. Roughly 55% of both women and men ≤50 years had a ≥50% combined rating, although there were differences with respect to individual service connected conditions. Women less often had service connected post traumatic stress disorder (23% vs 32%), but more often had major depression (15% vs 7%). While traumatic brain disease was more common in men, migraine headache was much more common in women (32% vs 18%). Less than half had a VA outpatient visit in the previous year. Conclusions: The findings of significant numbers of younger women with service connected PTSD, depression, or migraine headache should be considered within the context of post deployment health. These findings raise questions regarding outreach to women Veterans who have these conditions, but do not use VA health care.

To achieve a natural sound quality when listening through hearing devices, the sound pressure at the eardrum should replicate that of the open ear, modified only by an insertion gain if desired. A target approximating this reference condition can be computed by applying an appropriate correction function to the pressure observed at the device microphone. Such Target Response Correction Functions (TRCF) can be defined based on the directionally dependent relative transfer function between the location of the hearing device microphone and the eardrum of the open ear. However, it is unclear how exactly the TRCF should be derived, and how large the benefit of individual, versus generic, correction is. We present measurements of Head-Related Transfer Functions (HRTF) at the eardrum and at 9 microphone locations of a comprehensive set of 5 hearing device styles, including 91 incidence directions, and recorded in 16 subjects and 2 dummy heads. Based on these HRTFs, individualized and generic TRCF were computed for frontal (referred to as free-field) and diffuse-field sound incidence. Spectral deviations between the computed target and listening with the open ear were evaluated using an auditory model and virtual acoustic scenes. Results indicate that a correction for diffuse-field incidence should be preferred over the free field, and individual correction functions result in notably reduced spectral deviations to open-ear listening, as compared with generic correction functions. These outcomes depend substantially on the specific device style. The HRTF database and derived TRCFs are publicly available.

A critical step toward tailoring effective interventions for heterogeneous and medically complex patients is to identify clinically meaningful subgroups on the basis of their comorbid conditions. We applied Item Response Theory (IRT), a potentially useful tool to identify clinically meaningful subgroups, to characterize phenotypes within a cohort of high-risk patients. This was a retrospective cohort study using 68,400 high-risk Veteran's Health Administration (VHA) patients. Thirty-one physical and mental health diagnosis indicators based on ICD-9 codes from patients' inpatient, outpatient VHA and VA-paid community care claims. Results revealed 6 distinct subgroups of high-risk patients were identified: substance use, complex mental health, complex diabetes, liver disease, cancer with cardiovascular disease, and cancer with mental health. Multinomial analyses showed that subgroups significantly differed on demographic and utilization variables which underscored the uniqueness of the groups. Using IRT models with clinical diagnoses from electronic health records permitted identification of diagnostic constellations among otherwise undifferentiated high-risk patients. Recognizing distinct patient profiles provides a framework from which insights into medical complexity of high-risk patients can be explored and effective interventions can be tailored.

[This corrects the article DOI: 10.1371/journal.pone.0193996.].

We sought to determine the leading causes of cardiovascular (CV) hospitalization, and to describe and compare national rates of CV hospitalization by age, gender, race, ethnicity, region, and year, among U.S. veterans.We evaluated the electronic health records of all veterans aged ≥18 years who had accessed any healthcare services at either a VA healthcare facility or a non-VA healthcare facility that was reimbursed by the VA, between January 1 2010 and December 31 2014. Among these 8,452,912 patients, we identified the 5 leading causes of CV hospitalization and compared rates of hospitalization by age, gender, race, ethnicity, region, year and type of VA healthcare user.The top 5 causes of CV hospitalization were: coronary atherosclerosis, heart failure, acute myocardial infarction, stroke and atrial fibrillation. Overall, 297,373 (3.5%) veterans were hospitalized for one or more of these cardiovascular conditions. The percentage of veterans hospitalized for one or more of these CV conditions decreased over time, from 1.23% in 2010 to 1.18% in 2013, followed by a slight increase to 1.20% in 2014. There was significant variation in rates of CV hospitalization by gender, race, ethnicity, geographic region, and urban vs. rural zip code. In particular, older, male, Black, non-Hispanic, urban and Continental region veterans experienced the highest rates of CV hospitalizations.Among 8.5 million patients enrolled in the VA healthcare system from 2010 to 2014, there was substantial variation in rates of CV hospitalization by age, gender, race, geographical distribution, year, and use of non-VA (vs. VA only) healthcare care facilities.

Ongoing changes in Earth’s climate are shifting the elevation ranges of many plant species with non-native species often experiencing greater expansion into higher elevations than native species. These climate change-induced shifts in distributions inevitably expose plants to novel biotic and abiotic environments, including altered solar ultraviolet (UV)-B (280–315 nm) radiation regimes. Do the greater migration potentials of non-native species into higher elevations imply that they have more effective UV-protective mechanisms than native species? In this study, we surveyed leaf epidermal UV-A transmittance (TUV A) in a diversity of plant species representing different growth forms to test whether native and non-native species growing above 2800 m elevation on Mauna Kea, Hawaii differed in their UV screening capabilities. We further compared the degree to which TUV A varied along an elevation gradient in the native shrub Vaccinium reticulatum and the introduced forb Verbascum thapsus to evaluate whether these species differed in their abilities to adjust their levels of UV screening in response to elevation changes in UV-B. For plants growing in the Mauna Kea alpine/upper subalpine, we found that adaxial TUV A, measured with a UVA-PAM fluorometer, varied significantly among species but did not differ between native (mean = 6.0%; n = 8) and non-native (mean = 5.8%; n = 11) species. When data were pooled across native and non-native taxa, we also found no significant effect of growth form on TUV A, though woody plants (shrubs and trees) were represented solely by native species whereas herbaceous growth forms (grasses and forbs) were dominated by non-native species. Along an elevation gradient spanning 2600–3800 m, TUV A was variable (mean range = 6.0–11.2%) and strongly correlated with elevation and relative biologically effective UV-B in the exotic V. thapsus; however, TUV A was consistently low (3%) and did not vary with elevation in the native V. reticulatum. Results indicate that high levels of UV protection occur in both native and non-native species in this high UV-B tropical alpine environment, and that flexibility in UV screening is a mechanism employed by some, but not all species to cope with varying solar UV-B exposures along elevation gradients.

Vowel identification in noise using consonant-vowel-consonant (CVC) logatomes was used to investigate a possible interplay of speech information from different frequency regions. It was hypothesized that the periodicity conveyed by the temporal envelope of a high frequency stimulus can enhance the use of the information carried by auditory channels in the low-frequency region that share the same periodicity. It was further hypothesized that this acts as a strobe-like mechanism and would increase the signal-to-noise ratio for the voiced parts of the CVCs. In a first experiment, different high-frequency cues were provided to test this hypothesis, whereas a second experiment examined more closely the role of amplitude modulations and intact phase information within the high-frequency region (4-8 kHz). CVCs were either natural or vocoded speech (both limited to a low-pass cutoff-frequency of 2.5 kHz) and were presented in stationary 3-kHz low-pass filtered masking noise. The experimental results did not support the hypothesized use of periodicity information for aiding low-frequency perception.

Current cochlear implant (CI) strategies carry speech information via the waveform envelope in frequency subbands. CIs require efficient speech processing to maximize information transfer to the brain, especially in background noise, where the speech envelope is not robust to noise interference. In such conditions, the envelope, after decomposition into frequency bands, may be enhanced by sparse transformations, such as nonnegative matrix factorization (NMF). Here, a novel CI processing algorithm is described, which works by applying NMF to the envelope matrix ( envelopogram ) of 22 frequency channels in order to improve performance in noisy environments. It is evaluated for speech in eight-talker babble noise. The critical sparsity constraint parameter was first tuned using objective measures and then evaluated with subjective speech perception experiments for both normal hearing and CI subjects. Results from vocoder simulations with 10 normal hearing subjects showed that the algorithm significantly enhances speech intelligibility with the selected sparsity constraints. Results from eight CI subjects showed no significant overall improvement compared with the standard advanced combination encoder algorithm, but a trend toward improvement of word identification of about 10 percentage points at +15 dB signal-to-noise ratio (SNR) was observed in the eight CI subjects. Additionally, a considerable reduction of the spread of speech perception performance from 40% to 93% for advanced combination encoder to 80% to 100% for the suggested NMF coding strategy was observed.

OBJECTIVE: To determine the fraction of individuals with high total serum cholesterol who get diagnosed and effectively treated in eight high- and middle-income countries. METHODS: Using data from nationally representative health examination surveys conducted in 1998-2007, we studied a probability sample of 79 039 adults aged 40-79 years from England, Germany, Japan, Jordan, Mexico, Scotland, Thailand and the United States of America. For each country we calculated the prevalence of high total serum cholesterol (total serum cholesterol > 6.2 mmol/l or > 240 mg/dl) and the mean total serum cholesterol level. We also determined the fractions of individuals being diagnosed, treated with cholesterol-lowering medication and effectively controlled (total serum cholesterol < 6.2 mmol/l or < 240 mg/dl). FINDINGS: The proportion of undiagnosed individuals was highest in Thailand (78%; 95% confidence interval, CI: 74-82) and lowest in the United States (16%; 95% CI: 13-19). The fraction diagnosed but untreated ranged from 9% in Thailand (95% CI: 8-11) to 53% in Japan (95% CI: 50-57). The proportion being treated who had attained evidence of control ranged from 4% in Germany (95% CI: 3-5) to 58% in Mexico (95% CI: 54-63). Time series estimates showed improved control of high total serum cholesterol over the past two decades in England and the United States. CONCLUSION: The percentage of people with high total serum cholesterol who are effectively treated remains small in selected high- and middle-income countries. Many of those affected are unaware of their condition. Untreated high blood cholesterol represents a missed opportunity in the face of a global epidemic of chronic diseases.

Using the National Longitudinal Surveys of Youth (NLSY), this article examines the influence of a region's industrial composition on the educational attainment of children raised by parents who do not have college degrees. The NLSY's geo-coded panel allows for precise measurements of the local industries that shaped the parents' employment opportunities and the labor market that the children directly observed. For cohorts finishing school in the 1990s and early 2000s, concentrations of manufacturing are positively associated with both high school and college attainment. Concentrations of college-degree-intensive industries are positively associated with college attainment. I investigate several potential mechanisms that could relate the industrial composition to educational attainment, including returns to education, opportunity costs, parental inputs, community resources, and information.

Invariant Natural Killer T cells (iNKT) are a versatile lymphocyte subset with important roles in both host defense and immunological tolerance. They express a highly conserved TCR which mediates recognition of the non-polymorphic, lipid-binding molecule CD1d. The structure of human iNKT TCRs is unique in that only one of the six complementarity determining region (CDR) loops, CDR3beta, is hypervariable. The role of this loop for iNKT biology has been controversial, and it is unresolved whether it contributes to iNKT TCR:CD1d binding or antigen selectivity. On the one hand, the CDR3beta loop is dispensable for iNKT TCR binding to CD1d molecules presenting the xenobiotic alpha-galactosylceramide ligand KRN7000, which elicits a strong functional response from mouse and human iNKT cells. However, a role for CDR3beta in the recognition of CD1d molecules presenting less potent ligands, such as self-lipids, is suggested by the clonal distribution of iNKT autoreactivity. We demonstrate that the human iNKT repertoire comprises subsets of greatly differing TCR affinity to CD1d, and that these differences relate to their autoreactive functions. These functionally different iNKT subsets segregate in their ability to bind CD1d-tetramers loaded with the partial agonist alpha-linked glycolipid antigen OCH and structurally different endogenous beta-glycosylceramides. Using surface plasmon resonance with recombinant iNKT TCRs and different ligand-CD1d complexes, we demonstrate that the CDR3beta sequence strongly impacts on the iNKT TCR affinity to CD1d, independent of the loaded CD1d ligand. Collectively our data reveal a crucial role for CDR3beta for the function of human iNKT cells by tuning the overall affinity of the iNKT TCR to CD1d. This mechanism is relatively independent of the bound CD1d ligand and thus forms the basis of an inherent, CDR3beta dependent functional hierarchy of human iNKT cells.