Here, we show that the BX-795 cell line design principles used to achieve robustness dramatically influence whether robustness leads to evolvability. In simulation experiments, we find that purely redundant systems have remarkably low evolvability while degenerate, i.e. partially redundant, systems tend to be orders of magnitude more evolvable. Surprisingly, the magnitude of observed variation in evolvability can neither be explained by differences in the size north etopology of the neutral networks. This suggests that degeneracy, a ubiquitous characteristic in

biological systems, may be an important enabler of natural evolution. More generally, our study provides valuable new clues a bout the origin of innovations in complex adaptive systems. (C) 2009 Elsevier Ltd. All rights reserved.”
“People often fail to respond to an auditory target if they have to respond to a visual target presented at the same time, a phenomenon known as the Colavita visual dominance effect. To date, the Colavita effect has only ever been demonstrated in detection tasks in which participants respond to pre-defined visual, auditory, or bimodal audiovisual target stimuli. Here, we tested the Colavita effect when the target was defined by a rule, namely the repetition of any event (a picture, a sound, or both) in simultaneously-presented AZD5363 ic50 streams of pictures and sounds. Given previous findings that

PD173074 manufacturer people are better at detecting auditory repetitions than visual repetitions, we expected that the Colavita visual dominance effect might disappear (or even reverse). Contrary to this prediction,

however, visual dominance (i.e., the typical Colavita effect) was observed, with participants still neglecting significantly more auditory events than visual events in response to bimodal targets. The visual dominance for bimodal repetitions was observed despite the fact that participants missed significantly more unimodal visual repetitions than unimodal auditory repetitions. These results therefore extend the Colavita visual dominance effect to a domain where auditory dominance has traditionally been observed. In addition, our results reveal that the Colavita effect occurs at a more abstract, rule-based, level of representation than tested in previous research. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Artificial Endocrine Pancreas (AEP) is one of the most optimistic approaches in Type 1 Diabetes Mellitus (T1DM) treatment due to the novel technological advances in continuous glucose monitoring, exogenous insulin delivery, and their proofs in clinical assessments. The main goal of AEP is to replace the pancreatic insulin secretion in the blood glucose regulation loop by means of an automatic exogenous insulin in fusion. The joint element between glucose sensing and insulin delivering actions is an automatic algorithm-based decision.

During the study period, the amputation rate declined by 36% in women and 21% in men with PAD, and similarly, open procedures decreased by 36% and 30%. Endovascular procedures, however, increased by 150% in women and 144% in men. Procedural mortality was 4.95% vs 4.37% for men (P<.0001). Female mortality

rates were persistently higher after amputations (9.89% vs 8.90%, P<.0001), open (5.49% vs 4.00%, P<.0001), and endovascular procedures (2.87% vs 2.10%, P<.0001). Time trends showed improved mortality for men and women, with a stable difference between the two.

Conclusion: The analysis of representative state administrative databases of inpatient care records demonstrated improvements in mortality and amputation rates over time. However, a gender-related disparity in PAD outcomes remains that merits further investigation. (J Vasc Surg 20 10;51:372-9.)”
“OBJECTIVE: We report a rare case of thrombosis of the Epigenetics inhibitor superior sagittal sinus associated with a parafalcine meningioma resulting in a superior sagittal sinus dural arteriovenous fistula (dAVF). We conclude that dural sinus thrombosis is a significant predisposing factor for development

of a dAVF.

CLINICAL PRESENTATION: A 60-year-old man had a left parietal parafalcine meningioma that invaded the posterior third of his superior sagittal sinus, leading to its occlusion and presumably resulting in an associated FK506 cell line dAVF. The fistula was fed by the middle meningeal and superficial temporal arteries on MK5108 nmr both sides and drained through a superior interhemispheric cortical vein into the vein of Galen and straight sinus.

INTERVENTION

AND TECHNIQUE: The parafalcine mass, which involved the sagittal sinus, was excised via a left parieto-occipital craniotomy. It was decided to resect the dAVF at a later date. Seven days after the original operation, the patient underwent a parietal interhemispheric approach for occlusion of the dAVF. Dissection proceeded until a large arterialized vein and venous pouch with multiple feeders from both external carotid arteries were observed. The vein, which was partially embedded within the falx cerebri, was collapsed, and a second indocyanine green injection confirmed cessation of blood flow.

CONCLUSION: This report supports that dAVFs are acquired lesions and that venous outflow obstruction is a significant contributing factor to their development. In meningiomas associated with the dural sinuses, diagnostic evaluation for possible dAVFs should be considered. Treatment of these lesions should be based on risk factors because spontaneous resolution after tumor excision has been reported.”
“Background: Although technical success of renal artery stenting (RAS) is high and adverse events are infrequent, clinical success (improved blood pressure and renal function) and durability have been less predictable.

In order to propose a clean technology for the treatment of this effluent, we also investigated the exposure of mice to effluents treated by photoelectrooxidation process (PEO). Adult male Swiss albino mice (CF1 strain) were given free access to water bottles containing an effluent treated by a tannery (non-PEO) or PEO-treated tannery wastewater (0.1 and 1% in drinking water). Exposure to tannery wastewater induced behavioural changes

in the mice in elevated plus-maze. Exposure to non-PEO 1% decreased the percentage of time spent in the open arms, indicating anxiety-like behaviour. Bromosporine concentration Exposure to tannery wastewater did not alter immobility time in the forced swim test, suggesting that tannery effluents did not induce depression-like behaviour in the mice. These behavioural data suggest that non-PEO tannery effluent has an anxiogenic effect, whereas PEO-treated tannery effluents do not alter anxiety levels. (C) 2011 Elsevier Inc. All rights reserved.”
“Purpose: Meta-analysis has shown that bacillus Calmette-Guerin is less effective in females undergoing treatment for urothelial carcinoma. Urothelial carcinoma cells express immune regulatory

proteins as a consequence of bacillus Calmette-Guerin induced, nuclear factor kappa B signaling. Nuclear factor kappa B is influenced by estrogen receptor binding. We evaluated the effect of the physiological estradiol concentration on the expression of bacillus Calmette-Guerin induced, nuclear factor kappa B regulated

immune proteins.

Materials and Methods: We determined MLN2238 research buy the estrogen receptor expression status of human urothelial carcinoma cell lines by reverse transcriptase-polymerase chain reaction. The functional status of estrogen receptor signaling was established using estrogen receptor reporter constructs. We used gene expression profiling of urothelial carcinoma cells combined with reverse transcriptase-polymerase chain reaction to identify the nuclear factor kappa B dependent immune regulatory proteins Taselisib mw expressed in response to bacillus Calmette-Guerin. We determined the influence of the estradiol concentration on bacillus Calmette-Guerin dependent interleukin-6 and 8, chemokine (c-x-c motif) ligands 1 and 2, and chemokine (c-c motif) ligand 20 gene expression by quantitative reverse transcriptase-polymerase chain reaction.

Results: Urothelial carcinoma cell lines expressed functional estrogen receptor. Nuclear factor kappa B signaling was inhibited by estradiol in a dose and estrogen receptor dependent manner. Urothelial carcinoma cell expression of interleukin-6 and 8, chemokine (c-x-c motif) ligands 1 and 2, and chemokine (c-c motif) ligand 20 was up-regulated in response to bacillus Calmette-Guerin in a nuclear factor kappa B dependent manner. There was a significant dose dependent effect of estradiol on the expression of these genes in bacillus Calmette-Guerin treated urothelial carcinoma cells.

The participating neurosurgeons answered a questionnaire after the planning procedure and postoperatively. In a second prospective series of 33 patients, check details we used an autostereoscopic

monitor system (MD20-3-D; Setred SA, Sweden) to plan intracranial operations. A questionnaire regarding the value of surgery planning was answered preoperatively and postoperatively.

RESULTS: The Dextroscope could be integrated into daily surgical routine. Surgeons regarded their understanding of the pathoanatomical situation as improved, leading to enhanced intraoperative orientation and confidence compared with conventional planning. The autostereoscopic Setred system was regarded as helpful in establishing the surgical strategy and analyzing the pathoanatomical situation compared with conventional planning. Both systems were perceived as a backup in case of failure of the standard navigation system.

CONCLUSION: Improvement of display and interaction techniques adds to the realism of the planning process and enables

precise structural understanding preoperatively. This minimizes intraoperative guesswork and exploratory dissection. Autostereoscopic display techniques will further increase the value and acceptance of 3-dimensional planning and intraoperative navigation.”
“Traditionally, the dried flower of Echium amoenum (Boraginaceae) has been used in Iran as an anxiolytic and mood enhancer. This study investigated the efficacy and safety of an aqueous extract of E amoenum in treatment of obsessive-compulsive GSK J4 clinical trial disorder. Levetiracetam Forty-four patients were randomly assigned to receive either E amoenum aqueous extract (500 mg/day) or placebo in a 6-week, double blind, parallel-group trial. Patients were assessed before the study and during weeks 1, 2,4, and 6 by the Yale-Brown Obsessive Compulsive (Y-BOCS), the Hamilton Rating Scale for Anxiety (HAM-A), and a score sheet on adverse effects. In weeks 4 and 6, the extract showed a significant superiority over placebo in reducing obsessive and compulsive and anxiety

symptoms. There was no significant difference between the two groups in terms of adverse effects. The results suggest that E. amoenum aqueous extract has some anti obsessive and compulsive effects. However, further studies are needed to confirm these findings. Crown Copyright (C) 2009 Published by Elsevier Inc. All rights reserved.”
“Resistance to nucleoside reverse transcriptase (RT) inhibitors is conferred on human immunodeficiency virus type 1 through thymidine analogue resistance mutations (TAMs) that increase the ability of RT to excise chain-terminating nucleotides after they have been incorporated. The RT mutation M184V is a potent suppressor of TAMs. In RT containing TAMs, the addition of M184V suppressed the excision of 3′-deoxy-3′-azidothymidine monophosphate (AZTMP) to a greater extent on an RNA template than on a DNA template with the same sequence.

We report herein the preclinical validation of a potential F-18-labeled biphenylalkyne, AV-138, as a preliminary step toward developing the imaging agent for patients suspected of having Alzheimer’s disease.

Methods: PRT062607 In vitro binding was carried out in the homogenates prepared front postmortem AD brains with [I-125]IMPY as the radioligand.

[F-18]AV-138 was successfully prepared using a tosylate precursor and sumitomo modules for radiosynthesis. Similarly, specific binding of [F-18]AV-138 (0.02-0.05 nM) to homogenates, prepared from gray and white matters of pooled AD patients and control subjects, was performed. Specific binding to AV plaques was measured by autoradiography in AD brain sections (n=11), and the same brain sections were fluorescently stained with thioflavin-S (TF-S). Images of both radiolabeling and fluorescent staining of plaques obtained by a phosphor imager wore used for correlation image analysis.

Results: As expected, AV-138 displayed a high binding affinity (Ki=2.4 +/- 0.7 W) in AD gray matter homogenates (due to its high level of A beta www.selleckchem.com/products/pd-1-pd-l1-inhibitor-3.html plaque accummulation). Specific binding can be clearly measured in the AD gray matter homogenates, but not in the AD white matters. Control brain homogenates, due to a lack of A plaques, also showed no specific binding. Furthermore, in vitro autoradiography of postmortem AD brain sections showed that the high binding signal of [F-18]AV-138 was

specifically due to A plaques. Fluorescent staining of plaques: with TF-S correlated well with the radiolabeling of [F-18]AV-138 in AD brain sections (r>0.90).

Conclusion:

Taken together, these preliminary results strongly suggest that [F-18]AV-138 is potentially useful for imaging A beta plaques in the living human brain. (C) 2009 Elsevier Inc. All rights reserved.”
“Purpose: The tumor microenvironment significantly influences prostate cancer progression. Androgen receptor exerts Its effect through downstream target click here genes to regulate prostate cancer cell proliferation. The c-FLIP gene was recently shown to be an androgen receptor target gene. c-FLIP is an inactive homologue of caspase-8 and, thus, it inhibits the death receptor mediated apoptosis pathway. c-FLIP over expression was shown to accelerate the progression of prostate cancer cells to androgen independence. We evaluated the role of c-FLIP expression in stromal cells in prostate cancer development.

Materials and Methods: We examined c-FLIP expression in 53 androgen dependent and 21 androgen independent prostate cancer stromal cells by immunohistochemical analysis. The effects of c-FLIP over expression in stromal cells on the growth and invasion of LNCaP and PC3 prostate cancer cells were determined in indirect coculture systems.

Results: At the androgen dependent stage the stromal c-FLIP level was increased in prostate cancer tissue. The expression level of stromal c-FLIP was associated with tumor differentiation.

The study utilised a double-blind, placebo-controlled, between-group design in which 40 (24 female) healthy adults (M age = 22.0 years, SE = 0.7) were tested following placebo or sertraline for an average of 24 days. The LDAEP was assessed 6 h post-final dose, and

changes in the slope of amplitude of the N1/P2 across intensities (60, 70, 80, 90, 100 dB) were examined at Cz.

The sertraline group had a significantly smaller LDAEP than the placebo group [F(1,38) = 5.97, p = 0.02]. Drug plasma levels did not correlate with the LDAEP in the sertraline learn more group, and there was no influence of 5-HTTLPR genotype.

We show for the first time that chronically modulating serotonin neurotransmission alters the LDAEP in healthy adults, consistent with extant literature indicating a moderating role of serotonin on this neurophysiological biomarker. The findings from this study together with previous studies suggest that the LDAEP may be a more sensitive DihydrotestosteroneDHT research buy marker of long-term or chronic rather than acute changes in the serotonin system.”
“Background Violent off ending by veterans of the Iraq and Afghanistan conflicts is a cause for concern and there is much public debate about the proportion of ex-military personnel in the criminal justice system for violent offences.

Although the psychological effects of conflict are well documented, the potential legacy of violent off ending has yet to be ascertained. We describe our use of criminal records to investigate the effect of deployment, combat, and post-deployment mental health problems on violent off ending among military personnel relative to pre-existing risk factors.

Methods In this cohort study, we linked data from 13 856 randomly selected, serving and ex-serving selleck inhibitor UK military personnel with national criminal records stored on the Ministry of Justice Police National Computer database. We describe off ending during the lifetime of the participants and assess the risk factors for violent off ending.

Findings 2139 (weighted 17.0%) of 12 359 male UK military personnel had a criminal record for any offence during their

lifetime. Violent off enders (1369 [11.0%]) were the most prevalent off ender types; prevalence was highest in men aged 30 years or younger (521 [20.6%] of 2728) and fell with age (164 [4.7%] of 3027 at age >45 years). Deployment was not independently associated with increased risk of violent off ending, but serving in a combat role conferred an additional risk, even after adjustment for confounders (violent off ending in 137 [6.3%] of 2178 men deployed in a combat role vs 140 (2.4%) of 5797 deployed in a non-combat role; adjusted hazard ratio 1.53, 95% CI 1.15-2.03; p=0.003). Increased exposure to traumatic events during deployment also increased risk of violent off ending (violent off ending in 104 [4.1%] of 2753 men with exposure to two to four traumatic events vs 56 [1.

Neuronal ARS-1620 ic50 activity in posterior cingulate cortex – a key node in the default network – is known to vary with learning, memory, reward and task engagement. We propose that these modulations reflect the underlying process of change detection and motivate subsequent shifts in behavior.”
“Purpose: We designed and fully evaluated the performance of a nomogram to identify patients with prostate cancer who may be suitable for active surveillance.

Materials and Methods: We developed a nomogram to predict the probability of minimal

prostate cancer (total tumor volume less than 0.5 cc, organ confined disease and no Gleason pattern 4 or 5) using preoperative data on 2,525 Australian patients who underwent radical prostatectomy. Accuracy and error rates at multiple probability cutoffs were compared with those of contemporary Epstein criteria and the Prostate Cancer Research International: Active Surveillance trial inclusion criteria when applied to these patients. High risk disease was defined as 1 or more adverse CB-839 characteristics (including positive surgical margins, seminal vesicle invasion, extracapsular extension, 50% or greater Gleason pattern 4/5 and/or tumor volume 4.0 cc or greater) at radical prostatectomy.

Results: Minimal cancer was confirmed in 152 men (6.0%) at prostatectomy. The bootstrap corrected predictive accuracy of our nomogram was 93.3% vs 89.1% and 91.0% for Prostate Cancer Research International: Active

Surveillance and Epstein criteria, respectively. For men with a nomogram derived minimal cancer probability of 0% to 4.9%, 5.0% to 19.9%, 20.0% to 34.9%, 35.0% to 49.9% and 50.0% to 71.0% the rate of high risk disease was 70.8%, 37.8%, 22.4%, 9.0% and 3.8%, respectively. In contrast, the rate of high risk disease for men who met Prostate Cancer Research International: Active Surveillance and Epstein criteria were 17.1% and 13.9%, respectively.

Conclusions: A detailed breakdown of the expected rates of false-positive results and high risk disease associated

with the nomogram derived probability of minimal cancer would provide more MTMR9 complete information to clinicians and patients on which to base therapeutic clinical decisions for presumed early stage prostate cancer.”
“Purpose: Previous studies have revealed inconsistent findings regarding the association between the glyoxalase 1 protein (GL01) gene and autism. This study aimed to replicate the genetic association of the C419A of the GL01 gene with autism and to perform mutation screening of all the exons of the GL01 gene in a sample of Han Chinese patients with autism from Taiwan.

Methods: The sample included 272 patients with autism and 310 healthy controls. All the exons and the promoter region of the GL01 gene were PCR-amplified and sequenced for mutation screening and genotyping.

Results: We did not find significant differences of allelic and genotypic frequency distributions of C419A between the autism and control groups.

It fuses two genes encoding histone acetyltransferases (HATs), MYST3 located at 8p11 to CREBBP located at 16p13. Variant translocations involve other HAT-encoding genes such as EP300, MYST4, NCOA2 or NCOA3.

MYST3-linked acute myeloid leukemias GW786034 (AMLs) share specific clinical and biological features and a poor prognosis. Because of its rarity, the molecular biology of MYST3-linked AMLs remains poorly understood. We have established the genome and gene expression profiles of a multicentric series of 61 M4/M5 AMLs including 18 MYST3-linked AMLs by using array comparative genome hybridization (aCGH) (n = 52) and DNA microarrays (n = 44), respectively. We show that M4/5 AMLs have a variety of rare genomic alterations. One alteration, a gain of the MYB locus, was found recurrently and only in the MYST3-linked AMLs (7/18 vs 0/34). MYST3-AMLs have also a specific a gene expression profile, which includes overexpression of MYB, CD4 and HOXA genes. These features, reminiscent of T-cell acute lymphoid leukemia (ALL), suggest the

targeting of a common T-myeloid progenitor.”
“Responses to focal cerebral ischemia by neurons and adjacent microvessels are rapid, simultaneous, and topographically related. Recent observations indicate the simultaneous appearance of proteases by components of click here nearby microvessels that are also expressed by neurons in the ischemic territory, implying that the events could be coordinated. The structural relationship of neurons to their microvascular supply, the direct functional participation of glial cells, and the observation of a highly ordered microvessel-neuron response to ischemia suggest that these elements are arranged in and behave in a unitary fashion, the neurovascular unit. Their roles as a unit in the stimulation of cellular Epoxomicin inflammation and the generation of inflammatory mediators during focal cerebral ischemia have not been explored yet. However, components of the neurovascular unit both generate and

respond to these influences under the conditions of ischemia. Here we briefly explore the potential inter-relationships of the components of the neurovascular unit with respect to their potential roles in ischemia-induced inflammatory responses. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Transient leukemia (TL) has been observed in approximately 10% of newborn infants with Down syndrome (DS). Although treatment with cytarabine is effective in high-risk TL cases, approximately 20% of severe patients still suffer early death. In this study, we demonstrate abundant KIT expression in all 13 patients with GATA1 mutations, although no significant difference in expression levels was observed between TL and acute myeloid leukemia.

In a phase 1 clinical trial, we assessed the safety and pharmacokinetics of GDC-0449, a small-molecule inhibitor of SMO, and responses of metastatic or locally advanced basal-cell SCH772984 carcinoma to the drug.

Methods: We selected 33 patients with metastatic or locally advanced basal-cell carcinoma to receive oral GDC-0449 at one of three doses; 17 patients received 150

mg per day, 15 patients received 270 mg per day, and 1 patient received 540 mg per day. We assessed tumor responses with the use of Response Evaluation Criteria in Solid Tumors (RECIST), physical examination, or both. Molecular aspects of the tumors were examined.

Results: The median duration of the study treatment was 9.8 months. Of the 33 patients, 18 had an objective response to GDC-0449, according to assessment on imaging (7 patients), physical examination (10 patients), or both (1 patient). Of the patients who had a response, 2 had a complete response and 16 had a partial response. The other 15 patients had either stable

disease (11 patients) or progressive disease (4 patients). Eight grade 3 adverse events that were deemed to be possibly related to the study drug were reported in six patients, including four with fatigue, two with hyponatremia, one with muscle spasm, and one with atrial fibrillation. One grade 4 event, asymptomatic hyponatremia, was judged to be unrelated to GDC-0449. One patient withdrew from the study because click here of adverse events. We found evidence of hedgehog signaling in tumors LY411575 that responded to the treatment.

Conclusions: GDC-0449, an orally active small molecule that targets the hedgehog pathway, appears to have antitumor activity in locally advanced or metastatic basal-cell carcinoma. (ClinicalTrials.gov number, NCT00607724.)

N Engl J Med 2009;361:1164-72.”
“Angiotensin-(1-7), an active fragment of both angiotensins I and II, generally opposes the vascular and proliferative actions of angiotensin II. Here we evaluated effects of the angiotensin-(1-7) receptor Mas on renal physiology and

morphology using Mas-knockout mice. Compared to the wild-type animals, Mas knockout mice had significant reductions in urine volume and fractional sodium excretion without any significant change in free-water clearance. A significantly higher inulin clearance and microalbuminuria concomitant with a reduced renal blood flow suggest that glomerular hyperfiltration occurs in the knockout mice. Histological analysis found reduced glomerular tuft diameter and increased expression of collagen IV and fibronectin in the both the mesangium and interstitium, along with increased collagen III in the interstitium. These fibrogenic changes and the renal dysfunction of the knockout mice were associated with an upregulation of angiotensin II AT1 receptor and transforming growth factor-beta mRNA.

Regional WMH was measured using an MRI brain imaging segmentation pipeline and WM tract-based parcellation atlas.

Sixty-two (64%) of the participants were incontinent, mostly with urgency (37; 60%) and moderate-severe symptoms (36; 58%). Incontinent individuals were more likely to be

women with worse scores for depression and mobility. WMH located in right inferior frontal regions predicted UI severity, with no significant relationship with incontinence, incontinence type, bother, or functional impact. As regards WM tracts, WMH within regions normally occupied by the anterior Selleckchem Luminespib corona radiata predicted severity and degree of bother, cingulate gyrus predicted incontinence and severity, whereas cingulate (hippocampal portion) and superior fronto-occipital fasciculus predicted severity.

Presence of WMH in right inferior frontal regions

and selected WM tracts predicts incontinence, incontinence severity, and degree of bother. Our observations support the findings of recent functional MRI studies indicating a critical role for the cingulum in bladder control, while also suggesting potential involvement of other nearby WM tracts such as anterior corona radiata and superior fronto-occipital fasciculus.”
“Age-related depletion of androgens in men results in functional LY2835219 chemical structure impairments in androgen-responsive tissues, such as the brain, resulting in increased risk for Alzheimer’s disease. learn more To investigate the relationship between normal age-related hormone loss and Alzheimer’s disease risk, we evaluated the brain and serum levels of androgens and estrogen in aging male rats. We observed that increasing age was associated with a significant reduction in brain levels of the potent androgen dihydrotestosterone and a trend toward decreased testosterone. Brain levels of soluble beta-amyloid were observed to increase with age. Collectively, these findings highlight differences

in brain and circulating levels of androgens during aging, and identify an inverse correlation with beta-amyloid levels that may be relevant to Alzheimer’s disease risk. NeuroReport 20:1534-1537 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“The objective of this study was to assess the relation between serum levels of retinol and other antioxidants and hearing impairment in Japanese older adults.

This is a community-based cross-sectional study comprising 762 residents aged 65 years or older in Kurabuchi, Gumma, Japan. We measured serum retinol and other antioxidants (alpha- and gamma-tocopherols, and carotenoids including beta-cryptoxanthin, alpha- and beta-carotenes, lycopene, and lutein plus zeaxanthin) by high-performance liquid chromatography and divided each measurement into quartiles. Hearing impairment was defined as a failure to hear a 30-dB hearing level (HL) signal at 1 kHz and a 40-dB HL signal at 4 kHz in the better ear in pure-tone audiometric tests.