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Acoustic overexposure can cause a permanent loss of auditory nerve fibers without destroying cochlear sensory cells, despite complete recovery of cochlear thresholds (Kujawa and Liberman 2009), as measured by gross neural potentials such as the auditory brainstem response (ABR). To address this nominal paradox, we recorded responses from single auditory nerve fibers in guinea pigs exposed to this type of neuropathic noise (4- to 8-kHz octave band at 106 dB SPL for 2 h). Two weeks postexposure, ABR thresholds had recovered to normal, while suprathreshold ABR amplitudes were reduced. Both thresholds and amplitudes of distortion-product otoacoustic emissions fully recovered, suggesting recovery of hair cell function. Loss of up to 30% of auditory-nerve synapses on inner hair cells was confirmed by confocal analysis of the cochlear sensory epithelium immunostained for pre- and postsynaptic markers. In single fiber recordings, at 2 wk postexposure, frequency tuning, dynamic range, postonset adaptation, first-spike latency and its variance, and other basic properties of auditory nerve response were all completely normal in the remaining fibers. The only physiological abnormality was a change in population statistics suggesting a selective loss of fibers with low- and medium-spontaneous rates. Selective loss of these high-threshold fibers would explain how ABR thresholds can recover despite such significant noise-induced neuropathy. A selective loss of high-threshold fibers may contribute to the problems of hearing in noisy environments that characterize the aging auditory system.
- noise-induced hearing loss
- auditory nerve
auditory nerve (an) fibers transmit signals from cochlear inner hair cells (IHCs) to their brainstem targets in the cochlear nucleus. Each AN fiber receives signals from a single IHC via a single ribbon synapse (Liberman 1980; Spoendlin 1969), but each hair cell is contacted by 10–30 AN fibers depending on cochlear location and species (Bohne et al. 1982; Liberman et al. 1990; Stamataki et al. 2006). This multiple innervation is important in auditory processing, because the AN fibers contacting a single hair cell differ in spontaneous discharge rate (SR) and threshold to acoustic stimulation (Liberman 1978). The SR distribution recorded among AN fibers is fundamentally bimodal, and the low-SR (<20 sp/s) group has higher thresholds than the high-SR (>20 sp/s) group (Liberman 1978). In addition to increasing the dynamic range of the auditory periphery, the high-threshold, low-SR fibers are important for hearing in a noisy environment, by virtue of their resistance to masking by continuous background noise (Costalupes et al. 1984).
Recent work in both mouse (Kujawa and Liberman 2009) and guinea pig (Lin et al. 2011) has shown that acoustic overexposures causing reversible threshold elevations can lead to irreversible degeneration of AN fibers. The loss of hair cell synapses and AN peripheral terminals is rapid (within hours postexposure), while the loss of the AN cell bodies in the spiral ganglion is slow (months to years). The idea that cochlear neural degeneration could be a primary event, rather than only occurring secondarily to the loss of hair cells, was surprising but not paradoxical. The idea that roughly 40% of the AN cochlear synapses could be permanently destroyed without a permanent elevation of the thresholds for the auditory brainstem response, which reflects the summed activity of the AN fibers in its first wave (Melcher et al. 1996), could be explained by hypothesizing that the neural loss was selective for the subgroup of AN fibers with low SRs and high thresholds. This hypothesis was supported by the observed reduction in auditory brainstem response (ABR) wave 1 amplitudes at suprathreshold stimulus levels (Kujawa and Liberman 2009).
The aim of the present study was to directly test this hypothesis by recording from populations of AN fibers animals exposed to a noise designed to produce cochlear neuropathy without permanent threshold shift. We chose the guinea pig, because its larger size makes it easier to record from large populations of single AN fibers. We found that the surviving fibers in these noise-exposed ears show responses that are normal in all respects except that the proportion of fibers with low SR is significantly smaller than in unexposed ears. We speculate that this selective low-SR neuropathy contributes to the difficulties of hearing in noisy environments that constitute the classic audiometric deficit in the aging ear.
MATERIALS AND METHODS
Animals and groups.
Female, albino guinea pigs (Hartley strain) were used in all experiments. All procedures were approved by the Institutional Animal Care and Use Committee at the Massachusetts Eye and Ear Infirmary. Animals entered the protocol at 1 mo of age (∼250 g), when cochlear thresholds were tested by measurement of ABRs and distortion product otoacoustic emissions (DPOAEs). At least 2 days after recovery from the sedation required for this test, nine animals were sound exposed (4- to 8-kHz octave-band noise at 106 dB SPL for 2 h) and allowed to recover. The other 14 animals served as nonexposed controls. Control and exposed animals were caged together throughout the experimental protocol. Two weeks after exposure, ABRs and DPOAEs were remeasured, and single-fiber data were collected from the cochlear nerve. At the end of the terminal experiment, the cochleas were extracted, and tissue was proceessed for confocal microscopy.
ABR and DPOAE measures.
ABR and DPOAE responses were measured in an acoustically and electrically shielded chamber, heated to 30°C. Animals were anesthetized with a mixture of pentobarbital (25 mg/kg ip), fentanyl (0.15 mg/kg im), and droperidol (7.5 mg/kg im). Acoustic stimuli were delivered via a custom acoustic assembly comprising two earphones to deliver sound and an electret condenser microphone (Knowles FG-23329-P07) coupled to a probe tube to measure sound pressure level. For ABRs, needle electrodes were placed near the ear canal at its caudoventral aspect, the vertex of the skull, and a ground at the lower back. Stimuli were 4-ms tone pips, with a 0.5-ms rise/fall delivered at 30/s. Stimulus polarity was alternated to allow removal of microphonic potentials. Responses were averaged to 512 tone-pip pairs. Tone-pip frequency was varied from 2.8 to 45.2 kHz in half-octave steps, and stimulus level was varied from 10 to 80 dB SPL in 5-dB steps. ABR threshold was measured, by visual inspection of stacked waveforms, as the lowest SPL at which any ABR wave was visible, which was typically 5 dB less than the lowest level at which the peak-to-peak amplitude of the waveform emerged from the noise floor. DPOAEs were measured in response to two pure tones (f2 and f1 with f2/f1 = 1.2 and with a 10-dB level difference such that f1 = f2 + 10 dB). DPOAE response was measured as the amplitude of the 2f1-f2 peak extracted from a Fourier transform of the averaged probe tube microphone response. Both waveform and spectral averaging were used. DPOAE threshold was defined as the interpolated primary level (of f2) required to produce a DPOAE of 0 dB SPL.
Animals were anesthetized with a combination of urethane (900 mg/kg ip), fentanyl (0.15 mg/kg im), and droperidol (7.5 mg/kg im). Once a surgical plane of anesthesia was reached, ear canals were severed, and muscle tissue was removed from the bulla and the back of the skull. The bulla was opened, and a silver wire was placed close to the round window to monitor the compound action potential (CAP). The occipital bone was opened, the dura was resected, and the cerebellar lobes on one side were aspirated to expose the cochlear nucleus, which, when displaced medially and rostrally, revealed the auditory nerve trunk as it exits the internal auditory meatus. CAPs evoked by tone pips were monitored regularly, and the experiment was terminated if thresholds shifted by >10 dB. Single-fiber responses were recorded using glass micropipettes, filled with 2 M KCl, with impedances between 10 and 30 MΩ. Electrodes were advanced remotely, while presenting a broadband noise burst (70–80 dB SPL) as a search stimulus. Spikes were amplified using a low-noise, battery-powered amplifier (Ithaco Model 1201), and spike times were digitized with custom hardware and passed to the computer for analysis. Once a neuron was isolated, the SR was measured over a 30-s sample. Acoustic stimuli were always 50-ms tone bursts with a 2.5-ms rise-fall time, presented at 10/s. The tuning curves were measured with an algorithm designed to track the isorate contour (10 spikes/s > SR). To analyze postonset adaptation, poststimulus-time histograms were recorded in response to 200 tone-burst presentations at 30 dB above threshold at the characteristic frequency (CF). To assess dynamic range, rate vs. level functions were recorded using tone bursts at CF over a range of stimulus levels (0–80 dB SPL, 50 presentations per level, presented in random level order). Rate-level functions were fit using a model published previously (Taberner and Liberman 2005). Dynamic range was defined as the difference in stimulus SPL required to drive the neurons from 10% to 90% of the maximum discharge rate.
At the end of the single-fiber experiment, animals were perfused intracardially with 4% paraformaldehyde. After perfusion, cochleas were removed, the round and oval windows were opened, and cochleas were postfixed: either overnight at 4°C, or for 1 h at room temperature if anti-GluA2 was one of the immunostains. Cochleae were then decalcified for 3 wk in EDTA (120 mM, pH 7.0) at room temperature. The organ of Corti was then microdissected into 11 pieces and immunostained. When quantitative data were to be extracted, cochleas were processed in pairs, with control and exposed ears treated with the same solutions on the same days. Tissue was permeabilized in 30% sucrose for 20 min, blocked for 1 h in 5% NHS with 1% Triton, then incubated overnight at 37°C in primary antibodies. Primary antibodies included mouse anti-CtBP2 (1:50, BD Transduction Labs, #612044), goat anti-Na/K ATPase (1:100, Santa Cruz, #sc-16052), rabbit anti-myosinVIIa (1:100, Proteus BioSciences, #25-6790), and mouse (IgG2a) anti-GluA2 (1:1,000, Millipore, #MAB397). Tissue was rinsed in PBS and then incubated for 1 h at 37°C in a two-step process of secondary antibody linkage: step 1: biotinylated donkey anti-mouse (1:200, Jackson ImmunoResearch, #7115-065-150), AlexaFluor488 chicken anti-goat (1:1,000, Invitrogen, #A21467), and donkey anti-rabbit-AF647 (1:200, Invitrogen, #A31573); step 2: streptavidin-conjugated AlexaFluor568 (1:1,000, Invitrogen, #S11226), AlexaFluor488 goat anti-chicken (1:1,000, Invitrogen, #A11039), and donkey anti-rabbit-AF647 (1:200, Invitrogen, #A31573).
Microscopy and image analysis.
A cochlear frequency map for each case was produced using a custom plug-in to ImageJ (http://www.masseyeandear.org/research/ent/eaton-peabody/epl-histology-resources/) with which the user traces the inner spiral bundle in each dissected piece, and the plug-in measures position along the spiral and applies a physiological place-frequency map (Tsuji and Liberman 1997) to overlay frequencies onto the montaged cochlear pieces. With this “road map” as a guide, IHC synaptic zones were imaged in each case at eight log-spaced frequency locations (0.5, 1, 2, 4, 8, 16, 32, and 45 kHz) on a Leica SP2. Confocal z-stacks (0.25-mm vertical spacing) were acquired with a ×100 oil-immersion objective (N.A. 1.4) and ×2 digital zoom. Each stack encompassed ∼8 IHCs.
Stacks were analyzed offline using Amira (Visage Imaging). For each stack, presynaptic ribbons and postsynaptic glutamate receptor patches were counted, and their volumes estimated, using the “connected components” tool in Amira. This tool takes a user-specified pixel-intensity criterion and identifies all the voxel spaces within which all the pixels exceed the criterion intensity. By displaying each of these connected components as a surface contour superimposed on the maximum projection, the user can determine if the selected criterion captures the elements of interest, e.g., synaptic ribbons. For those cochleas from which three-dimensional volumes of synaptic elements were extracted, image stacks from control and noise-exposed ears were acquired with the same laser and photomultiplier gains, and the same pixel-intensity criterion was applied. The Amira output provides each element's xyz coordinates and volume. Further analysis of the Amira output was carried out in MATLAB (Mathworks) and with a custom C program that generates high-power thumbnail images of the native z-stack, each centered at the xyz positions captured in Amira (Liberman et al. 2011). These thumbnails allowed for easy identification of orphan ribbons or receptor patches.
Noise-induced neuropathy after reversible threshold shift.
In guinea pig, exposure to an octave-band noise (4–8 kHz) at 106 dB for 2 h results in an acute threshold shift of 40–50 dB, when measured within 12–24 h postexposure, but these thresholds recover completely within 1–2 wk (Lin et al. 2011). Prior study showed that when cochlear function is assessed via DPOAEs, both threshold and suprathreshold responses recover completely. Since DPOAEs require only the “presynaptic” component of the cochlear sensory epithelium, i.e., an intact population of outer hair cells to create distortions in the process of mechanoelectric transduction and reverse-transduce these distortions back to mechanical motions and (ultimately) ear-canal sound pressures, the DPOAE recovery suggests full recovery of cochlear hair cell function. In contrast, the summed neural response, particularly wave 1 of the ABR constituting the summed responses of AN fibers, fails to recover at suprathreshold sound pressure levels, suggesting a partial degeneration of the AN (Kujawa and Liberman 2009).
Here, we replicated this neuropathic exposure in animals prior to recording from populations of single AN fibers. Two weeks after exposure to the 4- to 8-kHz octave band at 106 dB for 2 h, the ABR and DPOAE thresholds have recovered almost completely to the preexposure levels measured from the same ears (Fig. 1, A and B). Thresholds for the compound action potential (the summed AN response recorded from the cochlear capsule) were also similar in control and exposed ears (data not shown). Evaluation of suprathreshold responses suggested the presence of permanent neural damage: although the amplitude-vs.-level functions for the DPOAE responses recovered completely (Fig. 1D), the summed activity of the AN, seen as wave 1 of the ABR, showed a permanent deficit, i.e., a roughly 40% reduction in suprathreshold amplitudes (Fig. 1C).
The presence of primary neural degeneration (i.e., in the absence of hair cell loss) was confirmed by histological analysis of the cochleas after completion of the single-fiber studies. As schematized in Fig. 2D, the synapses on each inner hair cell are visualized by combining an immunolabel for the presynaptic ribbon within the hair cell (anti-CtBP2) and another for the postsynaptic glutamate receptor patch on the AN terminal (anti-GluA2). In a normal ear (Fig. 2A), synapses appear as pairs of puncta: a CtBP2-positive patch and a closely apposed GluA2-positive patch. The synapses are distributed around the basolateral membrane of the inner hair cell in the subnuclear zone, as clearly seen in the z-stack “side view” shown in Fig. 2Ayz. In the exposed ear (Fig. 2B), the number of synapses is reduced (Fig. 2Bxy) and the distribution around the basolateral membrane appears less tightly clustered (Fig. 2Byz). High-power thumbnails of the synapses (Fig. 2C) reveal that in the exposed ear, some of the ribbons are no longer paired with postsynaptic receptor patches.
Quantitative synaptic analysis from a large sample of exposed and control cochleas (Fig. 3A) shows a reduction in synaptic counts for all cochlear regions in the basal half of the cochlea (frequencies ≥ 4 kHz). The intergroup differences were highly significant (P ⪡ 0.01 by 2-way ANOVA). The normalized data (Fig. 3B) show that the fractional synaptic reduction increases steadily towards the base with a maximum loss of close to 30% at 32 kHz. The high-power analysis (Fig. 3C) reveals that 1) in both normal and noise-exposed ears, more than 95% of all ribbons are paired with glutamate receptor patches (i.e., likely represent true synapses), and 2) there is a modest increase in the number of “orphan” ribbons (i.e., without paired receptor patches) in the basal turn of the exposed ears.
Responses of single AN fibers after reversible threshold shift.
The frequency tuning of AN fibers is dominated by cochlear mechanics, which, in turn, is shaped, at low sound pressure levels, by the cochlear amplification provided by the electromechanical motors of the outer hair cell (Cheatham et al. 2004). Given the complete postexposure recovery of DPOAEs (Fig. 3), and the implied recovery of outer hair cell function, no postrecovery changes in AN frequency tuning were expected in the exposed ears. Indeed, frequency tuning curves of single ANs measured in exposed ears were similar to those in unexposed controls, as illustrated in Fig. 4A, in which representative pre- and postexposure curves are paired by matching the CF, which also pinpoints the location of each fiber's hair cell synapse along the cochlear spiral (Liberman 1982a).
One commonly used metric of AN tuning is the “quality factor,” or Q, defined as the CF divided by the bandwidth, typically measured 10 dB above the minimum threshold (Kiang et al. 1965). As shown by comparing the data in Figs. 4, B and C, the distributions of Q10 in exposed vs. unexposed groups were not significantly different: after separating by SR [low-SR <1 sp/s, high-SR >20 sp/sec, with medium-SR in between (Tsuji and Liberman 1997)] and by CF (low CF ≤4 kHz; high CF >4 kHz), none of the exposed vs. unexposed differences was significant by the Kolmogorov-Smirnov test (P > 0.05).
Given the near-complete postexposure recovery of ABR thresholds (Fig. 1A), we expected near-complete recovery of AN thresholds, certainly for the low-threshold, fiber population with high SRs. Indeed, the high-SR fibers in the exposed ears (Fig. 4D) showed mean thresholds similar to those seen in high-SR fibers in the unexposed ear (Fig. 4D): the two groups were statistically indistinguishable (P > 0.01 by Kolmogorov-Smirnov). The mean thresholds of the medium-SR groups were slightly higher in the postexposure group for CFs >4 kHz. However, the differences were not significant (P > 0.05 by Kolmogorov-Smirnov). The effect of the exposure on low-SR thresholds is more difficult to gauge, because the prevalence of low-SR fibers in the postexposure sample appears to be significantly reduced, especially for CF regions at and above the exposure band (Fig. 4C).
A disproportionate loss of low-SR fibers is borne out by the statistical analysis summarized in Fig. 5: out of a total sample of 367 fibers from 14 control animals, and 382 fibers from 9 exposed animals, the proportion of fibers with SR <20 sp/s was reduced at high CF (>4 kHz), where noise-induced loss of synapses was observed (Fig. 3, A and B). For CF >4 kHz, low- and medium-SR fibers comprised 47% of the total population in control ears vs. 29% in the exposed ears, a fractional loss of 38% and a highly significant difference between the control and exposed distributions (Kolmogorov-Smirnov, P ⪡ 0.01). In contrast, in the apical half of the cochlea (CF ≤4 kHz), where noise-exposure effects on synaptic counts were minimal (Fig. 3, A and B), the distribution of SRs postexposure was similar to that seen in unexposed controls, and the differences between distributions were not statistically significant (P > 0.05 by Kolmogorov-Smirnov).
To look for signs of synaptic dysfunction in remaining AN fibers of all SR groups, we evaluated several additional aspects of AN response that are shaped, at least in part, by the process of synaptic transmission.
The first of these was dynamic range. For most AN fibers, there is a relatively small range of stimulus levels between that eliciting a just detectable response (threshold) and that evoking a maximum (saturated) rate. In guinea pigs, dynamic range is typically <30 dB for high-SR fibers and can be as large as 60 dB for low-SR fibers, with little dependence on CF (Winter et al. 1990). Indeed, our rate-level functions underestimate the dynamic range of some low-SR fibers, because discharge rate is often still growing at the highest levels routinely presented (80 dB SPL: see Fig. 6 inset). As shown in Fig. 6, we saw no significant effect of the noise exposure on the measured dynamic ranges, and the differences between distributions, after separating by SR and CF, were not statistically significant (P > 0.05 by Kolmogorov-Smirnov).
The second set of postsynaptic response features evaluated was the time constants of postonset adaptation, thought to represent the depletion of different pools of synaptic vesicles (Neef et al. 2007). In response to tone bursts, the poststimulus-time histograms of AN fibers show a prominent onset response followed by a decreasing response probability that approaches a lower steady-state rate with a decay function that is well fit as the sum of two exponentials (Westerman and Smith 1984). In the normal mouse AN, those time constants average roughly 1 and 10 ms (Fig. 7, A and C). No significant changes in the time constants of postonset adaptation were observed postexposure (Fig. 7, B and D). Intergroup differences, after segregating by SR and by CF, were not significant (P > 0.05 by Kolmogorov-Smirnov).
The last response features we evaluated were the first-spike latency (Fig. 7, E and F) and the variance of the first-spike latency (Fig. 7, G and H). In response to tone bursts, the latency of the first spike increases with decreasing CF largely because of the slowing of the cochlear traveling wave as it progresses from base to apex (Kiang et al. 1965). More relevant to synaptic processes is the variance of the first spike latency, which is greatly increased, in mice, by a mutation affecting the coupling of the synaptic ribbon to the presynaptic active zone (Buran et al. 2010). Neither the first-spike latency, nor the variance of the first-spike latency, was affected by the noise exposure. Intergroup differences, after segregating by SR and CF, were not significant (P > 0.05 by Kolmogorov-Smirnov).
Modiolar/pillar gradients in hair cell synaptic morphology after reversible threshold shift.
Single-fiber labeling studies have shown that AN fibers are spatially segregated around the inner hair cell circumference according to SR group (Liberman 1982b). As schematized in Fig. 2D, high-SR fibers tend to contact the side of the hair cell closer to the pillar cells while the low- and medium-SR fibers tend to contact the side closer to the cochlear nerve trunk (modiolus). Furthermore, the presynaptic ribbons at low-SR synapses tend to be larger and more complex than those at high-SR synapses (Liberman et al. 1990; Merchan-Perez and Liberman 1996). This normal modiolar/pillar gradient in ribbon size, first described in cat, is visible in data from the unexposed guinea pigs in the present study, as shown in Fig. 8 for cochlear regions tuned to 2 kHz (Fig. 8, A and G), 16 kHz (Fig. 8, C and H), and 32 kHz (Fig. 8, E and I).
Given the disproportionate loss of low- and medium-SR fibers noted in the physiological analysis (Fig. 5), we might have expected a trend towards smaller ribbons on the modiolar side of the hair cell. Surprisingly, the data suggest the opposite, i.e., an increase in the ribbon size on the pillar side of the hair cell, especially in the high-CF cochlear regions (Fig. 8, H and I) where the neuropathy was most pronounced (Fig. 3, A and B), and a trend towards smaller ribbons on the modiolar side in the most apical region (Fig. 8G). We also observed a general disorganization of the synaptic zones, with more synapses distributed relatively farther from the basal pole of the hair cell (Fig. 8, B, D, F), as noted in reference to the representative confocal images reproduced in Fig. 2 (A vs. B).
Effects of noise on low- vs. high-SR fiber neurophysiology.
The observations that AN fibers differ in threshold sensitivity, and that threshold is closely correlated with SR, were first described in cat (Liberman 1978), but the same relations have since been described in guinea pig (Tsuji and Liberman 1997), gerbil (Schmiedt 1989), mouse (Taberner and Liberman 2005), and rabbit (Borg et al. 1988), suggesting the low- vs. high-SR distinction represents a general mammalian plan for the auditory periphery. In cat and guinea pig, the distributions of spontaneous rate are fundamentally bimodal, suggesting that there are (at least) two very different groups of fibers rather than a continuum (Liberman and Kiang 1978; Tsuji and Liberman 1997).
The striking differences in central projections of low- vs. high-SR fibers (Liberman 1991) reinforce the notion that these neuronal groups play different roles in auditory processing. Clearly, connecting the sensory cells to the brain via fibers with a range of sensitivities must be important in extending the dynamic range of the auditory periphery. Perhaps more importantly, low-SR fibers, by virtue of their higher thresholds, are more resistant to masking by continuous background noise (Costalupes et al. 1984). Thus, to a certain extent, we must hear with our high-SR fibers in quiet backgrounds, but rely increasingly on the low-SR population as background noise increases. It has also been suggested that low-SR fibers are particularly important in driving the sound-driven reflexes to the auditory periphery, the middle-ear muscle reflex, and the medial olivocochlear bundle (Liberman 1988).
Suggestions that low-SR fibers are more vulnerable to cochlear insult have appeared in prior neurophysiological studies of acoustic trauma (Liberman 1978) and aging (Schmiedt et al. 1996). In an early study of alterations in AN response associated with noise-induced cochlear damage (Liberman 1978), some exposed ears showed a relative paucity of low-SR units, and a later study of aging gerbils (Schmiedt et al. 1996) noted a reduction in the proportion of low-SR fibers among AN fibers sampled. However, in both studies, there was a general elevation of cochlear thresholds: thus the lack of low-SR fibers could have arisen not because they had disappeared, but because they were bypassed when their thresholds rose above the level of the search stimulus used to identify neuronal contact when advancing the electrode.
Prior study in both mouse (Kujawa and Liberman 2009) and guinea pig (Lin et al. 2011) has shown that acoustic overexposures causing significant, but ultimately reversible, cochlear threshold elevations can lead to significant loss of cochlear nerve fibers. This neural degeneration is seen first, i.e., within 24 h, as a loss of synapses on the IHCs throughout the basal half of the cochlea, and much more slowly, i.e., in months to years, as a loss of spiral ganglion cells and their central projections (Kujawa and Liberman 2009; Lin et al. 2011). The similarity of postexposure thresholds in DPOAEs and ABRs suggested that temporary threshold shifts are due predominately to reversible damage to the cochlear amplifier, i.e., the outer hair cells. Indeed, full recovery of hair cells was confirmed histologically. Two observations suggested that noise-induced primary neural degeneration might be selective for low-SR fibers: 1) the neuronal loss was roughly 40%, which is comparable to the proportion of low-SR fibers in an unbiased sample of cochlear neurons (Liberman 1978; Tsuji and Liberman 1997), and 2) a selective loss of high-threshold fibers would provide a natural explanation for the full recovery of ABR thresholds and the persistence of suprathreshold amplitude decreases.
The present results (Fig. 5) provide strong support for the idea that noise-induced synaptopathy is selective for the low-SR fiber group. However, given the nature of the experimental approach, it is impossible to rule out the possibility that SR of individual fibers is changed by the acoustic overexposure. Indeed, studies of acoustic trauma that produce permanent noise-induced threshold shifts have suggested that IHC stereocilia loss, which commonly underlies these irreversible changes, reduces the SR of all fibers, presumably because the loss of transduction channels decreases the resting current through the hair bundles, which in turn slightly hyperpolarizes the IHC and decreases spontaneous vesicle release (Liberman and Dodds 1984). In the presence of stereocilia damage, ANF SRs are never greater than ∼40 sp/s (Liberman and Dodds 1984), rather than the 150 sp/s maximum seen in the present study. Thus, the simplest interpretation of the data in Fig. 5 is that SRs of the surviving fibers are unchanged.
Regardless of whether this simple interpretation is correct, the present study also shows that the noise exposure has caused a loss of fibers with high thresholds and large dynamic ranges (Figs. 4 and 6B). Regardless of what their preexposure SR was, this loss should decrease the information content in the auditory nerve, particularly in the presence of continuous background noise. This partial deafferentation may also be an important contributor to the generation of hyperactivity in the central auditory pathways that is commonly seen after acoustic overstimulation (e.g., Mulders et al. 2011). This, in turn, may be one source of tinnitus, the phantom auditory percept that is commonly associated with acoustic overexposure (Schmuzigert et al. 2006). Indeed, recent human studies have reported reductions in ABR wave 1 amplitude in tinnitus vs. non-tinnitus subjects with matching (normal) audiometric thresholds (Gu et al. 2012; Schaette and McAlpine 2011).
Effects of noise on low- vs. high-SR fiber morphology.
Prior studies of the normal cochlea, at the light- and electron-microscopic level and in both cat and guinea pig, have shown that, although both low- and high-SR fibers contact a single IHC via a single terminal bouton, low-SR terminals tend to be smaller in caliber and their synapses are usually found on the modiolar-facing side of the IHC basolateral membrane (Liberman 1982b; Tsuji and Liberman 1997). An ultrastructural study of labeled, physiologically identified, ANFs in cat revealed the additional counterintuitive fact that low-SR synapses are characterized by exceptionally large, and often multiple, presynaptic ribbons, whereas high-SR ribbons are small singlets (Merchan-Perez and Liberman 1996). A subsequent light-microscopic confocal study in mouse confirmed the ribbon size gradient (larger ribbons on the modiolar side) and suggested that an opposing gradient of glutamate receptor-patch size (smaller patches on the modiolar side) could contribute to the differences in neuronal sensitivity (Liberman et al. 2011). The present study confirms the ribbon size gradient in the normal guinea pig ear (Fig. 8); however, a clear-cut glutamate patch gradient was not observed. The significance of this discrepancy is not clear.
Prior studies of noise-induced neuropathy in the mouse and guinea pig relied mainly on counts of presynaptic ribbons to assess the changes in afferent innervation in the IHC area (Kujawa and Liberman 2009; Lin et al. 2011). However, in the guinea pig study, quantification of AN terminals was attempted by immunostaining for neurofilament and assessing the apposition of ribbons and terminals. In the normal ear, 20% of ribbons were not opposed by terminals, and in the noise-exposed ear that percentage rose to ∼40% (Lin et al. 2011). In the present study, using glutamate-receptor immunostaining to assess the postsynaptic elements, we saw a similar trend, i.e., that the numbers of orphan (unpaired) ribbons rises after noise exposure; however, the absolute numbers were 10× lower: i.e., 2% in control ears rising to ∼4% in exposed ears (Fig. 3). This discrepancy likely arises because neurofilaments do not always invade the terminal bouton, thus the apposition between pre- and postsynaptic immunostaining is not as reliably close as that seen with the glutamate receptor label. Serial section ultrastructural work shows that orphan ribbons are indeed very rare in the normal ear (Liberman 1980; Stamataki et al. 2006), thus we believe that the present results (showing 98% of normal ribbons paired with postsynaptic terminals) are more accurate than those seen with neurofilament immunostaining, which will overestimate the number of orphan ribbons. The relatively small number of orphan ribbons, even after noise exposure, further suggests that ribbon counts are a very good proxy for synaptic counts in this model system.
The synaptic changes observed in the present study were not those predicted from simply eliminating the low-SR elements (i.e., large ribbons on the modiolar side) from the normal synaptic architecture. Rather, there was an increase in mean ribbon size, these abnormally large ribbons were found on both sides of the IHC, and there was no obvious decrease in the proportion of modiolar vs. pillar ribbons (Fig. 8). These observations suggest that ribbon size is plastic and that synapses may redistribute around the IHC circumference after the disappearance of a (putatively low-SR) subset of the afferent terminals. They also suggest that the normal inverse correlation between ribbon size and SR is not causal, since a postexposure increase in ribbon size was seen here despite a postexposure increase in mean spontaneous rate. The dramatic morphological changes in the remaining ribbons are noteworthy given the lack of physiological changes in the surviving postsynaptic neurons. However, this is perhaps not surprising given the normality of many aspects of AN response in mutant mice with complete absence of presynaptic ribbons in the IHCs (Buran et al. 2010).
Excitotoxicity and the special vulnerability of low-SR fibers.
Numerous prior studies have noted that acoustic overstimulation causes dramatic swelling of the ANF terminals in the IHC area, if the ear is fixed with 24- to 48-h postexposure (Liberman and Mulroy 1982; Robertson 1983). Similar swelling of terminals can be seen after perfusing the cochlea with glutamate agonists, and the appearance of noise-induced swelling can be partially blocked by perfusing the cochlea with glutamate antagonists (Pujol et al. 1993). Neither the noise-induced, nor the kainate-induced, terminal swelling is seen in the terminals of type II fibers contacting outer hair cells. Together, these observations have suggested that the phenomenon is a type of glutamate excitotoxicity and that the pathology is restricted to the IHC area because the type II terminals do not express the same AMPA type glutamate receptors (e.g., GluA2) as do the type I terminals (Liberman et al. 2011).
The present results suggest that the low-SR fibers are more vulnerable to this putative glutamate excitotoxicity. Despite their lower thresholds to acoustic stimulation, spike rate in high-SR AN fibers tends to saturate within 30 dB of threshold (Winter et al. 1990); thus, the steady-state discharge rate in response to the traumatic noise band at 106 dB SPL will likely be the same, or less, in low- vs. high-SR fibers. The heightened vulnerability of low-SR fibers could arise in a number of ways. It is possible, for example, that the clearance of released glutamate is less effective on the modiolar, than on the pillar, side of the IHC; indeed, immunostaining for the GLAST transporter, which clears glutamate from the synaptic cleft into the IHC's supporting cells, is less intense on the low-SR (modiolar) side of the IHC (Furness and Lawton 2003). Another hypothesis is that the differences arise from the fact that low-SR fibers contain many fewer mitochondria than high-SR fibers, a difference that presumably reflects the increased demand on Na+/K+ pumping in those neurons that are discharging at rates of up to 100 sp/s even in complete quiet (Liberman 1980). Studies of glutamate excitotoxicity in central neurons suggest that Ca2+ entry is an important upstream event in the excitotoxicity cascade, and that mitochondria are a crucial source of Ca buffering capacity (Szydlowska and Tymianski 2010).
If low-SR fibers are indeed less well equipped to deal with steady glutamate release during a 2-h acoustic overexposure such as in the present study, it is possible that they are also more vulnerable to repeated stimulation at much lower SPLs, i.e., those presented in the course of everyday acoustic environments, and, thus, that the normal process of aging may also be characterized by a type of low-SR neuropathy. Given the view that low-SR fibers may be particularly important to hearing in a noisy environment, a selective and progressive low-SR neuropathy may be an important contributor to the increasing hearing impairments that characterize the aging human population.
This work was supported by research, core, and training grants from National Institute on Deafness and Other Communication Disorders RO1 DC-00188 (M. C. Liberman), P30 DC-05029 (M. C. Liberman), R01 DC-08577 (S. G. Kujawa), and T32 DC-00038 (A. C. Furman).
No conflicts of interest, financial or otherwise, are declared by the author(s).
A.C.F., S.G.K., and M.C.L. conception and design of research; A.C.F. performed experiments; A.C.F., S.G.K., and M.C.L. analyzed data; A.C.F., S.G.K., and M.C.L. interpreted results of experiments; A.C.F. and M.C.L. prepared figures; A.C.F. and M.C.L. drafted manuscript; A.C.F., S.G.K., and M.C.L. edited and revised manuscript; A.C.F., S.G.K., and M.C.L. approved final version of manuscript.
The skillful assistance of Leslie Dodds in cochlear immunochemistry is gratefully acknowledged.
- Copyright © 2013 the American Physiological Society

domain: literature


text:
May 25th, 2011
The public tuned in Tuesday for the opening statements of the Casey Anthony trial where Anthony finally stated her defense. Back in 2008 this case was showcased on news outlets everywhere, leading many to believe that Casey Anthony murdered her 2-year-old daughter Caylee.
During the opening statements we heard two different stories. The prosecutors claimed that Caylee suffocated from duct tape placed on her nose and mouth while defendants argued that Caylee drowned in the family pool. To complicate this trial even more, the autopsy was not able to determine how Caylee died.
An article in Seattle pi quotes Casey Anthony’s criminal defense attorney, Jose Baez saying that
“Casey should have called 911. That’s what she’s guilty of, she’s not guilty of murder. This is not a murder case.”
The article goes into more specifics as to what the defense is arguing in favor of Anthony including accusations that the police performed a “botched investigation” to feed the media a story of a murdering mother.
To further explain Casey Anthony’s bizarre behavior following her daughter’s disappearance, the defense contends that Casey was sexually molested by her father from the time she was 8 years old. This was a very dysfunctional family that had secrets, dirty secrets. The defense made specific challenges to the evidence the state will likely introduce and better be able to back up those claims through cross-examination or in their own case. One thing is for sure, Casey Anthony is going to have to take the witness stand after that opening statement.
May 19th, 2011
We’ve all seen it in the movies; “cop” bangs on door, people inside scatter and hide weapons/drugs, someone answers the door and “cops” search the home. Pretty standard right? This is not what happened in a recent case in Kentucky…
According to an article from the Orlando Sentinel, Kentucky police were following a man who they believed to be a drug dealer. The man went into an apartment building but the law enforcement officials lost track of which unit he entered. The police smelled marijuana coming from one door and knocked on it. They heard rummaging and announced they were coming in. They did not find the drug dealer but instead found Hollis King with marijuana and cocaine. King convicted of drug trafficking but later his conviction was overturned by the Kentucky Supreme Court accusing the officers of violating his 4th Amendment (unreasonable search and seizure). The U.S Supreme Court then heard an appeal from prosecutors and reversed the ruling. Justice Samuel A. Alito Jr said
“…the police conduct in this case ‘was entirely lawful,’ and they were justified in breaking down the door to prevent the destruction of the evidence.”
The Supreme Court passed a ruling allowing law enforcement to enter homes without a search warrant. If law officers knock loudly on the door and hear suspicious noises coming from inside, they can enter the home without a warrant or consent. Before this ruling, the law stood that officials could only enter the home without a search warrant if they had consent from the owner or if there was an emergency situation.
In the article, Justice Ruth Bader Ginsburg argues
“the court’s approach arms the police with a way routinely to dishonor the 4th Amendment’s warrant requirement in drug cases. She said the police did not face a ‘genuine emergency’ and should not have been allowed to enter the apartment without a warrant.”
This new law could potentially complicate the job of criminal defense lawyers because in the past, there was a logical defense when police didn’t have the explicit right to enter the home of the suspect. Now, we may come across the gray area of what was thought to have been heard and what the accused says happened. The line of violating the 4th Amendment could become blurred.
The Supreme Court arrived at an 8-1 decision allowing law enforcement officials to enter without a warrant if they are in pursuit of someone with drugs, knock loudly and can hear the destruction of evidence.
May 12th, 2011
The media plays an influential role in our life everyday, but will it play a role in the outcome of the very publicized Casey Anthony case?
Anthony is accused of murdering her two year old daughter in Orlando. A very public search was conducted to find the “missing” girl, who’s remains were found months later and fingers were pointed at mother Casey Anthony.
According to Anthony’s defense attorney Jose Baez, the standard microphones that are found in every courtroom are picking up private conversations between Anthony and Baez. Under the legal process, all conversations between the defendant and lawyer should be private. Baez requested that all the microphones to be removed excluding the Judge’s and the juror’s.
Judge Belvin Perry took many steps to make sure that the media was not an influence on the juror’s decision. Jurors pulled from Pinellas County were questioned more specifically about what they had heard about the case and how they felt about the death penalty. Perry decided to pull jurors from Pinellas County because the media coverage was not as extreme.
According to an article from the St. Pete Times, Jonathan Green really didn’t want to have jury duty. Green was fined $450 for contempt of court when he admitted to talking about the case to someone else. Green said, “I just wanted to get out of jury duty.” It is almost hard to blame Pinellas County citizens to not want to be a juror for this case. The jurors are expected to be in the Orlando courtroom everyday for 6-8weeks.
May 10th, 2011
Sunset Beach, a popular beach in Treasure Island, may be facing a ban of alcohol on their beaches- one of their biggest crowd drawing specs! Treasure Island officials say that the drinking has gotten out of hand.
According to a 10 News article, “the ordinance would ban alcohol on weekends from 8 a.m to 6 p.m, including holidays.” The City Commission voted unanimously for the drinking ban.
Many people opposed to the ordinance showed up at the meeting last week. Some argued that it would hurt small business owners because of the crowd that has drawn specifically because the beach permits alcohol. Others argued that is was unfair to ban alcohol all together just because of other people’s actions. But residents from the Sunset Beach area who are for the ban argued that the allowance of alcohol leads to inappropriate behavior and fights in their neighborhoods.
There will be a second meeting to discuss this ordinance sometime next week and if it passes again, the ban will immediately take effect. It will be interesting to see how officials will regulate the ban on alcohol at Sunset Beach.
May 6th, 2011
This doesn’t mean your case will go away. All this means, is that any incriminating statements that you had made cannot be used against you in court. If the officer wants to ask you questions other than your name and address, s/he will then read your rights. At this time, you do not have to answer any questions because they will be used against you in the court of law.
A tactic that law enforcement sometimes use is asking you questions before reading you rights, getting you to admit something and then reading you your rights and asking the questions again. For the most part, the person under question would assume since they already made a confession or incriminating statement, the officers already know the truth so how else could it hurt them? This is false. Since they got you to admit something after reading you your rights, all statements thereafter will be used against you. Anything you say before your rights are read cannot and will not be used as incriminating evidence. The most important thing you can do while being investigated after an arrest is to call a criminal defense lawyer and make no statements before doing so.
May 4th, 2011
So we’ve talked about Facebook before, how Sheriff’s offices utilize it to post pictures/videos of open cases, how some Attorney’s use Facebook in the juror selection process and now, how Facebook is cited in 90% of divorce cases.
According to a St. Petersburg 10 News article, the American Academy of Matrimonial Lawyers discovered that Facebook is involved in one in five divorce cases. Whether it is from parents allowing illegal activities like underage drinking, or if it is a picture a spouse out on the town, lawyers are seeing more and more encounters with Facebook.
With all this action coming from Facebook, Attorney’s have no choice but to become a master at internet photo searches. A simple Google image search can result in pictures that some are unaware are even out on the internet. Untagged pictures or pictures from a deactivated Facebook account can still be found. Divorce Attorney Carin Constantine was interviewed by the St. Petersburg 10 news team and commented,
“Those pictures are still accessible by us, and we can still print them and we can still use them as evidence in your divorce case.”
Privacy settings are controlled by the individual, but the default settings that Facebook sets you up with are not ideal. The best advice would be to go into those settings and make it so only those people who you want to see your personal information/pictures can. For the future, ask friends and family not to tag you in any pictures if you want to avoid any controversy.

domain: news


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text:
What will it take for people to stop?
What will it take for people to see what they are doing?
All I hear is he/she where high on drugs, had a bad child hood, depression the list goes on and on, but does that help some who’s 3 month old baby just passed or a 10 year old who passed also no and I’m not sorry but it has to stop NOW. We are supposed to live in a beautiful country where we can be free, but we aren’t, we look over our should so we don’t get bashed, mugged, stabbed etc.
I had a bad child hood due to the loss of my baby boy I suffer depression but there is no way,no way I would hurt or kill the innocent there is no EXCUSE NONE.
No bail for the anyone who does crimes no matter age and especially and most importantly the violent, if kids in detention smash it up let them live in it and give them nothing NOTHING .
It is time for a change in the system let’s get our Australia back.
Posted by Becca j, 23rd January 2017

domain: sociology


News & Events
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Lavango Group to double its presence at Klaipeda FEZ
Leading global food industry technology manufacturer Lavango Group has announced that it is expanding its presence at Klaipeda FEZ. The company, which produces equipment for the food industry, has acquired an additional 0,32 ha of land in Klaipeda FEZ territory to build their new facilities, which will allow them to increase their present production capacity. This is the second phase of the company’s expansion, the first of which was completed in 2017 when it transferred all its operations to its present 0,38 ha facilities at Klaipeda FEZ. Lavango Group is set to invest 0,8 m Eur in the new building, and along with the purchasing of new equipment for the facility, the company projects that around 15 new FTE’s will be created.
This new expansion has been precipitated by rising demand in the European market for its products – equipment used in the food industry for raw material processing, packaging and transportation.
“The expansion of our plant is a result of the rising revenue and export of the company. Our current goal is strengthening our positions in Scandinavian markets, namely, in manufacturing equipment for fish-processing vessels and food processing plants,” says Vygandas Srebalius, CEO at Lavango Group.
The company generates most of its revenue from its key markets, which at present include Scandinavia, the Baltics, Russia, Belarus, Germany and Spain.
Mr Srebalius attributes much of Lavango Group’s ability to expand its business to the innovations that it put in place after movingto Klaipeda FEZ.
“One of them was investing into our own metal processing lathes and sanding technology. This allowed us to improve the quality of the parts we produce. Not only that, we also began to provide lathing services for other clients.”
Klaipeda FEZ has seen a number of its clients expanding their operations in 2018, with the most notable examples thus far being NEO GROUP and Retal Baltic, whose expansion projects combined amounted to investments of 54 m Eur. Indeed, such expansion projects account for a considerable amount of the entire investments made annually at Klaipeda FEZ, around 20%, according to Eimantas Kiudulas, CEO at Klaipeda FEZ Management Company. It is the relative ease with which such projects can be implemented that is one of the main drivers for this, as Mr. Kiudulas explains:
“The ability to launch operations as soon as possible is becoming of increasing importance to many investors, that is why Klaipeda FEZ also leases land with building permits that have already been set up. For instance, the first stage of Lavango Group’s launch at Klaipeda FEZ in 2017 took as little as 6 months.”
Lavango Group’s new facility is set to be opened in Summer 2019.


text:
Essential characteristics of a contract of sale of goods are given below:
1. Two parties:
The first essential is that there must be two distinct parties to a contract of sale, viz., a buyer and a seller, as a person cannot buy his own goods. However, there may be a contract of sale between one part-owner and another, e.g., if A and B jointly own a computer, A may sell his ownership in the computer to B, thereby making B sole owner of the goods [Sec. 4(1)]. Similarly, a partner may buy the goods from the firm in which he is a partner and vice-versa.
2. Transfer of property:
‘Property’ here means ‘ownership’. Transfer of property in the goods is another essential of a contract of sale of goods. A mere transfer of possession of the goods cannot be termed as sale. To constitute a contract of sale the seller must either transfer or agree to transfer the property in the goods to the buyer.
The subject-matter of the contract of sale must be ‘goods’. According to Section 2(7), “goods means every kind of movable property other than actionable claims and money; and includes stock and shares, growing crops, grass, and things attached to or forming part of the land which are agreed to be severed before sale or under the contract of sale.”
Thus every kind of movable property except actionable claim and money is regarded as ‘goods’. Goodwill, trademarks, copyrights, patents right, water, gas, electricity, decree of a court of law, are all regarded as goods. Shares and stock are also included in goods.
‘Actionable claims’ means claims which can be enforced by a legal action or a suit, e.g., a book debt (i.e., a debt evidenced by an entry by the creditor in his Account Book or Bahi). A book debt is not goods because it can only be assigned as per the Transfer of Property Act but cannot be sold.
‘Money’ means current money:
It is not regarded goods because it is the medium of exchange through which goods can be bought. Old and rare coins, however, may be treated as goods and sold as such.
It may be mentioned that sale of immovable property is governed by the Transfer of Property Act, 1882.
The consideration for a contract of sale must be money consideration called the ‘price.’ If goods are sold or exchanged for other goods, the transaction is barter, governed by the Transfer of Property Act and not a sale of goods under this Act. But if goods are sold partly for goods and partly for money, the contract is one of sale (Aldridge vs Johnson).
5. Includes both a ‘sale’ and ‘an agreement to sell:
The term ‘contract of sale’ is a generic term and includes both a ‘sale’ and an ‘agreement to sell’ [as is clear from the definition of the term as per Section 4(1) given earlier)].
Sale. Where under a contract of sale the property in the goods is immediately transferred at the time of making the contract from the seller to the buyer, the contract is called a ‘sale’ [Sec. 4(3)]. It refers to an ‘absolute sale’, e.g., an outright sale on a counter in a shop.
There is immediate conveyance of the ownership and mostly of the subject-matter of the sale as well (delivery may also be given in future). It is an executed contract.
An agreement to sell:
Where under a contract of sale the transfer of property in the goods is to take place at a future time or subject to some condition thereafter to be fulfilled, the contract is called ‘an agreement to sell’ [Sec. 4(3)]. It is an executory contract and refers to a conditional sale.
(a) On 1 January, A agrees with B that he will sell B his scooter on 15 January for a sum of Rs 3,000. It is an agreement to sell, since A agrees to transfer the ownership of the scooter to B at a future time.
A agrees to purchase B’s Car for Rs 50,000 provided B stands surety for him with C. It is an agreement to sell for B. It becomes a sale when the condition is fulfilled by B.
B agrees to buy A’s car for Rs 30,000 and pay for it, if his solicitor approves. It is an agreement to sell for A and an agreement to buy for B.
A buys some furniture for Rs 2,000 and agrees to pay for that in two monthly instalments, the ownership to pass to him on the payment of second instalment. There is an agreement to sell for the furniture dealer.
‘An agreement to sell’ becomes a ‘sale’ when the time elapses or the conditions are fulfilled subject to which the property in the goods is to be transferred [Sec. 4 (4)].
6. No formalities to be observed (Sec. 5):
The Sale of Goods Act does not prescribe any particular form to constitute a valid contract of sale. A contract of sale of goods can be made by mere offer and acceptance. The offer may be made either by the seller or the buyer and the same must be accepted by the other.
Neither payment nor delivery is necessary at the time of making the contract of sale. Further, such a contract may be made either orally or in writing or partly orally and partly in writing or may be even implied from the conduct of the parties.
Where articles are exhibited for sale and a customer picks up one and the sales assistant packs the same for him, there has resulted a contract of sale of goods by the conduct of the parties.

domain: law


text:
Chic is characterized by being trendy and fashionable. It is a type of statement to make oneself look smart and striking. Whoever follows this style makes sure to choose well tailored stylish designs that are pretty classy. Strong colors which are not extravagant, comes as a part of the chic style. It is something that relates to being casual in not so casual way. If you are part of this style, your wardrobe is a symbol of style.
One of the most adorable fashion styles, it definitely is a blast from the past. From flapper dresses to pinup clothing and from retro swimwear to indie clothing, the vintage look is a culmination of fashion from the 20’s to the 70’s. It is the one trend that overcame the test of time. Look these celebrities who are feature for their vintage style.
Stella McCartney went fresh from graduation at Central Saint Martins to chief designer at Chloé in 1997. Le Style Stella – a raunchy mix of rock ‘n’ roll and girly glamour – established Chloé as the best selling label in Paris and its designer as a card-carrying member of the fashion aristocracy. In 2000, McCartney left Chloé and signed a deal with the Gucci Group to launch her successful signature label.
Every collection of this talented designer is doomed for success. His works can be unhesitatingly called masterpieces: he’s never afraid of expressing himself in the wackiest, the most sophisticated, out-of-this-world shapes and colors. Pierre Cardin is the inventor of the ‘bubble dress’. His works can be easily told from the others: Cardin’s models look like they’ve come out from the SCI-FI novels :).
Top-handled and either cutesy and retro or super-sleek in plain leathers, the most influential bag trend of the season will most definitely be anything that feels extra-ladylike and old-fashioned. Although jumbo totes and teeny-tiny mini bags could also be seen on the autumn runways, neither is particularly practical, unlike these this breed of elegant styles. "I find when something is vintage that piece has a much longer staying power since the style feels inherently classic, like the frame bag," says Lisa Aiken, Fashion Director at Moda Operandi. Roomy enough to fit your essentials into, classic enough to last an eternity and offered in enough variations to girls with multiple style personalities sated indeed.
“Intuition is a strong feminine quality. I have applied that instinct to my career“. This is one our favorite quotes by Carolina Herrera and we think she is a true inspiration to women in fashion, and more, around the world. Carolina started to be known by regularly appearing on the International Best Dressed List in the 80’s. Her trend marks are classy pieces like pencil skirts paired with crisp white cotton shirts. In 2008 she was awarded the Lifetime Achievement Award from the Council of Fashion Designers of America.
Tastes differ. And when it comes to fashion, they differ even more. However, I’ve managed to come up with a list of top 5 fashion designers that can’t leave any woman indifferent. They are adored by fashion artists and their regular customers all over the world, and their incredible, jaw-dropping collections speak for themselves. Check out the list of the most famous fashion designers of all time:
The India’s dearest and beloved designer, known & appreciated not only by Bollwood’s-leading-ladies and men but also designs for Hollywood-superstars like Reese-Witherspoon and supermodels Naomi-Campbell nd Kate-Moss. He’s the one who brought vivacity, energy and colors to blockbuster movies like kuch-kuch-hota-hai, Dil-to-pagal-hai….He was also asked to design-clothes for Michael Jackson. He’s linked with the top international companies of Thai-Gems & Jewellers Association, Deutche-Bank, American-Express-Bank, Wizcraft, Moet and Henessey..
A big hello to my intimates! Here I have another article of great consequence, yeah it is pertaining to the best Indian fashion-designers. As the time is eluding, trends are changing and we’re getting slaves to fashion! It’s an era of style and vogue, where dressing well is considered a form of good manners! Therefore every year , in every season fashion designers launch their prêt-line. Designers endeavor to design dresses that are both functional and aesthetically satisfying. The fashion-industry of India is flourishing by leaps and bounds and has got successful in achieving fame and popularity through the world as a fashion-centric-nation! Previously , not many people knew about India and it’s fashion but it’s emerging and mounting industry has made it’s mark not only in the neighboring countries but in the international fashion-industry as well! And it is because of it’s designers that India is now in the top list of countries. Specially Indian fabric and it’s attire called “Saree” is well liked and admired throughout the world.
Considered by many one of the greatest tailors of the century, Pierre Balmain was born in Saint Jean de Maurienne, France in 1914. After studying at the school of Architecture, in Paris he founded in 1945 the Maison Balmain as a couture house, with a lucrative sideline in fragrances. In that year he showed long, bellshaped skirts with small waists; a line that became popular in 1947 as part of Dior’s New Look.
In this stage designer create a brand name or logo. The philosophy and identity of a range can be continued into promotional activities such as branding and styling. To promoting and marketing fashion goods it is very important. Normally the branding would be a graphic designer’s job. It is the interesting use of the language or words can produce visual effects, such as, iMac (Internet ready Macintosh computer), O2 (mobile phone provider), FCUK (French Connection United Kingdom).
Another India’s old hand and expert designer, from New-Delhi and designs both for men and women! His outfits are worn by Bollywood-actresses and has been in the field since 1980’s. He was given a title of “India’s-Master-Of-Fabric-And-Fantasy”, in 1996 by Time magazine. He has quite perfect sense of creativity & each of his invention is crafed to excellence. He did his graduation from St. Stephen College of NewDelhi with a first class(hons.) degree in history and created his first traditional line for men back in 1990. His client celebrities include Pamela Anderson, Cindy Crawford, Naomi Cambell, Anna Koirnikova nd Uma Thurman and most of his fashion-shows are done in Singapore, NewYork, India and Paris and also is the brand-ambassador of Omega-watches since 2001.
A pattern maker (also referred as pattern master or pattern cutter) drafts the shapes and sizes of a garment's pieces. This may be done manually with paper and measuring tools or by using a CAD computer software program. Another method is to drape fabric directly onto a dress form. The resulting pattern pieces can be constructed to produce the intended design of the garment and required size. Formal training is usually required for working as a pattern marker.
In 1995, Rodriguez became design director of TSE, where he presented the first ready-to-wear collections for men and women. In 1996, Carolyn Bessette asked Rodriguez to create the gown she wore to marry John F. Kennedy Jr, putting the designer firmly on the fashion radar. Rodriguez was soon appointed design director of Cerruti in Paris. After that a consequence, Loewe appointed Rodriguez as design director of the women’s ready to wear collection. Rodriguez held the position until 2001.
In the 60’s, Valentino made a decision that would enhance his reputation; he sent Jacqueline Kennedy, the American First Lady and fashion icon, a series of his pieces to look over. She was enchanted with his designs, and even chose to wear one of his dresses when she married her second husband, Greek shipping tycoon Aristotle Onassis: her influence led to greater fame and fortune in North America.
Thomas Burberry was born in 1835 in Brockham Green, Surrey. Burberry opened his own small clothing outfitters in Basingstoke in 1857. At that time Basingstoke was a small country town. Nowadays, the Burberry Group is a leading global fashion brand which now sells womenswear, menswear, non-apparel and children’s wear. It is famous for its iconic trademarked check design and British heritage branding.
Everyone knows this guy, and I bet you do, too. He’s one of the international fashion icons. Yves Saint Laurent became popular as a designer who re-designed menswear into feminine, beautiful garments for women. His name is also closely associated with the phenomenon of ‘ready-to-wear’ fashion clothing, ‘power suits’ for women and ‘smoking jackets’ for men.
There's a puff-sleeve personality for everyone, according to the runways. Maybe you'll like yours neat and rounded out at the shoulder for autumn (see Givenchy), or maybe you'll want something decadent and entirely inappropriate for anything that involves dipping sauces (see Emilia Wickstead's gigantic-sleeved floral dresses). Whatever route you choose to go down there is a huge amount on offer from edgy to prim.
Ottavio Missoni started their own fashion design company with his wife Rosita. First they started with stripes, the easiest design which could be made with the ch. They use up to twenty different fabrics, including wool, cotton, linen, rayon and silk and some 40 different colours for each of their collections. Their clothes range from sweaters to skirts, dresses and jackets. Ottavio Missoni has also diversified from clothes to tapestries and carpets. Ottavio died last year leaving Rosita being the head of the business.
"We saw the 'army' mood return, but in a more effortless and understated way than previous seasons. A utility and combat mood was a favorite in Milan, particularly from the likes of Prada and Miu Miu, who offered full army-inspired looks. I loved Isabel Marant’s oversized styles which similarly drew inspiration with oversized vests and pocket-detailed trousers. A favourite piece had to be Stella McCartney's full khaki green jumpsuit, which looks great with an oversized jacket in the same hue and a pair of pumps," says Hsu.
When you hear ‘casual’, you probably think ‘frumpy’; and the casual fashion style could really be ANYTHING but frumpy! Women who indulge in the casual fashion style don’t grab the exotic and bold items off the shelves. They would much rather prefer a simple white tee and a pair of black pants with a coordinating and trendy purse. The entire look is very modern and uncluttered with an extra touch of subtle elegance.

domain: artistic


text:
salt and tinnitus
Tinnitus refers to a ringing in the ears that frequently accompanies hearing loss. Based on the stats from the Hearing Health Foundation, an estimated 48 million people in the US and practically 477 million around the world experience these symptoms, particularly as they age. While initial tinnitus rarely shows a major condition, it can be very challenging to cope with as it progresses and ends up being more serious. salt and tinnitus
There could be numerous possible causes of tinnitus. It could differ from exposure to loud noises, age, genetic factors, or even specific restrictions in one’s diet plan. Regrettably, when tinnitus sets in, it is extremely tough to get rid of the ringing noise. There are some medical treatments for it, however due to its restricted success at totally restoring good hearing, people now want to alternative natural options to supply relief or even avoid it from taking place altogether.
In the myriad of available solutions, consumers can get extremely confused as to which are excellent alternatives to take to resolve their tinnitus obstacles. We aim to examine the readily available choices and sift out the finest tinnitus relief supplements for 2021. salt and tinnitus
Current research study indicates that hearing ringing sound in ears is merely a sign. That’s why, even using ear plugs do not stop the constant ringing. Instead, the origin of tinnitus is swelling happening in the brain.
Silencil consists of a blend of 28 thoroughly mixed plant extracts and vitamins. These components are specially chosen to minimize swelling in the brain and to motivate brain repair work and healing. The description video lay it out in an easy 5-step method to recovering from Tinnitus as a simple explanation of how Silencil works. salt and tinnitus
We do not have a complete list of all the 28 organic ingredients. In addition, they do have research backing on their effectiveness in improving brain health.
- Oat Straw
- Mucuna Pruviens
- Vitamin B1, B2 and B6
- More different component compared to the other two recommendations in this post, which might indicate more range of brain enhancing nutrients in it.
- It is a 100% natural non-GMO organic formula, made to a high level of pureness.
- Suitable for Diabetics
- Ingredient options supported by research papers
- Hassle-free to use, in an easy capsule type
- FDA approved and GMP certified producing center is used for making Silencil
- Tried and checked by 122,000 females and guys.
- Try it safe with the 60-day refund guarantee salt and tinnitus
- Supply is rather minimal, so may need to act fast to reserve it.
Who is it for?
Chronic inflammation is something that impacts an individual’s entire health and not just the brain. If you observe other symptoms of inflammation in your body, it might likewise be impacting your brain. As such, you might wish to give Silencil a shot to assist you to prevent or ease you of Tinnitus.
Tried and tested by 197,357 individuals, Quietum Plus is a hassle-free natural extract formula which is designed to help people to relief Tinnitus, a continuous ringing in their ears. In its proprietary mix, it contains 12 plant extracts which is backed by research to be able to have therapeutic result in handling and improving Tinnitus. salt and tinnitus
What are the 12 natural active ingredients in there? Here they are:
- Plant Isoflavones and Vitex Berry as the “emergency treatment duo” that cools off your nervous system and makes certain nothing hinders your healing.
- Black Cohosh and Sage to fix up the nerve cells
- Licorice and Red Clover to repair and regrow your nerve cells to eliminate any damage
- Blessed Thistle and Red Raspberry to improve neural networks communication
- Blazing-Star, Squaw Vine to Supercharge your brain, strengthen your nerves & take your psychological health to the next level
- Dong Quai and Meixcan Wild Yam to bulletproof your whole nervous system & never ever worry about hearing diseases or brain disorders once again
- The selected 12 plant extracts in the formula are backed by research to help in handling and improving Tinnitus.
- Made from an entirely natural blend, non-GMO and no use of herbicides
- Produced at an FDA registered and GMP accredited facility that had a high-level disinfection policy to keep any germs or infections at bay
- Simple and practical pill type.
- 197,357 people have actually gained from this formula
- Other side advantages observered: sleeping better, mind feels sharper and clearer
- It has an Iron-clad 60-day cash back ensure refund policy. salt and tinnitus
- Need constant use of Quietum Plus for a minimum of 90 days to be able to get finest results.
Who is it for?
Quietum Plus benefits anybody seeking to manage their Tinnitus condition or avoid it from occurring and is searching for a 100% natural solution to it. You can try it risk free for 60 days. salt and tinnitus
Synapse XT is a 100% natural method that attend to the root cause of Tinnitus which is thought to be in the brain. With its mix of 8 Powerful Herbal Ingredients that operate in synergy, it possibly can provide on health advantages such as much better interaction between brain cells, support your memory and brain health for clearer thinking and hearing.
What are the 8 Powerful Ingredients utilized? They are Hibiscus, Hawthorn Berry, Garlic and Specific B-Vitamins to reverse the years of brain degeneration, and Green Tea Extract to multiply vital neural connections, Juniper Berries to clear your brain of toxins and Vitamin C to protect your brain versus diseases. salt and tinnitus
These active ingredients are then blended in a particular ratio and in a specific order for best outcomes. The manufacturing center at which Synapse XT is made is FDA approved and GMP licensed.
- 100% natural herbal blend, which reduces danger of side effects from common drugs
- The active ingredients’ therapeutic ability is supported by pertinent research study posts.
- Convenient capsule type, for easy use.
- More than 50,000 satisfied clients
- Safe and Quality manufacturing: FDA approved and GMP certified.
- 60-day refund Policy, reveals strong self-confidence in their own item.
- Least variety of active ingredients amongst the 3 recommendations in this post. salt and tinnitus
Who is it for?
If you have actually tried the above 2 recommendation and yet is still searching for another service, then I ‘d say absolutely provide Synapse XT a shot. Because different components could work differently for various individuals, that’s why.
What was our selection criteria for the 3 Best Tinnitus Relief Supplements?
- Natural Ingredients — We particularly checked out the ingredient identifies to guarantee the active ingredients were natural extracts. Not simply a list of chemicals.
- Scientific evidence — We searched for scientific research proof backing up the use of the picked components in each case and validated that it existed. salt and tinnitus
- Safety – Quality manufacturing and purity of item has much to do with guaranteeing security of an item. We only shortlisted supplements with high purity, quality manufacturing that is FDA authorized and GMP certified.
- Refund Policy — Typically, having a customer friendly refund policy indicates the self-confidence a company has in their own product. All picked choices in this short article has a 60-day money back reimburse policy.
Different components have various degree of therapeutic results on different people. Select which ingredients list resonate with you finest. salt and tinnitus

domain: medical


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Ghana’s former President, Flt Lt Jerry John Rawlings has called on managers of the National Health Insurance scheme to work hard to break the knot of institutional bureaucracy that affects its implementation.
President Rawlings said: “the procedure for processing poor patients who cannot afford to pre-finance the purchase of drugs and other in-patient needs is burdensome and leads sometimes to unfortunate fatalities.”
The former President praised the Health Insurance scheme as playing a positive role but lamented how officialdom and paperwork was affecting the true value of the scheme.
President Rawlings who spoke as the Guest of Honour at the 9th Matriculation and 4th Graduation ceremony of the Narh-Bita College in Tema on Tuesday, also called on nurses who administer the NHIS to put a human face to its challenges, to ease the pain patients have to endure.
He called on the graduates to be patient-friendly and professional when they soon enter various health institutions as nurses and heath-care assistants.
Please find the full text of President Rawlings’ address below:
NARH-BITA COLLEGE 9TH MATRICULATION & 4TH GRADUATION CEREMONY
ADDRESS BY H.E. JERRY JOHN RAWLINGS, FORMER PRESIDENT OF GHANA AND VERY SPECIAL GUEST OF HONOUR TUESDAY NOVEMBER 20, 2012
Reverend Ayeh Kumi, Chairman for the occasion, President of Narh-Bita College, Dr Edward Narh, the Director-General of the Ghana Health Service, Dr. Appiah Denkyira, Ms. Veronica Darko, Registrar of the Nurses and Midwives Council, Niimei, Lecturers and Students of Narh-Bita College, Distinguished Guests, Ladies and Gentlemen:
It is an honour to join you here today on the occasion of the 9th Matriculation and 4th Graduation ceremony of the Narh-Bita College.
Quality and effective healthcare in Ghana is a matter of concern to every Ghanaian. Our health indices confirm that a lot of hard work is required in order to improve health delivery systems in the country.
According to the World Bank, the infant mortality rate per 1000 for 2010 was 53.8, it increases to 81.1 for between birth and under five years and Life Expectancy at birth is 62.3.
Ladies and Gentlemen, Ghana’s health delivery has seen a metamorphosis between 1979, when Narh-Bita Clinic was born and now. Under the PNDC and first NDC governments, a conscious effort was made to improve Primary Healthcare facilities across the country.
The country’s health systems were in dire straits and we had to institute measures to combat the six childhood killer diseases - measles, tetanus, diphtheria, poliomyelitis, tuberculosis and whooping cough.
We also ensured the expansion of health infrastructure through regional and district hospitals and embraced the establishment of privately sponsored health care facilities.
Ladies and gentlemen, it is no coincidence that Narh-Bita Clinic was established in 1979. The situation with the provision of health called for all to join hands in providing trusted healthcare.
We must commend the initiators of the Narh-Bita project, Dr and Mrs Narh for their sense of vision and ambition to defy the odds in introducing state-of-the-art private healthcare.
Narh-Bita, having grown from a clinic in 1979 to a hospital in 1987 then graduated to a School of Nursing before attaining college status in 2008.
It is particularly impressive that the Narh-Bita College was borne by the desire to confront the problem of shortage of healthcare workers. It is also worthy of praise that the College, unlike many others has striven to maintain the highest standards by associating itself with the University of Ghana, the Ghana Health Service and the Nurses and Midwives Council which directs and supervises the academic programme.
Distinguished Guests, Ladies and Gentlemen; as you hold your graduation and matriculationceremonies today, it is imperative that we focus on the role nurses play in the healthcare delivery chain.
Nurses serve as a first point of contact for patients at almost every healthcare facility. They are customer service executive who are to ensure that their customers or patients feel comfortable upon arrival at the facility.
Nurses assist doctors to perform their duties and always maintain a first-hand contact with both the patient and the doctor. A smart nurse understands the needs of her patient and has a fair idea of what the doctor requires to bring the patient back to excellent health.
Ladies and gentlemen; a lot has been learnt at the college, but your true worth as a nurse is how fast you can learn on the job and how professional and patient-friendly you can be when the demands and challenges of the job affect your day-to-day life.
Nursing may not be rewarding financially, but what is more rewarding than bringing a smile on the face of a patient who is in pain, what is more commendable than having a life-long desire to see sick persons recuperate and what is more of an achievement that having doctors admire you for your high-level of competence?
Patients have complained about some nurses who are cold, abusive and insensitive to their plight. It is important that you do not adopt such habits when you join the service. For those who are matriculating today your years of study at Narh-Bita should inculcate in you positive ideals that society will be proud of.
Ladies and gentlemen; healthcare delivery is a difficult task because many patients cannot afford to procure the required medication needed for effective recuperation. Nurses on a daily basis have to manage difficult situations of patients who have no resources but still seek effective healthcare.
The National Health Insurance, which had its beginnings during my administration, is playing quite a positive role but it is still grappling with heavy bureaucracy and nurses grapple every day to offer hope to all patients every minute, every day. Ayekoo is not enough for your efforts.
I call on the managers of the NHIS to urgently look into instituting machinery that would ensure the smooth processing of patients who have no money at all when they enter hospitals. This is because the procedure for processing poor patients who cannot afford to pre-finance the purchase of drugs and other in-patient needs is burdensome and leads sometimes to unfortunate fatalities. I have had reports of patients accosting other patient to beg for money to procure drugs when the Health Insurance process should guarantee that basic right.
Nurses who help the Health Insurance scheme to process patients in hospitals should also endeavour to put a very human face to the procedure. Making it complex and cumbersome means many patients prefer to go begging for money than to take advantage of the insurance scheme. It is disheartening to note that in a few hospitals the non-NHIS patients who can afford to pay for their healthcare find themselves being fast-tracked ahead of the slow never-ending NHIS queue.
We can do better.
To the management and staff of the Narh-Bita College and hospital I say thank you for serving as a viable source of medical care to the people of Tema and beyond. You have established very high standards but it is imperative that those standards are maintained. Management is encouraged to reward staff adequately for their services and not compromise on quality. I hope that your plans to collaborate with the famous George Washington University would come to fruition.
To all the graduates I say congratulations for the successful conclusion of your various academic programmes and to the new students, welcome to Narh-Bita College.
Mr. Chairman, Distinguished Guests, Ladies and Gentlemen; thank you for offering me the opportunity to be part of this beautiful ceremony.
Good Luck and God Bless.
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domain: design


NEW DELHI ― India’s ongoing negotiations with Russia for the $5 billion-plus purchase of five S-400 Triumf long-range surface-to-air missile systems are in deadlock yet again.
Indian Ministry of Defence officials, top brass with Russian arms export agency Rosoboronexport, and Almaz-Antey, the original equipment manufacturer and designer, have failed to reach a settlement on the price, training, service support and transfer of technology of the missiles, a top MoD official said.
“Russia is demanding $5.5 billion for the five [S-400] units, very high training fee and refusing to give technology transfer of three types of guided missiles,” the official said, adding that no plan has yet been offered for service and a spares-support package.
Another MoD official said the final contract is not going to be signed anytime soon, and India will not pay more than $4.5 billion for the systems. He noted that the deal would incorporate a Make in India economic policy in regard to the manufacturing of spares, the guided missiles and a life-time service support package.
Rosoboronexport executives were unavailable for comment.
India and Russia signed an intergovernmental agreement on the sale of the S-400 systems during a bilateral summit in October 2016 in Goa, India, in the presence of Russian President Vladimir Putin and Indian Prime Minister Narendra Modi.
The MoD’s apex procurement body, the Defence Acquisition Council, approved in December 2015 the purchase of five S-400s at a cost of about $4.5 billion.
“The service has already carried out two separate rounds of trails in Russia last year, but our air defense personnel have to undergo robust training to successfully operate S-400 Triumf systems before they are inducted,” a senior Indian Air Force official said.
The Russian-built S-400 systems are capable of intercepting and destroying airborne targets at a distance of up to 400 kilometers (250 miles) and can simultaneously engage up to six targets. Each S-400 comprises tracking and search radar systems, eight launchers, 112 guided missiles, and command and support vehicles.
Another Air Force official said the S-400s will help the service counter ballistic missiles and target stealth aircraft. He added that the system would have three types of guided missiles. He also asserted that an India-owned S-400 would easily overpower Pakistan’s air defense capabilities and prove a match against China’s strategic assets.
India will be the second customer after China to acquire S-400 systems from Russia.
India is currently developing and testing is ballistic missile defense grid that is essentially an anti-missile system. The grids includes indigenously developed Prithvi Air Defence for high-altitude interception (above 75 kilometers) and Advanced Air Defence for low-altitude interception (below 15 kilometers).
In addition, India is developing medium-range surface-to-air missile systems reportedly capable of taking out an incoming missile with its range of more than 70 kilometers.
The state-owned Defence Research and Development Organization is also in talks with Israeli defense companies to develop an anti-cruise missile system, but there are currently no details available.
India is also seeking to develop and acquire systems that can counter ballistic missiles and cover a 2,000- to 5,000-kilometer range.
Vivek Raghuvanshi is the India correspondent for Defense News.


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In honor and memory of Ursula K. Le Guin.
I created these editorial illustrations for Reveal, an excellent podcast from the Center for Investigative Reporting. These images traveled alongside episodes about America's e-waste dumping grounds, a French reporter's complex relationship with the refugee crisis, and the risks and costs of in vitro fertilization.
Pokemon Go in Charts
Bustle + Romper Editorial
Late Night Bites
As part of a major redesign, Airbnb asked me to create twenty spot illustrations that embody various concepts central to their brand to be used in materials unveiling the transformation.
A series of quick editorial illustrations on the concepts of time, mortality, and decision-making.


"Several key defence acquisition programs were deferred for many years. The first of the new submarines to replace the Collins class now is not scheduled to be operational until at least 2028 and some in government are favouring cheap, limited-capability European boats. These small vessels would be outclassed in the western Pacific in the 2030s and 40s."
A submarine that is available and works beats a fantasy super-sub dream with no industry capability to back it up; every time. A 212 being out-classed. That is an interesting theory.
Although I am interested in Mr. Babbage's definition of outclassed. Does he mean in the manner of how the F-35 will be outclassed in the Pacific Rim?


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This sorry excuse for an Anderson County Council is more concerned with promoting nonprofits, offering unnecessary tax-breaks (fee-in-lieu) to companies to locate in this county and the warm, fuzzy concept of animal welfare than in the welfare of Anderson County residents who will bear the tax burden for the incompetence of this current Anderson County Council.It is a fact that Duke Energy pays Anderson County around $8 million per year in Anderson County property taxes. Duke Energy is a top rated company that serves Anderson County and makes money for its investors. How can anyone in Anderson County government think that a company that is only going to pay $5 million in Anderson County property taxes over a 30 year period is a good deal?This current “under-the-table, done-deal” is just another example of utter despair (incompetence) by this group of clowns on Anderson County Council. This group of misfits doesn’t have the intelligence or business common sense to make a decent, business deal. Anderson County has the basic business assets in place for good economic development (I-85 Corridor with a mid-point between Atlanta-Charlotte, ample power-water supply and a willing non-union work force) without the need for long-term bribery (30 year fee-in-lieu) to negotiate with a prospective, interested company. Anderson County’s main problem is this incompetent, current Anderson County Council. This group of clowns has undermined economic development in Anderson County with its business unfriendly attitude and total deficiency in business common sense amplified by lack of professionalism in the operation-end of county government with inadequate leadership. Folks, this past four years has been an excellent example of an out-of-control county council not solving any county problems but creating additional hurdles (problems) for economic development and annually raising taxes (fees) on Anderson County residents.
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domain: finance


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(HENDERSON, NEVADA AND NEW YORK, June 28, 2022) — Ones Basketball League (OBL) — the first-ever elite competition that celebrates the most skilled one-on-one players on the planet and created by Basketball Hall of Famer Tracy McGrady — today announced that The Dollar Loan Center in Henderson, Nevada, will host the first-ever OBL Finals on Friday, July 15 and Saturday, July 16.
A limited number of tickets will be made available to the public for the event at https://bit.ly/OBL-LV. Friday’s event will start at 3 p.m. PDT, with the Championship Finals starting on Saturday at 8 p.m.
“Our proof-of-concept season for the OBL has played out better than we had planned, and The Dollar Loan Center is the perfect stage for us to crown our king,” said McGrady. “OBL talent is top notch, the competition is intense, and the atmosphere for our first-ever finals will be second to none with $250,000 cash on the OBL throne waiting for the winner.”
“Dreams are coming true inside the OBL and Tracy’s vision for change has been spot on,” said Jeffrey Pollack, OBL strategic advisor. “Over the last eight weeks we’ve started to demonstrate that our game has soul, our competition matters, and our events are electric. The gifted and gutsy athletes of the OBL deserve a world-class stage for our championship and that’s what we will create at The Dollar Loan Center.“
“There are few basketball legends and entrepreneurs more astute than Tracy McGrady, and we are proud to welcome his team to our new state-of-the-art arena in Henderson for the OBL’s inaugural championship,” said Kerry Bubolz, CEO of the Foley Entertainment Group, which operates The Dollar Loan Center. “In a city all about action, this promises to be the summer’s most intense event.”
The 22 qualifiers for the OBL Finals are coming to Las Vegas from Regional Championships in Houston, Atlanta, Chicago, New York, the DMV, and Los Angeles. The field was culled from over 200 entrants, including many of the best one-on-one athletes in the world with decades of professional and elite college experience. The winner of each OBL Regional took home a $10,000 cash prize, joining the second and third place finishers plus four “wild cards” with invitations to the OBL Finals. In addition to the $250,000 cash prize, the winner in the head-to-head single elimination OBL Finals will be crowned “Ruler of the Court.”
The qualifiers are: Grant Anderson, Chicago (Chicago 3rd); George Beamon, Roslyn, N.Y. (Los Angeles 1st); Isaiah Brown, Queens, N.Y. (New York 1st); Yoshi Craig, Chicago (Chicago 2nd); Darien Davis, Coram, N.Y. (New York 3rd); Randy Gill, Los Angeles and Laurel, Md. (Los Angeles 3rd); Marcus Hall, Denver and Houston (Los Angeles 2nd); Antonio Hester, Miami (Atlanta 2nd); Terry Hosley, Baltimore (DMV, wild card); John Jordan, Houston (Houston 1st); Matt Kiatipis, Newmarket, Ontario (Houston 2nd); Kevin Kuteyi, Lanham, Md. (DMV 1st); Eugene Lawrence, Brooklyn, N.Y. (New York, wild card); Zach Radz, Troy, N.Y. (New York 2nd); Glen Rice Jr., Marietta, Ga. (Atlanta 1st); Ridge Shipley, Carrolton, Texas (Houston, wild card); Mario Smith, Kalamazoo, Mich. (Chicago 1st); Chris Staples, Saginaw, Mich (L.A., wild card); Myron Taylor, Killeen, Texas (Houston, 3rd); Tiras Wade, Tampa (Atlanta 3rd); Andrew Washington, Washington, D.C. (DMV 2nd); and Donte Wright, Jackson, S.C. (DMV 3rd).
OBL media partners include SHOWTIME Sports, SLAM Media, Playmaker, and Heart and Hustle Productions.
Follow Ones Basketball League at www.oblhoops.com.
– OBL –
About The Dollar Loan Center
The Dollar Loan Center is an all-new multi-purpose venue in Henderson, NV, just minutes from the Las Vegas Strip, featuring a 5,567 fixed seating capacity for hockey and indoor football. A product of a public-private partnership between the City of Henderson and a group of investors led by Bill Foley, The Dollar Loan Center opened in March 2022 and is operated by the Foley Entertainment Group. The Dollar Loan Center is the home of the American Hockey League’s Henderson Silver Knights, the Indoor Football League’s Vegas Knight Hawks, the Big West Basketball Championships, the Southern Nevada Sports Hall of Fame, the Craggy Range Sports Bar & Grill and The Saddlery team store. For the latest news and information on The Dollar Loan Center visit thedollarloancenter.com and follow the arena on Facebook, Twitter and Instagram.


We are using Opc.Ua.Core.dll and Opc.Ua.Client.dll ( Version 1.4.354 ) in our application . Our application is targeted to .NET framework 4.6. Basically we have upgraded the OPC foundation SDK from Version 1.3.342 to version 1.04.354.
When we try to communicate our OPC UA client application to any OPC UA server with any security mode ( Basic128Rsa15 , Basic 256 ) We are getting the error message
“SHA1 signed certificates are not trusted” .
It works fine with NONE security .
based on the reference https://github.com/OPCFoundati.....issues/306,
We have added below nodes under ‘SecurityConfiguration’ in our configuration file
But the ApplicationConfiguration.SaveToFile() function removes the node "RejectSHA1SignedCertificates" from the configuration file .
Could you please advice us any solution for this?