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reVITAlize w/ Ryan Frank in Elkhart, IN
Ryan Frank
Wednesday, March 27, 2013 from 11:30 AM to 2:00 PM (EDT)
Event Details
Reserve Your Spot!
REGISTRATION DEADLINE is Monday, March 25!
Here's what we have planned:
Networking opportunities. You'll meet children's ministry leaders and volunteers just like yourself. And the cool part? These are people in your area!
A nice lunch. Come hungry. We'll have the food ready!
Great teaching from Ryan Frank. Ryan serves as Vice President of Innovative Strategies at Awana and is the Executive Director of KidzMatter. Ryan also serves on the board of directors for the International Network of Children's Ministry. He is the author of 9 Things They Didn't Teach Me in College About Children's Ministry (Standard). Ryan and his wife, Beth, live in Converse, Indiana, with their two daughters.
Games and prizes. We can't let you in on all the surprises, but we can tell you that no one will leave empty-handed!
You won't want to miss this epic event held at Bristol United Methodist Church in Bristol, Indiana!
A glimpse at the schedule:
11:30 - Lunch
12:00 - Game Time! (We'll give you some great game ideas to share in your ministry.)
12:30 - Music Time w/ Worship Artist Keith Conner
1:00 - Awesome Training from Ryan Frank (Ryan will address current trends and challenges in today's Kidmin world.)
2:00 - Prize Time! (Get a goodie bag worth over $100 plus lots more!)
Registration is limited to the first 85 people. Sign up and save your spot now!
When & Where
Bristol United Methodist Church
201 S Division St
Wednesday, March 27, 2013 from 11:30 AM to 2:00 PM (EDT)
Add to my calendar
Ryan Frank
PO Box 253, Converse, IN 46919


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Branch Banking and Retail Liabilities
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"My definition of success is to live your life in a way that causes you to feel a ton of pleasure and very little pain - and because of your lifestyle, have the people around you feel a lot more pleasure than they do pain."
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Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinson's disease patients
Parkinson's disease, caused by the loss of dopaminergic nigrostriatal projections, is a debilitating neurodegenerative disease characterized by bradykinesia, rigidity, tremor and postural instability. The dopamine precursor levodopa (l-dopa) is the most effective treatment for the amelioration of Parkinson's disease signs and symptoms, but long-term administration can lead to disabling motor fluctuations and l-dopa -induced dyskinesias (LIDs). Studies in rat striatal slices have shown dopamine to be an essential component of activity-dependent synaptic plasticity at the input to the basal ganglia, but dopamine is also released from ventrally projecting dendrites of the substantia nigra pars compacta (SNc) on the substantia nigra pars reticulata (SNr), a major output structure of the basal ganglia. We characterized synaptic plasticity in the SNr using field potentials evoked with a nearby microelectrode (fEPs), in 18 Parkinson's disease patients undergoing implantation of deep brain stimulating (DBS) electrodes in the subthalamic nucleus (STN). High frequency stimulation (HFS—four trains of 2 s at 100 Hz) in the SNr failed to induce a lasting change in test fEPs (1 Hz) amplitudes in patients OFF medication (decayed to baseline by 160 s). Following oral l-dopa administration, HFS induced a potentiation of the fEP amplitudes (+29.3% of baseline at 160 s following a plateau). Our findings suggest that extrastriatal dopamine modulates activity-dependent synaptic plasticity at basal ganglia output neurons. Dopamine medication state clearly impacts fEP amplitude, and the lasting nature of the increase is reminiscent of LTP-like changes, indicating that aberrant synaptic plasticity may play a role in the pathophysiology of Parkinson's disease.
- Parkinson's disease
- substantia nigra
- synaptic plasticity
- microelectrode recordings
- basal ganglia
Parkinson's disease is a hypokinetic movement disorder characterized by the loss of dopaminergic projections from the substantia nigra pars compacta (SNc) to various targets, including the striatum, the input of the basal ganglia. Reduced dopaminergic input to the striatum is thought to ultimately result in increased neuronal firing of the inhibitory basal ganglia output and disturbed firing patterns with increased synchronization (Albin et al., 1989; DeLong, 1990; Levy et al., 2002; Brown, 2003). Such changes bring about bradykinesia, rigidity, tremor and postural instability, although the underlying mechanisms leading to these symptoms are still poorly understood. Currently, levodopa (l-dopa) administration is the most common and effective therapeutic treatment. However, long-term l-dopa treatment is not without its own serious side effects. Abnormal involuntary movements (dyskinesias) are motor complications that arise in the majority of Parkinson's disease patients undergoing this treatment (Obeso et al., 2000a, b).
In addition to its dopaminergic nigrostriatal projections, the SNc also sends ventrally projecting dendrites to the substantia nigra pars reticulata (SNr) (Geffen et al., 1976; Korf et al., 1976; Cheramy et al., 1981; Robertson et al., 1991). However, little is known of the effects of dopamine released from these ventral SNc projections, either in animal models or humans, despite the fact that basal ganglia output structures seem intimately tied to dyskinesia. Deep brain stimulation (DBS) electrodes implanted in the subthalamic nucleus (STN), a basal ganglia structure that sends glutamatergic projections to the SNr and GPi, have proven remarkably efficacious as a treatment of Parkinson's disease and l-dopa induced dyskinesia (Kleiner-Fisman et al., 2006; Perlmutter and Mink, 2006). While STN DBS does not provide a greater degree of benefit for Parkinson's disease symptoms than optimal therapy with l-dopa (Krack et al., 2003; Pahwa et al., 2005), it does lessen the time a patient spends in the 'OFF' state when the benefit from an individual dose of medication has diminished, and permits the reduction of dopaminergic medications and their adverse side effects including dyskinesia (Moro et al., 1999; Jaggi et al., 2004; Kleiner-Fisman et al., 2006). DBS appears to mimic the effect of beneficial lesions instead of exacerbating the hyperactivity in the basal ganglia output neurons, but despite the discernible clinical benefits of STN DBS, its mechanism of action remains unclear.
Corticostriatal slice work suggests that abnormal involuntary movements such as dyskinesia are the result of alterations to synaptic plasticity at the basal ganglia input. Long-term potentiation (LTP) at the corticostriatal synapse is induced with high frequency stimulation (HFS) and reversed with low frequency stimulation (LFS) in healthy adult Wister rats (Picconi et al., 2003; Picconi et al., 2008). LTP is absent in dopamine lesioned (6-OHDA) rats, but can be restored with chronic l-dopa treatment. Additionally, several paired associative stimulation (PAS) studies have shown that motor evoked potential (MEP) amplitudes in the motor cortex of Parkinson's disease patients are modulated by dopaminergic medication state and that these changes are LTP-like in nature (Morgante et al., 2006; Ueki et al., 2006). PAS increased MEP amplitude in controls but not in patients OFF medication irrespective of their dyskinesia state. l-dopa administration restored the potentiation of MEP amplitudes by PAS in non-dyskinetic but not dyskinetic patients (Morgante et al., 2006). These findings indicate that LTP-like plasticity is absent from the motor cortex in a dopamine deprived state and, taken together, these studies in cortex and striatum suggest that a lack of plasticity in the absence of dopamine may play an important role in the disabling motor symptoms of Parkinson's disease. However, to this point, a suitable methodology for direct measures of synaptic plasticity in the human central nervous system has been lacking (Cooke and Bliss, 2006).
The aim of this study was to characterize synaptic plasticity at the basal ganglia output during in vivo recordings in Parkinson's disease patients undergoing implantation of DBS electrodes in the STN. Employing a novel methodology for evoking and measuring field evoked potentials (fEPs) in SNr using a pair of microelectrodes, we found the amplitude of these positive fEPs were modulated both by tetanizing trains and l-dopa, implicating extrastriatal dopamine actions in the pathophysiology of Parkinson's disease.
Patients and methods
Using intraoperative microelectrode recordings, we studied 18 patients undergoing stereotactic surgery for implantation of bilateral STN-DBS electrodes. The clinical characteristics of the patients and their daily doses of anti- Parkinson's disease medications are shown in Table 1. The group, consisting of 14 men and four women, had a mean age (±SD) of 58.9 ± 6.8 years and mean disease duration (±SD) of 13.3 ± 4.4 years. Six patients were most affected on their right side, while nine patients were most affected on their left side. Three patients were severely affected bilaterally. Patients normally underwent a minimum of 12 h of anti- Parkinson's disease medication withdrawal before testing, and were awake with local anesthesia for measures of synaptic plasticity in SNr following completion of the electrophysiological mapping of the STN. The UPDRS III OFF motor scores given in Table 1 are also following 12 h of anti-Parkinson's disease medication withdrawal. Six patients were studied first in the 'OFF' state following 12 h withdrawal and then in the 'ON' state after oral administration of 100 mg of levodopa (Sinemet 100/25) in the contralateral hemisphere. An additional six patients were studied only in the OFF state in order to avoid the occurrence of severe dyskinesia during surgery. In four cases the patient was given one tablet of Sinemet 100/25 immediately before the procedure as it was deemed medically necessary for the patient (Patients 4, 6, 8 and 9 in Table 1). UPDRS motor scores indicate that all patients had some degree of motor improvement when ON l-dopa with an average improvement (±SD) of 61.5 ± 13.0% in the ON state. The experiments were approved by the University Health Network and University of Toronto Research Ethics Boards. Patients provided written informed consent prior to the procedure.
|Age/sex/ worst side
|Disease duration (years)
|Medication (daily dose)
|l-dopa equivalence (mg/day)
|Improvements (%)
|l-dopa 800 mg, Pramipexole 2 mg, Amantadine 200 mg
|OFF and ON
|l-dopa 1100 mg, Pergolide 2 mg, Selegiline 10 mg
|l-dopa 675 mg, Pramipexole 2 mg
|OFF and ON
|l-dopa 1400 mg, Amantadine 100 mg, Carbergoline 2 mg
|l-dopa 1500 mg
|l-dopa 300 mg, Requip 16 mg
|l-dopa 1450 mg
|l-dopa 412.5 mg, Amantidine 100 mg, Mirapex 3 mg
|l-dopa 1150 mg, Requip 15 mg
|l-dopa 1150 mg, Tasmar 300 mg, Amantidine 200 mg
|l-dopa 1100 mg
|l-dopa 1600 mg, Comtan 800 mg
|OFF and ON
|l-dopa 825 mg, Mirapex 2.25 mg
|l-dopa 650 mg, Comtam 800 mg, Requip 20 mg
|OFF and ON
|l-dopa 1950 mg, Amantidine 200 mg
|OFF and ON
|l-dopa 1450 mg, Comtan 200 mg
|OFF and ON
|l-dopa 1600 mg, Comtan 800 mg
|l-dopa 500 mg, Mirapex 2.25 mg, Amantidine 300 mg
|58.9 ± 6.8
|13.3 ± 4.4
|1301 ± 409
|39.0 ± 8.9/15.1 ± 5.5
|61.5 ± 13.0
Surgical procedure and microelectrode recordings
Extracellular recordings were made with dual independently driven microelectrodes (about 25 μm tip length, axes 600 μm apart, 0.2–0.4 MΩ impedance at 1000 Hz) during the electrophysiological mapping procedure used to obtain physiological data for localizing the target for DBS quadripolar electrodes (Medtronic Model 3387, Minneapolis, MN). Recordings were amplified 5000–10 000 times and filtered at 10–5000 Hz (analog Butterworth filters: high-pass, one pole; low-pass, two poles) using two Guideline System GS3000 amplifiers (Axon Instruments, Union City, CA). Microelectrode data were sampled and digitized at 12 kHz with a CED 1401 [Cambridge Electronic Design (CED), Cambridge, UK] and EMG of ipsi- and contralateral wrist and foot flexor and extensor was sampled at 500 Hz to monitor any dyskinetic movements.
Pre-surgery, the tentative STN target was identified by brain imaging (MRI) on the basis of the stereotactic coordinates and direct imaging of STN. Coordinates of the tentative target were 12 mm lateral to the midline, 2–4 mm posterior to the mid-commissural point and 3 mm below the AC–PC line (Hutchison and Lozano, 2000) Target nuclei were then localized via characteristic neuronal discharge patterns described elsewhere in detail (Hutchison et al., 1998). Briefly, after passing through thalamus and STN, the SNr was identified by the presence of neurons with a significantly higher discharge rate and more regular firing pattern (versus STN). The SNr neurons also displayed characteristically low thresholds (2–4 μA) for microstimulation-induced inhibition of firing (Dostrovsky et al., 2000). An example of a typical trajectory is shown in Fig. 1. All recording sites were deemed to be near the region of the soma and the spike amplitude was continuously monitored in order to confirm stability of electrode position.
fEPs were recorded from one electrode while stimulating with single pulses (100 μA, 0.3 ms biphasic pulse width) from a second electrode separated mediolaterally by 0.5–1.0 mm at the same dorsoventral level within the SNr. Depth profiles were examined in some cases by moving the stimulating electrode in 250 um increments above and below the recording site for up to a 3 mm separation. Input–output curves were constructed by varying the pulse width (0.05, 0.1, 0.2, 0.3, 0.5 and 1 ms) in order to avoid saturation of the fEP amplitude during the tetanus. A paired pulse response (PPR) curve was constructed for one patient using a variety of paired pulse interstimulus intervals (20, 30, 50, 100 and 200 ms) by comparing the ratio of the peak amplitude of the second fEP to the first fEP.
After obtaining a stable baseline of peak fEP amplitudes at 1 Hz, HFS was given, consisting of four 100 Hz trains, 2 s in length, repeated four times every 10 s (100 μA, 0.3 ms pulse width). Blocks of ten pulses were tested every 30 s for at least 2 min, or until a stable plateau had occurred.
Plasticity was quantified using fEP amplitudes in both OFF and ON dopaminergic medication states, with the first side being done after 12 h off medication and the second side following administration of Sinemet 100/25®. Typically, 25–30 min had elapsed between the time of administration (Sinemet 100/25® was given as recording began on the 'ON' track) and SNr testing. The sites where synaptic plasticity was tested are shown in Fig. 1 and were determined by track reconstruction using neurophysiological landmarks and a customized brain atlas-based programme.
Analysis of neuronal activity and statisitics
The recordings were analyzed offline using Spike2 software version 5 (CED, Cambridge, UK). Post stimulus time histograms (PSTHs, 250 us bin width, time base 150 ms normalized to firing rate in hertz) were constructed of the high frequency spiking of putative GABAergic output neurons of SNr in two patients. Spike analysis was performed using a spike matching template algorithm in Spike2. For PSTHs, only those spikes identified as belonging to the same template were included, i.e. a single unit was used for analysis.
fEP amplitudes were normalized to a percent scale, with the average of baseline measures in each patient considered as 100%, and sorted by medication state (OFF versus ON). Synaptic potentiation was evaluated in each patient in all medication states by fitting an exponential function to the fEP amplitudes using Sigma Plot software (SPSS, Chicago, USA): y = y0 + ae−bx where y0 is the plateau value (relative to baseline fEP amplitude) to which the function decays, a is the difference of the maximum (first) value of the exponential curve to yo, and b describes the steepness of the curve. Population data was fit with a regression line if the fit had a significance value of P < 0.05.
All statistical comparisons were conducted using Sigmastat software (Systat Software Inc., San Jose, USA). A two-way ANOVA was performed on the normalized data testing the main effects of DRUG (ON versus OFF) and TIME following HFS. A post hoc Bonferroni t-test tested all pairwise comparisons between ON and OFF at each time point.
fEP test site location
All sites tested for a field evoked response were located in the SNr. We tested a total of 23 SNr sites in 18 patients. The approximate location of test sites included in the study is shown in Fig. 1. Recordings took place in dorsolateral SNr and test locations were independent of medication state. fEPs could not be evoked in the STN region using the stimulation protocols described above.
Field potential characteristics
Blocks of 1 Hz test pulses at incrementally increased stimulation distance were conducted in three patients and revealed a positive field persisting for 2.5 mm dorsoventrally through the SNr with the peak field amplitude having a latency (±SD) of 5.5 ± 0.8 ms (Supplementary Fig. 1). Post stimulus time histograms of the cell firing were analyzed in two cases and both revealed that the positive peak of the fEP occurred during inhibition of firing (Fig. 2). Additionally, the enhancement of fEP amplitude in the ON state post HFS was associated with a slower recovery of the spontaneous firing rate (Fig. 2), and an overall reduction in firing rate was observed for up to 30 s (Supplementary Fig. 2).
A paired pulse response curve was constructed in a patient by comparing the paired pulse ratio before and after high frequency stimulation at a range of interstimulus intervals (Fig. 3). Paired pulse depression is most apparent at short (20 and 30 ms) interstimulus intervals, both before and after HFS, evidenced by small paired pulse ratios (PPR). Before HFS, the PPRs at 20 and 30 ms intervals were 0.48 ± 0.018 and 0.76 ± 0.014, respectively. Following HFS, paired pulse depression was similar in magnitude at short interstimulus intervals (20 ms = 0.31 ± 0.11; 30 ms =0.74 ± 0.19). However, as the interstimulus interval increased, there was a marked increase in PPR. Before HFS, the PPRs for intervals of 50, 100 and 200 ms were 1.10 ± 0.050, 1.12 ± 0.051 and 1.07 ± 0.072, respectively. Following HFS the PPRs at the same intervals were 0.88 ± 0.037, 0.94 ± 0.065 and 0.94 ± 0.072. Thus, paired pulse depression is greatest at 20–30 ms, and is significantly greater in all tests following HFS (P = 0.015). Interstimulus intervals causing maximal paired pulse depression (20 and 30 ms) are of the same time scale as the inhibition of SNr firing to the single pulses used for evoking the fEPs shown in Fig. 2.
Dopaminergic modulation of synaptic plasticity in the SNr
l-dopa treatment of Parkinson's disease patients markedly improved motor UPDRS in all patients preoperatively (Table 1). Note that the total daily l-dopa equivalences are approximately 10× greater than the dose administered intraoperatively. Thirteen measures of fEP amplitude were made in patients in the OFF state. In these patients (see Table 1 for daily medication use and l-dopa equivalence), HFS did not induce a lasting change in fEP amplitude (Fig. 4A). A typical example is shown in Fig. 4C (open circles), where a modest increase in fEP amplitude returned to baseline by ∼50–100 s. However, in some patients a larger initial increase fEP amplitudes was seen, with a subsequent rapid decay toward baseline (Supplementary Fig. 3). In this case, the patient reported that he was only about 50% of his worst OFF state. We found a close inverse linear relation (r2 = 0.81, P < 0.001) between the patients' clinical OFF rating based on UPDRS III motor subscale (high values indicate worse motor symptoms) and the peak of activity-dependent synaptic plasticity induced by HFS (Fig. 5A). Patients with a higher UPDRS OFF score underwent less change in fEP amplitudes following HFS. The population data for the OFF group shown in Fig. 5B (open circles) reveals a significant initial 28.9 ± 4.9% increase in fEP amplitude following HFS that then decayed by 100 s to baseline. Regression analysis on population data from the OFF group revealed a yo fEP amplitude plateau value no different than baseline (2.3 ± 3.8% above baseline).
Following administration of l-dopa, the same HFS protocol induced a much larger increase in fEP amplitudes (Fig. 4B). Such fEP amplitude increases persisted over several minutes of testing (Fig. 4C; closed circles). There was no significant correlation between patients' clinical ON rating based on UPDRS III motor subscale and the maximum value of activity-dependent synaptic plasticity induced in the ON group (r2 = 0.02, data not shown). Twelve measures of fEP amplitude were made in patients in the ON state (Fig. 5B; closed circles). The largest fEP amplitude measures occurred immediately following the tetanus (200.3 ± 19.5%) with subsequent measures showing a decrease in fEP amplitude at each time point with an exponential decay function. Regression analysis on population data from the ON group's fEP amplitude measures revealed a yo plateau value of 29.3 ± 5.2% above baseline. The regression function for the OFF and ON groups was highly significant with plateau values at P < 0.001. Additionally, for the ON group, a b value describing the steepness of the curve was determined to be 0.019 ± 0.0036 (P < 0.05), which corresponds to a half-life (1/0.019) of 52.6 s for the decay function. The OFF group's b value was slightly higher at 0.0258 ± 0.0152 (not significant), corresponding to shorter half life of 38.8 s.
A two-way ANOVA of population data revealed a highly significant difference between ON and OFF groups (df = 1, f = 799, P < 0.001) and a significant difference between time points (df = 5, f = 69, P < 0.001). It also revealed an interaction between medication state and time, i.e. the ON/OFF amplitude is also dependent on the time of measurement (df = 5, f = 17, P < 0.001).
The present study describes the characteristics of the positive fEP in the SNr of Parkinson's disease patients, both OFF and ON dopaminergic medication. It is unique in providing human data supporting dopamine regulation of synaptic plasticity in the human basal ganglia, and suggests an important role for activity-dependent synaptic plasticity in basal ganglia dysfunction.
The SNr receives numerous projections from a multitude of sources, chief among them the inhibitory GABAergic projection from medium spiny neurons of the striatum (Parent and Hazrati, 1995a, b; Bolam et al., 2000). The external segment of the globus pallidus (GPe) also sends a small, but significant, GABAergic contribution to the SNr (Smith and Bolam, 1989). Additionally, the STN sends excitatory projections to the SNr. These glutamatergic projections from the STN to the output structures of the basal ganglia have been shown to form asymmetric synapses (Ribak et al., 1981), primarily on the dendrites and shafts, but with a very small number of boutons terminating on the somata (Kita and Kitai, 1987). The vast majority of the terminals in the region form symmetric synapses with the somata and are GABAergic in nature (Ribak et al., 1979, 1981). The rapid inhibitory responses characteristic of GABAergic transmission in basal ganglia structures are mediated by the activation of GABAA receptors, which are found exclusively at symmetric synapses (Galvan et al., 2006).
Based on several observations, our stimulation protocol is primarily activating the inhibitory GABAergic projections, either from the striatum or the GPe. During our field recording measurements, all of the field potential measurements in the SNr are positive. Precht and Yoshida demonstrated the inhibitory nature of a positive field in the SNr by observing that spontaneous activity of neurons located in the SNr was strongly suppressed conjointly with the occurrence of the caudate-evoked (GABAergic) positivity (Precht and Yoshida, 1971; Yoshida and Precht, 1971). They also demonstrated that the time course of the intracellularly measured IPSP was the same as the positive fEP, and that the potential was blocked in its entirety by the GABA antagonist picrotoxin. In the present study, we also saw a positive fEP and its time course was the same as the inhibition of SNr activity, suggesting that the observed stimulation-evoked positive fEP is associated with an inhibitory event, most likely local GABA release.
Our paired pulse studies also point to activation of the GABAergic projections. In the SNr, dopamine D1 receptors are present at the terminals of the GABAergic striatonigral projection (Altar and Hauser, 1987; Barone et al., 1987). Previous striatal studies have shown that paired pulse depression predominates at synapses under the influence of D1 receptors, whereas paired pulse facilitation predominates at synapses at which D2 receptors are active (Guzman et al., 2003). In this study, paired pulse depression was evident at short interstimulus intervals prior to HFS and at all interstimulus intervals following HFS, suggesting that stimulation was involving the presynaptic D1 receptors. Slice studies indicate that stimulation of D1 receptors found in the SNr increases extracellular GABA (Floran et al., 1990; Aceves et al., 1991; Aceves et al., 1995; Timmerman and Abercrombie, 1996) and that this facilitated GABA release in turn enhances GABAA IPSCs in non-dopaminergic neurons of the SNr (Radnikow and Misgeld, 1998). Taken together, these observations suggest that our positive fEP is inhibitory and GABAergic in nature and that dopamine plays a role in presynaptic regulation of GABA release in this region. Dopamine action in the basal ganglia is usually considered in terms of its modulation (or lack thereof in Parkinson's disease) of indirect and direct striatal output via the dopaminergic nigrostriatal projection. In this region, dopamine concomitantly provides excitatory inputs mediated by D1 receptor activation in the direct pathway and inhibitory inputs mediated by D2 receptor activation in the indirect pathway (Albin et al., 1989; DeLong, 1990). However, dopamine can also have dramatic effects in other regions of the basal ganglia. Indeed, nigral dopamine depletion has been shown to impair motor performance independent of striatal dopamine neurotransmission, while increased nigral dopamine release can counteract striatal dopamine impairments (Andersson et al., 2006). Here, we posit that dopamine can also act directly in the SNr by influencing synaptic plasticity at striatonigral synapses.
Previous studies have suggested a link between LTP and dopamine at the corticostriatal synapse. Indeed, LTP is absent in dopamine lesioned (6-OHDA) rats, but can be restored with chronic l-dopa treatment (Picconi et al., 2003). Here, we sought to characterize activity-dependent synaptic plasticity in basal ganglia output neurons in 18 Parkinson's disease patients, all of whom experienced a significant improvement in motor function during their preoperatively measured ON state (Table 1).
HFS did not induce a lasting change in fEP amplitude in patients in the OFF state. However, there was a strong correlation between the patients' clinical OFF rating based on the UPDRS (high values indicate worse motor symptoms) and the initial degree of activity-dependent synaptic plasticity that could be induced in the same 12 h defined OFF state. Although the long-duration response to l-dopa (Nutt et al., 1995) and the variable half-life of some dopamine agonists (Rinne et al., 1997) could have interfered with the severity of the OFF state, 12 h of anti-Parkinson's disease medication withdrawal induced a noticeable increase in UPDRS III motor scores in the patients included in this study (Table 1), and all measures of fEP amplitudes were done following a similar period of anti-Parkinson's disease medication withdrawal.
Comparatively, during their intraoperative ON state, l-dopa intake coupled with HFS caused an increased fEP amplitude response in a manner reminiscent of LTP-like changes, in addition to decreased SNr firing rates. When including all patients categorized as being ON, there was no correlation between patients' clinical ON rating based on UPDRS III motor subscale and the maximum inducible activity-dependent synaptic plasticity. The lack of correlation in the ON group is likely the result of variability in intraoperative ON states. Such variability could be derived from a number of sources including, but not limited to, ineffectiveness of a single dose of l-dopa in patients taking high doses, the timing of the transient ON period of a single dose, and when the measurements were performed.
The rate model predicts that the administration of l-dopa reduces the elevated firing rates of basal ganglia output neurons in the OFF state (Hutchison et al., 1997). Our observations of lowered SNr firing rates, coupled with enhanced inhibitory synaptic plasticity are consistent with the rate model, and give further hints as to how the loss of dopamine can directly affect GABAergic striatonigral synapses.
Limitations of the current study prevented the testing of whether dopaminergic regulation of GABAergic activity was achieved by a pre or postsynaptic mechanism, but previous work suggests that such actions are likely presynaptic. Enhancement in miniature inhibitory post-synaptic currents (mIPSCs) in the SNr via D1 receptor activity has previously been shown to be coupled with the formation of cAMP in the pre synaptic terminal (Jaber et al., 1996). The enhancing effects of D1 receptor stimulation on mIPSC activity in the SNr can be mimicked by forskolin, which is known to activate adenylate cyclase (Radnikow and Misgeld, 1998). A more recent study has proposed that D1-receptor mediated GABA release involves the cAMP/PKA pathway, with PKA ultimately phosphorylating key targets involved with GABA exocytosis, such as P/Q-type voltage-activated Ca2+ channels (to enhance Ca2+ influx), synapsins (to enhance vesicle trafficking) and SNARE proteins (to enhance vesicle docking, priming, and fusion) (Arias-Montano et al., 2007). Nevertheless, rapid postsynaptic changes in the SNr may also affect GABAergic activity. Recent work has demonstrated that neuronal activity can directly regulate the number of cell surface GABAARs by modulating their ubiquitination and consequent proteosomal degragation in the secretory pathway (Saliba et al., 2007). However, a link between dopamine and the level of GABAAR insertion and subsequent post-synaptic accumulation has not been established to date, but demonstration of such a link would support a post-synpatic action of dopamine. Dopamine is thought to have diverse and complex actions on the physiological activity of the basal ganglia. It can both inhibit and enhance neuronal activity, depending on the level of membrane depolarization and physiological state of the neuron (Calabresi et al., 2007).
The results here indicate that synaptic plasticity can be measured in basal ganglia output neurons of Parkinson's disease patients and that the presence of plasticity is sensitive to low doses of l-dopa. In the absence of dopaminergic medication, plasticity is lacking following HFS. Conversely, following administration of dopaminergic medication, synaptic plasticity is facilitated in the SNr by HFS. The close correlation between motor behaviour and the potential of nigral synapses to undergo activity-dependent changes suggests that dysfunction of direct dopaminergic action at the basal ganglia output plays an important role in Parkinson symptomatology.
Supplementary material
Supplementary material is available at Brain online.
The authors would like to acknowledge Joo Lee, Jonathan Brotchie and the support of the Parkinson Society Canada.
- Abbreviations:
- Abbreviations
- deep brain stimulating
- fEP
- field evoked potential
- high frequency stimulation
- long-term potentiation
- SNc
- substantia nigra pars compacta
- SNr
- substantia nigra pars reticulata
- subthalamic nucleus
- © The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: email@example.com


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General Banter / Re: Friday Travel League 2/1/13?????« on: February 02, 2013, 06:30:05 AM »
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Tony and I.
Southern Grandview is a black hole for everyone :\
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Let me check with a guy who lost car keys there this fall I may know the owner. (But come to think of it, he may not own that car anymore.) I'll still check with him.
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Michelle Ochs and Carly Cushnie at a party in Venice Beach toasting Cushnie et Ochs' collaboration with Forward by Elyse Walker.
A look at the Rick Owens store in Milan.
Paris Men's Fashion Week street style
Kerry Washington in Dolce & Gabbana and Kevin Hart at the BET Awards.
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The first high jewelry collection by Hong Kong-based Qeelin was showcased at the "Mogaoku in Paris" exhibition.
Pilar Moraga, the subject of this week's Model Call, outside WWD's office.
A designer favorite, Keira Knightley showed off her effortlessly chic style this week while promoting her new film, "Begin Again."
Debbie Harry
For the 2014 edition of her Black Label Masterpiece Butterfly, Cindy Chao teamed with Sarah Jessica Parker.
Spike Lee talked to WWD about his third and final collaboration with headwear brand New Era, called the Heritage Series.
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Nip Pellew
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- Nip Pellew — one of the greatest fielders of all time
- Nip Pellew, born September 21, 1893, was a member of Warwick Armstrong's splendid Australian team of 1921 and one of the best outfielders the game has seen. Arunabha Sengupta looks back at the life and career of the man who is considered greatest ...
- Cuts and Glances: Adelaide electric choice for first night Test match
- One star player, Gil Langley, went on to represent Australia after the war, while a previous Test cricketer, 'Nip' Pellew, was a senior administrator.
- Arthur Dolphin: Yorkshire stumper, hatless umpire
- England did not stand a chance against Warwick Armstrong's men: with three world-class all-rounders (Jack Gregory, Charles Kelleway, and Armstrong himself), backed by Herbie Collins, Charlie Macartney, Nip Pellew, Warren Bardsley, and Arthur Mailey, ...
- History of Ashes: How the urn changed hands, Part 2 of 4, of Bradman and Bodyline
- In addition, there were Herbie Collins (557 runs at 62); Nip Pellew (319 at 54); Charlie Macartney (260 at 87); and Arthur Mailey (36 wickets at 26). England had no chance. 1926: Hobbs and Sutcliffe at The Oval.
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The Bin Laden tapes
Started by Guest , Dec 13 2001 11:48 AM
1 reply to this topic
#1 Guest__*
Posted 13 December 2001 - 11:48 AM
So did anyone see the Bin Laden tapes? I just read the transcript and looked at a few stills from the tape. Looks like no great revelation. Only confirms our suspicions that he is guilty.
It still amazes me how someone can plan the cold blooded murder of thousands and think of it like winning a sporting event (I'm referring to the reference to winning a soccer game). Oh well, I'm pretty sure we will get him. Dead or alive.
#2 Guest__*
Posted 13 December 2001 - 12:40 PM
I have a feeling we will have him by the end of the month.
Now I am waiting for the Bin Laden Video on DVD, with enhanced features and sound and Dolby Digital 5.1 audio. (Just kidding!)


text:
Editor's Note: For those who are wondering about the retro title of this black history series, please take a moment to learn about historian Joel A. Rogers, author of the 1934 book 100 Amazing Facts About the Negro With Complete Proof, to whom these "amazing facts" are an homage.
(The Root) — Amazing Fact About the Negro No. 30: What is one of the most novel ways a slave devised to escape bondage?
Here you see a man by the name of Henry Brown,
Ran away from the South to the North,
Which he would not have done but they stole all his rights,
But they'll never do like again.
Chorus: Brown laid down the shovel and the hoe,
Down in the box he did go; No more slave work for Henry Box Brown,
In the box by Express he did go.
–"Song Composed by Henry Box Brown on His Escape From Slavery," Narrative of the Life of Henry Box Brown, Written by Himself
Job ben Solomon, as we saw in an earlier column, was the first and probably the only slave who literally wrote his way out of American slavery. He penned a letter in Arabic to his father, from his jail cell in Maryland, which led quite circuitously to its translation at Oxford, England, and then to his purchase, release and repatriation to Senegambia in 1734 — only after a stop in London where he was feted by British royalty and the intellectual elite, had his portrait painted and a book about his remarkable escapades published.
But another slave plotted his own escape from bondage in even more astonishing and harrowing way, and his name was Henry Brown.
If Job ben Solomon expressed his desperate quest for freedom in a letter, Henry Brown expressed his own desperate desire to be free in an even more novel form: He actually mailed his own body from slavery to freedom, from Richmond to Philadelphia, from the slave state of Virginia to the free state of Pennsylvania, a distance of 250 miles.
Brown was the ultimate "escape artist," as Daphne Brooks brilliantly labels him in her book Bodies in Dissent. He was a precursor, she argues, to Houdini. And as we shall see, he not only performed his amazing — and quite dangerous — escape once, but reprised part of the journey during a lecture tour in England. But I get ahead of my story.
Henry Brown was born into slavery on a plantation called "The Hermitage" in Louisa County, Va., around 1815, fairly close to Charlottesville, where Thomas Jefferson was still living at Monticello. Upon his master's death, when Brown was 15, he was sent to work for his late owner's son, William, in his tobacco factory in Richmond. In about 1836, he married another slave (curiously, with their owners' consent), a woman named Nancy, who was owned by a bank clerk. Brown was able to rent a house for his family. Together, they had three children.
Over time, Nancy was sold twice. Her third owner, Samuel Cottrell, actually charged Brown $50 a year to keep Nancy from being sold. But in August 1848, Cottrell sold Nancy anyway, along with their three children, to a Methodist minister in North Carolina. Brown raced to the jail where his family was being held, but it was too late. As they were shuffled through the streets of Richmond, Brown held Nancy's hand for four miles. Nancy and the three children were marched on foot along with 350 other slaves, in the horrendous second Middle Passage, all the way to North Carolina. Nancy was pregnant with their fourth child. The two would never see each other again.


text:
Check out Episode 5 of VTV's entertainment and fashion program The Scoop. Host Lauren Mandel and her team of fashion and pop culture experts guide you through the latest in music, movies, and what to wear.
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Womens Resource of Greater Houston
Rating: 4.93 stars 27 27 reviews
730 North Post Oak Road, Suite 204 Houston TX 77024 USA
The Women's Resource of Greater Houston provides free financial education and research so that women and girls have the knowledge they need to make sound financial decisions and improve their lives.
Since we were founded in 1990, more than 30,000 Houstonians have completed a class.
Target demographics:
Low income women and girls
Direct beneficiaries per year:
5,827 class participants and 194 Project LEAD students.
Geographic areas served:
48 zip codes in Harris and Ft. Bend Counties
The Women's Resource annually teaches free personal finance classes to 6,000 low income and financially illiterate Houstonians in 38 zip codes. Using the acclaimed FDIC Money Smart and Department of Labor Wi$e Up curricula, we help those outside the financial mainstream enhance their money skills and build financial knowledge and confidence. Now in its ninth year, Project LEAD remains the only research based program for at risk ninth and tenth grade girls that proactively counters the high dropout rate, helps girls avoid financial pitfalls, and teaches life skills. LEAD reaches 200 girls each year and is held onsite at public and charter schools in the Fall and Spring semesters.
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Reviews for Womens Resource of Greater Houston
I believe in the Women's Resource of Greater Houston's mission. They are a great organization providing a valuable service that is much needed. Financial Literacy is vital to an individual's survival. And all too often is something that is taken for granted by many. By educating young girls and women how to budget and plan for their futures they are setting the path for financial stability. I will continue to support them in many ways through volunteering, donating, and creating awareness every opportunity I have.
Rebeca Rodriguez
Junior Partner


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AdvocateThe Right to Know Coalition advocates for improved access to information, open government and transparency within Nova Scotia's provincial government.
EducateThe Right to Know Coalition strives to educate our stakeholders by providing up to date information on the latest changes, movements, and initiatives related to our quest for improved access to information and transparency.
MobilizeThe Right to Know Coalition needs your input for our latest initiative. Click the link below to find out how you can help.
Latest News
Get involved With Right to Know! Posted May 29, 2016 By Admin
My name is Charles and I am the newest volunteer for the Nova Scotia Right to Know Coalition, a non-profit legal advocacy organization that campaigns
Study Finds HRM Needs to Improve its Openness Posted Feb 16, 2016 By Admin
Today, the Right to Know Coalition of Nova Scotia is launching the results of a study into the openness policies of the Halifax Regional Municipality
Liberals and NDP Pledge Access to Information Reform Posted Oct 16, 2015 By Admin
One month ago, a coalition of 22 NGOs from across Canada signed a Joint Letter calling on the leaders of Canada's political parties to make


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Security at World Youth Day has always been an issue. When millions of people gather for a public event, in general, security can be a challenge. Add to this the fact that the pope will be on the scene and the concerns about safety grow drastically.
But Pope Francis doesn't seem to be very concerned about security at all. On the streets of Rio de Janeiro, he appeared to relish in the fact that his car made a wrong turn and people mobbed the vehicle to try to touch him or just get a glimpse of him.
After a week of what could be a draining non-stop schedule of events, Pope Francis, in his late 70s, was fed by the energy of the young people who surrounded him:
This trip has been very good; spiritually, it has done me good … meeting people always does good, as in doing so we receive many good things from others. With less security, I was able to stay with the people, to embrace them, greet them, without armored cars … it is the security of trusting in people … yes, there's always the danger of encountering a madman, but then there is always the Lord who protects us, isn't there? It is also madness to separate a bishop from his people, and I prefer this kind of madness
In today's world, we often live in fear. And Pope Francis wants us to understand that we need not fear one another. I've been writing a series of posts on my personal blog about the George Zimmerman verdict and death of Trayvon Martin, which include reflection on my own fear of growing up in a dangerous neighborhood. I was taught to fear the other in that neighborhood and there is good and bad in that fear. After all, there are madmen and people who do wish to do others harm in the world. However, the pope also sees madness in this fear. Fear separates us and keeps us in armored cars and behind locked doors. Fear stops dialogue and hinders work for peace in the world. Fear keeps rival gangs shooting at one another instead of coming together to solve the problems of poverty and crime in their neighborhoods and working for peace and justice.
Pope Francis has seen that fear and knows the results of it. All those years of visiting people who lived in the slums of Argentina have changed him. The experiences have given the pope a heart for the poor that does not allow the walls of fear to separate him from the people who need him. Those that have no voice need to see that the pope will be their voice. They need to see that the pope will be present to them.
Check this out:
Enough said. Way to go, Papa Francisco. Enjoy the quiet for a few days. You earned it.


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"Late nights and early mornings are part of my professional reality, but looking exhausted or sounding deflated is simply not an option. A weekly or at very least biweekly visit to BBS sorts me out...their nutritional supplements ensure sustained energy and step up where late-night junk food fails me!"
"I used to get frustrated with the fact that I'm so often cast as the flirty seductress in series… but I realised that it does make sense, because the team here do achieve staggering results! My skin appears nourished; pores are smaller and its natural tendency to appear red, has been tamed. "
"I have found my new home at Best Body Skin. I've had skin rejuvenation for an instant lift and glow, a non-surgical rhinoplasty, Botox®, filler and The Vampire Facelift. They are so professional, but they also know how to make you feel at home. Thank you again Hardus and the Best team – you are my Team of Choice!"
- Hardus Bester CEO Best Body Skin
- Janelle Monáe
- Harry Winston
The Cosmelan peels and carboxytherapy treatments I've had at Best have significantly reduced my acne marks and scars and have helped enormously with my terrible pigmentation. The Best team has taken such good care of me, and more importantly, their post-treatment care is excellent. What to expect The procedure is especially effective in treating static wrinkles, expression lines, pigmentation like freckles or sun spots, scars, vascular conditions like blood-filled blisters or a constant flush of facial redness, and loss of skin tone.
It's about what you put in. Much like a car that needs fuel, oil and water to work properly, our bodies require very specific foods to function. We can HOOK you up with the Science- Backed program today!
Results vary from one individual to the next and testimonials and Before & After images on this website represent a client's individual response to our treatments and products. We cannot guarantee a similar outcome for all.
An effective skincare regimen is essential in maintaining and improving skin health. The SkinCeuticals product philosophy is built around the three fundamental principles of prevention, correction, and protection. SkinCeuticals is also committed to advanced skincare products that are backed by science.
With high potency formulas, which are proven to penetrate optimally into skin, the signs of ageing are corrected and future damage is prevented. This is all possible due to its high concentration of antioxidants, which results in no visible peeling after the peel. SkinCeuticals products are not only used by medical spas and pharmacies, but are also used and recommended by dermatologists and plastic surgeons.
This professional skin treatment system is designed to ensure that you have brighter and healthier looking skin. Optiphi consists of five different peel strengths, which include 25%, 30%, 35%, 50% and 70%. There is no visible peeling after the peel.
Entrepreneur Hardus Bester is the founding member and Marketing Director of Best Body Skin, Aesthetic Clinic. Having spent the past 20 years in the industry (he pioneered the aesthetic application of Botox in South Africa) his passion has been evident in an illustrious track record and a stellar client list that includes some of SA's most loved celebrities. For those in-the-know, Bester is the go-to person for all things aesthetic. With Best Body Skin, he intends to further the legacy of innovation and quality that has always characterized his success in the industry. Bester passionately believes in the potential of life-changing aesthetic treatments, "we have helped many clients achieve incredible results this is what makes what we do so rewarding". Along with his commitment to service excellence, clients can rest assured that they are being taken care of by some of the most capable and experienced hands in the business.
Dr. Lizelle Botha graduated in 1992 from the University of the Orange Free State. In her capacity as Assistant Surgeon, she is involved in open-heart surgery in the Cardio Thoracic Department at Vergelegen Hospital in Somerset-West. She received training in aesthetic medicine through the following pharmaceutical companies: Genop, Lamelle, Twinmed, Leenyx, Quest and Starfish. She describes aesthetic medicine as a personal passion and has been practicing in this discipline since 2004. She is an authority on minimally invasive and non-invasive techniques to enhance facial features.
Dr. Jan Nel graduated in 2008 from the University of Stellenbosch and currently practices as a GP in Cape Town. He is qualified in the ATLS, AMLS and ACLS emergency care and his patients may be rest assured that they are in very capable hands. Very early in his career as a medical doctor, aesthetic medicine became a particular field of interest, and while doing his internship and community service, Dr. Nel completed several aesthetic and skin rejuvenation courses. Dr Nel constantly updates his portfolio attending the latest seminars and courses in cutting edge Aesthetic techniques and procedures medicine
Having spent many years in the beauty industry we can definitely attest to the fact that when you feel good about yourself, you are more confident, inspired and geared for what life throws at you.
Our philosophy at Best Body Skin is to bring out the best in you. We assess each client's needs, starting by identifying your biggest concern and then following with the most effective course of action to reach your goal. We believe in treatments that respect the skin's integrity and offer long term results, quick fixes are superficial, temporary measures. Our proven method addresses your internal wellbeing integrated with state of the art external treatments that deliver the best results. An effortless wellness evaluation typically starts the process and a glowing, natural complexion is the end result.
We are proud of the recognition Best Body Skin received as one of SA's top 6 clinics in the Medi-Spa Awards category.
We look forward to making you glow inside and out
Best Love


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This program is intended to provide 7 hours of RACE accredited continuing education.
Dr. Beckman's radiographic positioning guide, lecture slides and lunch are provided.
For more information, please visit http://veterinarydentistry.net/nashville-tennessee/
10/19/2016Petplan Reveals a Sneak Peek at Potential Winners of the 2017 Veterinary Awards
10/7/2016Boehringer Ingelheim Vetmedica Inc. Enters Into an Agreement to Sell U.S. Feline, Canine and Rabies
9/26/2016 » 10/27/2016ECG Interpretation Module 2
9/27/2016 » 10/28/2016Communication & Conflict Management Module 2: Conflict Management, Resolution, & Mentoring


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Feb 25, 2013
Fitch has put Mexican Homebuilders Urbi, Javer, Homex, and Corporacion GEO on rating watch negative, it says, citing government policy likely to push "vertical...
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Athlete Profile
Athlete: Robert Hammond
- Region:
- South Central
- Team:
- C4 CrossFit Greatwood
- Affiliate:
- C4 CrossFit Greatwood
- Gender:
- Male
- Age:
- 48
- Height:
- 5'11"
- Weight:
- 181 lb
|Filthy 50
|Fight Gone Bad
|Sprint 400m
|Run 5k
|Clean & Jerk
|215 lb
|165 lb
|335 lb
|Back Squat
|275 lb
|Max Pull-ups
Weak and very asthmatic growing up, yet a decent athlete. Played and loved high school football. Stayed in decent shape in adulthood with running and globo gym type weight lifting. Found crossfit late 2006. Did for several years at Bally's, with people staring at us. At the time, there was one crossfit gym in Houston area, about an hour away. Was going to open up a gym, but found Atomic Crossfit close by. Great community and great coaching staff. CrossFit has greatly enriched my life,.. not just total fitness but mental fitness and toughness too. Ultimately, it's made me a better person in all aspects of my life, and continues to foster growth in all areas.
How I Eat
I weigh and measure my food
I eat strict Paleo
I eat quality foods but don't measure the amount
I eat 1-3 full cheat meals per week
My eatting fluctuates. If the scale battery goes out, it may be months before I replace it. Generally I used to eat Paleo/Zone with some fats replacing carb blocks. Lately, trying Atkins/Ketogenic.
How I Train
I workout mostly at a CrossFit Affiliate
C4 Greatwood
My Athletic Background
I played youth or high school level sports
My Experience With CrossFit
I began CrossFit by trying it alone (without a coach)
I have had a life changing experience due to CrossFit
Pretty consistent since 2006, continuous progress. My enthusiasm and love for it has only grown too. Overall makes me a better and better person. This last year and a half I've backed off a little, stopped taking it as serious as in the past. Learned to scale some and listen to my body more, injuries decreasing and overall happiness increasing... fitness still progressing even with PRs fluctuating.
My Work/Rest Schedule
I usually only do 1 workout a day
I typically rest 4 or more days per month
Usually about 2-3 wods a week, sometimes 4.
How long have you been doing CrossFit?
4+ years
Started CrossFit in Oct. of 2006.


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Watch Scrubs Season 9 Episode 4 online via TV Fanatic with over 6 options to watch the Scrubs S9E4 full episode. Affiliates with free and paid streaming include Amazon, iTunes, Vudu, YouTube Purchase, Google Play, and Hulu Plus.
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Episode Details
With their wives out of town, J.D. and Turk go out partying; Kelso bids a fond farewell to Ted and Gooch.
- Show:
- Scrubs
- Season:
- Scrubs Season 9
- Episode Number:
- 4


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In September, five months into the long season, you don't want to be asking questions. You want to know what you've got and what you'll get from your players. But going into this weekend's series against the Pirates, the Cardinals had a pretty big question mark to deal with as far as the recent struggles of staff ace Adam Wainwright. After Saturday night's well-spun start to blow away the Bucs, that's one question the Cardinals won't have to entertain after all.
Wainwright spun a masterpiece to pitch his team past the Pirates in the NL Central for a night. Allowing just four Pirates on base in seven shutout innings with eight whiffs, Wainwright was back to dealing the way he's expected to, a huge source of relief after he had taken back-to-back drubbings at the hands of the Reds. Overpowering the Pirates makes it look like the question over whether or not Wainwright had begun tipping his pitches has been fixed.
It might be easy to overstate these kinds of problems when everything involving these three teams running neck-and-neck in the NL Central is under the microscope. Fretting over Wainwright walking more men in half as many starts since the All-Star break as he did before reflects how incredible his season has been: Wainwright's post-break 4-to-1 K:BB ratio in the second half is tremendous, but it's less than half of the 9-to-1 ratio he put up before the break. But as good as he looked against the Pirates, it doesn't look like he has a problem.
Of course, it's always possible that the Reds may have picked up something more than tipping his pitches, setting up some potential for extra wild-card drama if the Reds and Redbirds have to face one another in the play-in game. Of course, the Cardinals would rather skip that exercise and just win the division outright, eliminating some questions as they answer others.
That's because Wainwright isn't the only Cardinal question mark this time of the year. David Freese going yard for the second time in three games was perhaps another proof of one of those kinks to the Cardinals' master plan getting ironed out. Freese's combined July and August performance was woeful: .649 OPS, plus a lone home run. Freese's value is pretty much tied up in his bat, with his defense generally getting low marks; that's reflected in evaluative defensive metrics like BIS's Defensive Runs Saved, where Freese's minus-13 is worse than everyone at third base not named Michael Young or Miguel Cabrera.
Hitting that badly in an organization as deep as the Cardinals', Freese had endangered his claim to everyday play, creating an opening for second baseman Kolten Wong in the infield (with Matt Carpenter rotating over to the hot corner), allowing Mike Matheny to get another left-handed bat into his lineup. In the abstract, it's a nice problem to have when you're the Cardinals. Unfortunately, Wong hasn't done anything at the plate since his call-up, leaving the Cardinals with another body but the same problem.
Again, these are the kinds of problems that crop up that provide a reminder that baseball is hard, hard even when you're among the best players on the planet. Wainwright might be the pitcher you pick to start a must-win game, but his talent isn't enough to armor him against opponents picking up the slightest bad habit. Like every other player in the game, one of its best is forced to continually adapt and adjust, to his opponents and to the changes in his game over time.
Freese may have been the terror of the Rangers for one magical week, but that doesn't buy him job security less than two years later in the Show-Me State: He has to keep showing something. As Jimmy Dugan said in "A League of Their Own": "It's supposed to be hard! If it wasn't hard, everyone would do it. The hard is what makes it great."
For the time being, this is the sort of happy in-season resolution that the Cardinals will take. It joins a lengthening list of things that are working out for them in-season, like how their bullpen has started to gel with Seth Maness and Randy Choate setting up Trevor Rosenthal and Edward Mujica, or Joe Kelly's pitching down the stretch. They'll still need to see whether or not they get Allen Craig back in fully operating order in time for October, but it reflects the organization's strength that even that question had an excellent fall-back answer in Matt Adams.
So now, with the three teams in the division fighting to earn that bye from the wild card and sudden death within two games of one another. Instead, for the next three weeks, we'll be focused on the big question: "Who wins the NL Central?" That one's going to be fun for you and me to kick around for the rest of the month, but for the Cardinals, Pirates and Reds, it's one all three teams would rather have answered already: "Us."
We'll see who pulls it off. We're already getting a race to remember. But if Adam Wainwright has his ace's wings back, the Birds could take flight and put the NL Central away the way people have expected them to for months. And if he's getting extra run support because David Freese is back, so much the better for them.
Christina Kahrl covers baseball for ESPN.com. You can follow her on Twitter.


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The bride's colors were red, white, black and silver. So we did a red velvet cake, black and white lace cup cake holders and silver frosting. The letters and doves are white chocolate.
CakeCentral.com is the world's largest cake community for cake decorating professionals and enthusiasts.
(if this is a private computer)
Yes please, register now!


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Profile: Artist in Sculpture and Graphics.
Qualifications: 1977-1983 Vilnius Academy of Arts (Lithuania),
Department of Sculpture (M.A. in arts).
2008-2013 Vytautas Magnus University (Kaunas, Lithuania), Department of Philosophy (B.A. in Philosophy).
2014-2015 Continuing studies for the Master's degree in Philosophy.
Employment: from 1983 – Teacher of arts (Kaunas Art Gymnasium); teaching sculpture, composition and drawing.
Email: sigitad(at)email.lt


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Sorry, this product is no longer available!
Merlin Maven Road Bike is no longer available at Merlin Cycles. However you may find an alternative or updated product below.
Merlin Maven Road Bike is no longer available at Merlin Cycles. However you may find an alternative or updated product below.
Merlin Maven Road Bike
This item was discontinued 14th May 2015.
If you require help finding an alternative to this product please contact customer services.
Code: MERLIN-MAVEN
- Merlin Maven road bike specification:
- Frame: 6061 Aluminium
- Fork: High Modulus Carbon
- Chainset: Shimano Sora 34/50 rings
- Brakeset: Shimano Sora
- STI Brake/Gear Levers: Shimano Sora 3500
- Front Derailleur: Shimano Sora
- Rear Derailleur: Shimano Sora
- Cassette & Chain: Shimano 11-23 ratio (12-25 for 2013 model)
- Headset: Integral
- Bars & Stem: Merlin aluminium black anodised
- Seatpost: Merlin aluminium black anodised
- Saddle: Velo
- Wheels: Q/R cassette hubs - Alex DC19 rims
- Tyres: 700 x 23mm
- Pedals: Wellgo platform including clips & straps
Please enter your e-mail address below then click Notify Me to be notified when this item comes back into stock. We will not use your e-mail address for any other purpose.
Shipping charges for this item to United States: $156.25
|$ 156.25
Mr PlumMy first road bike, and all I can say is that this is a really great bike! Tight, sturdy handling.. all sora gear with carbon fork makes it a steal. Thanks to the guys at Merlin! No fuss, speedy delivery. Came when they said.
Mr CookGreat bike and excellent value, I was looking for a road bike for a while and finally settled for the Merlin because of the excellent specification of the kit fitted on it. Had to change the stem because the 100mm stem and offset seat post made my riding position too stretched
Mr CroweGood bike, good price
Neil WilliamsI wanted a road bike for the 12 mile e/way daily commute. Two weeks after delivery, I can happily say that I am absolutely delighted with the service from Merlin Cycles. From my initial phone call requesting advice, through delivery and finally the quality of the bike itself - everything is first class. The bike is fantastic - with assured gear shifting, excellent brakes and precise steering. Thank you Merlin. Neil Williams, Telford


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Charming Shoppes, the specialty retailer based in Bensalem, Pa., has formed a joint venture with Monsoon PLC to bring the London-based fashion retailer's Monsoon and Accessorize store concepts to American soil beginning in mid-2001. If not exactly "I Want to Hold Your Hand," Charming is hoping for a few choruses of "I Want to Wear Your Clothes."
What is Charming — which is putting up 80 percent of the capital for the joint venture here — hoping to do that existing stores, including chic imports such as H&M and Zara, aren't? At a luncheon at the restaurant Daniel in New York last month, Charming's management team made it clear to an audience of financial analysts that its mission was fashion.
"The opportunity today, as we move into a new millennium, is to bring a new fashion concept to the U.S. market," noted Donna Schmid, the former Bon Marche general merchandise manager who's heading the U.S. Monsoon venture. "The consumer is bored with apparel, and even with home furnishings, and wants new brand concepts and new shopping experiences."
While Monsoon is chic, it hardly fits the "cheap" category. Monsoon describes its product as "better, fashion-forward and highly differentiated" and its customers as savvy and upscale with average household incomes of $65,000 and up. (With a product assortment that complements rather than defines the wardrobe, Accessorize caters to a slightly younger customer, 16 to 35 versus 25 to 45 at Monsoon, with average household incomes of $50,000 and up.)
But what Charming chief executive Dorrit Bern believes will make Monsoon and its sister division stand out in the U.S. retail marketplace is its affinity for "feminine clothing that's so hard to find in this country" amidst the informal tendencies of casually oriented stores and the buttoned-up proclivities of those offering business dress. To help bring the point home, Charming officials at the luncheon dressed in Monsoon outfits or, at the least, ornamented their outfits with Accessorize pieces. Models — including several children who immediately elicited ooh's and aah's from the assembled — showed off the breadth of Monsoon's offerings with outfits appropriate for activities ranging from a day at the beach to a night at the altar.
Although leases haven't yet been signed, plans are to open about 20 units in 2001, most of them under the Accessorize banner. Two Accessorize stores are slated for May, and both standalone and combination stores are a possibility.
Charming executives noted that Monsoon's broad assortments would be edited for the U.S. market and that additional pains would be taken to make sure that Monsoon merchandise complied with U.S. statutes and regulations. When Eric Specter, Charming's executive vice president and chief financial officer, noted that U.S. flammability standards differed from those of other markets, Lazard Frere's Todd Slater sardonically asked if the U.S. merchandise was expected to be more or less flammable.


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Suit seeks to overturn Tongass roadless exemption
ANCHORAGE, Alaska – An Alaska Native village joined in a lawsuit filed Dec. 22 that aims to protect some of the Tongass National Forest's remaining stands of old growth trees.
The Organized Village of Kake and other plaintiffs are seeking to end the 2003 decision under the Bush administration that exempted the Tongass from the Clinton-era Roadless Rule. The rule protects roadless areas in national forests from commercial logging and road building.
The 9.3 million-acre Tongass is covered by a separate rule on road construction under an agreement reached with then-Gov. Frank Murkowski.
The exemption was to be temporary but is still being implemented by the Forest Service, according to the lawsuit. The lawsuit seeks to set aside the exemption for the Tongass and all Forest Service decisions that are not consistent with the 2001 rule.
Plaintiffs' lawyer Thomas S. Waldo of Earthjustice described the four reasons for the exemption as "phony" and "unsupported."
"We are going straight at those reasons," he said.
Andrew Ames, a Department of Justice spokesman, said the agency would review the complaint and respond in court.
The lawsuit says the Forest Service continues to operate on the premise that the Roadless Rule does not apply to the Tongass as evidenced by two timber sales authorized last year requiring road construction in roadless areas of the forest.
Mike Jackson with the Organized Village of Kake said the forest lands are important sources for food and medicine while also fulfilling artistic and spiritual needs.
"Our deer hunting and other customary uses of the forest have suffered too much already from past logging," he said. "We must not lose roadless areas here."
Jackson said there have been more than 50 timber sales on Kupreanof Island over the years, but the tribe has benefited little.
"We have nothing to show for all the money made off our rural resource here," he said.
The village, which is a federally recognized tribe of about 400 members, was joined in the lawsuit by half a dozen conservation groups, a tourism group and a company that relies on tourism.
Hunter McIntosh, vice president of operations for The Boat Company, said his company operates high-end cruises between Juneau and Sitka and relies on Alaska's pristine vistas to keep customers satisfied.
"Folks come from the Lower 48 to see pristine wilderness, to fish for salmon and see eagles and bears," he said. "If you take those pretty places away, you put people like us out of business."
Copyright 2009 Associated Press. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
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Anesthesiologist (pain control)
20 years of experience
20 years of experience
Somers Point
1 E New York Ave
Somers Point, NJ 08244 Phone number & directions
1 E New York Ave
Somers Point, NJ 08244 Phone number & directions
License & Identifications
A medical license is required for a doctor to practice medicine in a particular state. Requirements vary by state but most require, at a minimum, post-graduate training in the doctor's specific specialty. An NPI number is a national identifier unique to an individual health care provider and is managed by the Center for Medicare & Medicaid Services (CMS).
Learn more about Dr. Ilya Allahverdi:
View the full profile to get information on:
- Qualifications
- What's important to you
View full profile
Patient Reviews
Patient comments (0)
The overall average patient rating of Dr. Ilya Allahverdi is Average.
Specialties & Research
Dr. Ilya Allahverdi, MD is board certified in Anesthesiology.
Education & Awards
Dr. Allahverdi graduated from Stony Brook University.
Dr. Allahverdi has 1 hospital affiliations:
- Shore Memorial Hospital
Home > Find an Anesthesiologist > NJ > Somers Point Anesthesiologists > Dr. Ilya Allahverdi, MD
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- Additional Information
- Dr. Ilya Michael Allahverdi MD is a male Anesthesiologist, has 20 years of experience and practices in Anesthesiology.
- Where does Dr. Ilya M. Allahverdi practice?
- Dr. Ilya Allahverdi has 1 office location.
Dr. Ilya Allahverdi practices Anesthesiology near Somers Point, NJ.
See Somers Point Anesthesiologists.