It's time for the Cavaliers to reinsert J.R. Smith into the starting lineup, says Stephen A. Smith of ESPN.
Pretty much everyone has their own suggestions on the adjustments the Cleveland Cavaliers must make as they head to Game 2 of their first-round playoff series against the Indiana Pacers on Wednesday night at Quicken Loans Arena.
That includes Stephen A. Smith of ESPN, who said on First Take that Cavaliers coach Tyronn Lue should reinsert J.R. Smith into the starting lineup.
Smith, who was a starter on the three Cleveland teams that reached the last three NBA Finals, was sent to the bench late in the season by Lue after a regular-season performance filled with inconsistency.
Stephen A., though, said the time has come to go back to J.R., who had 15 points off the bench in the 98-80 loss to the Pacers in Game 1.
1 Comment on "Stephen A: Cavs need JR back in the starting lineup"
Whom ever is responsible for the lineup mismanagement creating a quandry, disjointed, out of sorts non team oriented approach is destroying the cavaliers chances of a successful season. A coach facilitates a way to guide his team to as close as the best possible chances to win games. Accomplished by utilizing lineups from start to finish that have good team chemistry, and have positive point differentials. This is referred to as optimizing lineups and allowing the interconnection of the players to have a synnergy and where the whole is greater than the sum of the parts. That is not happening by the coachingb staff. Try a stable lineup of: thompson,love,james,smith hill the bench: clarkson,korver,hood,green, nance. If smith, thompson or hill play poorly immediately insert clarkson, hood, nance with one substitution, even green could enter with four new players: james,green,nance,hood,clarkson. Last season the team had: shumpert,frye,jefferson,korver, and williams inferior to this superior group the cavaliers have. This is a fine team capable of getting to the finals. Yet the coaching staff is not allowing this to occur.


text:
Q: Grouping inside for-each based on child element values in xslt 2.0 I have a XML as below -
<Page14 xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"
        xmlns:statutorytype="us-stat-2020-annual-stmt-pc"
        xmlns:xbrli="http://www.xbrl.org/2001/instance"
        xmlns:iso4217="http://www.xe.com/iso4217.htm"
        xmlns:stat="urn:www-iasa-org/tempuri">
      <RegionRow>
      <Region>HI</Region>
      <EachUniqueCombo>
         <CurrentGroup>20000|16 Workers' Compensation|IBNR Loss Reserves|Pooled</CurrentGroup>
         <LedgerAccount>20000</LedgerAccount>
         <LOB>16 Workers' Compensation</LOB>
         <SpendCategory>IBNR Loss Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-31</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>20100|16 Workers' Compensation|IBNR ALAE D&CC Reserves|Pooled</CurrentGroup>
         <LedgerAccount>20100</LedgerAccount>
         <LOB>16 Workers' Compensation</LOB>
         <SpendCategory>IBNR ALAE D&CC Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-1</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>24000|16 Workers' Compensation||Pooled</CurrentGroup>
         <LedgerAccount>24000</LedgerAccount>
         <LOB>16 Workers' Compensation</LOB>
         <SpendCategory/>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-45.13</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>40000|16 Workers' Compensation||Pooled</CurrentGroup>
         <LedgerAccount>40000</LedgerAccount>
         <LOB>16 Workers' Compensation</LOB>
         <SpendCategory/>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-65</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>40010|16 Workers' Compensation||Pooled</CurrentGroup>
         <LedgerAccount>40010</LedgerAccount>
         <LOB>16 Workers' Compensation</LOB>
         <SpendCategory/>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-5.34</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>50000|16 Workers' Compensation|Change in IBNR Loss Reserves|Pooled</CurrentGroup>
         <LedgerAccount>50000</LedgerAccount>
         <LOB>16 Workers' Compensation</LOB>
         <SpendCategory>Change in IBNR Loss Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-16</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>50100|16 Workers' Compensation|Change in IBNR ALAE D&CC Reserves|Pooled</CurrentGroup>
         <LedgerAccount>50100</LedgerAccount>
         <LOB>16 Workers' Compensation</LOB>
         <SpendCategory>Change in IBNR ALAE D&CC Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>1</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>51000|16 Workers' Compensation|Change in Commission Reserves|Pooled</CurrentGroup>
         <LedgerAccount>51000</LedgerAccount>
         <LOB>16 Workers' Compensation</LOB>
         <SpendCategory>Change in Commission Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-1</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>51000|16 Workers' Compensation|Paid Commissions|Pooled</CurrentGroup>
         <LedgerAccount>51000</LedgerAccount>
         <LOB>16 Workers' Compensation</LOB>
         <SpendCategory>Paid Commissions</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-0.05</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>20000|17.1 Other Liability - Bodily Injury, Occurrence|IBNR Loss Reserves|Pooled</CurrentGroup>
         <LedgerAccount>20000</LedgerAccount>
         <LOB>17.1 Other Liability - Bodily Injury, Occurrence</LOB>
         <SpendCategory>IBNR Loss Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-28</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>20100|17.1 Other Liability - Bodily Injury, Occurrence|IBNR ALAE D&CC Reserves|Pooled</CurrentGroup>
         <LedgerAccount>20100</LedgerAccount>
         <LOB>17.1 Other Liability - Bodily Injury, Occurrence</LOB>
         <SpendCategory>IBNR ALAE D&CC Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>135</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>24000|17.1 Other Liability - Bodily Injury, Occurrence||Pooled</CurrentGroup>
         <LedgerAccount>24000</LedgerAccount>
         <LOB>17.1 Other Liability - Bodily Injury, Occurrence</LOB>
         <SpendCategory/>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>19.17</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>40000|17.1 Other Liability - Bodily Injury, Occurrence||Pooled</CurrentGroup>
         <LedgerAccount>40000</LedgerAccount>
         <LOB>17.1 Other Liability - Bodily Injury, Occurrence</LOB>
         <SpendCategory/>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>22</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>40010|17.1 Other Liability - Bodily Injury, Occurrence||Pooled</CurrentGroup>
         <LedgerAccount>40010</LedgerAccount>
         <LOB>17.1 Other Liability - Bodily Injury, Occurrence</LOB>
         <SpendCategory/>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-21.24</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>50000|17.1 Other Liability - Bodily Injury, Occurrence|Change in IBNR Loss Reserves|Pooled</CurrentGroup>
         <LedgerAccount>50000</LedgerAccount>
         <LOB>17.1 Other Liability - Bodily Injury, Occurrence</LOB>
         <SpendCategory>Change in IBNR Loss Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-261</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>50100|17.1 Other Liability - Bodily Injury, Occurrence|Change in IBNR ALAE D&CC Reserves|Pooled</CurrentGroup>
         <LedgerAccount>50100</LedgerAccount>
         <LOB>17.1 Other Liability - Bodily Injury, Occurrence</LOB>
         <SpendCategory>Change in IBNR ALAE D&CC Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-135</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>51000|17.1 Other Liability - Bodily Injury, Occurrence|Change in Commission Reserves|Pooled</CurrentGroup>
         <LedgerAccount>51000</LedgerAccount>
         <LOB>17.1 Other Liability - Bodily Injury, Occurrence</LOB>
         <SpendCategory>Change in Commission Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>1</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>51000|17.1 Other Liability - Bodily Injury, Occurrence|Paid Commissions|Pooled</CurrentGroup>
         <LedgerAccount>51000</LedgerAccount>
         <LOB>17.1 Other Liability - Bodily Injury, Occurrence</LOB>
         <SpendCategory>Paid Commissions</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-3.3</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>20000|17.1 Other Liability - Physical Damage, Occurrence|IBNR Loss Reserves|Pooled</CurrentGroup>
         <LedgerAccount>20000</LedgerAccount>
         <LOB>17.1 Other Liability - Physical Damage, Occurrence</LOB>
         <SpendCategory>IBNR Loss Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>1</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>50000|17.1 Other Liability - Physical Damage, Occurrence|Change in IBNR Loss Reserves|Pooled</CurrentGroup>
         <LedgerAccount>50000</LedgerAccount>
         <LOB>17.1 Other Liability - Physical Damage, Occurrence</LOB>
         <SpendCategory>Change in IBNR Loss Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-1</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>20000|24 Surety|IBNR Loss Reserves|Pooled</CurrentGroup>
         <LedgerAccount>20000</LedgerAccount>
         <LOB>24 Surety</LOB>
         <SpendCategory>IBNR Loss Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-458</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>20100|24 Surety|IBNR ALAE D&CC Reserves|Pooled</CurrentGroup>
         <LedgerAccount>20100</LedgerAccount>
         <LOB>24 Surety</LOB>
         <SpendCategory>IBNR ALAE D&CC Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-24</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>24000|24 Surety||Pooled</CurrentGroup>
         <LedgerAccount>24000</LedgerAccount>
         <LOB>24 Surety</LOB>
         <SpendCategory/>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>354.28</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>40010|24 Surety||Pooled</CurrentGroup>
         <LedgerAccount>40010</LedgerAccount>
         <LOB>24 Surety</LOB>
         <SpendCategory/>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-819</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>50000|24 Surety|Change in IBNR Loss Reserves|Pooled</CurrentGroup>
         <LedgerAccount>50000</LedgerAccount>
         <LOB>24 Surety</LOB>
         <SpendCategory>Change in IBNR Loss Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>-292</Sum>
      </EachUniqueCombo>
      <EachUniqueCombo>
         <CurrentGroup>50100|24 Surety|Change in IBNR ALAE D&CC Reserves|Pooled</CurrentGroup>
         <LedgerAccount>50100</LedgerAccount>
         <LOB>24 Surety</LOB>
         <SpendCategory>Change in IBNR ALAE D&CC Reserves</SpendCategory>
         <PooledWorktag>Pooled</PooledWorktag>
         <Sum>24</Sum>
      </EachUniqueCombo>
   </RegionRow>
   <RegionRow>
   <Region>AL</Region>
    ----
   </RegionRow>

</Page14>

For the above XML, I need to write an xslt that runs for each RegionRow element and within each region, I need to group first based on LOB element and then under that I need to do a sum of element 'Sum' based on certain ledger accounts.
I am trying to write the xslt as below -
<?xml version="1.0" encoding="UTF-8"?>
<xsl:stylesheet xmlns:xsl="http://www.w3.org/1999/XSL/Transform"
    xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:wd="urn:com.workday.report/CR_Page_14_EMC"
    xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"
    xmlns:statutorytype="us-stat-2020-annual-stmt-pc"
    xmlns:xbrli="http://www.xbrl.org/2001/instance" xmlns:iso4217="http://www.xe.com/iso4217.htm"
    xmlns:stat="urn:www-iasa-org/tempuri" exclude-result-prefixes=" wd xs" version="2.0">

    <xsl:output indent="yes" method="xml"/>

    <xsl:variable name="single_quote">
        <xsl:text>'</xsl:text>
    </xsl:variable>
    <xsl:variable name="ampersand">
        <xsl:text>&</xsl:text>
    </xsl:variable>

    <xsl:template match="Page14">
        <OutputOfNextXSL>
            <xsl:for-each select="RegionRow">
                <RowData>
                    <Region>
                        <xsl:value-of select="Region"/>
                    </Region>
                    <xsl:for-each-group select="EachUniqueCombo" group-by="EachUniqueCombo[LOB = '24 Surety']">
                        <CellOneAllied>
                            <!-- ledger account xyz, -->
                            <xsl:value-of
                                select="-1 * sum(EachUniqueCombo[LedgerAccount = '40000' or LedgerAccount = '20000']/xs:decimal(Sum))"/>

                        </CellOneAllied>
<CellTwoAllied>
</CellTwoAllied>
---
--
                    </xsl:for-each-group>
<xsl:for-each-group select= EachUniqueCombo group-by=EachUniqueCombo[LOB = '16 Workers' Compensation']">
  <!-- Sum here based on one or multiple ledger accounts-->
</xsl:for-each-group>

The group by can be based on 1 LOB or multiple and similarly the ledger account/spend category inside that grouping based on which I need to do a sum can also be single or multiple. I am not able to get any value based on above group-by logic and then also cannot reach the ledger account or spend category inside the group to be able to do a sum.
Can someone please help achieve this?

A: So you just want to "group" the same "LedgerAccount"-Tag with the sum von "Sum"-Tag in each "RegionRow"-Tag
Following XSLT-Code will make this:
XSLT
<?xml version="1.0" encoding="UTF-8"?>
<xsl:stylesheet xmlns:xsl="http://www.w3.org/1999/XSL/Transform" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" exclude-result-prefixes="#all" version="2.0">
  <xsl:output method="xml" encoding="UTF-8"/>
  <xsl:template match="/">
<RegionRow>

  <xsl:for-each select="//RegionRow"> <!-- seach all RegionRow-Tags -->
     <xsl:for-each-group select="./EachUniqueCombo" group-by="LedgerAccount"> <!-- in each RegionRow-Tag group same LedgerAccounts -->
     <xsl:variable name="key" select="current-grouping-key()"/> <!-- save current key in variable "key" to get the right siblings -->
          <EachUniqueCombo>
               <key><xsl:value-of select="$key"/></key>
               <Sum><xsl:value-of select="sum(current-group()/Sum)"/></Sum> <!-- sum of all same LedgerAccounts / get each Sum-Tag, which has a sibling with the current LedgerAccount (key) -->
          </EachUniqueCombo>
     </xsl:for-each-group>
  </xsl:for-each>

</RegionRow>

  </xsl:template>
</xsl:stylesheet>

XML-Output for our Sample for the first
<?xml version="1.0" encoding="UTF-8"?>
<RegionRow>
    <EachUniqueCombo>
        <key>20000</key>
        <Sum>-516</Sum>
    </EachUniqueCombo>
    <EachUniqueCombo>
        <key>20100</key>
        <Sum>110</Sum>
    </EachUniqueCombo>
    <EachUniqueCombo>
        <key>24000</key>
        <Sum>328.32</Sum>
    </EachUniqueCombo>
    <EachUniqueCombo>
        <key>40000</key>
        <Sum>-43</Sum>
    </EachUniqueCombo>
    <EachUniqueCombo>
        <key>40010</key>
        <Sum>-845.58</Sum>
    </EachUniqueCombo>
    <EachUniqueCombo>
        <key>50000</key>
        <Sum>-570</Sum>
    </EachUniqueCombo>
    <EachUniqueCombo>
        <key>50100</key>
        <Sum>-110</Sum>
    </EachUniqueCombo>
    <EachUniqueCombo>
        <key>51000</key>
        <Sum>-3.3499999999999996</Sum>
    </EachUniqueCombo>
</RegionRow>

XSLT incl. Group-by LOB-Substring (first 3 Characters)
<RegionRow>
  <xsl:for-each select="//RegionRow">
     <xsl:for-each-group select="./EachUniqueCombo" group-by="substring(LOB,1,3)">
     <xsl:variable name="LOB-key" select="./LOB"/>
          <EachUniqueCombo>
            <LOB>
               <LOB_SubStr_Value><xsl:value-of select="substring($LOB-key,1,3)"/></LOB_SubStr_Value>
                    <xsl:for-each select="//LedgerAccount[../LOB=$LOB-key]">
                    <xsl:variable name="key" select="."/>
                              <key><xsl:value-of select="$key"/></key>
                              <Sum><xsl:value-of select="sum(current-group()/Sum[../LedgerAccount/text()=$key])"/></Sum> <!-- sum of all same LedgerAccounts in LOB_Substr_Value -->
                    </xsl:for-each>
               </LOB>
          </EachUniqueCombo>
     </xsl:for-each-group>
  </xsl:for-each>
</RegionRow>

Output incl. Group-by LOB-Substring (first 3 Characters)
<?xml version="1.0" encoding="UTF-8"?>
<RegionRow>
    <EachUniqueCombo>
        <LOB>
            <LOB_SubStr_Value>16 </LOB_SubStr_Value>
            <key>20000</key>
            <Sum>-31</Sum>
            <key>20100</key>
            <Sum>-1</Sum>
            <key>24000</key>
            <Sum>-45.13</Sum>
            <key>40000</key>
            <Sum>-65</Sum>
            <key>40010</key>
            <Sum>-5.34</Sum>
            <key>50000</key>
            <Sum>-16</Sum>
            <key>50100</key>
            <Sum>1</Sum>
            <key>51000</key>
            <Sum>-1.05</Sum>
            <key>51000</key>
            <Sum>-1.05</Sum>
        </LOB>
    </EachUniqueCombo>
    <EachUniqueCombo>
        <LOB>
            <LOB_SubStr_Value>17.</LOB_SubStr_Value>
            <key>20000</key>
            <Sum>-28</Sum>
            <key>20100</key>
            <Sum>135</Sum>
            <key>24000</key>
            <Sum>19.17</Sum>
            <key>40000</key>
            <Sum>22</Sum>
            <key>40010</key>
            <Sum>-21.24</Sum>
            <key>50000</key>
            <Sum>-261</Sum>
            <key>50100</key>
            <Sum>-135</Sum>
            <key>51000</key>
            <Sum>-2.3</Sum>
            <key>51000</key>
            <Sum>-2.3</Sum>
        </LOB>
    </EachUniqueCombo>
    <EachUniqueCombo>
        <LOB>
            <LOB_SubStr_Value>24 </LOB_SubStr_Value>
            <key>20000</key>
            <Sum>-458</Sum>
            <key>20100</key>
            <Sum>-24</Sum>
            <key>24000</key>
            <Sum>354.28</Sum>
            <key>40010</key>
            <Sum>-819</Sum>
            <key>50000</key>
            <Sum>-292</Sum>
            <key>50100</key>
            <Sum>24</Sum>
        </LOB>
    </EachUniqueCombo>
</RegionRow>

redpajama_set_name: RedPajamaStackExchange


Parking is available in a pull-off on either side of Mill Road near the boat launch. It may not be plowed in winter. It's an easy walk with the usual New England roots and rocks in places. Many people walk dogs here. It's a popular fishing area, but not good for kayaking, as there are submerged stumps everywhere. I give it four stars for lack of diversity, but it is a nice easy walk with lovely lake views along the entire trail.


text:
"Samira Ahmed wins BBC equal pay tribunal" BBC News
Presenter Samira Ahmed has won the employment tribunal she brought against the BBC in a dispute over equal pay.
"Ahmed claimed she was underpaid by £700,000 for hosting audience feedback show Newswatch compared with Jeremy Vine's salary for Points of View.
The unanimous judgement said her work was like that done by Vine, and the BBC had failed to prove the pay gap wasn't because of sex discrimination.
Ahmed said she was "glad it's been resolved".
"No woman wants to have to take action against their own employer," she said, adding: "I love working for the BBC.""
On this day: on 7 June 1968 women from Ford went on Strike

redpajama_set_name: RedPajamaCommonCrawl


Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. These trials did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in subjects aged 65 and older [see WARNINGS AND PRECAUTIONS].
APLENZIN tablets are supplied for oral administration as 174 mg, 348 mg, and 522 mg white to off-white extended-release tablets. Each tablet contains the labeled amount of bupropion hydrobromide and the inactive ingredients: ethylcellulose, glyceryl behenate, polyvinyl alcohol, polyethylene glycol, povidone, and dibutyl sebacate. Carnauba wax is included in the 174 mg and 348 mg strengths. The tablets are printed with edible black ink.
APLENZIN® (bupropion hydrobromide extended-release tablets) is indicated for the treatment of major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual (DSM).
APLENZIN is indicated for the prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD).
APLENZIN should be swallowed whole and not crushed, divided, or chewed. APLENZIN should be administered in the morning and may be taken with or without regard to meals.
See Table 1 for equivalent daily doses of APLENZIN (bupropion hydrobromide) and bupropion hydrochloride.
The recommended starting dose for MDD is 174 mg once daily in the morning. After 4 days of dosing, the dose may be increased to the target dose of 348 mg once daily in the morning.
It is generally agreed that acute episodes of depression require several months or longer of antidepressant treatment beyond the response in the acute episode. It is unknown whether the APLENZIN dose needed for maintenance treatment is identical to the dose that provided an initial response. Periodically reassess the need for maintenance treatment and the appropriate dose for such treatment.
The recommended starting dose for SAD is 174 mg once daily. After 7 days of dosing, the dose may be increased to the target dose of 348 mg once daily in the morning. Doses above 300 mg of bupropion HCl extended-release (equivalent to APLENZIN 348 mg) were not assessed in the SAD trials.
For the prevention of seasonal MDD episodes associated with SAD, initiate APLENZIN in the autumn, prior to the onset of depressive symptoms. Continue treatment through the winter season. Taper and discontinue APLENZIN in early spring. For patients treated with 348 mg per day, decrease the dose to 174 mg once daily before discontinuing APLENZIN. Individualize the timing of initiation, and duration of treatment should be individualized, based on the patient's historical pattern of seasonal MDD episodes.
When discontinuing treatment in patients treated with APLENZIN 348 mg once daily, decrease the dose to 174 mg once daily prior to discontinuation.
In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose is 174 mg every other day. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see Use In Specific Populations and CLINICAL PHARMACOLOGY].
Consider reducing the dose and/or frequency of APLENZIN in patients with renal impairment (glomerular filtration rate less than 90 mL/min) [see Use In Specific Populations and CLINICAL PHARMACOLOGY].
At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of therapy with APLENZIN. Conversely, at least 14 days should be allowed after stopping APLENZIN before starting an MAOI antidepressant [see CONTRAINDICATIONS and DRUG INTERACTIONS].
Do not start APLENZIN in a patient who is being treated with a reversible MAOI such as linezolid or intravenous methylene blue. Drug interactions can increase risk of hypertensive reactions. In a patient who requires more urgent treatment of a psychiatric condition, non-pharmacological interventions, including hospitalization, should be considered [see CONTRAINDICATIONS].
In some cases, a patient already receiving APLENZIN therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of hypertensive reactions in a particular patient, APLENZIN should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with APLENZIN may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.
The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg per kg with APLENZIN is unclear. The clinician should, nevertheless, be aware of the possibility of a drug interaction with such use [see CONTRAINDICATIONS and DRUG INTERACTIONS].
APLENZIN Extended-Release Tablets, 174 mg of bupropion hydrobromide, are white to off-white, round tablets printed with "BR" over "174".
APLENZIN Extended-Release Tablets, 348 mg of bupropion hydrobromide, are white to off-white, round tablets printed with "BR" over "348".
APLENZIN Extended-Release Tablets, 522 mg of bupropion hydrobromide, are white to off-white, round tablets printed with "BR" over "522".
APLENZIN® Extended-Release Tablets, 174 mg of bupropion hydrobromide, are white to off-white, round tablets printed with "BR" over "174" in bottles of 30 tablets (NDC 0187-5810-30).
APLENZIN® Extended-Release Tablets, 348 mg of bupropion hydrobromide, are white to off-white, round tablets printed with "BR" over "348" in bottles of 30 tablets (NDC 0187-5811-30).
APLENZIN® Extended-Release Tablets, 522 mg of bupropion hydrobromide, are white to off-white, round tablets printed with "BR" over "522" in bottles of 30 tablets (NDC 0187-5812-30).
Manufactured for: Valeant Pharmaceuticals North America LLC, Bridgewater, NJ 08807 USA. Revised: May 2017.
300 mg/day of bupropion HCl sustained-release (equivalent to APLENZIN 348 mg/day): anorexia, dry mouth, rash, sweating, tinnitus, and tremor.
400 mg/day of bupropion HCl sustained-release (equivalent to APLENZIN 464 mg/day): abdominal pain, agitation, anxiety, dizziness, dry mouth, insomnia, myalgia, nausea, palpitation, pharyngitis, sweating, tinnitus, and urinary frequency.
APLENZIN is bioequivalent to bupropion HCl extended-release, which has been demonstrated to have similar bioavailability both to the immediate-release formulation of bupropion and to the sustained-release formulation of bupropion. The information included under this subsection and under the subsection 6.2 is based primarily on data from controlled clinical trials with the sustained-release and extended-release formulations of bupropion hydrochloride.
In placebo-controlled clinical trials with bupropion HCl sustained-release, 4%, 9%, and 11% of the placebo, 300 mg/day and 400 mg/day groups, respectively, discontinued treatment because of adverse reactions. The specific adverse reactions leading to discontinuation in at least 1% of the 300 mg/day or 400 mg/day groups and at a rate at least twice the placebo rate are listed in Table 3.
Table 4 summarizes the adverse reactions that occurred in placebo-controlled trials in patients treated with bupropion HCl sustained-release 300 mg/day and 400 mg/day. These include reactions that occurred in either the 300 mg or 400 mg group at an incidence of 1% or more and were more frequent than in the placebo group.
— Hyphen denotes adverse reactions occurring in greater than 0 but less than 0.5% of patients.
The following additional adverse reactions occurred in controlled trials of bupropion HCl immediate-release (300 to 600 mg per day) at an incidence of at least 1% more frequently than in the placebo group were: cardiac arrhythmia (5% vs. 4%), hypertension (4% vs. 2%), hypotension (3% vs. 2%), tachycardia (11% vs. 9%), appetite increased (4% vs. 2%), dyspepsia (3% vs. 2%), menstrual complaints (5% vs. 1%), akathisia (2% vs. 1%), impaired sleep quality (4% vs. 2%), sensory disturbance (4% vs. 3%), confusion (8% vs. 5%), decreased libido (3% vs. 2%), hostility (6% vs. 4%), auditory disturbance (5% vs. 3%), and gustatory disturbance (3% vs. 1%).
In placebo-controlled clinical trials in SAD, 9% of patients treated with bupropion HCl extended-release and 5% of patients treated with placebo discontinued treatment because of adverse reactions. The adverse reactions leading to discontinuation in at least 1% of patients treated with bupropion and at a rate numerically greater than the placebo rate were insomnia (2% vs. <1%) and headache (1% vs. <1%).
Table 5 summarizes the adverse reactions that occurred in patients treated with bupropion HCl extended-release for up to approximately 6 months in 3 placebo-controlled trials. These include reactions that occurred at an incidence of 2% or more and were more frequent than in the placebo group.
Table 6 presents the incidence of body weight changes (≥5 lbs) in the short-term MDD trials using bupropion HCl sustained-release. There was a dose-related decrease in body weight.
Table 7 presents the incidence of body weight changes (≥5 lbs) in the 3 SAD trials using bupropion HCl extended-release. A higher proportion of subjects in the bupropion group (23%) had a weight loss ≥5 lbs, compared to the placebo group (11%). These were relatively long-term trials (up to 6 months).
The following adverse reactions have been identified during post-approval use of APLENZIN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Postural hypotension, stroke, vasodilation, syncope, complete atrioventricular block, extrasystoles, myocardial infarction, phlebitis, and pulmonary embolism.
Bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between APLENZIN and drugs that are inhibitors or inducers of CYP2B6.
Concomitant treatment with these drugs can increase bupropion exposures but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of APLENZIN may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see CLINICAL PHARMACOLOGY].
Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of APLENZIN may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see CLINICAL PHARMACOLOGY ].
While not systemically studied, these drugs may induce metabolism of bupropion and may decrease bupropion exposure [see CLINICAL PHARMACOLOGY ]. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded.
Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of APLENZIN with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include certain antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g., haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, and flecainide). When used concomitantly with APLENZIN, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.
Drugs that require metabolic activation by CYP2D6 to be effective (e.g., tamoxifen), theoretically could have reduced efficacy when administered concomitantly with inhibitors of CYP2D6 such as bupropion. Patients treated concomitantly with APLENZIN and such drugs may require increased doses of the drug [see CLINICAL PHARMACOLOGY ].
Use extreme caution when coadministering APLENZIN with other drugs that lower the seizure threshold (e.g., other bupropion products, antipsychotics, antidepressants, theophylline, or systemic corticosteroids). Use low initial doses of APLENZIN and increase the dose gradually [see WARNINGS AND PRECAUTIONS].
Bupropion, levodopa, and amantadine have dopamine agonist effects. CNS toxicity has been reported when bupropion was coadministered with levodopa or amantadine. Adverse reactions have included restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. It is presumed that the toxicity results from cumulative dopamine agonist effects. Use caution when administering APLENZIN concomitantly with these drugs.
In postmarketing experience, there have been rare reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients who were drinking alcohol during treatment with APLENZIN. The consumption of alcohol during treatment with APLENZIN should be minimized or avoided.
Bupropion inhibits the reuptake of dopamine and norepinephrine. Concomitant use of MAOIs and bupropion is contraindicated because there is an increased risk of hypertensive reactions if bupropion is used concomitantly with MAOIs. Studies in animals demonstrate that the acute toxicity of bupropion is enhanced by the MAO inhibitor phenelzine. At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of treatment with APLENZIN. Conversely, at least 14 days should be allowed after stopping APLENZIN before starting an MAOI antidepressant [see DOSAGE AND ADMINISTRATION and CONTRAINDICATIONS].
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases [see BOX WARNING and Use In Specific Populations].
Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for APLENZIN should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
APLENZIN is not approved for smoking cessation treatment; however, bupropion HCl sustained-release is approved for this use. Serious neuropsychiatric adverse events have been reported in patients taking bupropion for smoking cessation. These postmarketing reports have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide [see ADVERSE REACTIONS]. Some patients who stopped smoking may have been experiencing symptoms of nicotine withdrawal, including depressed mood. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication. However, some of these adverse events occurred in patients taking bupropion who continued to smoke.
Neuropsychiatric adverse events occurred in patients without and with pre-existing psychiatric disease; some patients experienced worsening of their psychiatric illnesses. Observe patients for the occurrence of neuropsychiatric adverse events. Advise patients and caregivers that the patient should stop taking APLENZIN and contact a healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior. The healthcare provider should evaluate the severity of the adverse events and the extent to which the patient is benefiting from treatment, and consider options including continued treatment under closer monitoring, or discontinuing treatment. In many postmarketing cases, resolution of symptoms after discontinuation of bupropion was reported. However, the symptoms persisted in some cases; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve.
APLENZIN can cause seizure. The risk of seizure is dose-related. The dose should not exceed 522 mg once daily. Increase the dose gradually. Discontinue APLENZIN and do not restart treatment if the patient experiences a seizure.
The risk of seizures is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment with APLENZIN. APLENZIN is contraindicated in patients with a seizure disorder or conditions that increase the risk of seizure (e.g., severe head injury, arteriovenous malformation, CNS tumor or CNS infection, severe stroke, anorexia nervosa or bulimia, or abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see CONTRAINDICATIONS]. The following conditions can also increase the risk of seizure: concomitant use of other medications that lower the seizure threshold (e.g., other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, and systemic corticosteroids), metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia), or use of illicit drugs (e.g., cocaine) or abuse or misuse of prescription drugs such as CNS stimulants. Additional predisposing conditions include diabetes mellitus treated with oral hypoglycemic drugs or insulin, use of anorectic drugs, excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates.
The incidence of seizure with APLENZIN has not been formally evaluated in clinical trials. In studies using bupropion HCl sustained-release up to 300 mg per day (equivalent to APLENZIN 348 mg per day) the incidence of seizure was approximately 0.1% (1/1000 patients). In a large prospective, follow-up study, the seizure incidence was approximately 0.4% (13/3200) with bupropion HCl immediate-release in the range of 300 mg to 450 mg per day (equivalent to APLENZIN 348 mg to 522 mg per day).
Additional data accumulated for bupropion immediate-release suggests that the estimated seizure incidence increases almost tenfold between 450 and 600 mg/day (equivalent to APLENZIN 522 mg and 696 mg per day). The risk of seizure can be reduced if the APLENZIN dose does not exceed 522 mg once daily and the titration rate is gradual.
Treatment with APLENZIN can result in elevated blood pressure and hypertension. Assess blood pressure before initiating treatment with APLENZIN, and monitor periodically during treatment. The risk of hypertension is increased if APLENZIN is used concomitantly with MAOIs or other drugs that increase dopaminergic or noradrenergic activity [see CONTRAINDICATIONS].
Antidepressant treatment can precipitate a manic, mixed, or hypomanic manic episode. The risk appears to be increased in patients with bipolar disorder or who have risk factors for bipolar disorder. Prior to initiating APLENZIN, screen patients for a history of bipolar disorder and the presence of risk factors for bipolar disorder (e.g., family history of bipolar disorder, suicide, or depression). APLENZIN is not approved for the treatment of bipolar depression.
Depressed patients treated with bupropion have had a variety of neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion. Some of these patients had a diagnosis of bipolar disorder. In some cases, these symptoms abated upon dose reduction and/or withdrawal of treatment. Discontinue APLENZIN if these reactions occur.
Angle-Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant drugs including APLENZIN may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.
Anaphylactoid/anaphylactic reactions have occurred during clinical trials with bupropion. Reactions have been characterized by pruritus, urticaria, angioedema, and dyspnea, requiring medical treatment. In addition, there have been rare, spontaneous postmarketing reports of erythema multiforme, Stevens-Johnson Syndrome, and anaphylactic shock associated with bupropion. Instruct patients to discontinue APLENZIN and consult a healthcare provider if they develop an allergic or anaphylactoid/anaphylactic reaction (e.g., skin rash, pruritus, hives, chest pain, edema, and shortness of breath) during treatment.
Inform patients, their families, and their caregivers about the benefits and risks associated with treatment with APLENZIN and counsel them in its appropriate use.
A patient Medication Guide about "Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions," "Quitting Smoking, Quit-Smoking Medications, Changes in Thinking and Behavior, Depression, and Suicidal Thoughts or Actions," and "What Other Important Information Should I Know About APLENZIN?" is available for APLENZIN. Instruct patients, their families, and their caregivers to read the Medication Guide and assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.
Advise patients regarding the following issues and to alert their prescriber if these occur while taking APLENZIN.
Although APLENZIN is not indicated for smoking cessation treatment, it contains the same active ingredient as ZYBAN® which is approved for this use. Inform patients that some patients have experienced changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation and suicide when attempting to quit smoking while taking bupropion. Instruct patients to discontinue APLENZIN and contact a healthcare professional if they experience such symptoms [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].
Educate patients on the symptoms of hypersensitivity and to discontinue APLENZIN if they have a severe allergic reaction.
Instruct patients to discontinue and not restart APLENZIN if they experience a seizure while on treatment. Advise patients that the excessive use or the abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can increase the risk of seizure. Advise patients to minimize or avoid the use of alcohol.
Patients should be advised that taking APLENZIN can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle-closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible [see WARNINGS AND PRECAUTIONS].
Educate patients that APLENZIN contains the same active ingredient (bupropion) found in ZYBAN, which is used as an aid to smoking cessation treatment, and that APLENZIN should not be used in combination with ZYBAN or any other medications that contain bupropion hydrochloride (such as WELLBUTRIN XL, the extended-release formulation, WELLBUTRIN SR, the sustained-release formulation, and WELLBUTRIN, the immediate-release formulation). In addition, there are a number of generic bupropion HCl products for the immediate, sustained, and extended-release formulations.
Advise patients that any CNS-active drug like APLENZIN tablets may impair their ability to perform tasks requiring judgment or motor and cognitive skills. Advise patients that until they are reasonably certain that APLENZIN tablets do not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. APLENZIN treatment may lead to decreased alcohol tolerance.
Counsel patients to notify their healthcare provider if they are taking or plan to take any prescription or over-the-counter drugs, because APLENZIN tablets and other drugs may affect each other's metabolism.
Instruct patients to swallow APLENZIN tablets whole so that the release rate is not altered. Instruct patients if they miss a dose, not to take an extra tablet to make up for the missed dose and to take the next tablet at the regular time because of the dose-related risk of seizure. Instruct patients that APLENZIN tablets should be swallowed whole and not crushed, divided, or chewed. APLENZIN can be taken with or without food.
Data from epidemiological studies including pregnant women exposed to bupropion in the first trimester indicate no increased risk of congenital malformations. All pregnancies regardless of drug exposure have a background rate of 2% to 4% for major malformations and 15% to 20% for pregnancy loss. No clear evidence of teratogenic activity was found in reproductive developmental studies conducted in rats and rabbits. However, in rabbits, slightly increased incidences of fetal malformations and skeletal variations were observed at doses approximately equal to the maximum recommended human dose (MRHD) and greater and decreased fetal weights were seen at doses twice the MRHD and greater. APLENZIN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Bupropion and its metabolites are present in human milk. In a lactation study of ten women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. The average daily infant exposure (assuming 150 mL/kg daily consumption) to bupropion and its active metabolites was 2% of the maternal weight-adjusted dose. Exercise caution when APLENZIN is administered to a nursing woman.
Safety and effectiveness in the pediatric population have not been established. When considering the use of APLENZIN in a child or adolescent, balance the potential risks with the clinical need [see BOX WARNING and WARNINGS AND PRECAUTIONS].
Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys. The risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be necessary to consider this factor in dose selection; it may be useful to monitor renal function [see DOSAGE AND ADMINISTRATION, Renal Impairment, and CLINICAL PHARMACOLOGY].
Consider a reduced dose and/or dosing frequency of APLENZIN in patients with renal impairment (glomerular filtration rate: <90 mL/min). Bupropion and its metabolites are cleared renally and may accumulate in such patients to a greater extent than usual. Monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].
In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum APLENZIN dose is 174 mg every other day. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].
APLENZIN is contraindicated in patients with a seizure disorder.
APLENZIN is contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa as a higher incidence of seizures was observed in such patients treated with APLENZIN [see WARNINGS AND PRECAUTIONS].
APLENZIN is contraindicated in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].
The use of MAOIs (intended to treat psychiatric disorders) concomitantly with APLENZIN or within 14 days of discontinuing treatment with APLENZIN is contraindicated. There is an increased risk of hypertensive reactions when APLENZIN is used concomitantly with MAOIs. The use of APLENZIN within 14 days of discontinuing treatment with an MAOI is also contraindicated. Starting APLENZIN in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is contraindicated [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].
APLENZIN is contraindicated in patients with known hypersensitivity to bupropion or other ingredients of APLENZIN. Anaphylactoid/anaphylactic reactions and Stevens-Johnson Syndrome have been reported [see WARNINGS AND PRECAUTIONS].
Following chronic dosing of APLENZIN 348 mg once-daily tablets, the mean peak steady-state plasma concentration and area under the curve of bupropion were 134.3 (±38.2) ng/mL and 1409 (±346) ng•hr/mL, respectively. Steady-state plasma concentrations of bupropion were reached within 8 days. The elimination half-life (±SD) of bupropion after a single dose is 21.3 (±6.7) hours.
In a study comparing 10-day dosing with APLENZIN 348 mg once-daily and bupropion HCl extended-release 300 mg once-daily, (following a 3-day titration with bupropion HCl extended-release 150 mg once-daily), APLENZIN peak plasma concentration and area under the curve for bupropion and the 3 metabolites (hydroxybupropion, threohydrobupropion, and erythrohydrobupropion) were equivalent to bupropion HCl extended-release 300 mg, with the average being 8 to 14% lower.
In a single dose study, two APLENZIN tablets 174 mg once-daily and one APLENZIN tablet 348 mg once-daily were evaluated. Equivalence was demonstrated for peak plasma concentration and area under the curve for bupropion and the 3 metabolites.
A multiple dose study compared 14-day dosing with APLENZIN tablets 522 mg once-daily to dosing with three APLENZIN tablets 174 mg once-daily, following a 3-day titration with one APLENZIN tablet 174 mg once-daily, and a succeeding 5-day titration with two APLENZIN tablets 174 mg once-daily. Equivalence was demonstrated for peak plasma concentration and area under the curve for bupropion and the 3 metabolites.
These findings demonstrate that APLENZIN tablets 174 mg, 348 mg, and 522 mg are dose proportional.
Following single oral administration of APLENZIN tablets to healthy volunteers, the median time to peak plasma concentrations for bupropion was approximately 5 hours. The presence of food did not affect the peak concentration and time to peak plasma concentration of bupropion; the area under the curve was increased by 19%.
In vitro tests demonstrated that bupropion is 84% bound to human plasma proteins at concentrations up to 200 mcg/mL. The extent of protein binding of the hydroxybupropion metabolite is similar to that for bupropion, whereas the extent of protein binding of the threohydrobupropion metabolite is about half that of bupropion.
Following chronic administration in healthy volunteers, peak plasma concentration of hydroxybupropion occurred approximately 6 hours after administration of APLENZIN. The peak plasma concentrations of hydroxybupropion were approximately 9 times the peak level of the parent drug at steady state. The elimination half-life of hydroxybupropion is approximately 24.3 (±4.9) hours, and its AUC at steady state is about 15.6 times that of bupropion. The times to peak concentrations for the erythrohydrobupropion and threohydrobupropion metabolites are similar to that of hydroxybupropion. However, the elimination half-lives of erythrohydrobupropion and threohydrobupropion are longer, approximately 31.1(±7.8) and 50.8 (±8.5) hours, respectively, and steady-state AUCs were 1.5 and 6.8 times that of bupropion, respectively.
Bupropion and its metabolites exhibit linear kinetics following chronic administration of 300 mg to 450 mg/day of bupropion hydrochloride (equivalent to 348 mg and 522 mg of APLENZIN, respectively).
There is limited information on the pharmacokinetics of bupropion in patients with renal impairment. An inter-trial comparison between normal subjects and subjects with end-stage renal failure demonstrated that the parent drug Cmax and AUC values were comparable in the 2 groups, whereas the hydroxybupropion and threohydrobupropion metabolites had a 2.3-and 2.8-fold increase, respectively, in AUC for subjects with end-stage renal failure. A second study, comparing normal subjects and subjects with moderate-to-severe renal impairment (GFR 30.9 ± 10.8 mL/min) showed that after a single 150 mg dose of sustained-release bupropion, exposure to bupropion was approximately 2-fold higher in subjects with impaired renal function, while levels of the hydroxybupropion and threo/erythrohydrobupropion (combined) metabolites were similar in the 2 groups. Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and subsequently excreted by the kidneys. The elimination of the major metabolites of bupropion may be reduced by impaired renal function. APLENZIN should be used with caution in patients with renal impairment, and a reduced frequency and/or dose should be considered [see DOSAGE AND ADMINISTRATION and Use In Specific Populations].
In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between APLENZIN and drugs that are inhibitors or inducers of CYP2B6. In addition, in vitro studies suggest that paroxetine, sertraline, norfluoxetine, fluvoxamine, and nelfinavir inhibit the hydroxylation of bupropion.
Ticlopidine, Clopidogrel: In a study in healthy male volunteers, clopidogrel 75 mg once daily or ticlopidine 250 mg twice daily increased exposures (Cmax and AUC) of bupropion by 40% and 60% for clopidogrel, by 38% and 85% for ticlopidine, respectively. The exposures of hydroxybupropion were decreased.
A longer-term, placebo-controlled, randomized withdrawal trial demonstrated the efficacy of bupropion HCl sustained-release in the maintenance treatment of MDD. The trial included adult outpatients meeting DSM-IV criteria for MDD, recurrent type, who had responded during an 8-week open-label trial of bupropion 300 mg per day. Responders were randomized to continuation of bupropion 300 mg per day or placebo for up to 44 weeks of observation for relapse.
Response during the open-label phase was defined as a CGI-Improvement Scale score of 1 (very much improved) or 2 (much improved) for each of the final 3 weeks. Relapse during the double-blind phase was defined as the investigator's judgment that drug treatment was needed for worsening depressive symptoms. Patients in the bupropion group experienced significantly lower relapse rates over the subsequent 44 weeks compared to those in the placebo group.
Although there are no independent trials demonstrating the efficacy of APLENZIN or bupropion HCl extended-release in the acute treatment of MDD, studies have demonstrated similar bioavailability between the immediate-, sustained-, and extended-release formulations of bupropion HCl under steady-state conditions (i.e., the exposures [Cmax and AUC] for bupropion and its metabolites are similar among the 3 formulations). Furthermore, clinical studies have demonstrated that APLENZIN is bioequivalent to bupropion HCl extended-release.
The efficacy of bupropion hydrochloride extended-release in the prevention of seasonal major depressive episodes associated with SAD was established in 3 randomized, double-blind, placebo-controlled trials in adult outpatients with a history of MDD with an autumn-winter seasonal pattern (as defined by DSM-IV criteria). Bupropion treatment was initiated prior to the onset of symptoms in the autumn (September to November). Treatment was discontinued following a 2 week taper that began during the first week of spring (fourth week of March), resulting in a treatment duration of approximately 4 to 6 months for the majority of patients. Patients were randomized to treatment with bupropion HCl extended-release or placebo. The initial bupropion dose was 150 mg once daily for 1 week, followed by up-titration to 300 mg once daily. Patients who were deemed by the investigator to be unlikely or unable to tolerate 300 mg once daily were allowed to remain on, or had their dose reduced to, 150 mg once daily. The mean bupropion doses in the 3 trials ranged from 257 mg to 280 mg per day. Approximately 59% of patients continued in the study for 3 to 6 months; 26% continued for <3 months, 15% continued for >6 months.
It is not known if APLENZIN is safe and effective in children under the age of 18.
This section of the Medication Guide is only about the risk of changes in thinking and behavior, depression and suicidal thoughts or actions with drugs used to quit smoking. Although APLENZIN is not a treatment for quitting smoking, it contains the same active ingredient (bupropion) as ZYBAN® which is used to help patients quit smoking.
Stop taking APLENZIN and call your healthcare provider right away if you, your family, or caregiver notice any of these symptoms. Work with your healthcare provider to decide whether you should continue to take APLENZIN. In many people, these symptoms went away after stopping APLENZIN, but in some people symptoms continued after stopping APLENZIN. It is important for you to follow up with your healthcare provider until your symptoms go away. Before taking APLENZIN, tell your healthcare provider if you have ever had depression or other mental health problems. You should also tell your healthcare provider about any symptoms you had during other times you tried to quit smoking, with or without bupropion.
The chance of having seizures increases with higher doses of APLENZIN. For more information, see the sections "Who should not take APLENZIN?" and "What should I tell my healthcare provider before taking APLENZIN?" Tell your healthcare provider about all of your medical conditions and all the medicines you take. Do not take any other medicines while you are taking APLENZIN unless your healthcare provider has said it is okay to take them.
If you have a seizure while taking APLENZIN, stop taking the tablets and call your healthcare provider right away. Do not take APLENZIN again if you have a seizure.
High blood pressure (hypertension). Some people get high blood pressure that can be severe, while taking APLENZIN. The chance of high blood pressure may be higher if you also use nicotine replacement therapy (such as a nicotine patch) to help you stop smoking (see the section of this Medication Guide called "How should I take APLENZIN?").
Unusual thoughts or behaviors. Some patients have unusual thoughts or behaviors while taking APLENZIN, including delusions (believe you are someone else), hallucinations (seeing or hearing things that are not there), paranoia (feeling that people are against you), or feeling confused. If this happens to you, call your healthcare provider.
Severe allergic reactions. Some people can have severe allergic reactions to APLENZIN. Stop taking APLENZIN and call your healthcare provider right away if you get a rash, itching, hives, fever, swollen lymph glands, painful sores in the mouth or around the eyes, swelling of the lips or tongue, chest pain, or have trouble breathing. These could be signs of a serious allergic reaction.
APLENZIN should be used with a patient support program. It is important to participate in the behavioral program, counseling, or other support program your healthcare professional recommends.
Who should not take APLENZIN?
are taking any other medicines that contain bupropion, including WELLBUTRIN, WELLBUTRIN SR, WELLBUTRIN XL, ZYBAN, or FORFIVO XL®. Bupropion is the same active ingredient that is in APLENZIN.
are allergic to the active ingredient in APLENZIN, bupropion, or to any of the inactive ingredients. See the end of this Medication Guide for a complete list of ingredients in APLENZIN.
What should I tell my healthcare provider before taking APLENZIN?
Tell your healthcare provider about all the medicines you take, including prescription, over–the-counter medicines, vitamins, and herbal supplements. Many medicines increase your chances of having seizures or other serious side effects if you take them while you are taking APLENZIN.
How should I take APLENZIN?
Start APLENZIN before you stop smoking to give APLENZIN time to build up in your body. It takes about 1 week for APLENZIN to start working.
Pick a date to stop smoking that is during the second week you are taking APLENZIN.
Take APLENZIN exactly as prescribed by your healthcare provider. Do not change your dose or stop taking APLENZIN without talking with your healthcare provider first.
APLENZIN is usually taken for 7 to 12 weeks. Your healthcare provider may decide to prescribe APLENZIN for longer than 12 weeks to help you stop smoking. Follow your healthcare provider's instructions.
Swallow APLENZIN tablets whole. Do not chew, cut, or crush APLENZIN tablets. If you do, the medicine will be released into your body too quickly. If this happens you may be more likely to get side effects including seizures. Tell your healthcare provider if you cannot swallow tablets.
APLENZIN tablets may have an odor. This is normal.
Take your doses of APLENZIN at least 8 hours apart.
You may take APLENZIN with or without food.
It is not dangerous to smoke and take APLENZIN at the same time. But, you will lower your chance of breaking your smoking habit if you smoke after the date you set to stop smoking.
You may use APLENZIN and nicotine patches (a type of nicotine replacement therapy) at the same time, following the precautions below.
You should only use APLENZIN and nicotine patches together under the care of your healthcare provider. Using APLENZIN and nicotine patches together may raise your blood pressure, and sometimes this can be severe.
Tell your healthcare provider if you plan to use nicotine patches. Your healthcare provider should check your blood pressure regularly if you use nicotine patches with APLENZIN to help you quit smoking.
If you miss a dose, do not take an extra dose to make up for the dose you missed. Wait and take your next dose at the regular time. This is very important. Too much APLENZIN can increase your chance of having a seizure.
If you take too much APLENZIN, or overdose, call your local emergency room or poison control center right away.
Do not take any other medicines while taking APLENZIN unless your healthcare provider has told you it is okay.
What should I avoid while taking APLENZIN?
Limit or avoid using alcohol during treatment with APLENZIN. If you usually drink a lot of alcohol, talk with your healthcare provider before suddenly stopping. If you suddenly stop drinking alcohol, you may increase your chance of having seizures.
Do not drive a car or use heavy machinery until you know how APLENZIN affects you. APLENZIN can affect your ability to do these things safely.
What are possible side effects of APLENZIN?
APLENZIN can cause serious side effects. See the sections at the beginning of this Medication Guide for information about serious side effects of APLENZIN.
If you have trouble sleeping, do not take APLENZIN too close to bedtime.
These are not all the possible side effects of APLENZIN. For more information, ask your healthcare provider or pharmacist.
How should I store APLENZIN?
Store APLENZIN at room temperature between 59°F and 86°F (15°C to 30°C).
Keep APLENZIN and all medicines out of the reach of children.
General information about the safe and effective use of APLENZIN.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use APLENZIN for a condition for which it was not prescribed. Do not give APLENZIN to other people, even if they have the same symptoms you have. It may harm them.
If you take a urine drug screening test, APLENZIN may make the test result positive for amphetamines. If you tell the person giving you the drug screening test that you are taking APLENZIN, they can do a more specific drug screening test that should not have this problem.
This Medication Guide summarizes important information about APLENZIN. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about APLENZIN that is written for health professionals. For more information about APLENZIN, go to www.APLENZIN.com or call 1-800-321-4576.
What are the ingredients in APLENZIN?
Inactive ingredients: ethylcellulose, glyceryl behenate, polyvinyl alcohol, polyethylene glycol, povidone, and dibutyl sebacate. Carnauba wax is included in the 174 mg and 348 mg strengths. The tablets are printed with edible black ink.


text:
Sydney Abraham Callard
Sydney Abraham Callard was born in Dartmouth towards the end of 1880. He was the youngest son of Samuel Callard, a labourer, and his second wife, Elizabeth Bell, née Peek.
Samuel Callard (senior) was born in Totnes where he lived and worked on the river as a boatman and lighterman. He married his first wife, Susan Maria Hawkins, on 17th June 1855, at St Mary's Totnes. Samuel and Susan had four daughters, but only one survived into adulthood. The St Mary's baptism and burial records show:
Ellen Maria Callard, baptised 7th June 1857, buried 9th June 1857, aged four months
Elizabeth Susan Callard, baptised 8th August 1858, buried 23rd October 1860, aged two
Sarah Ann Callard, baptised 2nd August 1863, buried 27th July 1866 aged three
Minnie Ellen Callard, baptised 27th December 1868
So the 1871 Census recorded only Samuel, Susan and Minnie, aged two, living at St Peter's Quay, Totnes. Samuel was still working as a lighterman.
When Minnie was seven, her mother Susan died, aged only 42; she too was buried at St Mary's, Totnes, on 22nd December 1875. Samuel and Minnie moved to Dartmouth, where he met Elizabeth Honor Bell, née Peek.
Elizabeth Peek was the daughter of Amos Peek and his wife Susan Treby, and was born and brought up in Dartmouth. Amos was also a bargeman and lighterman, so perhaps this was how Samuel and Elizabeth met. Elizabeth was also widowed; her first husband, Edward Alford Bell, was a shipwright and mason, from Dartmouth, and they had married in St Saviours on 8th December 1861. Elizabeth had five sons by her first marriage: Edward Andrew, John Amos, William Henry, George Alford, and Frederick Thomas, only a baby when his father died. They were all baptised at St Saviours on 21st March 1872, a few months after their father's early death in 1871, aged 35.
Samuel and Elizabeth were married in 1878. Their first son, Charles Samuel, was born in 1879, followed by Sydney about eighteen months later. The 1881 Census recorded the combined family living in Oxford Slip, off Lower Street, Dartmouth. Edward and John, Elizabeth's oldest boys, were both working as labourers, as was Samuel. William, George, Frederick, Minnie, and even Charles, aged 2, were all "scholars". Sydney, the baby of the family, was 5 months old.
By the time of the 1891 Census, the two eldest Bell brothers had left home and both had married. Elizabeth's third son, William Henry Bell, had died, aged 21, in 1888. The rest of the family still lived in Oxford Slip and Samuel still worked as a general labourer, as did his stepson Frederick. Minnie now worked in domestic service. Charles and Sydney were still at school. Their immediate neighbours in Oxford Slip were the Chase family, including Charles Henry, also on our database.
In 1901, the family were recorded in Lower Street. Though he was 69 years old, Samuel was now working as a coal-lumper, like his neighbour Charles Chase (senior). At home were Minnie, who took in washing at home; Charles, who was a fisherman, and Sydney, who worked as a labourer. The family's other neighbours were the Trevassas. Louis Trevassa is also on our database.
On 22nd January 1910, Sydney married Alice Maud Hodge, at St Clements Townstal. By this time, Sydney was working as a clerk, and living in Higher Street. Alice worked in domestic service, and lived in Clarence Hill. Alice was the daughter of John Thomas Hodge, a labourer, and his wife Sarah, and had been born and brought up in Dartmouth. See the stories of her two brothers, Thomas John Hodge and Frank Hodge. The 1911 Census recorded them living in a two-room apartment in Bayards Cove. Sydney's occupation was described as "SS Boarding Clerk" in the "coaling industry", so he was presumably working for one of the coal companies in Dartmouth.
Sydney's father Samuel had died in 1908, but his mother, aged 73, lived in Higher Street, nearby. Minnie, Frederick and Charles were all married and living in Dartmouth.
Sydney's service records have not survived, like so many. However, his name was published in the Dartmouth Chronicle of 3rd December 1915 as one of those who had recently volunteered to serve. Although this was the time at which the "Derby Scheme" was being implemented (see the story of Thomas Charles) it would appear that Sydney was not recruited under this scheme but had joined up in the usual way. The paper reported that he had joined the 3rd Battalion of the Devonshire Regiment, the training battalion for the regulars of the Regiment, and he was posted to the 1st Battalion some time during the first part of 1916. When he joined them is not known.
The 1st Battalion had arrived on the Somme very early, on 31st July 1915. For their experiences during 1915 and 1916, including their involvement in the Battle of the Somme, see the story of George Peters.
Along with George Peters, Sydney was reported wounded in a casualty list dated 28th October 1916, which appeared in the Western Morning News on that day and in the Western Times on 30th October 1916. Although it does not explicitly say so, the names of those from the 1st Bn Devonshire Regiment appear to be those killed or wounded during the battle of Morval, fought on 25th September 1916.
There are no records surviving of Sydney's progress along the "casualty evacuation chain" but it would seem that he reached one of the hospitals in Béthune before he died. Wounded were treated at the town's general hospital and at the College Saint Vaast, a school which was taken over as a hospital and became the location of the 33rd Casualty Clearing Station.
The Hospital in Béthune
Sydney died of his wounds on 5th January 1917, and Alice placed an announcement in the Dartmouth Chronicle of the following week (Sydney's age appers to be incorrect):
Callard - January 5th 1917 died of wounds in France, Pte S Callard, 1st Devon Regt, the dearly beloved husband of A Callard, Bayards Cove, Dartmouth, age 33 years.
This was followed in the edition of 26th January 1917 by an announcement from his mother:
Callard - January 5th 1917, died of wounds in France, Private Sydney A Callard, 1st Devon Regt, aged 33 years. Deeply mourned by his mother and only brother Charley, and his four step-brothers.
He did his duty and died for his country.
Elizabeth had already lost two of her grandsons: Frederick Bell and William John Bell (though William's death had yet to be confirmed).
News of Sydney's death reached his family well before it was officially announced in a casualty list published at the end of January, which the Dartmouth Chronicle also recorded, in its edition of February 2nd 1917:
Died of wounds: In Monday night's casualty list Pte S A Callard 20338 (Dartmouth) of the Devon Regt was reported to have died of wounds.
Sydney was buried in Béthune Town Cemetery and his grave is marked with a Commonwealth War Graves Commission headstone.
As one of the 579,206 casualties in the region of Nord-Pas-de-Calais, Sydney is also commemorated on the new memorial at Notre Dame de Lorette, "The Ring of Memory".
Ring of Memory memorial at Notre Dame de Lorette
In Dartmouth he is commemorated on the Town War Memorial, on the St Saviour's Memorial Board, and on the St Petrox Memorial Boards.
Surname: Callard
Forenames: Sydney Abraham
Service Number: 20558
Military Unit: 1st Bn Devonshire Regiment
Cause of Death: Died of wounds
Action Resulting in Death: Battle of the Somme
Place of Death: Béthune, France
Place of Burial: Béthune Town Cemetery, France
On St Petrox Memorials? Yes
This information was last updated on Friday 02 November 2018 at 18:42:33.


text:
Q: Проигрывани музыки в discord боте на python пытаюсь научить бота проигрывать музыку на сервере, но при попытке проиграть ничего не происходит. Вот мой код
    @client.command(pass_context=True)
async def join(ctx):
    channel = ctx.author.voice.channel
    await channel.connect()

@client.command(pass_context=True)
async def play(ctx, url : str):
    song_there = os.path.isfile('song.mp3')
    try:
        if song_there:
            os.remove('song.mp3')
    except PermissionError:
        await ctx.send('wait bruh')
    voice = get(client.voice_client, guild = ctx.guild)

    ydl_opts = {
        'format': 'bestaudio/best',
        'postprocessor': [{
            'key': 'FFmpegExtractAudio',
            'preferredcodac': 'mp3',
            'preferredquality': '192',
        }],
    }

    with youtube_dl.YoutubeDL(ydl_opts) as ydl:
        for file in os.listdir('./'):
            if file.endwith('.mp3'):
                name = file
                os.rename(file, 'song.mp3')
    voice.play(discord.FFmpegPCMAudio('song.mp3'), after = lambda e: print(f'[log]{name} конец'))
    voice.source = discord.PCMVolumeTransformer(voice.source)
    voice.source.volume = 0.07
    song_name = name.rsplit('-', 2)
    await ctx.send(f'сейчас играет {song_name[0]}')

Помогите пожалуйста найти проблему. Всем заранее спасибо за ответы

A: Для реализации такой команды нужен FFMPEG - .exe файл, необходимый для запуска звука. Этот экзешник запускается через Discord API.
Скачать его можно здесь. Также можете скачать архив (Загрузка начнется сразу)
В папке должно быть 3 файла: ffmpeg.exe, ffplay.exe, ffprobe.exe.
Запускам с явным указанием исполняемого файла ffmpeg.exe:
FFMPEG_OPTIONS = {'before_options': '-reconnect 1 -reconnect_streamed 1 -reconnect_delay_max 5', 'options': '-vn'}

voice.play(discord.FFmpegPCMAudio(executable="путь\\к\\файлу\\ffmpeg.exe", source = 'song.mp3', **FFMPEG_OPTIONS))

Полноценный код можете найти здесь


text:
The Waffle Palace at the Horizon Theatre
Dr. Wilson Trivinohorizon theatre, theater, Theatre, Waffle House, Waffle Palace May 12, 2012
The Waffle House is only one place that 24/7 is sure to have two of my favorite things: smiles and warm food. Finally a play based on this southern hot spot, The Waffle Palace: Smothered, Covered & Scattered 24/7/365 at the Horizon Theatre.
Opening night was packed as director Lisa Adler shared that the idea for this play germinated when Eddie Levi Lee shared that he collected articles about the crazy things that happen at the Waffle House and she did the same thing. This world premiere comedy is part of the New South Play Festival.
This story is set in Atlanta and suddenly the Waffle Palace is threatened to be torn down by developers. The owner John (Larry Larson) has a family history within the walls of the Waffle Palace, his customers are more than customers their practically kin.
During the course of the a few days in this story you discover community and get a peek into the facts of life: lust, love, and death all the while the aroma of fried goodness lingers in the air.
A talented cast brings the Waffle Palace to life; Enoch King is a standout as he brings in his roaring humor as the cook, the preacher, and the suspicious Yankee. Lala Cochran also adds her flair for the dramatic from the seductress to the straight talking cop.
So come on down and sit a spell and enjoy a night with your friends at The Waffle Palace. It will make you yearn for a waffle and a warm cup of joe.
The Waffle Palace is playing through July 1 at the Horizon Theatre, for details visit: www.HorizonTheatre.com
About the Playwrights
LARRY LARSON & EDDIE LEVI LEE (playwrights) Larry Larson and Eddie Levi Lee's acting, writing and directing credits extend back to the 1970s with numerous collaborative projects for the Academy Theatre Main Stage, Tour Team, Lab Theatre and Children's Theatre. At the Alliance Theatre, Larson and Lee partnered to write and direct The Grubb Chronicles, Tales of Rat Alley, Merlin!, and Treasure Island for the Alliance Children's Theatre. They also wrote and acted extensively with The Southern Theatre Conspiracy in the 80's. Their numerous writing and acting credits for STC include: The Blood Orgy Trilogy, Mirandolina Unchained, Some Things You Need to Know Before the World Ends: A Final Evening with the Illuminati, and Tent Meeting. Some Things…Illuminati and Tent Meeting went on to Actors Theatre of Louisville's Humana Festival, and have been subsequently produced at many theatres in the U.S. and overseas. Tent Meeting received the TCG/HBO award for Best New Play in 1986. Larson and Lee's published plays are Tent Meeting, Some Things…Illuminati, Isle of Dogs and The Salvation of Iggy Scrooge—available from Dramatists Play Service and Samuel French Publishing, Inc. Other plays by Larson and Lee include: Charm School, which premiered at Horizon Theatre and won the 2007 Gene-Gabriel Moore Playwriting Suzi Bass Award, and The Bench: A Story of Christmas, which premiered at the Alliance Theatre in 2003.
About the Cast
Lala Cochran (Various Characters) is always happy to be back home at Horizon Theatre whereshe first appeared in Escape from Happiness in 1995. Recent credits includeSpring Awakening at Actor's Express and Superior Donuts, Night Blooms, and TrueLove Lies here at Horizon. A favorite role is Diane in A Little Dog Laughed atTheatre in the Square for which she won the Suzi Bass Award for Outstanding Lead Actress in a Play in 2008. When not doing this, the greatest of jobs, LaLa enjoys pedaling her bike around Atlanta looking for better shortcuts and finessing her recipe for pimento cheese. Infinite thanks to all of you who support live theatre by showing up, coming back, and telling your friends how great it is to hear and see live theatre.
Allan Edwards* (Various Characters) lastappeared at Horizon Theatre as Voltaire in Legacy of Light and made his first appearance at Horizon as Comer in Algae Eaters back in 1999. Recently he was Sir Walter in Theater Emory's Persuasion and Walter in Becky's New Car at Georgia Ensemble Theater. Atlanta audiences may remember himas Grown-up Ralphie in A Christmas Story, as Gloucester in King Lear,and as Enobarbus in Antony and Cleopatraat Georgia Shakespeare. He has performed at The Guthrie Theater of Minneapolis, TheaterVirginia in Richmond, Triad Stage in Greensboro, Charlotte Repertory Theater, and at The North Carolina Shakespeare Festival.
Marguerite Hannah* (Connie) was last seen on Horizon Theatre's stage as Geneva Willis in Night Blooms. Horizon patrons will also remember her as Benita in A Cool Drink A Water. Marguerite has worked the regional stages of The Oregon Shakespeare, Arena Stage, DC, Playmakers' Rep, NC, People's Light, PA, Players' Theatre, OH, St. Louis Black Rep, Alliance Theatre, Delaware Theatre Company, Alabama Shakespeare, The Huntington, Boston, and Arkansas Rep. Atlanta audiences may also remember her the last few years in Theatre in the Square's Flying West, Kenny Leon's True Colors' Amen Corner, 7 Stages' A Song for Coretta, and Theatrical Outfit's Waiting to be Invited.
Enoch King* (Walter/Various) Recent credits: The Ladies Man (Theatre in the Square), The Santaland Diaries (Horizon Theatre), Fool For Love, The Colored Museum, Broke-ology (True Colors Theatre). TV Credits: House of Payne, BET's Let's Stay Together, Golden Corral commercial. Up next for Enoch is Sheddin' here at Horizon. Order up!
Larry Larson* (John) returns to Horizon Theatre after last appearing in the world premiere of Charm School. Previous performances at Horizon include Boy Gets Girl, The Joy of Going Somewhere Definite, and The Drawer Boy. Larson's acting career began in the early 1970s as a member of Frank Wittow's Academy Theatre Acting Company. He has performed on nearly every Atlanta stage in over fifty productions including numerous plays at the Alliance Theatre such as Smart Cookie, Managing Maxine, Gem of the Ocean, Glengarry Glen Ross, and the Larson and Lee world premiere production of The Bench. His film and television credits include For Us the Living, Breaking Away, Door to Door; My Father, My Son; The Bill Tush Show, and the Disney feature film, Mr. 3000. Larson is currently the host of The Morning Ride on AM 1690 – The Voice of the Arts in Atlanta.
Eric Mendenhall* (Various Characters) was last seen at Horizon Theatre as Carlos in In Darfur. Eric returns to the stage in Atlanta after spending the last year and half working regionally – Florida Rep (Bedroom Farce), Florida Stage (The Cha-Cha of a Camel Spider), Hippodrome State Theatre (Dracula) – and working in Film/TV with roles in the feature films What to Expect When You're Expecting, Trouble With the Curve, Echo at 11 Oak Dr, 42, and Lawless. Other Atlanta Credits: Georgia Shakespeare (A Midsummer Night's Dream, Romeo & Juliet), Theatre in the Square (Tradin' Paint), Theatrical Outfit (A Confederacy of Dunces, Big River, The Chase), Georgia Ensemble Theatre (What I Did Last Summer, Last Night of Ballyhoo). Other TV/Film: Army Wives, Ben 10: Alien Sward, I Can Do Bad All By Myself, and Coma (on A&E this spring). Eric is a member of Actors' Equity Association. For more information visit www.ericmendenhall.com.
Maria Rodriguez-Sager (Esperanza) is delighted make her Horizon Theatre debut. Theatre credits: That Other Woman's Child (Song of Solomon) at New York Musical Theatre Festival, Spanish world premiere of Barrio Hollywood (Graciela) at Aurora Theatre, Women + War (ensemble) and Expecting Isabel (Pat/Lupe) 2008 Suzi Bass nominee at Synchronicity Theatre, Speech and Debate (Diwata) 2009 Suzi Bass nominee at Theatre in the Square, Urinetown: The Musical (Little Sally), The Boyfriend (Hortense), Dog Sees God (Van's Sister), Mr. Marmalade (Emily/Cactus), Marat/Sade (Charlotte Corday). TV/Film credits: Fifth season of BET's The Game and a recurring role on Dylan Kussman's web series The Steps. She received her theatre degree at the University of Southern Mississippi. Love to John for his continued love and support. Muchos thank yous to Lisa, Jeff, Larry, and Eddie for inviting her to be a part of this wonderful experience and giving her the opportunity to work with this brilliant cast and crew. Mucho amor y gratitud to Mr. Alexis and Marty for making your casa her casa too! And an abundance of thanks to YOU for your continued support of local theatre. She hopes you'll encourage others to do the same, that together we may keep the theatre community in Atlanta alive and well. Bless and be blessed!
About the Creative Team
LISA ADLER (Director) is Co-Founder and Co-Artistic/Producing Director of Horizon Theatre Company, now in its 28th season of producing Atlanta, Southeastern, and world premieres of contemporary plays. She has directed or dramaturged over 50 plays at Horizon over the past 28 years and founded the New South Play Festival. Recent directing credits include Tree,Third, In Darfur, and Charm School. Her Horizon productions of In Darfur, The Syringa Tree, Skylight, Escape from Happiness, and The Heidi Chronicles were all voted top productions of their year by local media. Other favorite Horizon directing credits include the world premiere of The Perfect Prayer, Quills, and The Good Times Are Killing Me. She is a recipient of a Lexus Leaders in the Arts Award and An Abby Award for Outstanding Arts Professional, and she was named one of Atlanta's "Defining Women in the Arts" by the Atlanta History Center. Lisa is a past participant in the Lincoln Center Director's Lab in NY and holds a BFA in Acting from the University of Illinois, Champaign-Urbana. Lisa's favorite role is mother to Sophie, her dramatic 11-year old.
JEFF ADLER (Director) has directed numerous productions for Horizon Theatre, beginning with Horizon's first production Bonjour, la, Bonjour in 1983. Other Horizon favorites include Shooting Star, Altar Boyz, Madame Melville, The Lonesome West, Racing Demon, Voir Dire, Marvin's Room, The Film Society, Aunt Dan and Lemon, Heathen Valley, The Secret Rapture, Full Moon, Mere Mortals, All in the Timing, Wonder of the World, TimeFlies, Charm School, and Almost, Maine. He has also directed at other theatres and colleges including LaGrange College, Gainesville Theatre Alliance and GMT Productions. He is a 1999 recipient of a Lexus Leaders in the Arts Award and the Arts and Business Council's Abby Award for Outstanding Arts Professional. As Founding Co-Artistic/Technical Director, Jeff has been behind the scenes of every set build for Horizon Theatre productions.
ISABEL & MORIAH CURLEY-CLAY (Scenic & Costume Designers) are pleased to be back at Horizon Theatre for The Waffle Palace. They always love working on Horizon's plays and productions. Some favorite recent Atlanta credits include scenic design for Freud's Last Session at Theatrical Outfit, scenic and costume design for A Body of Water at Aurora Theatre, as well as their Suzi nominated scenic design for Superior Donuts here at Horizon Theatre, and their 2011 Suzi Award-winning scenic design for Avenue Q. Moriah and Isabel are glad to be working with such a wonderful cast and group of artists. Enjoy the show!
JUDE FUTRAL (Stage Manager) is back at Horizon Theatre for her 5th production, including two runs of the Suzi-Award winning Avenue Q. In Atlanta, Jude has also worked at Actor's Express, Atlanta Lyric Theatre, Brooks & Company Dance, Essential Theatre, Fly-By Theatre, Moving in the Spirit, Theater Emory, and True Colors Theatre Company. Thank you for supporting live performance in Atlanta and enjoy the show.
THOM JENKINS (Sound Designer) is a composer, musician, sound designer, and educator based in Atlanta. He is delighted to be back working with his friends at Horizon Theatre. His recent work includes: Dr. Jekyll & Mr. Hyde at Aurora Theatre; Black Pearl Sings, Shakin' the Mess Outta Misery,Tree, The Santaland Diaries, and Madeline's Christmas at Horizon Theatre;Don Quixote at The Center for Puppetry Arts; Frankenstein at Theater Emory; A Confederacy of Dunces at Theatrical Outfit; and Stealing Dixie, The 39 Steps, Circle Mirror Transformation, and On Golden Pond at Theatre in the Square in Marietta.
KATE BIDWELL LaFOY (Prop Designer) is very excited to be working on The Waffle Palace at Horizon Theatre. She thinks of Horizon as her second home where she doubles as the house manager. Her previous credits include Horizon's productions of Superior Donuts, Night Blooms, The Clean House, Madeline's Christmas, The Santaland Diaries, The 13th of Paris, and Shooting Star. She has also designed props for Theatre in the Square, Synchronicity Theatre, The Red Clay Theatre, and Aurora Theatre. As always, to her husband Cam- I love you lots like purple spots.
MACLARE "MC" PARK (Prop Designer) is a freelance prop artisan who is also the resident Prop Master at Georgia Ensemble Theater of Roswell. This year's prop work includes: Avenue Q (Horizon Theatre), Freud's Last Session (Theatrical Outfit), In the Next Room or the vibrator play (Synchronicity Theatre ) Gut Bucket Blues (True Colors Theater), The Foreigner (Georgia Ensemble), Red (Theatrical Outfit), and Panhandle Slim (Georgia Ensemble).
MARY PARKER (Lighting Designer) is thrilled to return to Horizon Theatre as a resident designer. Over the seven years that Mary has called Atlanta home, she has had the pleasure of designing for almost every professional theatre company in town, as well as several regional theatres throughout the Southeast. Recent favorites include:Avenue Q and Tree at Horizon; How I Became A Pirate at South Carolina's Children's Theatre; Spelling Bee and Inherit The Wind at Georgia Ensemble Theatre; Little Foxes and Ghost-Writer at Theatre in the Square; Assistant design Bring It On at the Tony Award Winning Alliance Theatre. Mary is super grateful to be the recipient of the Suzi Bass Award and Theater Fan award for her work here at Horizon on Avenue Q.
from www.horizontheatre.com
Dr. Wilson Triviño is a speaker and writer for ABC Vision and may be reached at [email protected] or www.T4Vista.com
Theater /
"A Christmas Carol" at Theatre in the Square Brings the Holiday Cheer!
The New Theatre in the Square Marietta is Back and Better Than Ever!
Pure Magic! Cinderella at The Fox Theatre!
‹ Jason Michael Carroll at the new 120 Tavern and Music Hall› Bass player Donald 'Duck' Dunn dies in Tokyo


text:
Karzjew () ist ein Dorf (chutor) in Südrussland. Es gehört zur Adygeja und hat 77 Einwohner (Stand 2019). Im Ort gibt es 2 Straßen.

Geographie
Das Dorf im Südosten des Giaginski Rajon am linken Ufer des Flusses Fars, 7 km südlich des Dorfes Sergijevskoje, 41 km südöstlich des Dorfes Giaginskaja und 29 km nordöstlich der Stadt Maikop. Dneprowski, Kozopoljanski, Tambowski, Farsowski sind die nächsten Siedlungen.

Einzelnachweise

Ort in der Republik Adygeja

redpajama_set_name: RedPajamaWikipedia


That one's condition will never change.
The fire that will penetrate the soul without destroying it. A terrible suffering since it is a purely spiritual fire, lit by God's anger.
Continual darkness and a terrible suffocating smell, and despite the darkness, the devils and the souls of the damned see each other and all the evil, both of others and their own.
The constant company of Satan.
Horrible despair, hatred of God, vile words, curses and blasphemies.


The Competition Council of the Hungarian Competition Authority (Gazdasági Versenyhivatal - GVH) established in its decision, issued on 3 October 2006, that OTP Bank, the largest commercial bank in Hungary, infringed the provisions on the prohibition of unfair manipulation of consumer choice of the Hungarian Competition Act.
In the competition supervision proceedings the Competition Council of the GVH concluded that the advertisements of OTP Bank were misleading consumers because it stated that the credit card owner does not have to pay interest during a certain period when using his/her OTP Bank credit card, although this was not true, as this possibility was subject to certain conditions (i.e. the credit card owner had to have no accounts payable).
The Competition Council of the GVH imposed a fine of HUF 100 million (approx. EUR 357.000) on OTP Bank for its unlawful behaviour.
1054 Budapest, V., Alkotmány u.5.


text:
Council Progresses €1.4m Civic Plaza Plan
Mallow Town Council is to begin site investigation work this month for the €1.4 million streetscape refurbishment project in the Clock House/Tuckey's Hill area. The council has already advertised a Part 8 planning application for the project, and plans for the scheme are at present on display in the Town Hall, Library and Co. Council office in Anna-bella. The application will come before members of the council in March for a decision and if approved funding will be sought to proceed with the work.
Under the plan, a civic plaza will be created in Tuckey's Hill, with traffic reduced to a single lane in order to allow for widened footpaths, plus seating, planting, a water feature, innovative street lighting, regeneration of laneways and the erection of a statue commemorating Thomas Davis. Under the plan, the existing mini-roundabout will be removed and replaced with traffic lights and pedestrian crossing areas, while Bridewell Lane at the rear of the Clock House will be one-way in terms of traffic.
It is hoped that some or all of the works will be completed by the end of 2014, the bicentenary of the birth of Thomas Davis.


Dearborn Academy provides a great chance for students to take charge of their high school learning. The school prides itself on its strong academic program, individual attention and one-on-one learning supports that will help our older adolescents improve their critical thinking skills while building (or re-building) important academic skills and content knowledge. At its base, the core curriculum is aligned with the Massachusetts Curriculum Frameworks. In addition to strong core academics, however, Dearborn offers a highly respected shops and studio program, health and physical education, a diverse selection of electives and opportunities for all students to gain work experience and professional skills.
As a school concerned with each student's emotional health and well being, Dearborn's school day includes individual and group therapy for students and their families. Our teachers, milieu staff and clinical specialists work closely together to support each student navigating the challenges of adolescence. Learn more about our clinical and milieu services, or download a more detailed description here.
What is equally important for many students and families is that no student graduates from Dearborn High School without a road map for the future. Seniors work hard on a personalized transition plan during the last part of their senior year and get lots of support and guidance setting up a plan for success for after graduation. Our distinguished career guidance services have received commendations for excellence from the state's department of education. We offer both career and life skills workshops and college guidance and support.
Finally in addition to a nine-month academic year, Dearborn offers a six-week summer program.
View the school calendar to explore the wide range of activities and events that reflect our dynamic and engaging high school community.