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CPI-613, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
|ClinicalTrials.gov Identifier: NCT01768897
Recruitment Status : Completed
First Posted : January 16, 2013
Last Update Posted : July 3, 2018
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
|Condition or disease
|Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Recurrent Adult Acute Myeloid Leukemia
|Drug: CPI-613 Drug: cytarabine Drug: mitoxantrone hydrochloride Other: laboratory biomarker analysis Other: pharmacological study
|Phase 1
I. To determine the safety and maximum tolerated dose (MTD) of CPI-613 when administered with high dose cytarabine, and mitoxantrone (mitoxantrone hydrochloride).
I. To determine the pharmacokinetics (PKs) of CPI-613 following intravenous (IV) administration in combination with high dose cytarabine and mitoxantrone.
II. To observe the response rate (complete response [CR], complete response with incomplete platelet recovery [CRi] and partial response [PR]) of CPI-613 in combination with high dose cytarabine and mitoxantrone.
III. To observe the overall survival of patients treated with CPI-613 in combination with high dose cytarabine and mitoxantrone.
OUTLINE: This is a dose-escalation study of CPI-613.
Patients receive CPI-613 intravenously (IV) over 2 hours on days 1-5, cytarabine IV over 3 hours every 12 hours for 5 doses beginning on day 3, and mitoxantrone hydrochloride IV over 15 minutes after the 1st, 3rd, and 5th doses of cytarabine. . Treatment repeats every 14 days for up to 2 courses* in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients undergoing a second course of therapy receive CPI-613 IV over 2 hours on days 1-3, cytarabine IV over 3 hours every 12 hours for 5 doses beginning on day 2, and mitoxantrone hydrochloride IV over 15 minutes after the 1st and 3rd doses of cytarabine.
After completion of study treatment, patients are followed up for 6 months.
|Study Type :
|Interventional (Clinical Trial)
|Actual Enrollment :
|67 participants
|Intervention Model:
|Single Group Assignment
|None (Open Label)
|Primary Purpose:
|Official Title:
|An Open Label, Dose-Escalation Study to Evaluate Safety, Tolerability, Maximum Tolerated Dose (MTD), Efficacy, and Pharmacokinetics (PKs) of CPI-613 Given With High Dose Cytarabine and Mitoxantrone in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)
|Actual Study Start Date :
|January 2013
|Actual Primary Completion Date :
|January 2016
|Actual Study Completion Date :
|January 2016
Experimental: Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)
Patients receive CPI-613 IV over 2 hours on days 1-5, cytarabine IV over 3 hours every 12 hours for 5 doses beginning on day 3, and mitoxantrone hydrochloride IV over 15 minutes after the 1st, 3rd, and 5th doses of cytarabine. Treatment repeats every 14 days for up to 2 courses* in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients undergoing a second course of therapy receive CPI-613 IV over 2 hours on days 1-3, cytarabine IV over 3 hours every 12 hours for 5 doses beginning on day 2, and mitoxantrone hydrochloride IV over 15 minutes after the 1st and 3rd doses of cytarabine.
Drug: CPI-613
Given IV
Other Name: alpha-lipoic acid analogue CPI-613
Drug: cytarabine
Given IV
Other Names:
Drug: mitoxantrone hydrochloride
Given IV
Other Names:
Other: laboratory biomarker analysis
Optional correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
- MTD of CPI-613 based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE 3.0) [ Time Frame: 14 days ]
- Response rate (CR, CRi, and PR) [ Time Frame: Day 14 of course 1 ]Confidence intervals will be calculated.
- Overall survival [ Time Frame: Up to 6 months ]We will use Kaplan-Meier estimation.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:
|18 Years and older (Adult, Older Adult)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
Inclusion Criteria:
- Patients must have histologically or cytologically documented relapsed and/or refractory acute myeloid leukemia
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3
- Expected survival > 3 months
- Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation; (Note: Pregnant patients are excluded because the effects of CPI-613 on a fetus are unknown)
- Fertile men must practice effective contraceptive methods during the study period, unless documentation of infertility exists
- Mentally competent, ability to understand and willingness to sign the informed consent form
- No radiotherapy, treatment with cytotoxic agents (except CPI-613), treatment with biologic agents or any anti-cancer therapy within the 2 weeks prior to treatment with CPI-613; patients must have fully recovered from the acute, non-hematological, non-infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment); patients with persisting, non-hematologic, non-infectious toxicities from prior treatment ≤ grade 2 are eligible, but must be documented as such
- Aspartate aminotransferase ([AST]/serum glutamic oxaloacetic transaminase [SGOT]) =< 3 x upper normal limit (UNL), alanine aminotransferase ([ALT]/serum glutamate pyruvate transaminase [SGPT]) =< 3 x UNL (=< 5 x upper limit of normal [ULN] if liver metastases present)
- Bilirubin =< 1.5 x UNL
- Serum creatinine =< 1.5 mg/dL or 133 μmol/L
- International Normalized Ratio or INR must be < 1.5
Exclusion Criteria:
- Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, pericardial disease or New York Heart Association class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients' risk for toxicity
- Patients with active central nervous system (CNS) or epidural tumor
- Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
- Pregnant women, or women of child-bearing potential not using reliable means of contraception (because the teratogenic potential of CPI-613 is unknown)
- Lactating females because the potential of excretion of CPI-613 into breast milk (Note: Lactating females are excluded because the effects of CPI-613 on a nursing child are unknown)
- Fertile men unwilling to practice contraceptive methods during the study period
- Life expectancy less than 3 months
- Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
- Unwilling or unable to follow protocol requirements
- Patients with large and recurrent pleural or peritoneal effusions requiring frequent drainage (e.g. weekly); patients with any amount of clinically significant pericardial effusion
- Active heart disease including myocardial infarction within previous 6 months, symptomatic coronary artery disease, uncontrolled arrhythmias, or symptomatic congestive heart failure
- Albumin < 2.0 g/dL or < 20 g/L
- Evidence of ongoing, uncontrolled infection
- Patients with known human immunodeficiency virus (HIV) infection; (Note: Patients with known HIV infection are excluded because patients with an immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, and because there may be unknown or dangerous drug interactions between CPI-613 and anti-retroviral agents used to treat HIV infections)
- Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 2 weeks prior to initiation of CPI-613 treatment (the use of Hydrea is allowed)
- Patients who have received immunotherapy of any type within the past 4 weeks prior to initiation of CPI-613 treatment
- Requirement for immediate palliative treatment of any kind including surgery
- Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months
- A history of additional risk factors for torsade de pointes (e.g., clinically significant heart failure, hypokalemia, family history of long QT syndrome)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01768897
|United States, North Carolina
|Comprehensive Cancer Center of Wake Forest University
|Winston-Salem, North Carolina, United States, 27157
|Principal Investigator:
|Timothy Pardee
|Wake Forest University Health Sciences
|Responsible Party:
|Wake Forest University Health Sciences
|ClinicalTrials.gov Identifier:
|NCT01768897 History of Changes
|Other Study ID Numbers:
NCI-2012-02768 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA012197 ( U.S. NIH Grant/Contract )
CCCWFU 22112 ( Other Identifier: Wake Forest University Health Sciences )
|First Posted:
|January 16, 2013 Key Record Dates
|Last Update Posted:
|July 3, 2018
|Last Verified:
|June 2018
|Studies a U.S. FDA-regulated Drug Product:
|Studies a U.S. FDA-regulated Device Product:
Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors


text:
How to grow rhododendrons
Boring garden? Let rhododendrons ride to the rescue. Rhododendrons are a spectacular flowering plant that add a bit of drama and a pop of colour to your garden. Most people associate the name with a cold climate "mountain loving" plant, but more tropical varieties are also available that prefer more temperate climates.

subset: commoncrawl


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Library Media Services
School library staff can enjoy a wide variety of training opportunities�from half-day workshops to conferences and semester-long classes. SCOE�s Library/Media staff plan many short workshops during the school year and coordinate large vendor events twice a year. The California School Library Association offers regional trainings and an annual statewide conference. For more intense study, college and university classes and degree programs are available via distance learning.
Library/Media Training
California School Library Association: Annual Conference
CSLA�s annual conference is a phenomenal statewide event. Training sessions, special interest meetings, users groups, keynote speakers, and other special events fill the four-day schedule and hundreds of publishers and other vendors have booths in the exhibit hall. The professional development, purchasing, and networking that can be packed into this conference make it one of the most worthwhile events for school library staff. CSLA also offers regional workshops and maintains calendars of library related events and conferences.
Programs for Paraprofessionals
Library/Information Technology Programs at Cuesta College
Several of California�s community colleges offer certificate or degree programs for library technicians. Santa Rosa Junior College offers some library science classes, although it does not offer library science certification or a degree. Both certificate and Associate degree programs are available through Cuesta College (the community college in San Luis Obispo), with required classes and electives available in online formats. The program is designed to enhance individual skills and provide a sound knowledge base for paraprofessionals in a public, school, academic, or special library with coursework that includes general library practices and skills as well as specific electives about school libraries and literature for children.
Programs for Professionals
California Library Media Teacher Services Credential
Library Media teachers in California have both a teaching credential and a Library Media Teacher Services Credential. The California Commission on Teacher Credentialing (CTC) provides credential information and requirements and clarifies the duties and requirements for California�s Library Media Teacher credential.
California Library Media Teacher Credential Programs
Several college and university programs in California offer LMT service credential programs. The listing briefly describes the program and includes information on distance learning opportunities and a link directly to each program. In order to serve people from a wide geographic area, all of these programs have adapted their offerings to include classes that may be partially or fully online, available on weekends or in the summer, offered as intense short-term classes over winter break, taught at other sites, or provided via satellite to several sites. Note: Only San Jos� State offers both the California credential program and an ALA accredited Master�s Program in Library & Information Studies.
- San Jos� State University
- California State University, Chico
- California State University, Long Beach
- Azusa Pacific University
School Librarianship as a Career
Interested in being a school librarian? Have a few questions? The Recruitment to School Librarianship site from the American School Library Association explains what a school librarian does, shares information on education and training, and links to job postings.


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We managed to find a short term lease for the few months we were going to be spending in Toronto for the duration of the accelerator. We jumped into it right away, meeting with mentors, cohort dinners, meeting with investors, etc. Little did we know, we were going to take
The Accelerator
The first two months were spent just getting used to this new environment I had just jumped into. Learning new processes, working in a small team and wearing many "hats" was starting to become routine. After a few rough deployments of code, I was starting to get the hang of
First Startup
Having taken a long break from blogging, it was time to continue my startup story since my last post from 2 years ago.
In my previous post, I talked about wanting to start something new. My job at the university started to lose the appeal it once had. I
Startup Begining
Life was good. I was getting close to finishing my Computer Science degree at the University of Ottawa, I had a interesting job, it seemed like everything was just fine. Or was it?
My old job was a Webmaster position for the university. It was great and I learned a
Back to Normal? Not Really...
It's been a very "roller coaster" ride for me the last few months, in both my personal life and career. One would think that me finally posting would be a sign that everything is back to normal. Unfortunately it's not. For various reasons the life I had will never be
Server is Back
As you may have noticed (or maybe not), my website has been down for a while. I have been busy at work and haven't had time to fix my server... until now.
I used to host the website from a server at home. After all this downtime I decided to


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I. Introduction
Kael Drakkal is the home of the giants in Velious, populated by mostly storm giants but also frost giants. For you genuine newbies, there are three factions on Velious, Coldain (dwarf, city of Thurgadin), Kromzek/Kromrif (giants, city of Kael) and Claws of Veeshan (dragon, city of Skyshrine). All three cities have armor quests where you can turn in an armor drop and three gems to get quest armor. There is no way to get ally faction with all three, you can only get two, max.
The Kromriff are frost giants who wear blue armor and have long, white beards. Their primary feud is with the Coldain. The Kromzek storm giants look more like gladiators and have no beard. Their primary nemesis is the dragons. Frost giants are found in Iceclad Ocean (lowest level giants), Great Divide (the fort near the Eastern Wastes zone is a popular hunting spot), on the Eastern Wastes side of Kael and the Wakening Lands. There are some storm giants in WL but mostly they are inside Kael. The relations go something like this:
* Killing Kromrif will raise your Coldain faction and give you a slight CoV faction boost.
* Killing Kromzek will give NO Coldain faction but a bigger CoV hit.
* Killing CoV mobs will give you rif/zek faction, but no Coldain faction.
* Killing Coldain in EW, GD and Thurg will give you rif/zek faction and cost you Coldain/CoV.
Killing Coldain gives big Kromrif faction but negligible Kromzek faction. I turned in a few dozen Coldain heads to the Kromrif recruiter and went to amiable to the frost giants but still dubious to the Kromzek. The easiest way to get Kromzek faction is go to the courtyard in Skyshrine and kill Guardians and Sentrys. So you can ally with any two of the three. You need warmly faction with the Coldain for the quest armor, ally with the giants and dragons. To check, hail the quest giver and start asking things like 'what sleeves' or 'what gauntlets' and see if he answers. If the mob doesn't answer, your faction isn't high enough and they will eat the item.
There's three other factions, King Tormax, Lord Yelinak and Dain Frostreaver IV. They are the leaders of the giants, dragons and dwarves, respectively. Kromzek deaths raise Dain faction and lower Tormax faction, Coldain deaths do the opposite. Killing Tormax will raise your Yelinak and Dain faction, killing Dain will raise Tormax faction but do nothing for Yelinak, and killing Yelinak will raise Tormax faction but do nothing for Coldain. Got all that? :)
II. Quest Armor
People have to choose their faction based on what kind of armor they want. Generally speaking, it tends to be a guild decision although people tend to go Coldain/CoV for two reasons: most players tend to be "good" aligned, and the dwarves and dragons are considered a "good' race while giants are seen as evil, and two, Thurg armor is easy to get while Skyshrine armor is the best for saves and for casters. Skyshrine is known for saves and caster stats (int/wis) while Kael armor has far and away the best armor class and HP.
For the Thurgadin armor, you will need to hunt deep in Kael Drakkel. While the armor can drop anywhere, the Arena is where it is most likely to drop. You should look for the level 53+ Veterans, Adjutants, Legionnaires and Lieutenants, because they have the best chance of dropping the armor. There is a Lieutenant who spawns near the bank (see below) who often drops armor, too.
For the Kael Drakkel armor, you will need to hunt in the Temple of Veeshan in any area except the Halls of Testing (HoT) to the east of the central area and the entry. Everything here is 60+ so you need a lot of very high level people and high resists because so many are casters.
For the Skyshrine quests, you need to hunt in the Temple of Veeshan Halls of Testing. After running up the stairs and moving to the central area, it's to the right, or the east. There's only one thing to really remember about HoT: do NOT open the door until someone inside gives the all clear.
III. Busting into Kael
Ok, got sidetracked, on to Kael. Giants are a difficult fight because they cannot be stunned or mezzed, which makes life tough for enchanters. They can be slowed, although many of the Arena mobs will summon, so you can usually tell when the enchanter has tashed the giant. Giants can be charmed. Dire charm-capable enchanters often do this. I've seen AoW raids with 3-4 charmed giants. They have a tendency to break charm easily though, so keep an eye on the enchanter.
Frost giants guard the entrances from EW and WL. If you have Coldain heads from killing the dain, you turn them in to the Kromrif recruiter who stands at the entrance to Kael on the EW side. That gives some big faction boosts. These frost giants are rather low level. On the map below, you will find level 40 and lower frost giants. They drop no armor except for junky axes and swords, but they do drop heads and toes, which can be turned in in Thurgadin for faction.
The other way in is from the Wakening Lands side.
There are a lot of low-level frost giants here as well. It's not uncommon to see a three-man team just killing in this area, working on faction. There are also some low-level storm giants and one high level beast, Korakaz. He's a blue storm giant, level 54, hits very hard and fast. He drops something called Bear Skins of Rage, but no one knows what it's for. Going up the slope from the WL zone leads to the bank area.
Ok, below is where it gets fun.
Follow the blue line to get thru Kael to the WL zone. It's mostly a straight line with a hard right turn at the bridge, which is on the right side of the map. You'll go down a ramp, then turn left, go past the bank area, down a ramp and you're at the zone.
The Manor, some times referred to as "plate cycle" or "Iceshard Keep" when people do camp checks, is where you will find the highest level frost giants in the game. You can take a single group of 53+ people up to the manor, which is over a small lake that actually has a giant fishing at the shore, and stay outside the building and pull. There are a number of named frost giants, and some are shadowknights. Your puller will know which when he gets harmtouched. Some of the giants have the title "Oracle." These are the ones most likely to drop armor.
The manor has a 28 minute respawn timer, but there's plenty of giants to
kill. Klaggan Iceshard, who is in the throne room, drops Royal Kromrif Blood, which is used in the 7th Coldain
Prayer Shawl quest. If you clear the building, you can do the plate cycle, which
coincides with the 9th Coldain ring. Move your group inside to the throne, stand
at the edge of the throne and say "The Dain shall be slain for the peace we must
obtain." Doldigun Steinwielder, a Coldain, will spawn. Kill him, he dies
with one smack, and two level 51 giants will spawn. As you kill them a pair of level
54 giants will spawn. When you kill the two level 54s, a 57 giant will spawn, and when
he dies, a level 60
giant spawns, and he is totally MR.
After the level 60 giant dies, Doldigun will spawn in the throne room and start running. You have to kill him either way, whether you are doing the Coldain ring quest or not. If he despawns you won't be able to repeat the quest for 20 minutes. If you want to redo the plate cycle immediately, then you have to kill him. He's pretty tough this time, around level 55. Kill him and loot his head for the ring quest. It's one of the six heads you need for the Coldain traitors.
There is no limit on how many times you can do the plate cycle so long as you kill Doldigun. You can restart it and go it all over when you are done and do the cycle all over again. With each plate cycle, it's expected that one or two pieces of plate armor will drop, and only plate. So you can do it over and over to get tons of plate. Just remember, every 28 minutes the giants will respawn, and if they respawn during the plate cycle, your life can get very difficult.
The noble house is a popular spot for a single group. They hide in the corner outside the the house and pull to there. The group usually pulls from the area around it, the manor and the area marked "Bvellos," where Captain Bvellos and Staff Sergeant Drioc spawn. Both are used in various quests and are pretty hard to kill. Inside the manor is a noble named Wenglawks Kkeak, who actually won't attack you. He's used in several quests, so you don't HAVE to kill him.
People like to kill him and the Lesser Nobles who populate the house. Be careful of Noble Helssen, a level 60 giant who looks like Wenglawks. He's a caster and will gate back into the manor and summon players, and that can be rough. Inside the house is also a merchant. Con him, he'll be dubious even though you are KoS everywhere else. Don't pull him, they are a bitch of a fight and drop nothing.
The bank area is rather weak, with low level mobs like the Storm Giant Commoner. Kill them only because nothing else is up. In this area, a storm giant Lieutenant will frequently spawn. By all means, kill him. I've seen him drop plate arms and silk legs. Lieutenants are easy to spot because they are blue while most storm giants have a copperish armor color.
Ok, this is where the fun begins.
In case my illustration doesn't make it clear, the dark blue dots are spawn spots. After people were tramping through Kael totally unmolested, Sony decided to make us earn our keep by putting in giants that see invisible. That starts at the top of the ramp leading to the arena. At the top will be two pairs of giants, usually frost but some times storm, that will see invis and sneaking rogues. People like hanging at this spot, as it's a great pull location and you've got plenty of nearby giants to grab, both going into the arena and down the ramp, near the noble house, if no one is camping the nobles.
Be careful when going to the arena, it's easy to turn into the arena itself where supposedly gladiator fights take place and the stands are full of giant "spectators." There are two ramps that lead to the arena, one on each side. A giant stands guard on the opposite side of the ramp, as the spawn spot dots show. I have successfully run by them by hugging the ramp wall on the opposite side, so it can be done. But see how there's another giant spawn spot right near them? You have to be careful, because that giant will see you running up the ramp, and he roams. Wait for him to walk away, down that dead path behind him.
In the Arena you will have a host of giants to deal with. You want Veterans, Adjutants, Legionnaires and Lieutenants for armor drops. If you are leading a raid, collect all the storm giant toes and giant warrior helms. These can be turned into Sentry Kcor at the entrance to Skyshrine (WL side) for faction. Most raids have one loot nazi who divvies up the helms and toes after the raid is over to people who need them.
You will run into a lot of Protectors of Zek, nasty monsters from level 56 to 58 that hit for up to 350 a shot. You need some mature tactics here: pull with a monk and have an MA gain agro before calling in other melees and casters. Three spawn right next to each other inside the arena area, so separating them is a challenge for the monk, and often you need two monks to do the job. PoZs drop no armor, just their head. Wood elf Rangers need the head for the Helm of the Tracker quest on the Plane of Growth.
Quick rundown of the big name mobs in the Arena:
A Priest of Tallon Zek: Drops the Idol of Erosion for the high elf cleric quest Symbol of Tunarean Worship, a PoG quest.
A Cleric of Vallon Zek: Drops the Idol of Decay for the cleric quest.
Semkak Prophet of Vallon: Drops several quest items, including the third idol for the cleric quest.
Kallis Stormcaller: Tough giant, head is needed for the Helm of the Tracker quest.
Gkrean Prophet of Tallon: Drops a number of quest items, including the fourth idol. Teachings for for the Circlet of Falinken.
Bjrakor the Cold: Popular with monks for his Scepter of Mastery, a nice 1HB item for them.
Vkjor: Arena spectator, around level 60, druids Silver Steel Gauntlets, a nice pair of warrior gauntlets.
Vealok the Angry: Guess I'd be angry if I had no loot, too.
To the north of the arena is a bridge leading to the temple. Now, a warrior worshipper of Rallos Zek can walk through Kael largely unmolested, although he's dubious to everything until he works on his faction. Here, though, everyone is KoS. The bridge has three wandering mobs, two level 58 Temple Guardians and Derakor the Vindicator, a very nasty level 65 giant. Vindi is probably the most overrated mob in the game. His BP is nice, but considering what a tough fight he is (250,000 HP), his drops aren't that good. But killing him spawns the Statue of Rallos Zek, who in turn spawns the Idol of Rallos Zek, and killing that spawns the Avatar of War. But they are another story.
Compiled from numerous guides around the Web, plus my own experiences.


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Anti-Zionists insist their views aren't anti-Semitic. They're often lying...You are maybe wondering, does Zionism have any connection to the Fed?...Now, Zionism has an actual meaning. Zionism is simply Jewish nationalism and devotion to the state of Israel — as benign and natural as the devotion to their respective homelands of, say, Italians, Koreans, Armenians or Mexicans. And aside from not being "racism" or "colonialism," Zionism obviously has nothing to do with the Federal Reserve.
Read the rest here


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As of right now, the girls have paint on the walls! I am still trying to figure out if I should design them to be identical or not, within the color palette of each room. Some alike elements I know for sure are:
- Upholstered headboards
- Full size beds
- Storage options
- Extra Seating
- Desk/Vanity
|Via 1-2-3
|Via 1-2 (U R not going to believe what pic 2 is)
I find myself constantly working and reworking the space planning for there rooms until I get that feeling that I have just the perfect layout for each of their spaces. And again I keep toying with the idea of doing identical rooms. Here is my latest space plan:
Here is my latest quick sketch:
I am loving the idea of two-tone painted furniture. I am so into refurbishing a piece of furniture to make it your own which I have seen a lot of in the blogging world. The purple wardrobe is from the UK that comes in a variety of different colors. I am just glad I found one in purple. Here is two-tone in pink. Pretty huh! I came across this in the April 2010 issue of Traditional Home magazine. It was a Market Place profile article on kids furniture. This is the Savannah Dresser changer.
When it comes to the desk/vanity, I am thinking about splurging! I think the girls (10 &12) are old enough to handle the West Elm Parsons Mirror Console. There is no DIY in this.
Things I still have yet to consider are:
- Flooring - I plan to do a pink and purple shag in the corresponding rooms
- Lighting - General, task, and ambient
- Ceiling fan - Lowe's has a clear blade fan, but its pretty expensive. I wonder if I can purchase clear blades separately and do a refurb on a couple of fans from craigslist. (ANY IDEAS?)
- Window and pillow fabrics - (I actually found a couple but I am not feeling them anymore)
- Closet Organizers


text:
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text:
> <blockquote > cite="http://www.w3.org/TR/CSS3-selectors#adjacent-combinators"> > Direct adjacent combinators > > Direct adjacent combinators are made of the "+" > character that separates two sequences of simple > selectors. The elements represented by the two > sequences share the same parent in the document > tree and the element represented by the first sequence > immediately precedes the element > represented by the second one. > </blockquote> > I assume that immediately precedes excludes the > possibility of intervening anonymous content (although > anonymous content cannot be selected, so maybe not), > but it might be helpful if there was a note on this > point. Standalone #PCDATA is never counted in selectors. </Daniel>Received on Tuesday, 11 January 2000 09:50:56 UTC
This archive was generated by hypermail 2.3.1 : Monday, 2 May 2016 14:26:52 UTC


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This forum thread will be used to OOC plan out a limited conflict between Lourenne and Kalistan, with Kazulia coming in on Lourenne's side in a limited basis.
The scope worked out so far is that Kalistan is upset that Lourenne is arming the Anantonese Ocean, which creates a security crisis for Kalistan, who is attempting to restore its military. Right now, Kalistan has next to no serviceable weapons, so Lourenne feels Kalistan's complaints are an irritant, and Kalistan is not justified in complaining about Lourenne's own security concerns, which it declares are in no way a threat to Kalistan.
Where we are right now: There might be a limited hot conflict that sparks from perhaps some sort of incident where either Kalistan attacks a Lourenne ship that gets too close to Kalistan's shores, or Lourenne fires on Kalistan first and sparks reaction. We haven't worked this out yet. Lourenne wants to have several naval battles, and Kalistan is down with this, but has expressed that realistically, the conflict will have to be very low level, given the inequality of power on both sides. Kalistan would like to limit combat deaths to 100 at most, but is willing to take the majority of these casualties. Eventually, Lourenne will invite Kalistan to talks that will resolve things, one way or another. Max in Kazulia would like to join the RP, and can possibly launch a limited response with Lourenne against Kalistani shipping/navy, or could serve as mediator if they don't want to join the combat.
We need to pass RP resolutions in our countries, but we can continue the war of words meanwhile in the Press. I will work up a draft RP resolution in Kalistan to satisfy the rules. Meanwhile, we can use this thread to plan the RP.


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Hello peeps, Inuoko Shikami here! Earlier today, I brought you my handy guide to the Cinema Event [X]. I don't usually post photos of my home, but hey...why not? I wish to show you some of the items I picked up in a rather amusing way...
Rather if you're at home or at a movie theater, usually you start off upright and proper, only to end up pretty relaxed by the end, haha!
I love romances, so I figured i'd show you how I usually react to them. Usually they start off with some sort of mating-dance around each other, making us wait to see how long it takes for them to end up together. Once together, the sniffles begin.
Then a third person comes into play, which may jeopradize the new relationship, and i'm like "OH H*LL NO YOU LEAVE THEM BE!!!!".
Finally, if things go my way, the couple that I want together end up together at the end of the movie, alright!
Hahahaha! Well, this was a different way of showing you my LOTD I must say...it was fun doing it! I hope you all have as much fun as I did at Cinema!
- Inuoko Shikami \o/
Cinema Credits:
Hair: *Alice Project* - Sari
Eyes: .insufferable dastard. - Reflections - Sunset *Freebie, Useable Demo*
Tears: [Miseria] - Cry
Shirt: [Auxiliary] - Zombified - Cinema Special - Cropped Double - B
Pants: .evolve. - bloody.jeans. blue
Glasses: .insufferable dastard. - 3D Glasses *Freebie*
Cup Holding: Auxiliary Unicorn Bliss Swirlie *Freebie, Conecession Stand*
Floor Snacks: *Freebie, Conecession Stand*
Other Credits:
Skin: .The Sugar Garden. [X] - angel - C tone *New*
Lipstick: The Sugar Garden - Angel "Barbie Pink" Lipstick *New*
Nails: Izzie's - Gradient Nails
Ring: Noodles - Plastic Star Ring Black *New, C88*
Shoes: F-WINGS


text: The Cook Small 227×320 Medium 455×640 Large 728×1024 Download TIFF Original 1706×2400 | (901.8 KB) Description The Cook from Chaucer's Canterbury Tales. Illustrated by Agnus MacDonall. Keywords Agnus MacDonall, Chaucer's Canterbury Tales, cook, Geoffrey Chaucer, horse, Illustrator, kcanterbury Galleries Canterbury Tales, Horseback Riding, Individual Men, Literature: C Source: Katharine Lee Bates, Chaucer's Canterbury Pilgrims (Chicago: Rand McNally & Company, 1914130


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Why are you so tired all the time?
This article is a special one, out of all the questions we get asked, the most common are 'how can I get more energy?' and 'why am I always so tired?'. We will be exploring what factors could influence energy and what simple lifestyle changes you can make to adjust your own energy level, so you can do more of the things you want for longer.
In today's society, we are living more stressful lives and consuming less nutrient dense foods. Even the foods we believe to be nutrient dense, such as the vegetables you find at the supermarket or grocery store, you will find are no where near their real value of nutrition with some of the methods being used to farm a lot of our fruit and vegetables. So how can we maintain an energetic existence if our foods aren't even at the quality we need them to be? Well, it's about being smart in your own every day life and making the little changes that will mean so much to your overall health and vitality.
Better Sleep
This sounds very simple but one of the most common causes of fatigue is getting too little sleep. With all the electronics we use today as well as stress levels, this can effect our sleep patterns and how much rest our body gets. The NHS in the United Kingdom says around a third of us have bouts of insomnia. If you enjoy staying up nice and late, your lack of sleep may be causing fatigue.
Your age does make a difference to what your sleep requirements should be. A baby will need up to around 16 hours of sleep everyday and a teenager will need around 9. Most people into adulthood can function well off 7 or 8 hours of sleep. This sounds simple but one of the most common causes of fatigue is getting too little sleep.
Some tips to help increase sleep are: to shut off all electronics before you go to bed, have a dim light on in the room your are sleeping in, or no light at all and try to think of as little as possible to allow your mind to rest.
Anaemia is one of the top causes for fatigue and being run-down constantly. It occurs when your body doesn't carry enough red blood cells to carry enough oxygen to your muscles and organs. It can very easily be detected with a blood test.
Anaemia affects mainly post-menopausal women and roughly 1 in 20 men but it can also be even more common in women who are still having periods, especially if the periods are heavy.
The most common cause of anaemia is iron deficiency and can be corrected by eating plenty of iron-rich foods. Iron-rich foods include lean meat, shellfish and iron supplements.
Eating too little or the wrong foods
Another obvious reason you are showing signs of fatigue and no energy is because you may not be either eating enough, or eating the wrong foods. For example, if you have a pastry for breakfast your going to have a spike in your blood sugar and then it will crash. This will leave you feeling sluggish and dull for most of the day. Try to start your day well with a good healthy breakfast that includes proteins like eggs and good grains such as whole-wheat bread. Throughout the day snack on fruit, nuts and seeds and for lunch and dinner continue eating proteins as well as a vast array of vegetables with a mix of different colours. It really is as simple as that!
Underactive Thyroid
Your thyroid is a small gland in your neck and it controls your metabolism. Your metabolism basically controls the speed at which your body converts fuel to energy. When it is underactive your metabolism is functioning too slowly and this can lead to you feeling tired and gaining weight.
An underactive Thyroid Is 4 or 5 times more common in women than in men, especially over the age of 40. A simple blood test can confirm if you have low thyroid levels and medication can help you regulate those levels back to normal.
Chronic Fatigue Syndrome
Chronic Fatigue is possible if you are at a point where you cannot even handle simple day to day activities because you are so tired all the time. The main symptom of Chronic Fatigue is unexplained exhaustion.
There is real quick fix for Chronic Fatigue Syndrome apart from changing a person's daily routine, allowing them to rest and participate in light exercise.
Food Intolerance
A lack of energy and always feeling sleepy can come from a intolerance to certain foods. If you notice that your energy gets worse after eating certain things, you may have food intolerance. A supervised elimination diet could be your answer and this is something you can easily coordinate with your GP or if you would like to do this yourself, try by cutting out certain foods you've identified make you feel sluggish and see if you begin to feel any better.
Coeliac disease is when your body reacts badly to foods containing gluten. Such foods can be breads, pastas, cereals, pizza and cakes. According to the NHS in the United Kingdom around 1 in 100 people have Coeliac disease, however, 90% of sufferers don't realise they even have it. Tiredness, feeling sluggish and a lack of energy after eating is a symptom of coeliac disease, so is diarrhoea and anaemia. Your GP is able to detect if you have coeliac disease with a simple blood test.
Sleep Apnoea
This condition robs you of sleep without you even knowing about it. Sleep apnoea briefly stops you breathing many times during the night. Each time you are interrupted in your sleep, even though you may not be aware of it, it all stacks up and leads to a restless night not allowing your body to go into a deep enough sleep where your body gets the optimum rest. The result being that you end up sleep-deprived and feeling exhausted during the day, even though you think you had 8 hours of sleep.
It's most common among overweight middle-aged men. Alcohol and smoking can make it worse. The solution for sleep apnoea is to lose weight, become healthier, quit smoking and avoids alcohol during the evenings. There are devices which GP's and specialists can recommend such as a CPAP (continuous positive airway pressure) device which helps keep a persons airway passages open at night time.
Diabetes can be a big factor as why you are constantly feeling exhausted or tired. When you have diabetes the sugar from the foods you consume stays in the blood stream and continues to circulate instead of being absorbed by the body's cells, where they convert it into energy. This leads to a body that runs out of energy, despite eating enough foods. Diabetes Alive says one of the main undiagnosed symptoms of diabetes can include extreme tiredness. If you have persistent fatigue and feel like you cannot shake it off, you may need to go speak to your GP about being tested for diabetes. This can be tested with a very simple blood test.
With diabetes there are a variety of treatments available, these can be a change to lifestyle and foods, insulin therapy if your diabetes has become bad enough and medications.
Diabetes can be reversed if it is type 2 diabetes. Type 1 diabetes unfortunately cannot be reversed.
Depression doesn't only cause issues emotionally, it can also manifest into physical ailments as well. Fatigue, loss of appetite and headaches are among the most common physical symptom. If you are beginning to feel tired and down for more than a couple of weeks, you should look at alternative therapies to help with your depression. If you treat the depression the fatigue should lift as well.
Some people have constant, what can seem like uncontrollable symptoms of anxiety, which can be so strong that their life is significantly affected. People who are often worried and tired can often feel tired also.
A dwindling spiral can occur from this effect. A lack of sleep and fatigue can create a worsening mental health situation for you. A Mental Health Foundation study in the UK found that more than 1 in 3 people suffer from a sleep disorder which can put sufferers at greater risk of health problems like depression, anxiety and bipolar disorder.
Glandular Fever
Glandular fever is a viral infection that is commonly found amongst the general population. It causes tiredness as well as a fever, sore throat and swollen glands. Teenagers as well as young adults are most likely to have glandular fever. Symptoms generally clear up within four to six weeks, but fatigue can feel like it is still around for several more months.
Heart Disease
If everyday tasks like climbing stairs or walking down the street leave you feeling tired and exhausted, it can be a sign that your heart is not up to the job. It can be an early sign of heart disease. Often seeking medical advice and receiving the help of a GP can treat this. There are therapeutic as well as medication to help get heart disease under control.
Natural Solutions for increasing energy
Natural solutions for increasing energy can be found plain and simply in the diet you are consuming and the amount of exercise you consume. Eating well, with a good balance between proteins, grains, nuts, legumes and vegetables with plenty of water, will see you improve your health and should lead to an increase in your overall energy levels.
A regular exercise program of at least 30-40 minutes of exercise everyday should see you improve your overall fitness levels; this will help muscles receive more energy from the blood cells and also improve heart strength. All this contributes to improve levels of energy and not feeling exhaustion early throughout the day.
Something else to consider is boosting anti-oxidants. Anti oxidants not only reduce inflammation in the body but also allow the body to function and blood cells to deliver energy my effectively in the body.
Amaze Tea Co has a range of tea's, which offer a boost in anti-oxidants, and customers claim have improved their energy levels quite a bit. The two teas', which Amaze Tea Co has, which contributes to energy is 'The Daily Dose' and 'The Detox'.
'The Detox' and 'The Daily Dose' are both all natural and organic tea's. 'The Detox helps to detoxify the liver, boosts metabolism, helps energy, assists with clearing the skin and aids mental clarity.
'The Daily Dose' helps both to detoxify and distress the body. It is a tea for the every day and is almost like a multi-vitamin in a tea.
To purchase either of these products, please see below – if you sign up to the Amaze Tea Co newsletter you can receive 15% off you purchase.
sources: http://www.naturalhealth365.com/healing_food.html/ http://www.webmd.com/women/features/10-energy-boosters


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Did you know you can generate more leads and sales by offering content to your audience? As you can imagine, there is a strategy to be able to do it properly.
One of the keys is to go SMALL to go BIG? It might sound crazy but it will make sense once you listen to this episode with guest expert Joe Pulizzi.
Joe is an expert in content marketing and founder of the Content Marketing Institute. He's been able to work with enterprise brands like LinkedIn and many others!
In this segment, you'll hear Joe describe a content marketing plan that actually works! In addition, Joe shares tools you can use to connect with your audience and how being patient and honing in on one aspect of your business at a time can unlock massive growth.
Here's a glimpse of what you'll learn in this show:
- How Joe got his start – Why content marketing; [3:00]
- The biggest mistakes people make in marketing; [7:30]
- Game changing strategies you can put in place; [16:00]
- What you can learn from failure; [21:30]
- And more!
Resources mentioned on this episode:
- NEVER miss an episode of Growth To Freedom click HERE to subscribe!
- Connect with us on Twitter: twitter.com/dan_kuschell
- www.joepulizzi.com
- www.contentmarketinginstitute.com
- www.facebook.com/joe.pulizzi
- www.linkedin.com/in/joepulizzi
- twitter.com/joepulizzi
- Check out Joe's books!
- Think and Grow Rich
- Jab, Jab, Jab, Right Hook
- www.growthtofreedom.com/115
- www.growthtofreedom.com/114
People mentioned on this episode:
Dan Kuschell is a success driven business growth strategist, a media contributor, and thought leader. He helps entrepreneurs, leaders, and business owners grow and scale their companies 10x by driving the flow of elegant ideas, execution, and team-culture for greater clarity, confidence, and direction. Dan has been recognized worldwide for creating results with his resources, books, and strategies.
Meet Dan at http://www.DanKuschell.com
Watch/Listen to the show: http://www.growthtofreedom.com
Tweet us at: https://twitter.com/dan_kuschell
Follow us on Facebook: https://facebook.com/dankuschellpage
LinkedIn: http://www.linkedin.com/in/dankuschell
Instagram: http://www.instagram.com/dankuschell


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Mike's Obama et al birthday card
Lisa Kereszi passed this along: "This is a card made by Mike, one of the great artists at the LAND Studio and Gallery, an amazing offshoot of the League Treatment Ctr in Dumbo, Brooklyn, NY. Teachers work 5 days a week with developmentally-disabled adults to make artwork that is (affordably!) for sale to sustainably support the art program."


text:
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This is a set of sub frame bushings for your TR7 and TR8. Also bushings have graphite impregnated in them for long life so this will be the last set that you have to install.
We promise to never spam you, and just use your email address to identify you as a valid customer.
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Click the button below to add the Poly Subframe bushing kit TR8 & TR7 to your wish list.


text:
This article looks at the life of Japanese/Canadian karate pioneer, Masaru Shintani. Shintani created one of the largest karate organizations in North America. He also invented Shindo, a martial art facilitating the use of an ancient weapon, the short stick, with modern techniques. Many of Shintani's senior students provided helpful information.
SOURCE: Journal of Asian Martial Arts, Vol. 15 No. 4 (2006): 18 pages.


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That sounds easier and more accurate than measuring the clay on the piston when I put it together. I forget, what is considered a safe clearance?
I have an order from Summit that is at about $70. (including the springs) Need something else to get the free shipping and a $10 off special.


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Dawn and Alice - Photo by Sarah Wirth
I first met Dawn Wirth over 25 years ago through a mutual friend. She was taking photography classes and we soon found out that she was a talented photographer who was enthusiastic about documenting the new scene by taking pictures of the bands. I hadn't seen her since the late 1970's. We were recently reunited thanks to the internet.
Dawn was very involved in supporting the early scene bands. She used her photos to create promo items for the Weirdos and Mumps. In the days before the internet, the only way unsigned bands could get their name out was through fan clubs and flyers.
It is my honor to post a few of her photos, many of which have never been previously published. We wanted to post more, but we were unable to get them in time to run alongside this interview. We hope to be able to post more of her work in the months ahead.
Please click on the Women In Punk thumbnail to read Dawn's interview and see her some of her photos, which feature some of the best known figures in the early L.A. punk scene. Enjoy!


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GENE KELLY (1912-1996), born Eugene Curran Kelly
Haven't you seen Singin' in the Rain (1952)? - the ultimate film!
Watch this and then see these other four films.
An American in Paris (1951) - He's simply fantastic!
Summer Stock (1950) - Even though Judy gets most of the publicity for this movie, Gene did a marvelous job.
Brigadoon (1954) "Almost Like Being in Love" alone is worth the time it takes to watch the whole movie!
On the Town (1949) - It's just really cute, and like always, Gene is sweet.
*Contributed by: "Miska" Wed, May 9 2001 / 14:25:10 PST
Academy Awards®
1945 Nominated for Best Actor in a Leading Role: ANCHORS AWEIGH
1951 Honorary and Other Awards: In appreciation of his versatility as an actor, singer, director and dancer, and specifically for his brilliant achievements in the art of choreography on film. Winner presented a Statuette.